Characterisation of systemic reactions to subcutaneous immunotherapy with airborne allergens and classification according to WAO 2010

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Nam, M.R. Park, H.J. Nam, S.K. Lee, K.H. Kim, M.S. Roh, S.-J. Um, C.-H. Son" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Y.H." "apellidos" => "Nam" ] 1 => array:2 [ "nombre" => "M.R." "apellidos" => "Park" ] 2 => array:2 [ "nombre" => "H.J." "apellidos" => "Nam" ] 3 => array:2 [ "nombre" => "S.K." "apellidos" => "Lee" ] 4 => array:2 [ "nombre" => "K.H." "apellidos" => "Kim" ] 5 => array:2 [ "nombre" => "M.S." "apellidos" => "Roh" ] 6 => array:2 [ "nombre" => "S.-J." "apellidos" => "Um" ] 7 => array:2 [ "nombre" => "C.-H." "apellidos" => "Son" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613002772?idApp=UINPBA00004N" "url" => "/03010546/0000004300000001/v1_201501250943/S0301054613002772/v1_201501250943/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Characterisation of systemic reactions to subcutaneous immunotherapy with airborne allergens and classification according to WAO 2010" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "25" "paginaFinal" => "31" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "N. Santos, A.M. Pereira, R. Silva, J. Torres da Costa, J.L. Plácido" "autores" => array:5 [ 0 => array:4 [ "nombre" => "N." "apellidos" => "Santos" "email" => array:1 [ 0 => "natachalsantos@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A.M." "apellidos" => "Pereira" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Silva" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Torres da Costa" ] 4 => array:2 [ "nombre" => "J.L." "apellidos" => "Plácido" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Centro Hospitalar São João, E.P.E., Serviço de Imunoalergologia, Porto, Portugal" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "BackgroundSpecific immunotherapy with airborne allergens has been used for more than a century with proven efficacy in both allergic rhinitis and asthma.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>Systemic reactions (SR) with subcutaneous immunotherapy (SCIT) are unusual but potentially severe, ranging from mild rhinitis to fatal reactions.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Poorly-controlled asthma, large local reactions, administration during pollen season and dosing error are the more frequently implicated risk factors,<a class="elsevierStyleCrossRefs" href="#bib0020">4–6</a> although the evaluation of their relevance has been hampered by the use of different definitions and classifications of SR severity in previous studies.The European Academy of Allergy and Clinical Immunology (EAACI) has proposed two different SCIT SR classifications, which have been widely used,<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a> but not globally accepted. In 2010, the World Allergy Organization (WAO) published a new proposal for the classification of SCIT SR, suggesting that all these reactions should be promptly treated with adrenaline (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0025">5</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The aim of this study was to determine the frequency of SR to SCIT with airborne allergens, as well as to characterise and classify these reactions according to the WAO 2010 recommendations.MethodsStudy design and populationThis was a cross-sectional, retrospective, descriptive study. Immunotherapy record forms from all patients with at least one administration of SCIT with airborne allergens in the Immunoallergology Division of a University Hospital in Porto, Portugal, from January 2008 to December 2010 were evaluated.The immunotherapy record form was adapted to Portuguese in accordance to EAACI recommendations<a class="elsevierStyleCrossRef" href="#bib0040">8</a> and it was used to register patient and SCIT characteristics, administration date and dose, as well as local and systemic reactions. Immunotherapy record forms were analysed by at least two collaborators and data from patients with SR were collected. Moreover, emergency records of the Immunoallergology Division were also reviewed to guarantee that all the existing systemic reactions were included and accurately characterised.During the study period, 22,332 SCIT injections were administered in 3732 patients.Immunotherapy administration protocolSCIT was administrated in the Immunoallergology Division by trained nurses or medical staff, always under supervision by an allergist. Adequate means for SR treatment were available at all time, including an emergency kit and rescue equipment. All patients under SCIT gave their written informed consent for the treatment.Administered SCIT was of biologically standardised extracts in either depot (adsorbed in aluminium hydroxide or calcium phosphate) or polymerised formulations commercially available in Portugal. The administration schedules and dose adjustments were performed according to the producer's information and physician prescription. We defined immunotherapy schedules as conventional when maintenance dose was achieved in 3–6 months, ultra-rush when the maintenance dose was achieved in one day with two half-hour interval administrations, or rush when maintenance dose was achieved in 1–4 weeks. No cluster schedules were used.Before administration, patients were systematically asked about late local and systemic reactions after the previous administration, as well as any current symptoms. All patients with asthma had their peak expiratory flow (PEF) measured before administration. The administration was postponed in patients with exacerbation of their allergic disease, uncontrolled asthma (PEF<80% of their personal best), generalised cutaneous symptoms or recent infection. Pre-treatment with antihistamines or other drugs and dose adjustments in the pollen season are not routine practice in the Division. Pollen SCIT was started at least eight weeks before the pollen season.SCIT was administered by deep subcutaneous injection in the outer aspect of the median third of the arm. After administration, patients were kept under observation for a minimum period of 30min and all reactions were recorded.Classification of adverse reactionsSR were categorised as immediate (when occurring during the first 30min after administration) or late (when recorded in the following administration or requiring attendance of the immunoallergology emergency consultation/medical attention after the surveillance period). Manifestations and treatment were described based on the available information. The WAO 2010 severity classification was used to retrospectively assess severity.Local reactions were described taking into account the local swelling (wheal) size; those with a mean diameter of ≥8cm were considered as large local reactions.Pollen countsTo account for the influence of SCIT administration during pollen season, we reviewed the data from pollen counts available in the Portuguese aerobiology network website for Porto.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Pollen was collected weekly with a Burkard Seven Day Volumetric Spore-trape® located on the rooftop of Hospital São João, at an altitude of 80m above sea level. Results are shown as median pollen grain counts per cubic metre; counts between 1 and 30pollen/m3 are considered low, while >60pollen/m3 are considered high.Statistical analysisA descriptive analysis of the included variables was performed using frequencies and proportions for categorical variables and median with lower and upper limits for continuous variables.ResultsDuring the 3-year study period, 26 SCIT SR (0.1% of administrations) in 16 (0.6%) patients were recorded.Characteristics of the patients, administered immunotherapy and SR are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Patients with at least one SR had a median age of 22 years (11–50 years old), nine (56%) were male, all had rhinitis and nine (56%) also had asthma.