Prevalence of aspirin-exacerbated respiratory disease in patients with asthma in Turkey: A cross-sectional survey

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Santos, S. Jamelli, L. Costa, C. Baracho Filho, D. Medeiros, J.A. Rizzo, E. Sarinho" "autores" => array:7 [ 0 => array:2 [ "nombre" => "N.C." "apellidos" => "Santos" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Jamelli" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Costa" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Baracho Filho" ] 4 => array:2 [ "nombre" => "D." "apellidos" => "Medeiros" ] 5 => array:2 [ "nombre" => "J.A." "apellidos" => "Rizzo" ] 6 => array:2 [ "nombre" => "E." 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"apellidos" => "Bavbek" "email" => array:1 [ 0 => "bavbek@medicine.ankara.edu.tr" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "İ." "apellidos" => "Yılmaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "G." "apellidos" => "Çelik" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Ö." "apellidos" => "Aydın" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "F.Ö." "apellidos" => "Erkekol" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "A." 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"apellidos" => "Mısırlıgil" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:9 [ 0 => array:3 [ "entidad" => "Ankara University, School of Medicine, Department of Chest Diseases, Division of Immunology and Allergy, Ankara, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Osmangazi University, School of Medicine, Department of Chest Diseases, Department of Allergy, Eskisehir, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Uludağ University, School of Medicine, Department of Chest Diseases, Unit of Allergy, Bursa, Turkey" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Atatürk Chest Diseases & Thoracic Surgery Training and Research Hospital, Unit of Allergy, Ankara, Turkey" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Cumhuriyet University, School of Medicine, Department of Chest Diseases, Department of Allergy, Sivas, Turkey" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Süreyyapaşa Chest Diseases and Thoracic Surgery Education Hospital, Istanbul, Turkey" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Acıbadem University, Department of Chest Diseases, Istanbul, Turkey" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Atatürk Chest Diseases & Thoracic Surgery Training and Research Hospital, Chest Diseases Clinic, Ankara, Turkey" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Ankara University, School of Medicine, Department of Biostatistics, Ankara, Turkey" "etiqueta" => "i" "identificador" => "aff0045" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 584 "Ancho" => 1300 "Tamanyo" => 65198 ] ] "descripcion" => array:1 [ "en" => "Reactions types of ASA hypersensitivity." ] ] ] "textoCompleto" => "IntroductionA variety of hypersensitivity reactions, varying from cutaneous reactions to severe systemic reaction, related with aspirin (ASA) consumption have been frequently reported.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> The prevalence of ASA hypersensitivity changes with the method used for the diagnosis, however, a group of chronic diseases such as nasal polyp (NP), asthma and chronic urticaria are associated with a higher rate of ASA hypersensitivity than in the general population.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>ASA-exacerbated respiratory disease (AERD) is a distinct, clear-cut phenotype of asthma. The disease is characterised by a natural sequence of symptoms: first rhinitis related by most patients to a flu-like infection, then perennial eosinophilic rhinosinusitis/NP, followed by ASA-induced respiratory reaction. Precipitation of asthmatic attacks by ASA and other non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (COX)-1 constitute a hallmark of this clinical syndrome. The disease runs a protracted, usually severe course with about half of the patients requiring at least bursts of corticosteroids to control their rhinosinusitis and asthma.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> The prevalence of AERD in adult asthmatic patients ranges from 1% to 20%.<a class="elsevierStyleCrossRefs" href="#bib0005">1–4</a> A few studies have reported data regarding the frequency of ASA hypersensitivity, asthma and related issues in our country.<a class="elsevierStyleCrossRefs" href="#bib0025">5–7</a> However, these trials were single-centre based and none of them specifically targeted the prevalence of AERD among the adult population with asthma. Consequently, there has been no nationwide epidemiological study on the prevalence of AERD in Turkey. Therefore, in this multi-centre study, we first aimed to assess the prevalence of AERD in adult asthmatics, and secondarily aimed to document the clinical features of the disease and risk factors for our population.Material and methodsPatient selectionThis prospective, national and multi-centre study was conducted at seven different tertiary healthcare centres across Turkey. The tertiary healthcare centres for chest and allergic diseases were selected to be representative of the country according to the geographical distribution of specialists in Turkey as well as the distribution of investigators in relation to the type of institutions in which they work (university hospital, state chest diseases hospital). All adults with asthma were prospectively included in the study throughout 2007. The patients were assured of the voluntary nature of the study, and all gave verbal informed consent. The patients were regularly visiting their physicians and were on health care cover. Asthma diagnosis was based on criteria defined by the American Thoracic Society.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> The diagnosis of NP and rhinosinusitis was based on visualisation of bilateral polyps in nasal cavities by either endoscopic examination and/or by a CT scan of the paranasal sinuses, in addition to compatible history. The asthma control level was classified as controlled, partly controlled, and uncontrolled by means of physician assessment considering daytime/night-time symptoms, limitations of activities, need for rescue treatment, and the number of exacerbations, based on the Global Initiative for Asthma (GINA) guidelines.