Allergic asthma | Medicina Clínica (English Edition)

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PEF: peak expiratory flow; FENO: fractional exhaled nitric oxide; FEV1: forced expiratory volume." ] ] ] "textoCompleto" => "IntroductionAsthma is one of the most important allergic diseases in our country due to its high prevalence, chronic nature, its influence in patients’ quality of life and its economic repercussions. In the Alergológica 2005 study, asthma occupies the second place in frequency for consultation in the Allergy services, after allergic rhinitis, and in up to 80% of the cases, the allergic asthma diagnosis was confirmed.<a class="elsevierStyleCrossRef" href="#bib0235">1</a>At the moment, one of the most accepted definitions of asthma is the concept of chronic inflammatory disease of the respiratory tract, whose pathogenesis involves various types of cells and inflammation mediators. It is a process partly determined by genetic factors and is characterised by bronchial hyperresponsiveness (BHR) and varying degrees of airflow obstruction, which is total or partially reversible, either as a result of pharmacological action, or spontaneous event.<a class="elsevierStyleCrossRef" href="#bib0240">2</a>Importance of asthma and a good controlAsthma is a global health problem that affects 300 million people worldwide. In Spain, asthma prevalence in the paediatric population oscillates around 10%, whereas in adult population it is around 5%, and the last data indicate that the asthma prevalence increases in both children and adults. At present, it is known that asthma is, after the chronic obstructive pulmonary disease, the cause of greater number of absenteeism from work due to respiratory diseases. The World Health Organisation estimates 15 million years of life are lost annually adjusted for impairment due to the asthma.<a class="elsevierStyleCrossRef" href="#bib0245">3</a>According to the AsmaCost study of 2007, the economic cost of the asthmatic adult patient in Spain ascends to 1726 and 1533€ from the perspective of the society and the National Health System, respectively. The cost is higher in severe asthmatics (2635€) and in patients older than 65 years of age (2069€).<a class="elsevierStyleCrossRef" href="#bib0250">4</a> In children, the average annual cost in Spain in 2008 was of 1490€, and of 5380€ in the severe asthma cases.<a class="elsevierStyleCrossRef" href="#bib0255">5</a> In addition, it is known that around 70% of the total cost of the disease is determined by the poor control of the disease. The cost of hospitalisation, emergency department visits or death are major causes of the consumption of economic resources due to asthma.<a class="elsevierStyleCrossRefs" href="#bib0260">6,7</a>According to the Asthma Control in Spain study, more than two thirds of the studied patients had a poorly controlled asthma.<a class="elsevierStyleCrossRef" href="#bib0270">8</a> A recent study, conducted in our country in 1363 patients with asthma, shows that only 12% of the patients are well controlled based on the criteria of the Global Initiative for Asthma (GINA), although 60% of the patients consider their asthma is well controlled, and 50% of the doctors assume asthma can be controlled.<a class="elsevierStyleCrossRefs" href="#bib0275">9,10</a>Asthma diagnosed as a syndromeThe diagnostic process is based on the definition of the disease, which includes, on the one hand, the symptoms and the variable obstruction of the airflow, and on the other hand, the underlying inflammation and the BHR.The medical history of the patient and the symptoms are essential to establish the diagnosis. The relevant data we must gather in the medical history are summarised in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<a class="elsevierStyleCrossRef" href="#bib0285">11</a> In the allergic patient, it is important to assess extra-pulmonary manifestations of atopy such as atopic eczema, allergy to foods or the nasal inflammation in the allergic rhinitis that frequently accompanies the asthma. It is also relevant to look into possible intolerance to acetylsalicylic acid or to non-steroidal anti-inflammatory drugs (NSAIDs).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>To confirm the bronchial obstruction, its reversibility and/or the BHR, there should be conducted a lung basal function test, bronchodilator test, monitoring of the peak expiratory flow (PEF) and/or bronchoconstriction tests. The obstruction is defined as the ratio between the forced expiratory volume (FEV)1 in one second and the forced vital capacity (FVC), (FEV1/FVC) in the basal forced spirometry below the inferior limit of the reference values, which is arbitrarily established in 0.7. The reversibility of this obstruction is observed through the bronchodilator test, generally, with inhaled salbutamol and repeating the spirometry 15min later. The Spanish Guideline on the Management of Asthma (Guía Española para el Manejo del Asma, GEMA)<a class="elsevierStyleCrossRef" href="#bib0240">2</a> considers the test is positive if FEV1 or FVC increases by 12% and to more than 200ml compared to the previous (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In children, the bronchodilator test is positive when FEV1 increase on the baseline value is greater or equal to 12%. The BHR to different stimuli is quantified by means of the exposure to bronchoconstrictor agents, classified according to their mechanism of action (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The variability of the pulmonary function can be determined by means of portable devices to measure the PEF. The index of variability of PEF equal or higher than 20% is a criterion to asthma diagnosis.<a class="elsevierStyleCrossRefs" href="#bib0240">2,11,12</a>Unfortunately, all these lung function tests are not applicable to infants or to pre-school children with asthma. This is why GEMA and the American Thoracic Society/European Respiratory Society<a class="elsevierStyleCrossRefs" href="#bib0240">2,12</a> recommend alternative tests such as the forced impulse oscillometry (IOS), the measurement of occlusion resistances, flow volume/tidal volume curve analysis or the measurement of resistances by plethysmography. <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows the recommended diagnostic procedures to control severe asthma.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Diagnosis of allergic sensitisationThe allergy test has to be conducted in all patients diagnosed with asthma, due to the high prevalence of sensitisation to inhalant allergens and the comorbidity with other allergic manifestations. It is known that sensitisation to aeroallergens mediated by IgE antibodies constitutes a very significant risk factor to develop asthma.<a class="elsevierStyleCrossRefs" href="#bib0295">13,14</a> It has been confirmed that exposure to high concentrations of allergens increases the severity of the asthma, and that there exists a synergy between the allergic sensitisation and viral infections.<a class="elsevierStyleCrossRef" href="#bib0305">15</a>The skin test (prick-tests) is the diagnostic method of choice to detect sensitisation to allergens mediated by IgE, due to its high sensitivity and specificity. It is a safe, simple, fast and painless method. Generally, it is conducted with a series of allergens that are present in the geographic area where the patient lives. However, it is recommended to use a standard allergen battery to test all the European patients diagnosed with asthma (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRef" href="#bib0310">16</a> A positive skin test will only indicate sensitisation, which will be assessed according to the relation between allergen exposure and the symptoms of patient. The aeroallergens most frequently associated with allergic asthma in Spain are pollen (44%), the house dust mites (41%), the animal epithelia (20%) and fungi (8%) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRef" href="#bib0235">1</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The determination of IgE specific to whole allergen extracts or the IgE to individual recombinant or purified natural allergen molecules leads to a more accurate diagnosis of sensitisation. They are more specific than skin tests and will be useful in cases of dermatographic urticaria, extensive dermatitis and if the patient receives pharmacological treatments that inhibit the skin tests, besides confirming them.<a class="elsevierStyleCrossRefs" href="#bib0315">17,18</a> Moreover, it is important to distinguish, in patients that present sensitisation to multiple allergens, those patients who are genuinely sensitised to several allergenic sources from crossed-sensitised patients, since it will be relevant to establish strategies of avoidance and/or allergen immunotherapy.<a class="elsevierStyleCrossRef" href="#bib0325">19</a>In order to establish a relationship between the allergic sensitisation and the symptoms of the patient and, therefore, to establish their clinical relevance, it could be useful to use calendars of symptoms and/or the monitoring of the PEF to compare with the exposure to the allergen (for example, pollen count) or bronchial provocation tests to specific allergens, although this procedure is usually reserved for occupational asthma cases or for research.Assessment of the bronchial inflammation and other biomarkersIn the last few years, multiple biomarkers have appeared. They are proved to be useful for diagnosing and monitoring asthma.The patterns of eosinophilic inflammation in induced sputum are responsive and they change accompanying changes in the exposure to allergens and in the clinical control of the disease.<a class="elsevierStyleCrossRef" href="#bib0330">20</a> The limit in its regular use is the necessity to immediately process the sample.The exhaled nitric oxide fraction has been directly related to the degree of eosinophilic inflammation, and values higher than 30ppb are considered diagnoses, according to GEMA, in patients with a history of asthma.