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Ten (63%) patients were on mite immunotherapy. A polymerised extract with rush or ultra-rush schedule induction was used in 13 (81%) patients.Twenty-one (81%) SR occurred during induction phase and all in the first seven months of immunotherapy. Eight (31%) were immediate and 12 (46%) were in the first 3h after SCIT administration.When grading reactions according to WAO 2010, 12 (46%) were grade 1 and 14 (54%, in nine patients) were grade 2, of which 12 (86%) were late (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Most of the grade 2 reactions occurred in individuals with asthma and presented as cough and/or dyspnoea and/or asthma exacerbation (79%). Only two (29%) patients without asthma diagnosis had grade 2 reactions, both with cutaneous manifestations associated with lower respiratory symptoms; both patients required medical care, despite the late onset. No grade 3–5 reactions were recorded. Only one patient needed treatment with intramuscular adrenaline and no biphasic reactions were registered.One of the patients receiving pollen immunotherapy had a SR in March 2009, during a low pollen count week in Porto, while others had SR from September to November, outside the pollen season. Only two patients had a record of a local reaction in the previous administration, both with wheals ≤3cm in diameter.In six patients, a dose adjustment was made following the SR, with one patient only reaching the maintenance dose after five months. Two patients stopped immunotherapy.DiscussionIn this study, the frequency of SR to SCIT with airborne allergens (0.1% of administrations and 0.6% of patients) was similar to that reported by other recent studies in which mainly conventional induction schedules were used.<a class="elsevierStyleCrossRefs" href="#bib0050">10–18</a> Considering that most (96%) of the extracts used in our Division are polymerised and administered in rush or ultra-rush schedules,<a class="elsevierStyleCrossRef" href="#bib0095">19</a> we may conclude that these formulations do not have an increased risk of SR, while allowing a faster achievement of the maintenance dose, as previously shown in immunotherapy using different rush or ultra-rush schedules.<a class="elsevierStyleCrossRefs" href="#bib0100">20–22</a>In the present study, none of the frequently implicated risk factors could explain the occurrence of SR. Uncontrolled asthma was identified by an unstructured symptom questionnaire and PEF measurement. Dosing errors were minimised by the registration of the administered dose in the immunotherapy record form. No patients presented with previous large local reactions, in contrast to what other authors have reported,<a class="elsevierStyleCrossRefs" href="#bib0070">14,23</a> which may be related to the fact that these studies included hymenoptera venom immunotherapy and mostly conventional schedules with depot extracts. Also SCIT administration during pollen season has been reported as a risk factor for systemic reactions,<a class="elsevierStyleCrossRefs" href="#bib0020">4,12</a> but during our three-year study only one patient had a SR during pollen season, and it was in a low pollen count week.As shown by other authors,<a class="elsevierStyleCrossRefs" href="#bib0060">12,24</a> most reactions occurred during induction or early maintenance phase. The large number of late onset reactions reported in our study, frequently with exacerbation of the patient's allergic disease on the day after the administration and most without seeking medical observation, was probably due to the fact that the patients were systematically inquired about these types of reactions before SCIT administration. These late reactions without medical confirmation may overestimate the frequency and severity of the described SR.To our knowledge, this is the first European study to classify SCIT SR according to the WAO 2010 Grading System. In comparison with the American study by Phillips et al.,<a class="elsevierStyleCrossRef" href="#bib0120">24</a> a similar frequency of grade 1 (44%) reactions was found, although they have also reported grade 3 (6%) and grade 4 (9%) reactions.We consider that the WAO 2010 classification has the added value of not being influenced by time of onset as, for example, the EAACI 2006 classification<a class="elsevierStyleCrossRef" href="#bib0040">8</a>, since many of our reactions, including the most severe, were of late onset. However, we consider that this classification may not be adjusted to the subjective assessment of severity by both the patient and the physician, especially concerning SR classified as grade 2. In our population we report nine patients with grade 2 SR that can be clearly separated into two groups: first, the seven asthmatic patients with mild asthma exacerbations, most with no need for medical observation and/or treatment; and second, the two rhinitis patients who presented with generalised cutaneous symptoms and lower respiratory complaints and who, despite late presentation, required medical observation and were treated with systemic drugs. The importance of generalised cutaneous reactions, which may be the only initial symptom of anaphylaxis after specific immunotherapy, is emphasised by the 2010 Anaphylaxis Practice Parameter.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Also in the WAO 2010 document, it is stated that cutaneous manifestations may rapidly progress to more severe reactions,<a class="elsevierStyleCrossRef" href="#bib0025">5</a> despite being classified as grade 1.In relation to the SR treatment, most were completely resolved with antihistamines and/or inhaled ¿2-agonists, without the need for adrenaline administration, which is not in accordance with WAO 2010 recommendations. Thus, we propose that SR presenting in the target organ implied in the patient's respiratory allergic disease can be treated with medication directed at the implied organ, while symptoms that are not usually present in that patient, such as lower respiratory complaints in a non-asthmatic or generalised cutaneous reactions in any patient, should evoke immediate medical observation and treatment with adrenaline (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Despite only 31% of the presented SR were immediate, it is recommended to remain in observation for 30min, especially during the induction phase, since most severe reactions, which would be classified as grades 3–5, are described in this time period.<a class="elsevierStyleCrossRefs" href="#bib0065">13,15</a>We reinforce the importance of informing the patients that, despite being rare, late reactions may occur. Patients should have an action plan and be advised to have their relief medication available after the 30min observation period. They should also be advised to seek immediate medical observation in case of a more severe reaction.We also propose that, before each SCIT administration, rhinitis and asthma control should be assessed using a validated and structured questionnaire (for example, CARAT<a class="elsevierStyleCrossRef" href="#bib0130">26</a>) in addition to PEF measurement; this can improve the identification of patients with uncontrolled allergic disease and may help to further minimise the risk of immunotherapy administration.Lastly, an electronic and multicentre immunotherapy record form would be an important tool to improve the knowledge of immunotherapy administration, decrease the risk of undernotification and allow for analysis of risk factors for systemic reactions with subcutaneous immunotherapy.In conclusion, subcutaneous immunotherapy is a safe treatment when administered by trained and equipped staff. The WAO 2010 classification of systemic reactions might be used to retrospectively classify the severity of reactions but it seems to have flaws as a tool for treatment decision. Most reactions were treated without the need for adrenaline administration; however, we emphasise the potential severity of generalised cutaneous reactions.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this investigation.Confidentiality of dataThe authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.Right to privacy and informed consentThe authors have obtained the informed consent of the patients and/or subjects mentioned in the article. The author for correspondence is in possession of this document.DisclosureThe results of this study have been partially and briefly presented at the 30th Congress of European Allergy and Clinical Immunology: Santos N, Pereira AM, Silva R, Torres da Costa J, Plácido JL. Systemic reactions to subcutaneous immunotherapy with airborne allergens – a first characterization according to WAO's grading system. Allergy. 2011;66(Suppl. 94):138.Financial disclosureNone to declare.Conflict of interestNone to declare." 