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>QuestionnaireA specifically designed questionnaire was developed by the authors and used via face-to-face interview by a specialist in pulmonology and allergy to evaluate the prevalence of AERD. It consisted of questions about the patients’ demographics including age, gender, the duration of asthma, NP, rhinosinusitis/rhinitis, medications, and emergency room visit/hospitalisation for the preceding year. Additional items concerning the number of nasal polypectomies, family history of ASA respiratory hypersensitivity, and reactions to antibiotics or other drugs were included. Diagnosis of ASA hypersensitivity was based on either the patient's history and/or oral ASA provocation. Aspirin hypersensitivity was established by six questions including if there had ever been any reaction after ASA and/or other NSAIDs, the number of reactions, and details of the symptoms, which occurred following these medications. Nasal congestion/rhinorrhea, and/or shortening of breath and rapidly progressing bronchial obstruction within 30–120min following ingestion of ASA and/or other COX-inhibiting NSAIDs was considered a positive history for ASA hypersensitivity. Other extrabronchial symptoms including ocular, cutaneous or gastric symptoms accompanying respiratory symptoms were also accepted as being positive for ASA hypersensitivity. In those centres, which had experienced personnel and necessary equipment, oral ASA provocation was performed to confirm the diagnosis of ASA hypersensitivity. An oral provocation test with ASA was performed with the method previously described.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>Evaluation of atopyAtopy was defined as a positive skin prick (a mean diameter of 3mm greater than the negative control) and/or specific IgE (>0.35kU/l with ImmunoCAP system, Phadia, Uppsala, Sweden) to at least one of the aeroallergens. Glycerinated extracts of Dermatophagoides pteronyssinus, Dermatophagoides farinae, cockroach, grass, tree, weed pollens, cat, dog, and Alternaria and Cladosporium antigens (Stallergenes, Antony/France or ALK-Abello, Madrid/Spain) were used along with positive and negative controls.StatisticsNumerical values are given as mean±SEM and categorical/ordinal values as n (%). Numerical values and ordinal/categorical values of patients with AERD and patients with ASA-tolerant asthma were compared by unpaired samples T-test and Chi-square tests, respectively. A p-value less than 0.05 were considered as statistically positive. The significant factors obtained in the univariate analysis in the comparison of both groups were re-formulated for a multivariate logistic regression model. Data were given as odds ratio (OR) and 95% confidence interval.ResultsA total of 1344 patients with a mean age of 45.7±14.2 years were enrolled in this study (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Females were predominant (80.5%) and nearly half of the patients were atopic (47%). Mite was the most common sensitising allergen (n: 193, 31.8%), followed by pollens (n: 147, 24.3%), pollen plus mite (n: 184, 30.4%), moulds (n: 20, 3.3%). Of all patients, 829 patients (67.3%) had controlled (one or less than twice daily symptoms without any nocturnal symptom, need for rescue medication, activity limitation, and exacerbation), 268 (21.8%) had partly controlled, and 134 (10.9%) had uncontrolled asthma. The majority of patients (71%) were identified to be on combined drug treatment, either inhaled corticosteroids (ICS) and long acting beta-2 agonist: (LABA) in 927 patients (68.9%), or ICS+LABA+leukotriene receptor antagonist (LTRA) in 315 patients (23.9%). Fifty patients (3.7%) were on a systemic steroid, and 15 patients (1.16%) were using theophylline. A few patients were on only one controller such as ICS in 44 patients (3.27%), and LTRA in 28 patients (2.08%) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>A total of 180 (13.6%) asthma patients were diagnosed to be AERD. The diagnosis of ASA hypersensitivity was based on reliable history in 145 cases (80.5%), and ASA provocation was performed in 35 (19.5%) patients. Eight patients among the ASA-tolerant group were challenged with ASA, and two resulted in positive. In contrast, there were 4 patients who were negative to ASA provocation test among patients with a positive history to ASA and challenged with ASA. Aspirin was the major NSAID causing hypersensitivity reactions in 149 (82.7%) patients, and 108 (63.5%) patients reported hypersensitivity reaction to other NSAIDs in addition to ASA. In 31 (17.3%) of 180 patients with AERD, reactions were precipitated only by other NSAID, 9 (5%) reacted to COX-2 inhibitors, and 20 (11.6%) reacted to antibiotics. Clinical presentations of ASA hypersensitivity were lower respiratory in 58% (n=105), upper respiratory in 8% (n=14), upper and lower respiratory in 10% (n=18), respiratory and cutaneous in 15% (n=27), and systemic type in 9% (n=16) of the patients (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In the comparison of patients with AERD and ASA tolerant asthma, there were no significant differences in term of age, gender, smoking rate, presence of allergic rhinitis, and atopy between the groups. There was no difference in asthma control levels between AERD and ASA tolerant asthma (p>0.05). The ratio of the patients with controlled, partly controlled and uncontrolled asthma were 63.3% (n=112), 23.2% (n=41) and 13.6% (n=24), respectively, among the patients with AERD. Similarly, the ratio of patients with controlled, partly controlled, and uncontrolled asthma were 68% (717), 21.5% (n=227) and 10.4% (n=110), respectively, among the ASA tolerant group. However, AERD was significantly associated with the presence of NP, chronic rhinosinusitis/rhinitis, family history of ASA hypersensitivity, hypersensitivity to COX-2 inhibitors and antibiotics, the use of systemic steroid and LTRA, emergency department visits and hospitalisation due to asthma during the past year (p<0.05, p<0.001). The relationship between ASA hypersensitivity and numbers of polypectomies was statistically significant (p=0.016). The rate of three or more nasal polypectomies history was 35.2% in patients with AERD. This rate was 16.9% in patients not having ASA hypersensitivity (p<0.008). A total of 270 patients were diagnosed as having NP. Of them, 171 (63.3%) reported previous nasal polypectomy, and 40 (25%) had a history of more than three nasal polypectomies.When we compared the patients who are ASA tolerant or have AERD, all were in their early thirties and there was no statistically significant difference between mean ages at the onset of chronic rhinosinusitis/rhinitis, allergic rhinitis, NP and asthma (p>0.05) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Multivariate analysis indicated that family history of ASA hypersensitivity (p: 0.001, OR: 3.746, 95% CI: 1.769–7.929), history of rhinosinusitis/rhinitis 1.713 (p: 0.025, OR: 1.713 95% CI: 1.069–2.746) and presence of nasal polyposis (p<0.001, OR: 7.036, 95% CI: 4.831–10.247) were independent predictors for ASA hypersensitivity in patients with asthma (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>DiscussionThe present study demonstrated that the frequency of AERD was 13.6% in our country and its prevalence appeared to be affected by a family history of ASA hypersensitivity, the presence of NP, and chronic rhinosinusitis/rhinitis.The exact prevalence of AERD is unknown. A limited number of epidemiological studies reported that the prevalence of AERD ranges from 4% to 44%.