<a class="elsevierStyleCrossRef" href="#bib0240">2</a> At present, there are easy-to-use small devices that can be used daily for diagnosis and for monitoring of patients.Other methods, such as the temperature of the exhaled air,<a class="elsevierStyleCrossRefs" href="#bib0335">21,22</a> the analysis of condensation of the exhaled air<a class="elsevierStyleCrossRef" href="#bib0345">23</a> or electronic nose, for the analysis of the organic volatile components,<a class="elsevierStyleCrossRefs" href="#bib0350">24,25</a> are of experimental use.Classification of bronchial asthmaAsthma has traditionally been classified in accordance with its diagnosis (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). However, as the asthma is a variable disease, at present it has changed from that rigid classification in accordance with its severity to a more dynamic classification in accordance with the control of the disease (completely controlled, well controlled, partially controlled and not controlled asthma). The components assessed to determine the degree of control include daytime, nighttime and awakening symptoms, need for rescue treatment, limitation of activities, pulmonary function, risk of exacerbation throughout a year and/or the adverse events of the treatment.<a class="elsevierStyleCrossRefs" href="#bib0240">2,11,26</a> To assess the asthma control, there are simple questionnaires, translated and validated in Spanish, to be used in common practice practice.<a class="elsevierStyleCrossRefs" href="#bib0365">27,28</a><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Asthma has traditionally been classified as extrinsic or intrinsic, but in the last decade, new classifications based on different phenotype have appeared.<a class="elsevierStyleCrossRefs" href="#bib0375">29,30</a> A phenotype is the set of observable characteristics of an organism that constitute the result of the interaction between the genetic load and the environment. Even more recently, the concept of “endotypes” has been coined.<a class="elsevierStyleCrossRef" href="#bib0385">31</a> Endotype is a subtype of a disease defined by a functional or a pathophysiological mechanism, unique or distinctive (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). A phenotype can be present in more than one endotype and an endotype can contain more than one phenotype (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). These new concepts will help in the future to develop more specific therapeutic strategies.<a class="elsevierStyleCrossRef" href="#bib0390">32</a><elsevierMultimedia ident="fig0015"></elsevierMultimedia>Non-pharmacological treatmentThe primary objective of the treatment is to control and to maintain the control of the disease, to prevent the chronic airflow obstruction or to reduce morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0395">33</a> An essential part of the treatment includes the non-pharmacological measures. The different guidelines vary ostensibly from one another in the severity of their recommendations about the allergen avoidance measures. In this way, for the North American Expert Panel Report (EPR-3),<a class="elsevierStyleCrossRef" href="#bib0400">34</a> the avoidance of aeroallergens continues to be a fundamental aspect of the allergic asthma treatment. Other guidelines, such as GEMA,<a class="elsevierStyleCrossRef" href="#bib0240">2</a> or GINA,<a class="elsevierStyleCrossRef" href="#bib0285">11</a> consider this recommendation as less relevant. On the contrary, there seems to exist a clear consensus around the better control of asthma and the avoidance of exposure to the smoke of tobacco.Another risk factor that could be modified and that is related to asthma is the obesity, which has been associated to a greater incidence, severity and to a worse response to treatment and with an increase of the bronchial inflammatory response.<a class="elsevierStyleCrossRef" href="#bib0405">35</a>It is necessary to assess the individual tolerance to NSAIDs in asthmatic patients. Up to 20% of patients can present intolerance to NSAIDs, which can increase to 40% in case of chronic rhinosinusitis with or without concomitant polyps.<a class="elsevierStyleCrossRef" href="#bib0410">36</a> These patients usually present asthma that is difficult to control, and the administration of acetylsalicylic acid or NSAIDs can trigger very severe crises of bronchospasm. That is why an adequate avoidance of these drugs is essential. In many patients, the NSAIDs cyclo-osygenase 2 inhibitors can be tolerated.<a class="elsevierStyleCrossRef" href="#bib0415">37</a>The most recent guidelines for the asthma treatment<a class="elsevierStyleCrossRefs" href="#bib0360">26,38</a> unequivocally recommend to follow action plans for the education of asthma patients. These plans must be focused on the knowledge of the basics of the disease, the hygienic measures, the maintenance treatment and the recognition of the exacerbations with specific indications for action. They recommend to always verify that the inhalation technique is correct.Recently, a new non-pharmacological treatment called bronchial thermoplasty has appeared. It consists of the administration of thermal energy by means of radiofrequency through a catheter that is introduced in the bronchial tree (endoscopic technique). This therapeutic approach has been accepted as a complementary option in patients with severe asthma who, despite the fact that they receive medical treatment, they still remain symptomatic. However, its relevance and role in the clinical therapeutic are still to be defined.<a class="elsevierStyleCrossRef" href="#bib0425">39</a>Pharmacological treatmentIn the asthma treatment, we can differentiate between the pharmacological maintenance treatment and rescue drugs or drugs to relieve symptoms.<a class="elsevierStyleCrossRef" href="#bib0395">33</a> Maintenance medication, which must be administered for prolonged periods, include inhaled glucocorticosteroids, alone or in combination with long-acting beta-2 agonists (LABA), leukotriene antagonists, slow-release theophyllines, systemic glucocorticosteroids and monoclonal anti-IgE antibodies (omalizumab). Relief and rescue drugs are used to rapidly treat or prevent the bronchoconstriction. They include: inhaled short-acting β2, and as a second choice, inhaled anticholinergics (ipratropium bromide). Also, the fast-acting LABA medications can be used (formoterol).GEMA and GINA propose to start treatment according to severity initial classification, and to adjust it according to the degree of control.<a class="elsevierStyleCrossRefs" href="#bib0240">2,11</a> The 6 therapeutic stages proposed by GEMA guideline<a class="elsevierStyleCrossRef" href="#bib0240">2</a> for achieving asthma control are shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>.<elsevierMultimedia ident="fig0020"></elsevierMultimedia>Regarding the immunotherapy with allergens, the last review of Cochrane Library<a class="elsevierStyleCrossRef" href="#bib0430">40</a> states that the administration of subcutaneous specific immunotherapy provides a significant improvement of the symptoms, reduces the need of rescue and maintenance pharmacological treatments, and provides an improvement in the BHR. With respect to the sublingual immunotherapy, recent meta-analyses of trials, where the asthma effects have been assessed, aim to a reduction in the symptoms and in the use of medication, though they have important methodological limitations.<a class="elsevierStyleCrossRefs" href="#bib0435">41–44</a> Clinical tests with allergen immunotherapy for the specific indication of bronchial asthma are currently being developed, both with the classic modalities and with the new ones, such as sublingual immunotherapy with mite tablets.<a class="elsevierStyleCrossRef" href="#bib0455">45</a>Although there exist studies and systematic reviews that provide scientific evidence to recommend the administration of the flu vaccine and the pneumococcal vaccine to patients with asthma, the opinion of the clinical practice guidelines is opposed to this practice. While the British Thoracic Society<a class="elsevierStyleCrossRef" href="#bib0460">46</a> and GEMA<a class="elsevierStyleCrossRef" href="#bib0240">2</a> do not recommend vaccination, GINA<a class="elsevierStyleCrossRef" href="#bib0285">11</a> and North American EPR-3<a class="elsevierStyleCrossRef" href="#bib0400">34</a> do recommend it.New treatments for asthmaThere is a great number of new drugs in phase of development or of approval for the use in asthma treatment.<a class="elsevierStyleCrossRefs" href="#bib0390">32,33</a> These new treatments for asthma include muscarinic agents (tiotropium), beta-2-adrenergic agonists and combinations (indacaterol with mometasone [MGC-149], indacaterol and QAE 397, vilanterol and fluticasone furoate, carmoterol and budesonide), modifiers of the route of arachidonic acid (OC000459, antagonist of the homologous molecule of the expressed chemotactic receptor on Th2 cells), or selective phosphodiesterase inhibitors (roflumilast, phosphodiesterase 4 inhibitor). In addition, there are studies in development on diverse biological agents, such as monoclonal antibodies anti-interleukin-5 (IL) (mepolizumab, reslizumab, benralizumab), antagonists of route IL-4/IL-13 like altrakincept (human soluble recombinant IL-4Rα), monoclonal antibodies anti-IL-13 (anrukinzumab, IMA-026, QAX576, 354-CAT, lebrikizumab), or antagonists of the chain α of the IL-4 receptor, such as pitrakinra and dupilumab.Conclusions and future perspectivesAsthma is a complex disease considered by most of the authors a syndrome with a remarkable variability regarding its severity, natural history and the response to treatment. The high heterogeneity in its clinical expression makes it difficult to characterise it and, in most of the cases, to choose the suitable treatment. A greater knowledge of the physiopathology, the natural history and the relationship between the genotypes and their phenotypic manifestations in asthma will contribute to improve the treatment and the prognosis. In the last few years, a great importance has been given to the knowledge of the different asthma phenotypes and endotypes and to the identification of biomarkers for each one of them with the purpose of achieving a more precise and customised therapy for each patient.Conflict of interestThe authors declare that there are no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Importance of asthma and a good control" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Asthma diagnosed as a syndrome" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Diagnosis of allergic sensitisation" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Assessment of the bronchial inflammation and other biomarkers" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Classification of bronchial asthma" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Non-pharmacological treatment" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Pharmacological treatment" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "New treatments for asthma" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusions and future perspectives" ] 10 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-06-25" "fechaAceptado" => "2014-08-29" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Cardona V, Garriga T. Asma alérgica. Med Clin (Barc). 