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The use of different definitions and classifications hampered comparability between studies. AimsTo determine the frequency of SR to SCIT with airborne allergens, and to characterise and classify them according to the WAO 2010 recommendations. MethodsCross-sectional, retrospective study. Data on patients, immunotherapy and SR to SCIT were collected from the SCIT record forms. During the study period, 22,332 SCIT injections were administered (3732 patients). ResultsA total of 26 SR (0.1% of administrations) were recorded in 16 (0.6%) patients (median age 22 years, nine males, all with rhinitis and nine with asthma). Twenty-one (81%) SR occurred during the induction phase; eight (31%) in the first hour after administration. According to the WAO 2010 classification, 12 (46%) were grade 1 and 14 (54%) were grade 2. Most grade 2 reactions occurred in asthmatics, presented as mild asthma symptoms and resolved without need for medical observation. Only two individuals without asthma presented grade 2 reactions, both with concurrent cutaneous and low respiratory symptoms; both required medical observation and treatment despite late onset; 82% (n=12) of grade 2 reactions were late. No grade 3–5 reactions were registered and only one patient needed adrenaline treatment. No risk factors for SR to SCIT were identified in this study. ConclusionsSCIT is a safe treatment when administered by trained staff. The WAO 2010 classification might be useful for retrospectively classifying the severity of reactions, although its usefulness in treatment decision needs further research." ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Adapted from Cox et al.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>" "tabla" => array:2 [ "leyenda" => "The final report should include the first symptom(s)/sign(s), the time of onset after the subcutaneous allergen immunotherapy injection and a suffix reflecting if and when adrenaline was or was not administered: a: ≤5min; b: >5 to ≤10min; c: >10 to ≤20min; d: >20min; z: adrenaline not administered." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Grade 1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Grade 2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Grade 3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Grade 4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Grade 5 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Symptom(s)/sign(s) of 1 organ system:CutaneousorUpper respiratoryorConjunctivalorOtherNausea, metallic taste or headache \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symptom(s)/sign(s) of more than 1 organ systemorLower respiratoryorGastrointestinalorUterine cramps \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lower respiratory≥40% PEF or FEV1 drop or not responding to an inhaled bronchodilatororLaryngeal, uvula or tongue oedema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Respiratory failureorHypotension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Death \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab646884.png" ] ] ] ] "descripcion" => array:1 [ "en" => "World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System (WAO 2010)." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "IN: injection number; P: polymerised; D: depot; IV: intravenous; IM: intramuscular." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Patient</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Immunotherapy</th><th class="td" title="table-head " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Systemic reaction</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Allergic disease \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Extract \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Administration \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IN \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Phase \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Onset time \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Grade \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Medical observation (treatment) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ultra-rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Oropharyngeal pruritus, rhinorrhoea and sneezing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (anti-histamine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">D. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conventional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (unknown) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sneezing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinorrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (anti-histamine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">D. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conventional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nasal and facial pruritus and rhinorrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (anti-histamine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (6h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinosinusitis<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes – 1 week later \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conjunctival and facial pruritus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (unknown) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">D. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conventional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (2h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial pruritus, nasal and conjunctival congestion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nasal congestion and rhinorrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (unknown) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (1 day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nasal pruritus and rhinorrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (1 day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma exacerbation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (45min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Oropharyngeal pruritus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Maintenance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinorrhoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (anti-histamine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Maintenance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (1 day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinorrhoea and sneezing<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ultra-rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Maintenance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (unknown) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sneezing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (12h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cough and dyspnoea<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cough and dyspnoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (anti-histamine, IV corticosteroid) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ultra-rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Maintenance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Immediate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cough \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (no need) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (1 day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dyspnoea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ultra-rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (2 days) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma exacerbation<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (1 day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma exacerbation<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (1 day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma exacerbation<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (unknown) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma exacerbation<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asthma+rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ultra-rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (8h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Palpebral oedema, rhinorrhoea and dyspnoea<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (1 day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Palpebral oedema, rhinorrhoea and dyspnoea<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="11" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Pollen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ultra-rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (1h30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2z \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Generalised erythema→cough and wheezing<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (anti-histamine, IV corticosteroid, nebulised ¿2-agonist) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P. Mites \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rush \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Maintenance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Late (3h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Generalised erythema→nasal congestion, conjunctival erythema and dyspnoea<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes (anti-histamine, IV corticosteroid, IM epinephrine) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab646883.