<a class="elsevierStyleCrossRefs" href="#bib0015">3,11</a> This difference seems to be related with the heterogeneity of the population studied, as well as the methods and criteria used for determining ASA hypersensitivity. A recent systematic review reported that the pooled incidence of AERD is 21% (95% CI, 14% to 29%).<a class="elsevierStyleCrossRef" href="#bib0185">4</a>Most studies about the prevalence of ASA hypersensitivity have been on selected populations, such as patients with severe asthma or patients with required mechanical ventilation.<a class="elsevierStyleCrossRefs" href="#bib0185">4,12</a> Very few and reliable studies have targeted the frequency of ASA hypersensitivity in unselected asthma patients.<a class="elsevierStyleCrossRefs" href="#bib0065">13–16</a> In a large survey of a population-based random sample (n: 4300) in Finland, the prevalence of ASA hypersensitivity was 1.2% using a postal questionnaire but it was higher in patients with doctor-diagnosed asthma (8.8%).<a class="elsevierStyleCrossRef" href="#bib0065">13</a> In an Austrian postal questionnaire survey, the prevalence of physician diagnosed-AERD was 10–11%.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> More recently, in the largest random selected population study from Poland (n: 12,971), hypersensitivity to ASA/NSAIDs was observed in 12.9% of asthmatics via interview of subjects by medical students and nurses.<a class="elsevierStyleCrossRefs" href="#bib0075">15,16</a> We also worked with an unselected outpatient asthma population.The use of history alone in the assessment of ASA hypersensitivity among asthma patients has been associated with underestimation or overestimation of the real prevalence of AERD.<a class="elsevierStyleCrossRefs" href="#bib0185">4,17</a> A recent systematic review reported that history alone resulted in a much lower prevalence (2.7%) compared to the pooled incidence of AERD as 21%.<a class="elsevierStyleCrossRef" href="#bib0185">4</a> Lack of awareness of the patients, who are hypersensitive to ASA, or patients with asthma having been advised to avoid ASA may all contribute to the underdiagnosis of ASA hypersensitivity.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Furthermore, a recent review<a class="elsevierStyleCrossRef" href="#bib0185">4</a> showed that analyses based on the use of a questionnaire in doctor-diagnosed asthma resulted in a higher number of positive results for AERD (11–24%) than those based on the retrospective analysis of medical records (2–3%).When ASA provocation is performed, the prevalence of AERD can be as high as 21%.<a class="elsevierStyleCrossRefs" href="#bib0185">4,12,17</a> However, because of the potential for severe reactions, provocation tests are not a usual method used for studies of AERD. ASA provocation could be done in five centres in our trial. Since it was not systematically used in all patients in the study, we did not separately evaluate the prevalence of AERD in these centres.The typical patient with AERD is an adult who develops rhinosinusitis in the third-fourth decade of life. The typical clinical picture is completed with the addition of asthma and ASA hypersensitivity.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> In our trial, the mean ages of the patients at the onset of rhinosinusitis, NP, asthma, and ASA hypersensitivity were around the third decade, and the order of development of AERD was similar to that previously indicated.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>It is well known that AERD patients suffer from a more severe phenotype of persistent asthma than average with higher medication requirements.<a class="elsevierStyleCrossRefs" href="#bib0085">17–19</a> Supporting this, our patients with AERD were associated with a higher rate of systemic steroid and LTRA use in addition to ICS+LABA when compared to ASA tolerant patients. Similarly, as reported previously,<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> a high rate of emergency room visit/hospitalisation was associated with ASA hypersensitivity in our group.Several risk factors have been supposed for AERD including atopy, persistent rhinosinusitis and NP.<a class="elsevierStyleCrossRefs" href="#bib0110">22,23</a> The role of atopy as a risk factor is controversial<a class="elsevierStyleCrossRefs" href="#bib0015">3,23,24</a>. In this trial, the atopy rate of the whole group was significantly higher than that of the general adult population in Turkey (47% vs. 25%, p>0.05),<a class="elsevierStyleCrossRef" href="#bib0125">25</a> but it seems to be related with the presence of asthma rather than ASA hypersensitivity since the atopy ratio was not different in AERD than in ASA tolerant asthma.The prevalence of ASA hypersensitivity in patients with NP has been found to be 20–40%.<a class="elsevierStyleCrossRefs" href="#bib0015">3,26,27</a> Consistently, in our study, the presence of NP was a significant and independent risk factor for AERD. Moreover, NP has a high tendency for recurrence.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Likewise, there was a statistically significant (p=0.016) relationship between ASA hypersensitivity and the number of polypectomies in our patients.Cross-sensitivity to NSAIDs is a well-known feature of ASA hypersensitivity<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> and in our study 63.5% of patients with AERD also reported reactions to other COX-1 inhibitors. COX-2 inhibitors are generally considered safe in AERD, but some cutaneous and systemic reactions have been reported with them.<a class="elsevierStyleCrossRefs" href="#bib0140">28,29</a> In our trial a few (5%) AERD patients had a history of reaction to COX-2 inhibitors; unfortunately we do not have data about the type of reaction to these drugs.Drug reactions can aggregate in families.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Familial aggregation of ASA hypersensitivity was reported by 10.2% of our patients with AERD. As far as we know, there are no data regarding familial aggregation of ASA hypersensitivity with the exception of a multicentre study in which the family history of hypersensitivity to ASA has been reported by 6% of the families.