2015;144:216–222." ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1513 "Ancho" => 2166 "Tamanyo" => 334506 ] ] "descripcion" => array:1 [ "en" => "Algorithm for asthma diagnosis according to GEMA 2009.<a class="elsevierStyleCrossRef" href="#bib0240">2</a> *In children, an increase of 12% is sufficient for the response to be regarded as positive, even if it is less than 200ml. **In the cases in which the bronchoconstriction test is negative, a diagnosis of eosinophilic bronchitis should be considered. ***As an alternative, inhaled glucocorticosteroids can be used at very high doses, 1500–2000μg of fluticasone, taken 3 or 4 times a day over a period of 2–8 weeks. PEF: peak expiratory flow; FENO: fractional exhaled nitric oxide; FEV1: forced expiratory volume." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2512 "Ancho" => 1686 "Tamanyo" => 404103 ] ] "descripcion" => array:1 [ "en" => "Diagnostic procedures in the difficult control asthma. Different complementary examinations will be used according to medical history and the evolution of the patient. BHR: bronchial hyperresponsiveness; pANCA: perinuclear anti-neutrophil cytoplasmic antibodies; CT: computed tomography." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2385 "Ancho" => 2780 "Tamanyo" => 645879 ] ] "descripcion" => array:1 [ "en" => "Classification of asthma in accordance with phenotypes and endotypes. Based on the classifications proposed by Wenzel<a class="elsevierStyleCrossRefs" href="#bib0375">29,30</a> and Lötvall et al.<a class="elsevierStyleCrossRef" href="#bib0385">31</a> NSAIDs: non-steroidal anti-inflammatory drugs." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2389 "Ancho" => 2653 "Tamanyo" => 518734 ] ] "descripcion" => array:1 [ "en" => "Therapeutic steps in the maintenance treatment of asthma. There are similarities among different guidelines regarding therapeutic steps proposed for the asthma treatment. AL: anti-leukotriene; GC: glucocorticosteroids; IGC: inhaled glucocorticosteroids; LABA: long-acting beta-2 agonists; SABA: short-acting beta-2 agonists. (a) According to GEMA 2009<a class="elsevierStyleCrossRef" href="#bib0240">2</a> for adults. (b) According to Papadopoulos et al. ICON<a class="elsevierStyleCrossRef" href="#bib0360">26</a> for children." ] ] 4 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "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">Symptoms and signs that should lead to a suspicion of possible asthma \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">Expiratory wheezes, especially in the children (although an examination of normal thorax does not exclude asthma) \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">History of any of the following symptoms: recurrent nocturnal coughing, recurrent wheezing, recurrent dyspnoea, recurrent tightness of the chest \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">The symptoms appear or get worse at night, waking up the patient \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">The symptoms appear or get worse following a seasonal pattern \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">The patient also has eczema or a family history of asthma or atopic diseases \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">Symptoms appear or get worse in the presence of: \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">Animals with hair \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">Chemical agents \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">Changes of temperature \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">House dust mite \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">Medications (acetylsalicylic acid, beta-blockers) \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">Exercise \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">Pollen \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">Respiratory infections (viral) \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">Smoke of the tobacco \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">Emotional stress \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">Symptoms respond to anti-asthma treatment \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">The patient with flu feels “his chest falls” or takes more than 10 days to recover \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">Essential data on medical history \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">Characteristic clinical symptoms of the disease (dyspnoea, coughing, wheezing, tightness of the chest) \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">Other symptoms to exclude other diseases or comorbidities (posterior rhinorrhoea, heartburn, reduction of the urine output or emotional situation) \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">Family history \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">Smoking \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">Exposure to allergens at home, school or work \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">Medication used for the asthma (always asking about the technique, the tolerance and the compliance) \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">Risk factors of asthma exacerbations \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">Potentially modifiable \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">Exposure to tobacco smoke \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">Exposure to aeroallergens \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">Exposure to occupational allergens \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">Obesity \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">Gastroesophageal reflux \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">Sinusitis \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">Acetylsalicylic acid and other drugs \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">Psychological factors \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">Non-modifiable \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">Viral infections \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">Race/ethnic group \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">Pre-menstrual asthma \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">Genetic factors \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab943112.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Relevant clinical aspects for the diagnosis and follow-up of the bronchial asthma." ] ] 5 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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">Direct bronchoconstrictors \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">Cholinergic agonist: methacholine<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>, carbachol, acetylcholine \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">Histamine<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \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">Prostaglandin D2 \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">Cysteinyl leukotriene (LTC 4, LTD4, LTE4) \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">Indirect bronchoconstrictors \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">Osmotic stimuli: physical exercise<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>, mannitol<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>, hyperventilation with cold air, non-isotonic aerosols (distilled water, saline hypotonic, saline hypertonic) \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">Pharmacological stimuli: adenosine (AMP)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>, taquines, bradykinin, metabisulphite, propranolol, acetaldehyde \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">Endotoxins \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">Platelet-activating factor \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">Ozone \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">Others: allergens, non-steroidal anti-inflammatory drugs \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab943116.