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Dose adjustment in the following administration." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Stopped immunotherapy." ] ] ] "descripcion" => array:1 [ "en" => "Patients, immunotherapy and systemic reactions characterisation and classification according to WAO 2010 Grading System (grades 1–5)." ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Generalised pruritus, urticaria or flushing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Dyspnoea or wheezing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">with associated cutaneous or gastrointestinal symptoms, \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">in non-asthmatic patients, or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">without improvement with inhaled ¿2-agonist \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Laryngeal, uvula, or tongue oedema \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hypotension (systolic arterial pressure <90mmHg) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Loss of consciousness \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab646882.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Indications for immediate adrenaline administration in systemic reactions to airborne allergen subcutaneous immunotherapy." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Allergen injection immunotherapy for seasonal allergic rhinitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.A. Calderon" 1 => "B. Alves" 2 => "M. Jacobson" 3 => "B. Hurwitz" 4 => "A. Sheikh" 5 => "S. Durham" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2007" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Injection allergen immunotherapy for asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.J. Abramson" 1 => "R.M. Puy" 2 => "J.M. Weiner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2010" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990–2001" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.I. Bernstein" 1 => "M. Wanner" 2 => "L. Borish" 3 => "G.M. Liss" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2004.02.006" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2004" "volumen" => "113" "paginaInicial" => "1129" "paginaFinal" => "1136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15208595" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of near-fatal reactions to allergen immunotherapy injections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H.S. Amin" 1 => "G.M. Liss" 2 => "D.I. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/03010546/0000004300000001/v1_201501250943/S0301054614000287/v1_201501250943/en/main.assets" "Apartado" => array:4 [ "identificador" => "5554" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03010546/0000004300000001/v1_201501250943/S0301054614000287/v1_201501250943/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054614000287?idApp=UINPBA00004N"]

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N. Santos

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natachalsantos@gmail.com

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, A.M. Pereira, R. Silva, J. Torres da Costa, J.L. Plácido

Centro Hospitalar São João, E.P.E., Serviço de Imunoalergologia, Porto, Portugal

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Specific immunotherapy with airborne allergens has been used for more than a century with proven efficacy in both allergic rhinitis and asthma.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Systemic reactions (SR) with subcutaneous immunotherapy (SCIT) are unusual but potentially severe, ranging from mild rhinitis to fatal reactions.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Poorly-controlled asthma, large local reactions, administration during pollen season and dosing error are the more frequently implicated risk factors,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#8211;6</span></a> although the evaluation of their relevance has been hampered by the use of different definitions and classifications of SR severity in previous studies.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">European Academy of Allergy and Clinical Immunology</span> (EAACI) has proposed two different SCIT SR classifications, which have been widely used,<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> but not globally accepted. In 2010, the <span class="elsevierStyleItalic">World Allergy Organization</span> (WAO) published a new proposal for the classification of SCIT SR, suggesting that all these reactions should be promptly treated with adrenaline (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study was to determine the frequency of SR to SCIT with airborne allergens, as well as to characterise and classify these reactions according to the WAO 2010 recommendations.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Study design and population</span><p id="par0025" class="elsevierStylePara elsevierViewall">This was a cross-sectional, retrospective, descriptive study. Immunotherapy record forms from all patients with at least one administration of SCIT with airborne allergens in the Immunoallergology Division of a University Hospital in Porto, Portugal, from January 2008 to December 2010 were evaluated.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The immunotherapy record form was adapted to Portuguese in accordance to EAACI recommendations<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and it was used to register patient and SCIT characteristics, administration date and dose, as well as local and systemic reactions. Immunotherapy record forms were analysed by at least two collaborators and data from patients with SR were collected. Moreover, emergency records of the Immunoallergology Division were also reviewed to guarantee that all the existing systemic reactions were included and accurately characterised.</p><p id="par0035" class="elsevierStylePara elsevierViewall">During the study period, 22,332 SCIT injections were administered in 3732 patients.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Immunotherapy administration protocol</span><p id="par0040" class="elsevierStylePara elsevierViewall">SCIT was administrated in the Immunoallergology Division by trained nurses or medical staff, always under supervision by an allergist. Adequate means for SR treatment were available at all time, including an emergency kit and rescue equipment. All patients under SCIT gave their written informed consent for the treatment.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Administered SCIT was of biologically standardised extracts in either depot (adsorbed in aluminium hydroxide or calcium phosphate) or polymerised formulations commercially available in Portugal. The administration schedules and dose adjustments were performed according to the producer&#39;s information and physician prescription. We defined immunotherapy schedules as conventional when maintenance dose was achieved in 3&#8211;6 months, ultra-rush when the maintenance dose was achieved in one day with two half-hour interval administrations, or rush when maintenance dose was achieved in 1&#8211;4 weeks. No cluster schedules were used.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Before administration, patients were systematically asked about late local and systemic reactions after the previous administration, as well as any current symptoms. All patients with asthma had their peak expiratory flow (PEF) measured before administration. The administration was postponed in patients with exacerbation of their allergic disease, uncontrolled asthma (PEF<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>80% of their personal best), generalised cutaneous symptoms or recent infection. Pre-treatment with antihistamines or other drugs and dose adjustments in the pollen season are not routine practice in the Division. Pollen SCIT was started at least eight weeks before the pollen season.