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> As a limitation of our study, we did not confirm ASA hypersensitivity in family members. Individuals with a history of ASA hypersensitivity may be more likely to remember ASA hypersensitivity in family members or inadvertent interviewer bias could have influenced the results. A recent study evaluating familial aggregation of ASA-induced urticaria demonstrated LTC4S)-444C alleles aggregations in family members.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> Contrary to studies genetic background of AERD,<a class="elsevierStyleCrossRefs" href="#bib0160">32–34</a> there is no genetic study regarding familial aggregation of AERD. It would be interesting to see if there is any inheritance pattern in such patients.Another limitation of our study is the diagnosis of ASA hypersensitivity, which was mainly based on a detailed history. However, all patients were both recruited from centres, which specialise in allergy/pulmonology, and were also evaluated by specialists. A significant correlation between a history of ASA hypersensitivity and the result of oral challenge has been previously demonstrated.<a class="elsevierStyleCrossRefs" href="#bib0175">35,36</a> Therefore, despite this limitation, this questionnaire-based study provides nationwide data regarding the prevalence of AERD in our country for the first time.In conclusion, this nationwide survey showed that AERD is highly prevalent among our adult asthmatics and its prevalence seems to be affected by family history of ASA hypersensitivity, presence of NP, chronic rhinosinusitis and/or rhinitis.Conflict of interestThe authors have no conflict of interest. There is no financial support." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xres86136" "titulo" => array:6 [ 0 => "Abstract" 1 => "Background" 2 => "Objective" 3 => "Methods" 4 => "Results" 5 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec74295" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patient selection" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Questionnaire" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Evaluation of atopy" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistics" ] ] ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-03-01" "fechaAceptado" => "2011-05-02" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec74295" "palabras" => array:5 [ 0 => "Aspirin hypersensitivity" 1 => "AERD" 2 => "Asthma" 3 => "Aspirin intolerant asthma" 4 => "Epidemiology" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "BackgroundThere are no country-based data focused on aspirin (ASA)-exacerbated respiratory disease (AERD) in Turkey. ObjectiveTo assess the prevalence of AERD in adult patients with asthma. MethodsA structured questionnaire was administered via face-to-face interview by a specialist in pulmonology/allergy at seven centres across Turkey. ResultsA total of 1344 asthma patients (F/M: 1081/263: 80.5%/19.5%, mean age: 45.7±14.2 years) were enrolled. Atopy rate was 47%. Prevalence of allergic rhinitis, chronic rhinosinusitis/rhinitis, and nasal polyposis (NP) were 49%, 69% and 20%, respectively. Of 270 patients with NP, 171 (63.3%) reported previous nasal polypectomy and 40 (25%) had a history of more than three nasal polypectomies. Aspirin hypersensitivity was diagnosed in 180 (13.6%) asthmatic patients, with a reliable history in 145 (80.5%), and oral ASA provocation test in 35 (19.5%) patients. Clinical presentations of ASA hypersensitivity were respiratory in 76% (n=137), respiratory/cutaneous in 15% (n=27), and systemic in 9% (n=16) of the patients. Multivariate analysis indicated that a family history of ASA hypersensitivity (p: 0.001, OR: 3.746, 95% CI: 1.769–7.929), history of chronic rhinosinusitis/rhinitis (p: 0.025, OR: 1.713, 95% CI: 1.069–2.746) and presence of NP (p<0.001, OR: 7.036, 95% CI: 4.831–10.247) were independent predictors for AERD. ConclusionThis cross-sectional survey showed that AERD is highly prevalent among adult asthmatics and its prevalence seems to be affected by family history of ASA hypersensitivity, history of rhinosinusitis and presence of NP." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 584 "Ancho" => 1300 "Tamanyo" => 65198 ] ] "descripcion" => array:1 [ "en" => "Reactions types of ASA hypersensitivity." ] ] 1 => 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=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Demographics</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years) (mean±SEM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.7±14.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female gender, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1081 (80.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Current smoker, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">119 (9.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Disease characteristics</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Emergency care admission due to asthma in the last year, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">187 (13.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hospitalisation due to asthma in the last year, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">96 (7.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of atopy, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">613 (47%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients who were on ICS + LABA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">927 (68.8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients who were on only ICS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (3.27%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients who were on only LTRA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28 (2.08%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients who were on ICS+LABA+ LTRA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">315 (23.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Systemic CS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 (3.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of co-morbid disorders, n (%)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allergic rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">657 (49%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic rhinosinusitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">599 (44.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic rhinosinusitis and/or rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">923 (69%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nasal polyps \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">270 (20.