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Bronchoconstrictor agents more frequently used in provocation tests." ] ] ] "descripcion" => array:1 [ "en" => "Bronchoconstrictor agents used in bronchial hyperresponsiveness tests." ] ] 6 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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">Minimum aeroallergen battery to conduct in European patients diagnosed with asthma<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \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">Pollen \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">Betula verrucosa or mixes of Betulaceae \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">Cupressus sempervirens or other species of Cypress \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">Spring grasses \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">Artemisia vulgaris \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">Olea europaea or Fraxinus exelsior \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">Parietaria officinalis \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">Platanus occidentalis \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">Ambrosia elatior \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">Mites \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">Dermatophagoides pteronyssinus \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">Dermatophagoides farinae \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">Fungi \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">Alternaria alternata \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">Cladosporium album \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">Animals \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">Cat \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">Dog \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">Insects \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">Blatella sp. \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">Frequency of sensitisation to aeroallergens in the Spanish asthmatic population<a class="elsevierStyleCrossRef" href="#tblfn0015">b</a> \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">Pollen \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">Spring grasses, 32.4% \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">Olea europaea, 26.9% \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">Chenopodium album, 8.7% \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">Species of Cupressus, 7.5% \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">Platanus acerifolia, 6.9% \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">Plantago lanceolata, 6.8% \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">Salsola kali, 6.5% \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">Parietaria judaica, 4.6% \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">Artemisia vulgaris, 6.2% \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">Mites \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">Dermatophagoides pteronyssinus, 41.0% \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">Dermatophagoides farinae, 32.9% \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">Lepidoglyphus destructive, 7.7% \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">Tyrophagus putrescentiae, 5.6% \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">Euroglyphus maynei, 3.5% \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">Blomia tropicalis, 3.3% \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">Glycyphagus domesticus, 1.9% \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">Acarus siro, 1.3% \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">Fungi \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">alternata Alternaria, 8.3% \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">Species of Cladosporium, 1.4% \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">Species of Aspergillus, 1.4% \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">Animals \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">Cat, 15.3% \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">Dog, 13.7% \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">Horse, 2% \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">Rabbit, 0.6% \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">Hamster, 0.6% \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">Feathers, 0.5% \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">Insects \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">Blatella germanica, 0.6% \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">Blatella orientalis, 0.3% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab943115.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Source: Bousquet et al.<a class="elsevierStyleCrossRef" href="#bib0310">16</a>" ] 1 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "b" "nota" => "Source: Quirce.<a class="elsevierStyleCrossRef" href="#bib0235">1</a>" ] ] ] "descripcion" => array:1 [ "en" => "Most relevant inhaled allergens in Europe and Spain." ] ] 7 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "PEF: peak expiratory flow; FEV1: forced expiratory volume in one second.Classification proposed by GEMA<a class="elsevierStyleCrossRef" href="#bib0240">2</a> to determine the severity of the asthmatic patient without treatment." "tablatextoimagen" => array:2 [ 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="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Adult patients</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Intermittent \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">Mild persistent \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">Moderate persistent \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">Severe persistent \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">Daytime symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No (2 days or less a week) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">More than 2 days a week \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Daily symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Continuous symptoms (several times a day) \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">Relief medication \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No (2 days or less a week) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">More than 2 days a week, but not daily \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Several times a day \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">Nighttime symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No more than twice a month \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">More than twice a month \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">More than once a week \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Frequent \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">Limitations on activity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Some limitation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A fair degree of limitation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Considerable limitation \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">Pulmonary Function (FEV1or PEF theoretical %) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>60%; <80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≤60% \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">Exacerbations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">None \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">One or none a year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Two or more a year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Two or more a year \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab943114.png" ] ] 1 => 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="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Children</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Occasional episodic \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">Frequent episodic \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">Moderate persistent \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">Severe persistent \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">Episodes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lasting a few hours or days, less than one every 10–12 weeks. Maximum 4–5 attacks/year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Less than one every 5–6 weeks. Maximum 6–8 crises/year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Less than one every 4–5 weeks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Frequent \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">Inter-crises symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No symptoms with good tolerance to exercise \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Frequent \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">Wheezing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">With intense effort \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">With moderate effort \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">With minimum effort \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">Nighttime symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≤2 nights a week \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>2 nights a week \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">Relief medication \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≤3 days a week \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>3 days a week \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">Pulmonary Function \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></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">FEV1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>70%; <80% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><70% \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">Variability (PEF) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>20%; <30% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>30% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab943113.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Classification of severity of asthma in adults and children." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:46 [ 0 => array:3 [ "identificador" => "bib0235" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Asthma in Alergológica-2005" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S. 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Diagnosis and treatment