</p><p id="par0055" class="elsevierStylePara elsevierViewall">SCIT was administered by deep subcutaneous injection in the outer aspect of the median third of the arm. After administration, patients were kept under observation for a minimum period of 30<span class="elsevierStyleHsp" style=""></span>min and all reactions were recorded.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Classification of adverse reactions</span><p id="par0060" class="elsevierStylePara elsevierViewall">SR were categorised as immediate (when occurring during the first 30<span class="elsevierStyleHsp" style=""></span>min after administration) or late (when recorded in the following administration or requiring attendance of the immunoallergology emergency consultation/medical attention after the surveillance period). Manifestations and treatment were described based on the available information. The WAO 2010 severity classification was used to retrospectively assess severity.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Local reactions were described taking into account the local swelling (wheal) size; those with a mean diameter of &#8805;8<span class="elsevierStyleHsp" style=""></span>cm were considered as large local reactions.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Pollen counts</span><p id="par0070" class="elsevierStylePara elsevierViewall">To account for the influence of SCIT administration during pollen season, we reviewed the data from pollen counts available in the Portuguese aerobiology network website for Porto.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Pollen was collected weekly with a Burkard Seven Day Volumetric Spore-trape<span class="elsevierStyleSup">&reg;</span> located on the rooftop of Hospital S&atilde;o Jo&atilde;o, at an altitude of 80<span class="elsevierStyleHsp" style=""></span>m above sea level. Results are shown as median pollen grain counts per cubic metre; counts between 1 and 30<span class="elsevierStyleHsp" style=""></span>pollen/m<span class="elsevierStyleSup">3</span> are considered low, while &#62;60<span class="elsevierStyleHsp" style=""></span>pollen/m<span class="elsevierStyleSup">3</span> are considered high.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">A descriptive analysis of the included variables was performed using frequencies and proportions for categorical variables and median with lower and upper limits for continuous variables.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">During the 3-year study period, 26 SCIT SR (0.1% of administrations) in 16 (0.6%) patients were recorded.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Characteristics of the patients, administered immunotherapy and SR are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Patients with at least one SR had a median age of 22 years (11&#8211;50 years old), nine (56%) were male, all had rhinitis and nine (56%) also had asthma.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Ten (63%) patients were on mite immunotherapy. A polymerised extract with rush or ultra-rush schedule induction was used in 13 (81%) patients.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Twenty-one (81%) SR occurred during induction phase and all in the first seven months of immunotherapy. Eight (31%) were immediate and 12 (46%) were in the first 3<span class="elsevierStyleHsp" style=""></span>h after SCIT administration.</p><p id="par0100" class="elsevierStylePara elsevierViewall">When grading reactions according to WAO 2010, 12 (46%) were grade 1 and 14 (54%, in nine patients) were grade 2, of which 12 (86%) were late (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Most of the grade 2 reactions occurred in individuals with asthma and presented as cough and/or dyspnoea and/or asthma exacerbation (79%). Only two (29%) patients without asthma diagnosis had grade 2 reactions, both with cutaneous manifestations associated with lower respiratory symptoms; both patients required medical care, despite the late onset. No grade 3&#8211;5 reactions were recorded. Only one patient needed treatment with intramuscular adrenaline and no biphasic reactions were registered.</p><p id="par0105" class="elsevierStylePara elsevierViewall">One of the patients receiving pollen immunotherapy had a SR in March 2009, during a low pollen count week in Porto, while others had SR from September to November, outside the pollen season. Only two patients had a record of a local reaction in the previous administration, both with wheals &#8804;3<span class="elsevierStyleHsp" style=""></span>cm in diameter.</p><p id="par0110" class="elsevierStylePara elsevierViewall">In six patients, a dose adjustment was made following the SR, with one patient only reaching the maintenance dose after five months. Two patients stopped immunotherapy.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0115" class="elsevierStylePara elsevierViewall">In this study, the frequency of SR to SCIT with airborne allergens (0.1% of administrations and 0.6% of patients) was similar to that reported by other recent studies in which mainly conventional induction schedules were used.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;18</span></a> Considering that most (96%) of the extracts used in our Division are polymerised and administered in rush or ultra-rush schedules,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> we may conclude that these formulations do not have an increased risk of SR, while allowing a faster achievement of the maintenance dose, as previously shown in immunotherapy using different rush or ultra-rush schedules.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">In the present study, none of the frequently implicated risk factors could explain the occurrence of SR. Uncontrolled asthma was identified by an unstructured symptom questionnaire and PEF measurement. Dosing errors were minimised by the registration of the administered dose in the immunotherapy record form. No patients presented with previous large local reactions, in contrast to what other authors have reported,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,23</span></a> which may be related to the fact that these studies included hymenoptera venom immunotherapy and mostly conventional schedules with depot extracts. Also SCIT administration during pollen season has been reported as a risk factor for systemic reactions,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,12</span></a> but during our three-year study only one patient had a SR during pollen season, and it was in a low pollen count week.</p><p id="par0125" class="elsevierStylePara elsevierViewall">As shown by other authors,<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,24</span></a> most reactions occurred during induction or early maintenance phase. The large number of late onset reactions reported in our study, frequently with exacerbation of the patient&#39;s allergic disease on the day after the administration and most without seeking medical observation, was probably due to the fact that the patients were systematically inquired about these types of reactions before SCIT administration. These late reactions without medical confirmation may overestimate the frequency and severity of the described SR.</p><p id="par0130" class="elsevierStylePara elsevierViewall">To our knowledge, this is the first European study to classify SCIT SR according to the WAO 2010 Grading System. In comparison with the American study by Phillips et al.,<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> a similar frequency of grade 1 (44%) reactions was found, although they have also reported grade 3 (6%) and grade 4 (9%) reactions.</p><p id="par0135" class="elsevierStylePara elsevierViewall">We consider that the WAO 2010 classification has the added value of not being influenced by time of onset as, for example, the EAACI 2006 classification<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>, since many of our reactions, including the most severe, were of late onset. However, we consider that this classification may not be adjusted to the subjective assessment of severity by both the patient and the physician, especially concerning SR classified as grade 2. In our population we report nine patients with grade 2 SR that can be clearly separated into two groups: first, the seven asthmatic patients with mild asthma exacerbations, most with no need for medical observation and/or treatment; and second, the two rhinitis patients who presented with generalised cutaneous symptoms and lower respiratory complaints and who, despite late presentation, required medical observation and were treated with systemic drugs. The importance of generalised cutaneous reactions, which may be the only initial symptom of anaphylaxis after specific immunotherapy, is emphasised by the 2010 Anaphylaxis Practice Parameter.