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">History of drug hypersensitivity, n (%)</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ASA/NSAIDs hypersensitivity, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">180 (13.6%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypersensitivity to antibiotics, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 (5.1%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypersensitivity to other drugs, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (0.004%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Family history of ASA hypersensitivity, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">42 (3.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165538.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographics and disease characteristics of the study population (n=1344)." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "ASA: aspirin; NSAIDs: nonsteroidal anti-inflammatory drugs; LTRA: leukotriene receptor antagonist; COX: cyclooxygenase." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">AIA patientsn: 180 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Patients with ASA tolerancen: 1104 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (years (mean±SEM) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.9±12.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.6±14.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns<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="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female gender, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">147 (81.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">883 (79.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Current smoker, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (7.0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98 (9.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of allergic rhinitis, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93 (52%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">543 (49.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of atopy, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 (44.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">519 (48.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ns \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of nasal polyps, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">98 (54.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">155 (14.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of chronic rhinosinusitis, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">107 (59.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">464 (42.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Family history of ASA hypersensitivity, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 (10.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (2.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other NSAIDs hypersensitivity, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">108 (63.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypersensitivity to COX-2 inhibitors n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (5.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypersensitivity to antibiotics, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (11.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (3.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use of systemic corticosteroids, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (7.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (3.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">=0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use of LTRA, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76 (42.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">283 (25.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Admission to emergency care unit due to asthma, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (28.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">135 (12.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hospitalisation due to asthma, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27 (15.0%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69 (6.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">=0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥3 nasal polypectomies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (35.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (16.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">=0.008 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165540.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "ns=Non-significant." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of asthma patients with or without ASA hypersensitivity." ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">ASA hypersensitivity</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">p-value \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic rhinosinusitis/rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.5±11.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.9±12.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Allergic rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.7±11.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.0±12.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nasal polyposis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35.1±12.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.4±13.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34.6±12.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.3±13.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165537.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Mean age at onset of accompanying diseases according to ASA hypersensitivity." ] ] 4 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "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=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">O.R.* [95% CI] \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Family history of ASA hypersensitivity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.746 [1.769–7.929] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of nasal polyps \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.036 [4.831–10.247] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic rhinosinusitis and/or rhinitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.025 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.713 [1.069–2.746] \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Atopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.371 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.722 [0.354–1.474] \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165539.png" ] ] ] ] "descripcion" => 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Original article