Allergic asthma

Asma alérgica

Victòria Cardonaa,b,

Corresponding author

vcardona@vhebron.net
alergia@vhebron.net

Corresponding author.

, Teresa Garrigab,c

a Secció d’Al·lergologia, Servei de Medicina Interna, Hospital Vall d’Hebron, Barcelona, Spain

b Grup de Recerca d’Al·lergologia, Institut de Recerca Vall d’Hebron, Barcelona, Spain

c Unitat d’Al·lergologia Pediàtrica, Servei d’Al·lèrgia Pediàtrica, Pneumologia Pediàtrica i Fibrosi Quística, Hospital Universitari Materno-Infantil de la Vall d’Hebron, Barcelona, Spain

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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Algorithm for asthma diagnosis according to GEMA 2009&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> &#42;In children&#44; an increase of 12&#37; is sufficient for the response to be regarded as positive&#44; even if it is less than 200<span class="elsevierStyleHsp" style=""></span>ml&#46; &#42;&#42;In the cases in which the bronchoconstriction test is negative&#44; a diagnosis of eosinophilic bronchitis should be considered&#46; &#42;&#42;&#42;As an alternative&#44; inhaled glucocorticosteroids can be used at very high doses&#44; 1500&#8211;2000<span class="elsevierStyleHsp" style=""></span>&#956;g of fluticasone&#44; taken 3 or 4 times a day over a period of 2&#8211;8 weeks&#46; PEF&#58; peak expiratory flow&#59; FENO&#58; fractional exhaled nitric oxide&#59; FEV<span class="elsevierStyleInf">1</span>&#58; forced expiratory volume&#46;</p>"
        ]
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Asthma is one of the most important allergic diseases in our country due to its high prevalence&#44; chronic nature&#44; its influence in patients&#8217; quality of life and its economic repercussions&#46; In the Alergol&#243;gica 2005 study&#44; asthma occupies the second place in frequency for consultation in the Allergy services&#44; after allergic rhinitis&#44; and in up to 80&#37; of the cases&#44; the allergic asthma diagnosis was confirmed&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">At the moment&#44; one of the most accepted definitions of asthma is the concept of chronic inflammatory disease of the respiratory tract&#44; whose pathogenesis involves various types of cells and inflammation mediators&#46; It is a process partly determined by genetic factors and is characterised by bronchial hyperresponsiveness &#40;BHR&#41; and varying degrees of airflow obstruction&#44; which is total or partially reversible&#44; either as a result of pharmacological action&#44; or spontaneous event&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Importance of asthma and a good control</span><p id="par0015" class="elsevierStylePara elsevierViewall">Asthma is a global health problem that affects 300 million people worldwide&#46; In Spain&#44; asthma prevalence in the paediatric population oscillates around 10&#37;&#44; whereas in adult population it is around 5&#37;&#44; and the last data indicate that the asthma prevalence increases in both children and adults&#46; At present&#44; it is known that asthma is&#44; after the chronic obstructive pulmonary disease&#44; the cause of greater number of absenteeism from work due to respiratory diseases&#46; The World Health Organisation estimates 15 million years of life are lost annually adjusted for impairment due to the asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">According to the AsmaCost study of 2007&#44; the economic cost of the asthmatic adult patient in Spain ascends to 1726 and 1533&#8364; from the perspective of the society and the National Health System&#44; respectively&#46; The cost is higher in severe asthmatics &#40;2635&#8364;&#41; and in patients older than 65 years of age &#40;2069&#8364;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">4</span></a> In children&#44; the average annual cost in Spain in 2008 was of 1490&#8364;&#44; and of 5380&#8364; in the severe asthma cases&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">5</span></a> In addition&#44; it is known that around 70&#37; of the total cost of the disease is determined by the poor control of the disease&#46; The cost of hospitalisation&#44; emergency department visits or death are major causes of the consumption of economic resources due to asthma&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">6&#44;7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">According to the Asthma Control in Spain study&#44; more than two thirds of the studied patients had a poorly controlled asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">8</span></a> A recent study&#44; conducted in our country in 1363 patients with asthma&#44; shows that only 12&#37; of the patients are well controlled based on the criteria of the <span class="elsevierStyleItalic">Global Initiative for Asthma</span> &#40;GINA&#41;&#44; although 60&#37; of the patients consider their asthma is well controlled&#44; and 50&#37; of the doctors assume asthma can be controlled&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">9&#44;10</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Asthma diagnosed as a syndrome</span><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnostic process is based on the definition of the disease&#44; which includes&#44; on the one hand&#44; the symptoms and the variable obstruction of the airflow&#44; and on the other hand&#44; the underlying inflammation and the BHR&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The medical history of the patient and the symptoms are essential to establish the diagnosis&#46; The relevant data we must gather in the medical history are summarised in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">11</span></a> In the allergic patient&#44; it is important to assess extra-pulmonary manifestations of atopy such as atopic eczema&#44; allergy to foods or the nasal inflammation in the allergic rhinitis that frequently accompanies the asthma&#46; It is also relevant to look into possible intolerance to acetylsalicylic acid or to non-steroidal anti-inflammatory drugs &#40;NSAIDs&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">To confirm the bronchial obstruction&#44; its reversibility and&#47;or the BHR&#44; there should be conducted a lung basal function test&#44; bronchodilator test&#44; monitoring of the peak expiratory flow &#40;PEF&#41; and&#47;or bronchoconstriction tests&#46; The obstruction is defined as the ratio between the <span class="elsevierStyleItalic">forced expiratory volume</span> &#40;FEV&#41;<span class="elsevierStyleInf">1</span> in one second and <span class="elsevierStyleItalic">the forced vital capacity</span> &#40;FVC&#41;&#44; &#40;FEV<span class="elsevierStyleInf">1</span>&#47;FVC&#41; in the basal forced spirometry below the inferior limit of the reference values&#44; which is arbitrarily established in 0&#46;7&#46; The reversibility of this obstruction is observed through the bronchodilator test&#44; generally&#44; with inhaled salbutamol and repeating the spirometry 15<span class="elsevierStyleHsp" style=""></span>min later&#46; The Spanish Guideline on the Management of Asthma &#40;Gu&#237;a Espa&#241;ola para el Manejo del Asma&#44; GEMA&#41;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> considers the test is positive if FEV<span class="elsevierStyleInf">1</span> or FVC increases by 12&#37; and to more than 200<span class="elsevierStyleHsp" style=""></span>ml compared to the previous &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In children&#44; the bronchodilator test is positive when FEV<span class="elsevierStyleInf">1</span> increase on the baseline value is greater or equal to 12&#37;&#46; The BHR to different stimuli is quantified by means of the exposure to bronchoconstrictor agents&#44; classified according to their mechanism of action &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The variability of the pulmonary function can be determined by means of portable devices to measure the PEF&#46; The index of variability of PEF equal or higher than 20&#37; is a criterion to asthma diagnosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">2&#44;11&#44;12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Unfortunately&#44; all these lung function tests are not applicable to infants or to pre-school children with asthma&#46; This is why GEMA and the <span class="elsevierStyleItalic">American Thoracic Society&#47;European Respiratory Society</span><a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">2&#44;12</span></a> recommend alternative tests such as the forced impulse oscillometry &#40;IOS&#41;&#44; the measurement of occlusion resistances&#44; flow volume&#47;tidal volume curve analysis or the measurement of resistances by plethysmography&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows the recommended diagnostic procedures to control severe asthma&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Diagnosis of allergic sensitisation</span><p id="par0055" class="elsevierStylePara elsevierViewall">The allergy test has to be conducted in all patients diagnosed with asthma&#44; due to the high prevalence of sensitisation to inhalant allergens and the comorbidity with other allergic manifestations&#46; It is known that sensitisation to aeroallergens mediated by IgE antibodies constitutes a very significant risk factor to develop asthma&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">13&#44;14</span></a> It has been confirmed that exposure to high concentrations of allergens increases the severity of the asthma&#44; and that there exists a synergy between the allergic sensitisation and viral infections&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">15</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The skin test <span class="elsevierStyleItalic">&#40;prick-tests&#41;</span> is the diagnostic method of choice to detect sensitisation to allergens mediated by IgE&#44; due to its high sensitivity and specificity&#46; It is a safe&#44; simple&#44; fast and painless method&#46; Generally&#44; it is conducted with a series of allergens that are present in the geographic area where the patient lives&#46; However&#44; it is recommended to use a standard allergen battery to test all the European patients diagnosed with asthma &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">16</span></a> A positive skin test will only indicate sensitisation&#44; which will be assessed according to the relation between allergen exposure and the symptoms of patient&#46; The aeroallergens most frequently associated with allergic asthma in Spain are pollen &#40;44&#37;&#41;&#44; the house dust mites &#40;41&#37;&#41;&#44; the animal epithelia &#40;20&#37;&#41; and fungi &#40;8&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The determination of IgE specific to whole allergen extracts or the IgE to individual recombinant or purified natural allergen molecules leads to a more accurate diagnosis of sensitisation&#46; They are more specific than skin tests and will be useful in cases of dermatographic urticaria&#44; extensive dermatitis and if the patient receives pharmacological treatments that inhibit the skin tests&#44; besides confirming them&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">17&#44;18</span></a> Moreover&#44; it is important to distinguish&#44; in patients that present sensitisation to multiple allergens&#44; those patients who are genuinely sensitised to several allergenic sources from crossed-sensitised patients&#44; since it will be relevant to establish strategies of avoidance and&#47;or allergen immunotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">19</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In order to establish a relationship