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Also in the WAO 2010 document, it is stated that cutaneous manifestations may rapidly progress to more severe reactions,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> despite being classified as grade 1.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In relation to the SR treatment, most were completely resolved with antihistamines and/or inhaled ¿2-agonists, without the need for adrenaline administration, which is not in accordance with WAO 2010 recommendations. Thus, we propose that SR presenting in the target organ implied in the patient&#39;s respiratory allergic disease can be treated with medication directed at the implied organ, while symptoms that are not usually present in that patient, such as lower respiratory complaints in a non-asthmatic or generalised cutaneous reactions in any patient, should evoke immediate medical observation and treatment with adrenaline (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Despite only 31% of the presented SR were immediate, it is recommended to remain in observation for 30<span class="elsevierStyleHsp" style=""></span>min, especially during the induction phase, since most severe reactions, which would be classified as grades 3&#8211;5, are described in this time period.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,15</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">We reinforce the importance of informing the patients that, despite being rare, late reactions may occur. Patients should have an action plan and be advised to have their relief medication available after the 30<span class="elsevierStyleHsp" style=""></span>min observation period. They should also be advised to seek immediate medical observation in case of a more severe reaction.</p><p id="par0155" class="elsevierStylePara elsevierViewall">We also propose that, before each SCIT administration, rhinitis and asthma control should be assessed using a validated and structured questionnaire (for example, CARAT<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>) in addition to PEF measurement; this can improve the identification of patients with uncontrolled allergic disease and may help to further minimise the risk of immunotherapy administration.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Lastly, an electronic and multicentre immunotherapy record form would be an important tool to improve the knowledge of immunotherapy administration, decrease the risk of undernotification and allow for analysis of risk factors for systemic reactions with subcutaneous immunotherapy.</p><p id="par0165" class="elsevierStylePara elsevierViewall">In conclusion, subcutaneous immunotherapy is a safe treatment when administered by trained and equipped staff. The WAO 2010 classification of systemic reactions might be used to retrospectively classify the severity of reactions but it seems to have flaws as a tool for treatment decision. Most reactions were treated without the need for adrenaline administration; however, we emphasise the potential severity of generalised cutaneous reactions.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Ethical disclosures</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Protection of human and animal subjects</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Confidentiality of data</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Right to privacy and informed consent</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of the patients and/or subjects mentioned in the article. The author for correspondence is in possession of this document.</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Disclosure</span><p id="par0185" class="elsevierStylePara elsevierViewall">The results of this study have been partially and briefly presented at the 30th Congress of European Allergy and Clinical Immunology: Santos N, Pereira AM, Silva R, Torres da Costa J, Pl&aacute;cido JL. <span class="elsevierStyleItalic">Systemic reactions to subcutaneous immunotherapy with airborne allergens &#8211; a first characterization according to WAO&#39;s grading system</span>. Allergy. 2011;66(Suppl. 94):138.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Financial disclosure</span><p id="par0190" class="elsevierStylePara elsevierViewall">None to declare.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">None to declare.</p></span></span>"
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        8 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Financial disclosure"
        ]
        9 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Conflict of interest"
        ]
        10 => array:2 [
          "identificador" => "xack123026"
          "titulo" => "Acknowledgments"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-06-04"
    "fechaAceptado" => "2013-10-04"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec389950"
          "palabras" => array:3 [
            0 => "Allergen immunotherapy"
            1 => "Classification"
            2 => "Systemic reactions"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Systemic reactions (SR) to subcutaneous immunotherapy (SCIT) are rare but potentially severe. The use of different definitions and classifications hampered comparability between studies.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Aims</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the frequency of SR to SCIT with airborne allergens, and to characterise and classify them according to the WAO 2010 recommendations.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional, retrospective study. Data on patients, immunotherapy and SR to SCIT were collected from the SCIT record forms. During the study period, 22,332 SCIT injections were administered (3732 patients).</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 26 SR (0.1% of administrations) were recorded in 16 (0.6%) patients (median age 22 years, nine males, all with rhinitis and nine with asthma). Twenty-one (81%) SR occurred during the induction phase; eight (31%) in the first hour after administration. According to the WAO 2010 classification, 12 (46%) were grade 1 and 14 (54%) were grade 2. Most grade 2 reactions occurred in asthmatics, presented as mild asthma symptoms and resolved without need for medical observation. Only two individuals without asthma presented grade 2 reactions, both with concurrent cutaneous and low respiratory symptoms; both required medical observation and treatment despite late onset; 82% (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>12) of grade 2 reactions were late. No grade 3&#8211;5 reactions were registered and only one patient needed adrenaline treatment. No risk factors for SR to SCIT were identified in this study.</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">SCIT is a safe treatment when administered by trained staff. The WAO 2010 classification might be useful for retrospectively classifying the severity of reactions, although its usefulness in treatment decision needs further research.</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Adapted from Cox et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>"