S. Bavbeka,

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bavbek@medicine.ankara.edu.tr

Corresponding author.

, İ. Yılmaza, G. Çelika, Ö. Aydına, F.Ö. Erkekola, A. Ormanb, E. Kurtb, D. Edigerc, B. Dursund, Ö. Abadoğlue, F. Özşekerf, E. Akkayaf, G.P. Karakışg, S. Canbakanh, S. Yükseli, Z. Mısırlıgila

a Ankara University, School of Medicine, Department of Chest Diseases, Division of Immunology and Allergy, Ankara, Turkey

b Osmangazi University, School of Medicine, Department of Chest Diseases, Department of Allergy, Eskisehir, Turkey

c Uludağ University, School of Medicine, Department of Chest Diseases, Unit of Allergy, Bursa, Turkey

d Atatürk Chest Diseases & Thoracic Surgery Training and Research Hospital, Unit of Allergy, Ankara, Turkey

e Cumhuriyet University, School of Medicine, Department of Chest Diseases, Department of Allergy, Sivas, Turkey

f Süreyyapaşa Chest Diseases and Thoracic Surgery Education Hospital, Istanbul, Turkey

g Acıbadem University, Department of Chest Diseases, Istanbul, Turkey

h Atatürk Chest Diseases & Thoracic Surgery Training and Research Hospital, Chest Diseases Clinic, Ankara, Turkey

i Ankara University, School of Medicine, Department of Biostatistics, Ankara, Turkey