between the allergic sensitisation and the symptoms of the patient and&#44; therefore&#44; to establish their clinical relevance&#44; it could be useful to use calendars of symptoms and&#47;or the monitoring of the PEF to compare with the exposure to the allergen &#40;for example&#44; pollen count&#41; or bronchial provocation tests to specific allergens&#44; although this procedure is usually reserved for occupational asthma cases or for research&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Assessment of the bronchial inflammation and other biomarkers</span><p id="par0075" class="elsevierStylePara elsevierViewall">In the last few years&#44; multiple biomarkers have appeared&#46; They are proved to be useful for diagnosing and monitoring asthma&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The patterns of eosinophilic inflammation in induced sputum are responsive and they change accompanying changes in the exposure to allergens and in the clinical control of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">20</span></a> The limit in its regular use is the necessity to immediately process the sample&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The exhaled nitric oxide fraction has been directly related to the degree of eosinophilic inflammation&#44; and values higher than 30<span class="elsevierStyleHsp" style=""></span>ppb are considered diagnoses&#44; according to GEMA&#44; in patients with a history of asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> At present&#44; there are easy-to-use small devices that can be used daily for diagnosis and for monitoring of patients&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Other methods&#44; such as the temperature of the exhaled air&#44;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">21&#44;22</span></a> the analysis of condensation of the exhaled air<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">23</span></a> or electronic nose&#44; for the analysis of the organic volatile components&#44;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">24&#44;25</span></a> are of experimental use&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Classification of bronchial asthma</span><p id="par0095" class="elsevierStylePara elsevierViewall">Asthma has traditionally been classified in accordance with its diagnosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; However&#44; as the asthma is a variable disease&#44; at present it has changed from that rigid classification in accordance with its severity to a more dynamic classification in accordance with the control of the disease &#40;completely controlled&#44; well controlled&#44; partially controlled and not controlled asthma&#41;&#46; The components assessed to determine the degree of control include daytime&#44; nighttime and awakening symptoms&#44; need for rescue treatment&#44; limitation of activities&#44; pulmonary function&#44; risk of exacerbation throughout a year and&#47;or the adverse events of the treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">2&#44;11&#44;26</span></a> To assess the asthma control&#44; there are simple questionnaires&#44; translated and validated in Spanish&#44; to be used in common practice practice&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">27&#44;28</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Asthma has traditionally been classified as extrinsic or intrinsic&#44; but in the last decade&#44; new classifications based on different phenotype have appeared&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">29&#44;30</span></a> A phenotype is the set of observable characteristics of an organism that constitute the result of the interaction between the genetic load and the environment&#46; Even more recently&#44; the concept of &#8220;endotypes&#8221; has been coined&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">31</span></a> Endotype is a subtype of a disease defined by a functional or a pathophysiological mechanism&#44; unique or distinctive &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; A phenotype can be present in more than one endotype and an endotype can contain more than one phenotype &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; These new concepts will help in the future to develop more specific therapeutic strategies&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">32</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Non-pharmacological treatment</span><p id="par0105" class="elsevierStylePara elsevierViewall">The primary objective of the treatment is to control and to maintain the control of the disease&#44; to prevent the chronic airflow obstruction or to reduce morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">33</span></a> An essential part of the treatment includes the non-pharmacological measures&#46; The different guidelines vary ostensibly from one another in the severity of their recommendations about the allergen avoidance measures&#46; In this way&#44; for the North American <span class="elsevierStyleItalic">Expert Panel Report</span> &#40;EPR-3&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">34</span></a> the avoidance of aeroallergens continues to be a fundamental aspect of the allergic asthma treatment&#46; Other guidelines&#44; such as GEMA&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> or GINA&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">11</span></a> consider this recommendation as less relevant&#46; On the contrary&#44; there seems to exist a clear consensus around the better control of asthma and the avoidance of exposure to the smoke of tobacco&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Another risk factor that could be modified and that is related to asthma is the obesity&#44; which has been associated to a greater incidence&#44; severity and to a worse response to treatment and with an increase of the bronchial inflammatory response&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">35</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">It is necessary to assess the individual tolerance to NSAIDs in asthmatic patients&#46; Up to 20&#37; of patients can present intolerance to NSAIDs&#44; which can increase to 40&#37; in case of chronic rhinosinusitis with or without concomitant polyps&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">36</span></a> These patients usually present asthma that is difficult to control&#44; and the administration of acetylsalicylic acid or NSAIDs can trigger very severe crises of bronchospasm&#46; That is why an adequate avoidance of these drugs is essential&#46; In many patients&#44; the NSAIDs cyclo-osygenase 2 inhibitors can be tolerated&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">37</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The most recent guidelines for the asthma treatment<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">26&#44;38</span></a> unequivocally recommend to follow action plans for the education of asthma patients&#46; These plans must be focused on the knowledge of the basics of the disease&#44; the hygienic measures&#44; the maintenance treatment and the recognition of the exacerbations with specific indications for action&#46; They recommend to always verify that the inhalation technique is correct&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Recently&#44; a new non-pharmacological treatment called bronchial thermoplasty has appeared&#46; It consists of the administration of thermal energy by means of radiofrequency through a catheter that is introduced in the bronchial tree &#40;endoscopic technique&#41;&#46; This therapeutic approach has been accepted as a complementary option in patients with severe asthma who&#44; despite the fact that they receive medical treatment&#44; they still remain symptomatic&#46; However&#44; its relevance and role in the clinical therapeutic are still to be defined&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pharmacological treatment</span><p id="par0130" class="elsevierStylePara elsevierViewall">In the asthma treatment&#44; we can differentiate between the pharmacological maintenance treatment and rescue drugs or drugs to relieve symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">33</span></a> Maintenance medication&#44; which must be administered for prolonged periods&#44; include inhaled glucocorticosteroids&#44; alone or in combination with <span class="elsevierStyleItalic">long-acting beta-2 agonists</span> &#40;LABA&#41;&#44; leukotriene antagonists&#44; slow-release theophyllines&#44; systemic glucocorticosteroids and monoclonal anti-IgE antibodies &#40;omalizumab&#41;&#46; Relief and rescue drugs are used to rapidly treat or prevent the bronchoconstriction&#46; They include&#58; inhaled short-acting &#946;2&#44; and as a second choice&#44; inhaled anticholinergics &#40;ipratropium bromide&#41;&#46; Also&#44; the fast-acting LABA medications can be used &#40;formoterol&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">GEMA and GINA propose to start treatment according to severity initial classification&#44; and to adjust it according to the degree of control&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">2&#44;11</span></a> The 6 therapeutic stages proposed by GEMA guideline<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> for achieving asthma control are shown in <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Regarding the immunotherapy with allergens&#44; the last review of <span class="elsevierStyleItalic">Cochrane Library</span><a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">40</span></a> states that the administration of subcutaneous specific immunotherapy provides a significant improvement of the symptoms&#44; reduces the need of rescue and maintenance pharmacological treatments&#44; and provides an improvement in the BHR&#46; With respect to the sublingual immunotherapy&#44; recent meta-analyses of trials&#44; where the asthma effects have been assessed&#44; aim to a reduction in the symptoms and in the use of medication&#44; though they have important methodological limitations&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">41&#8211;44</span></a> Clinical tests with allergen immunotherapy for the specific indication of bronchial asthma are currently being developed&#44; both with the classic modalities and with the new ones&#44; such as sublingual immunotherapy with mite tablets&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">45</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Although there exist studies and systematic reviews that provide scientific evidence to recommend the administration of the flu vaccine and the pneumococcal vaccine to patients with asthma&#44; the opinion of the clinical practice guidelines is opposed to this practice&#46; While the <span class="elsevierStyleItalic">British Thoracic Society</span><a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">46</span></a> and GEMA<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> do not recommend vaccination&#44; GINA<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">11</span></a> and North American EPR-3<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">34</span></a> do recommend it&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">New treatments for asthma</span><p id="par0150" class="elsevierStylePara elsevierViewall">There is a great number of new drugs in phase of development or of approval for the use in asthma treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">32&#44;33</span></a> These new treatments for asthma include muscarinic agents &#40;tiotropium&#41;&#44; beta-2-adrenergic agonists and combinations &#40;indacaterol with mometasone &#91;MGC-149&#93;&#44; indacaterol and QAE 397&#44; vilanterol and fluticasone furoate&#44; carmoterol and budesonide&#41;&#44; modifiers of the route of arachidonic acid &#40;OC000459&#44; antagonist of the homologous molecule of the expressed chemotactic receptor on Th2 cells&#41;&#44; or selective phosphodiesterase inhibitors &#40;roflumilast&#44; phosphodiesterase 4 inhibitor&#41;&#46; In addition&#44; there are studies in development on diverse biological agents&#44; such as monoclonal antibodies anti-interleukin-5 &#40;IL&#41; &#40;mepolizumab&#44; reslizumab&#44; benralizumab&#41;&#44; antagonists of route IL-4&#47;IL-13 like altrakincept &#40;human soluble recombinant IL-4R&#945;&#41;&#44; monoclonal antibodies anti-IL-13 &#40;anrukinzumab&#44; IMA-026&#44; QAX576&#44; 354-CAT&#44; lebrikizumab&#41;&#44; or antagonists of the chain &#945; of the IL-4 receptor&#44; such as pitrakinra and dupilumab&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions and future perspectives</span><p id="par0155" class="elsevierStylePara elsevierViewall">Asthma is a complex disease considered by most of the authors a syndrome with a remarkable variability regarding its severity&#44; natural history and the response to treatment&#46; The high heterogeneity in its clinical expression makes it difficult to characterise it and&#44; in most of the cases&#44; to choose the suitable treatment&#46; A greater knowledge of the physiopathology&#44; the natural history and the relationship between the genotypes and their phenotypic manifestations in asthma will contribute to improve the treatment and the prognosis&#46; In the last few years&#44; a great importance has been given to the knowledge of the different asthma phenotypes and endotypes and to the identification of biomarkers for each one of them with the purpose of achieving a more precise and customised therapy for each patient&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflict of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that there are no conflicts of interest&#46;</p></span></span>"
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        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
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        1 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Importance of asthma and a good control"
        ]
        2 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Asthma diagnosed as a syndrome"
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        3 => array:2 [
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          "titulo" => "Diagnosis of allergic sensitisation"
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        4 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Assessment of the bronchial inflammation and other biomarkers"
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        5 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Classification of bronchial asthma"
        ]
        6 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Non-pharmacological treatment"
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          "identificador" => "sec0040"
          "titulo" => "Pharmacological treatment"
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        8 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "New treatments for asthma"
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        9 => array:2 [
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          "titulo" => "Conclusions and future perspectives"
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        10 => array:2 [
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          "titulo" => "Conflict of interest"
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          "titulo" => "References"
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    "fechaRecibido" => "2014-06-25"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Cardona V&#44; Garriga T&#46; Asma al&#233;rgica&#46; Med Clin &#40;Barc&#41;&#46; 2015&#59;144&#58;216&#8211;222&#46;</p>"
      ]
    ]
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        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
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        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Algorithm for asthma diagnosis according to GEMA 2009&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> &#42;In children&#44; an increase of 12&#37; is sufficient for the response to be regarded as positive&#44; even if it is less than 200<span class="elsevierStyleHsp" style=""></span>ml&#46; &#42;&#42;In the cases in which the bronchoconstriction test is negative&#44; a diagnosis of eosinophilic bronchitis should be considered&#46; &#42;&#42;&#42;As an alternative&#44; inhaled glucocorticosteroids can be used at very high doses&#44; 1500&#8211;2000<span class="elsevierStyleHsp" style=""></span>&#956;g of fluticasone&#44; taken 3 or 4 times a day over a period of 2&#8211;8 weeks&#46; PEF&#58; peak expiratory flow&#59; FENO&#58; fractional exhaled nitric oxide&#59; FEV<span class="elsevierStyleInf">1</span>&#58; forced expiratory volume&#46;</p>"
        ]
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Diagnostic procedures in the difficult control asthma&#46; Different complementary examinations will be used according to medical history and the evolution of the patient&#46; BHR&#58; bronchial hyperresponsiveness&#59; pANCA&#58; perinuclear anti-neutrophil cytoplasmic antibodies&#59; CT&#58; computed tomography&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Classification of asthma in accordance with phenotypes and endotypes&#46; Based on the classifications proposed by Wenzel<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">29&#44;30</span></a> and L&#246;tvall et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">31</span></a> NSAIDs&#58; non-steroidal anti-inflammatory drugs&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Therapeutic steps in the maintenance treatment of asthma&#46; There are similarities among different guidelines regarding therapeutic steps proposed for the asthma treatment&#46; AL&#58; anti-leukotriene&#59; GC&#58; glucocorticosteroids&#59; IGC&#58; inhaled glucocorticosteroids&#59; LABA&#58; <span class="elsevierStyleItalic">long-acting beta-2 agonists</span>&#59; SABA&#58; <span class="elsevierStyleItalic">short-acting beta-2 agonists</span>&#46; &#40;a&#41; According to GEMA 2009<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> for adults&#46; &#40;b&#41; According to Papadopoulos et al&#46; ICON<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">26</span></a> for children&#46;</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="elsevierStyleBold">Symptoms and signs that should lead to a suspicion of possible asthma</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Expiratory wheezes&#44; especially in the children &#40;although an examination of normal thorax does not exclude asthma&#41;</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">History of any of the following symptoms&#58; recurrent nocturnal coughing&#44; recurrent wheezing&#44; recurrent dyspnoea&#44; recurrent tightness of the chest</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">The symptoms appear or get worse at night&#44; waking up the patient</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">The symptoms appear or get worse following a seasonal pattern</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">The patient also has eczema or a family history of asthma or atopic diseases</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Symptoms appear or get worse in the presence of&#58;</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Animals with hair&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><span class="elsevierStyleHsp" style=""></span>Chemical agents&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><span class="elsevierStyleHsp" style=""></span>Changes of temperature&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><span class="elsevierStyleHsp" style=""></span>House dust mite&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><span class="elsevierStyleHsp" style=""></span>Medications &#40;acetylsalicylic acid&#44; beta-blockers&#41;&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><span class="elsevierStyleHsp" style=""></span>Exercise&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><span class="elsevierStyleHsp" style=""></span>Pollen&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><span class="elsevierStyleHsp" style=""></span>Respiratory infections &#40;viral&#41;&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><span class="elsevierStyleHsp" style=""></span>Smoke of the tobacco&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><span class="elsevierStyleHsp" style=""></span>Emotional stress&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><span class="elsevierStyleItalic">Symptoms respond to anti-asthma treatment</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">The patient with flu feels &#8220;his chest falls&#8221; or takes more than 10 days to recover</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
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">Essential data on medical history</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Characteristic clinical symptoms of the disease &#40;dyspnoea&#44; coughing&#44; wheezing&#44; tightness of the chest&#41;</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Other symptoms to exclude other diseases or comorbidities &#40;posterior rhinorrhoea&#44; heartburn&#44; reduction of the urine output or emotional situation&#41;</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Family history</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Smoking</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Exposure to allergens at home&#44; school or work</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Medication used for the asthma &#40;always asking about the technique&#44; the tolerance and the compliance&#41;</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
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleBold">Risk factors of asthma exacerbations</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Potentially modifiable</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Exposure to tobacco smoke&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><span class="elsevierStyleHsp" style=""></span>Exposure to aeroallergens&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><span class="elsevierStyleHsp" style=""></span>Exposure to occupational allergens&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><span class="elsevierStyleHsp" style=""></span>Obesity&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><span class="elsevierStyleHsp" style=""></span>Gastroesophageal reflux&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><span class="elsevierStyleHsp" style=""></span>Sinusitis&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><span class="elsevierStyleHsp" style=""></span>Acetylsalicylic acid and other drugs&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><span class="elsevierStyleHsp" style=""></span>Psychological factors&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><span class="elsevierStyleItalic">Non-modifiable</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Viral infections&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><span class="elsevierStyleHsp" style=""></span>Race&#47;ethnic group&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><span class="elsevierStyleHsp" style=""></span>Pre-menstrual asthma&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><span class="elsevierStyleHsp" style=""></span>Genetic factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Relevant clinical aspects for the diagnosis and follow-up of the bronchial asthma&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