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The final report should include the first symptom(s)/sign(s), the time of onset after the subcutaneous allergen immunotherapy injection and a suffix reflecting if and when adrenaline was or was not administered: a: &#8804;5<span class="elsevierStyleHsp" style=""></span>min; b: &#62;<span class="elsevierStyleHsp" style=""></span>5 to &#8804;10<span class="elsevierStyleHsp" style=""></span>min; c: &#62;<span class="elsevierStyleHsp" style=""></span>10 to &#8804;20<span class="elsevierStyleHsp" style=""></span>min; d: &#62;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>min; z: adrenaline not administered.</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Grade 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Grade 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Grade 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Grade 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Grade 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Symptom(s)/sign(s) of <span class="elsevierStyleItalic"><span class="elsevierStyleBold">1 organ system</span></span>:<span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Cutaneous</span></span><span class="elsevierStyleItalic">or</span><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Upper respiratory</span></span><span class="elsevierStyleItalic">or</span><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Conjunctival</span></span><span class="elsevierStyleItalic">or</span><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Other</span></span>Nausea, metallic taste or headache&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Symptom(s)/sign(s) of <span class="elsevierStyleItalic"><span class="elsevierStyleBold">more than 1 organ system</span></span><span class="elsevierStyleItalic">or</span><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Lower respiratory</span></span><span class="elsevierStyleItalic">or</span><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Gastrointestinal</span></span><span class="elsevierStyleItalic">or</span><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Uterine cramps</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Lower respiratory</span></span>&#8805;40% PEF or FEV1 drop <span class="elsevierStyleItalic">or</span> not responding to an inhaled bronchodilator<span class="elsevierStyleItalic">or</span><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Laryngeal, uvula or tongue oedema</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Respiratory failure</span></span><span class="elsevierStyleItalic">or</span><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Hypotension</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold"><span class="elsevierStyleUnderline">Death</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab646884.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System (WAO 2010).</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">IN: injection number; P: polymerised; D: depot; IV: intravenous; IM: intramuscular.</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Patient</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Immunotherapy</th><th class="td" title="table-head  " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Systemic reaction</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Allergic disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Extract&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Phase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Onset time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Grade&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Medical observation (treatment)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Pollen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ultra-rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oropharyngeal pruritus, rhinorrhoea and sneezing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (anti-histamine)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conventional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (unknown)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sneezing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinorrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (anti-histamine)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conventional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nasal and facial pruritus and rhinorrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (anti-histamine)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (6<span class="elsevierStyleHsp" style=""></span>h)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinosinusitis<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes &#8211; 1 week later&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conjunctival and facial pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (unknown)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conventional&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (2<span class="elsevierStyleHsp" style=""></span>h)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Facial pruritus, nasal and conjunctival congestion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nasal congestion and rhinorrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (unknown)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (1 day)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nasal pruritus and rhinorrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (1 day)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma exacerbation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (45<span class="elsevierStyleHsp" style=""></span>min)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oropharyngeal pruritus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Maintenance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinorrhoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (anti-histamine)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Maintenance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (1 day)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinorrhoea and sneezing<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Pollen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ultra-rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Maintenance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (unknown)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Sneezing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Pollen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (12<span class="elsevierStyleHsp" style=""></span>h)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cough and dyspnoea<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cough and dyspnoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (anti-histamine, IV corticosteroid)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Pollen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ultra-rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Maintenance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Immediate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cough&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (no need)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Pollen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (1 day)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dyspnoea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ultra-rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (2 days)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma exacerbation<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (1 day)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma exacerbation<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (1 day)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma exacerbation<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (unknown)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma exacerbation<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asthma<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ultra-rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (8<span class="elsevierStyleHsp" style=""></span>h)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Palpebral oedema, rhinorrhoea and dyspnoea<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (1 day)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Palpebral oedema, rhinorrhoea and dyspnoea<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="11" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Pollen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ultra-rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (1<span class="elsevierStyleHsp" style=""></span>h30)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2z&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Generalised erythema<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>cough and wheezing<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (anti-histamine, IV corticosteroid, nebulised ¿2-agonist)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">P. Mites&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rush&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Maintenance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Late (3<span class="elsevierStyleHsp" style=""></span>h)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Generalised erythema<span class="elsevierStyleHsp" style=""></span>&#8594;<span class="elsevierStyleHsp" style=""></span>nasal congestion, conjunctival erythema and dyspnoea<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes (anti-histamine, IV corticosteroid, IM epinephrine)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Patients, immunotherapy and systemic reactions characterisation and classification according to WAO 2010 Grading System (grades 1&#8211;5).