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is a distinct&#44; clear-cut phenotype of asthma&#46; The disease is characterised by a natural sequence of symptoms&#58; first rhinitis related by most patients to a flu-like infection&#44; then perennial eosinophilic rhinosinusitis&#47;NP&#44; followed by ASA-induced respiratory reaction&#46; Precipitation of asthmatic attacks by ASA and other non-steroidal anti-inflammatory drugs &#40;NSAIDs&#41; that inhibit cyclooxygenase &#40;COX&#41;-1 constitute a hallmark of this clinical syndrome&#46; The disease runs a protracted&#44; usually severe course with about half of the patients requiring at least bursts of corticosteroids to control their rhinosinusitis and asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The prevalence of AERD in adult asthmatic patients ranges from 1&#37; to 20&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a> A few studies have reported data regarding the frequency of ASA hypersensitivity&#44; asthma and related issues in our country&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a> However&#44; these trials were single-centre based and none of them specifically targeted the prevalence of AERD among the adult population with asthma&#46; Consequently&#44; there has been no nationwide epidemiological study on the prevalence of AERD in Turkey&#46; Therefore&#44; in this multi-centre study&#44; we first aimed to assess the prevalence of AERD in adult asthmatics&#44; and secondarily aimed to document the clinical features of the disease and risk factors for our population&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient selection</span><p id="par0015" class="elsevierStylePara elsevierViewall">This prospective&#44; national and multi-centre study was conducted at seven different tertiary healthcare centres across Turkey&#46; The tertiary healthcare centres for chest and allergic diseases were selected to be representative of the country according to the geographical distribution of specialists in Turkey as well as the distribution of investigators in relation to the type of institutions in which they work &#40;university hospital&#44; state chest diseases hospital&#41;&#46; All adults with asthma were prospectively included in the study throughout 2007&#46; The patients were assured of the voluntary nature of the study&#44; and all gave verbal informed consent&#46; The patients were regularly visiting their physicians and were on health care cover&#46; Asthma diagnosis was based on criteria defined by the American Thoracic Society&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The diagnosis of NP and rhinosinusitis was based on visualisation of bilateral polyps in nasal cavities by either endoscopic examination and&#47;or by a CT scan of the paranasal sinuses&#44; in addition to compatible history&#46; The asthma control level was classified as controlled&#44; partly controlled&#44; and uncontrolled by means of physician assessment considering daytime&#47;night-time symptoms&#44; limitations of activities&#44; need for rescue treatment&#44; and the number of exacerbations&#44; based on the Global Initiative for Asthma &#40;GINA&#41; guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Questionnaire</span><p id="par0020" class="elsevierStylePara elsevierViewall">A specifically designed questionnaire was developed by the authors and used via face-to-face interview by a specialist in pulmonology and allergy to evaluate the prevalence of AERD&#46; It consisted of questions about the patients&#8217; demographics including age&#44; gender&#44; the duration of asthma&#44; NP&#44; rhinosinusitis&#47;rhinitis&#44; medications&#44; and emergency room visit&#47;hospitalisation for the preceding year&#46; Additional items concerning the number of nasal polypectomies&#44; family history of ASA respiratory hypersensitivity&#44; and reactions to antibiotics or other drugs were included&#46; Diagnosis of ASA hypersensitivity was based on either the patient&#39;s history and&#47;or oral ASA provocation&#46; Aspirin hypersensitivity was established by six questions including if there had ever been any reaction after ASA and&#47;or other NSAIDs&#44; the number of reactions&#44; and details of the symptoms&#44; which occurred following these medications&#46; Nasal congestion&#47;rhinorrhea&#44; and&#47;or shortening of breath and rapidly progressing bronchial