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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">Direct bronchoconstrictors</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="elsevierStyleHsp" style=""></span>Cholinergic agonist&#58; methacholine<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#44; carbachol&#44; acetylcholine&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>Histamine<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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>Prostaglandin D<span class="elsevierStyleInf">2</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="elsevierStyleHsp" style=""></span>Cysteinyl leukotriene &#40;LTC 4&#44; LTD<span class="elsevierStyleInf">4</span>&#44; LTE<span class="elsevierStyleInf">4</span>&#41;&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">Indirect bronchoconstrictors</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="elsevierStyleHsp" style=""></span>Osmotic stimuli&#58; physical exercise<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#44; mannitol<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#44; hyperventilation with cold air&#44; non-isotonic aerosols &#40;distilled water&#44; saline hypotonic&#44; saline hypertonic&#41;&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>Pharmacological stimuli&#58; adenosine &#40;AMP&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&#44; taquines&#44; bradykinin&#44; metabisulphite&#44; propranolol&#44; acetaldehyde&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>Endotoxins&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>Platelet-activating factor&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>Ozone&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>Others&#58; allergens&#44; non-steroidal anti-inflammatory drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Bronchoconstrictor agents more frequently used in provocation tests&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Bronchoconstrictor agents used in bronchial hyperresponsiveness tests&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
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                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"><span class="elsevierStyleBold">Minimum aeroallergen battery to conduct in European patients diagnosed with asthma</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&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><span class="elsevierStyleItalic">Pollen</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Betula verrucosa</span> or mixes of <span class="elsevierStyleItalic">Betulaceae</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cupressus sempervirens</span> or other species of Cypress&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><span class="elsevierStyleHsp" style=""></span>Spring grasses&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Artemisia vulgaris</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Olea europaea</span> or <span class="elsevierStyleItalic">Fraxinus exelsior</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Parietaria officinalis</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Platanus occidentalis</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Ambrosia elatior</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mites</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dermatophagoides pteronyssinus</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dermatophagoides farinae</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Fungi</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Alternaria alternata</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cladosporium album</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Animals</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cat&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><span class="elsevierStyleHsp" style=""></span>Dog&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><span class="elsevierStyleItalic">Insects</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Blatella</span> sp&#46;&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="elsevierStyleBold">Frequency of sensitisation to aeroallergens in the Spanish asthmatic population</span><a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&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><span class="elsevierStyleItalic">Pollen</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Spring grasses&#44; 32&#46;4&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Olea europaea</span>&#44; 26&#46;9&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Chenopodium album</span>&#44; 8&#46;7&#37;&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><span class="elsevierStyleHsp" style=""></span>Species of <span class="elsevierStyleItalic">Cupressus</span>&#44; 7&#46;5&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Platanus acerifolia</span>&#44; 6&#46;9&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Plantago lanceolata</span>&#44; 6&#46;8&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Salsola kali</span>&#44; 6&#46;5&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Parietaria judaica</span>&#44; 4&#46;6&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Artemisia vulgaris</span>&#44; 6&#46;2&#37;&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><span class="elsevierStyleItalic">Mites</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dermatophagoides pteronyssinus</span>&#44; 41&#46;0&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dermatophagoides farinae</span>&#44; 32&#46;9&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Lepidoglyphus destructive</span>&#44; 7&#46;7&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tyrophagus putrescentiae</span>&#44; 5&#46;6&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Euroglyphus maynei</span>&#44; 3&#46;5&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Blomia tropicalis</span>&#44; 3&#46;3&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Glycyphagus domesticus</span>&#44; 1&#46;9&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Acarus siro</span>&#44; 1&#46;3&#37;&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><span class="elsevierStyleItalic">Fungi</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">alternata Alternaria</span>&#44; 8&#46;3&#37;&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><span class="elsevierStyleHsp" style=""></span>Species of <span class="elsevierStyleItalic">Cladosporium</span>&#44; 1&#46;4&#37;&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><span class="elsevierStyleHsp" style=""></span>Species of <span class="elsevierStyleItalic">Aspergillus</span>&#44; 1&#46;4&#37;&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><span class="elsevierStyleItalic">Animals</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cat&#44; 15&#46;3&#37;&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><span class="elsevierStyleHsp" style=""></span>Dog&#44; 13&#46;7&#37;&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><span class="elsevierStyleHsp" style=""></span>Horse&#44; 2&#37;&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><span class="elsevierStyleHsp" style=""></span>Rabbit&#44; 0&#46;6&#37;&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><span class="elsevierStyleHsp" style=""></span>Hamster&#44; 0&#46;6&#37;&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><span class="elsevierStyleHsp" style=""></span>Feathers&#44; 0&#46;5&#37;&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><span class="elsevierStyleItalic">Insects</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="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Blatella germanica</span>&#44; 0&#46;6&#37;&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><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Blatella orientalis</span>&#44; 0&#46;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Source&#58; Bousquet et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">16</span></a></p>"
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Source&#58; Quirce&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">1</span></a></p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Most relevant inhaled allergens in Europe and Spain&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">PEF&#58; peak expiratory flow&#59; FEV<span class="elsevierStyleInf">1</span>&#58; forced expiratory volume in one second&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Classification proposed by GEMA<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">2</span></a> to determine the severity of the asthmatic patient without treatment&#46;</p>"
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                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="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Adult patients</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">Intermittent&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">Mild persistent&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">Moderate persistent&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">Severe persistent&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"><span class="elsevierStyleItalic">Daytime symptoms</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No &#40;2 days or less a week&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">More than 2 days a week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Daily symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Continuous symptoms &#40;several times a day&#41;&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">Relief medication</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No &#40;2 days or less a week&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">More than 2 days a week&#44; but not daily&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Several times a day&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">Nighttime symptoms</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No more than twice a month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">More than twice a month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">More than once a week&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Frequent&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">Limitations on activity</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">None&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Some limitation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A fair degree of limitation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Considerable limitation&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">Pulmonary Function &#40;FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">or PEF theoretical &#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;80&#37;&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;20&#37;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Classification of severity of asthma in adults and children&#46;</p>"
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      "seccion" => array:1 [
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                        "tituloSerie" => "J Investig Allergol Clin Immunol"
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Article information

ISSN: 23870206
Original language: English

DOI:10.1016/j.medcle.2015.05.044

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