</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Generalised pruritus, urticaria or flushing</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>with associated cutaneous or gastrointestinal symptoms,&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>in non-asthmatic patients, or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>without improvement with inhaled ¿2-agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Laryngeal, uvula, or tongue oedema</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Hypotension (systolic arterial pressure &#60;90</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mmHg)</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Loss of consciousness</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Indications for immediate adrenaline administration in systemic reactions to airborne allergen subcutaneous immunotherapy.</p>"
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    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:26 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Allergen injection immunotherapy for seasonal allergic rhinitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M.A. Calderon"
                            1 => "B. Alves"
                            2 => "M. Jacobson"
                            3 => "B. Hurwitz"
                            4 => "A. Sheikh"
                            5 => "S. Durham"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2007"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Injection allergen immunotherapy for asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M.J. Abramson"
                            1 => "R.M. Puy"
                            2 => "J.M. Weiner"
                          ]
                        ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2010"
                      ]
                    ]
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                ]
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            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990&#8211;2001"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D.I. Bernstein"
                            1 => "M. Wanner"
                            2 => "L. Borish"
                            3 => "G.M. Liss"
                          ]
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                  "host" => array:1 [
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                      "doi" => "10.1016/j.jaci.2004.02.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2004"
                        "volumen" => "113"
                        "paginaInicial" => "1129"
                        "paginaFinal" => "1136"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15208595"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of near-fatal reactions to allergen immunotherapy injections"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H.S. Amin"
                            1 => "G.M. Liss"
                            2 => "D.I. Bernstein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2005.10.010"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2006"
                        "volumen" => "117"
                        "paginaInicial" => "169"
                        "paginaFinal" => "175"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16387602"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Speaking the same language: the World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L. Cox"
                            1 => "D. Larenas-Linnemann"
                            2 => "R.F. Lockey"
                            3 => "G. Passalacqua"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2009.10.060"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2010"
                        "volumen" => "125"
                        "paginaInicial" => "569"
                        "paginaFinal" => "574"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20144472"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Allergen immunotherapy: a practice parameter second update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L. Cox"
                            1 => "J. Li"
                            2 => "R. Lockey"
                            3 => "H. Nelson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2007.06.019"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2007"
                        "volumen" => "120"
                        "paginaInicial" => "S25"
                        "paginaFinal" => "S85"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17765078"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
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                        "tituloSerie" => "Allergy"
                        "fecha" => "2010"
                        "volumen" => "65"
                        "paginaInicial" => "1042"
                        "paginaFinal" => "1048"
                        "link" => array:1 [
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    "agradecimientos" => array:1 [
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        "identificador" => "xack123026"
        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0200" class="elsevierStylePara elsevierViewall">To the nurses of our Immunoallergology Division: Aida Feiteira, Liliana Castro, Fernanda Campos, Fernando Monteirinho, Jo&atilde;o Carlos Fonseca and Fernanda Santos, for their collaboration with the immunotherapy registration form and daily dedication.</p>"
        "vista" => "all"
      ]
    ]
  ]
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    "identificador" => "5554"
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  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054614000287?idApp=UINPBA00004N"
]

Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2013.10.006

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	3	0	3
2024 October	18	3	21
2024 September	43	3	46
2024 August	30	6	36
2024 July	15	2	17
2024 June	12	4	16
2024 May	15	8	23
2024 April	13	8	21
2024 March	28	6	34
2024 February	19	5	24
2024 January	21	8	29
2023 December	18	7	25
2023 November	18	4	22
2023 October	25	4	29
2023 September	20	2	22
2023 August	21	5	26
2023 July	43	7	50
2023 June	23	9	32
2023 May	55	11	66
2023 April	35	3	38
2023 March	18	3	21
2023 February	16	6	22
2023 January	15	8	23
2022 December	43	9	52
2022 November	42	5	47
2022 October	12	7	19
2022 September	18	15	33
2022 August	16	6	22
2022 July	15	7	22
2022 June	12	4	16
2022 May	13	12	25
2022 April	17	7	24
2022 March	15	11	26
2022 February	7	9	16
2022 January	12	8	20
2021 December	11	9	20
2021 November	17	17	34
2021 October	19	12	31
2021 September	10	10	20
2021 August	12	4	16
2021 July	11	14	25
2021 June	15	11	26
2021 May	19	6	25
2021 April	38	11	49
2021 March	9	23	32
2021 February	9	18	27
2021 January	15	18	33
2020 December	0	7	7
2020 November	0	4	4
2020 October	0	2	2
2020 September	0	4	4
2020 August	0	6	6
2020 July	0	4	4
2020 June	0	1	1
2020 May	0	10	10
2020 April	0	2	2
2020 March	0	9	9
2020 February	0	2	2
2020 January	0	12	12
2019 December	0	8	8
2019 November	0	3	3
2019 October	0	6	6
2019 September	0	7	7
2019 August	0	2	2
2019 July	0	13	13
2019 June	0	4	4
2019 May	0	57	57
2019 April	0	18	18
2019 March	0	2	2
2019 February	0	6	6
2018 December	0	7	7
2018 July	0	3	3
2018 February	4	5	9
2018 January	10	5	15
2017 December	4	3	7
2017 November	15	9	24
2017 October	8	3	11
2017 September	8	9	17
2017 August	16	8	24
2017 July	16	4	20
2017 June	8	22	30
2017 May	12	12	24
2017 April	16	9	25
2017 March	11	40	51
2017 February	5	9	14
2017 January	9	6	15
2016 December	14	10	24
2016 November	16	12	28
2016 October	40	5	45
2016 September	7	13	20
2016 August	14	12	26
2016 July	10	6	16
2016 June	18	11	29
2016 May	12	13	25
2016 April	14	22	36
2016 March	16	13	29
2016 February	21	15	36
2016 January	18	10	28
2015 October	0	1	1
2015 April	2	4	6
2015 March	2	3	5
2015 February	3	6	9

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

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