obstruction within 30&#8211;120<span class="elsevierStyleHsp" style=""></span>min following ingestion of ASA and&#47;or other COX-inhibiting NSAIDs was considered a positive history for ASA hypersensitivity&#46; Other extrabronchial symptoms including ocular&#44; 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to at least one of the aeroallergens&#46; Glycerinated extracts of <span class="elsevierStyleItalic">Dermatophagoides pteronyssinus</span>&#44; <span class="elsevierStyleItalic">Dermatophagoides farinae</span>&#44; cockroach&#44; grass&#44; tree&#44; weed pollens&#44; cat&#44; dog&#44; and <span class="elsevierStyleItalic">Alternaria</span> and <span class="elsevierStyleItalic">Cladosporium</span> antigens &#40;Stallergenes&#44; Antony&#47;France or ALK-Abello&#44; Madrid&#47;Spain&#41; were used along with positive and negative controls&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistics</span><p id="par0030" class="elsevierStylePara elsevierViewall">Numerical values are given as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SEM and categorical&#47;ordinal values as <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&#46; Numerical values and ordinal&#47;categorical values of patients with AERD and patients with ASA-tolerant asthma were compared by unpaired samples <span class="elsevierStyleItalic">T</span>-test and Chi-square tests&#44; respectively&#46; A <span class="elsevierStyleItalic">p</span>-value less than 0&#46;05 were considered as statistically positive&#46; The significant factors obtained in the univariate analysis in the comparison of both groups were re-formulated for a multivariate logistic regression model&#46; Data were given as odds ratio &#40;OR&#41; and 95&#37; confidence interval&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">A total of 1344 patients with a mean age of 45&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;2 years were enrolled in this study &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Females were predominant &#40;80&#46;5&#37;&#41; and nearly half of the patients were atopic &#40;47&#37;&#41;&#46; Mite was the most common sensitising allergen &#40;<span class="elsevierStyleItalic">n</span>&#58; 193&#44; 31&#46;8&#37;&#41;&#44; followed by pollens &#40;<span class="elsevierStyleItalic">n</span>&#58; 147&#44; 24&#46;3&#37;&#41;&#44; pollen plus mite &#40;<span class="elsevierStyleItalic">n</span>&#58; 184&#44; 30&#46;4&#37;&#41;&#44; moulds &#40;<span class="elsevierStyleItalic">n</span>&#58; 20&#44; 3&#46;3&#37;&#41;&#46; Of all patients&#44; 829 patients &#40;67&#46;3&#37;&#41; had controlled &#40;one or less than twice daily symptoms without any nocturnal symptom&#44; need for rescue medication&#44; activity limitation&#44; and exacerbation&#41;&#44; 268 &#40;21&#46;8&#37;&#41; had partly controlled&#44; and 134 &#40;10&#46;9&#37;&#41; had uncontrolled asthma&#46; The majority of patients &#40;71&#37;&#41; were identified to be on combined drug treatment&#44; either inhaled corticosteroids &#40;ICS&#41; and long acting beta-2 agonist&#58; &#40;LABA&#41; in 927 patients &#40;68&#46;9&#37;&#41;&#44; or ICS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>LABA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>leukotriene receptor antagonist &#40;LTRA&#41; in 315 patients &#40;23&#46;9&#37;&#41;&#46; Fifty patients &#40;3&#46;7&#37;&#41; were on a systemic steroid&#44; and 15 patients &#40;1&#46;16&#37;&#41; were using theophylline&#46; A few patients were on only one controller such as ICS in 44 patients &#40;3&#46;27&#37;&#41;&#44; and LTRA in 28 patients &#40;2&#46;08&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">A total of 180 &#40;13&#46;6&#37;&#41; asthma patients were diagnosed to be AERD&#46; The diagnosis of ASA hypersensitivity was based on reliable history in 145 cases &#40;80&#46;5&#37;&#41;&#44; and ASA provocation was performed in 35 &#40;19&#46;5&#37;&#41; patients&#46; Eight patients among the ASA-tolerant group were challenged with ASA&#44; and two resulted in positive&#46; In contrast&#44; there were 4 patients who were negative to ASA provocation test among patients with a positive history to ASA and challenged with ASA&#46; Aspirin was the major NSAID causing hypersensitivity reactions in 149 &#40;82&#46;7&#37;&#41; patients&#44; and 108 &#40;63&#46;5&#37;&#41; patients reported hypersensitivity reaction to other NSAIDs in addition to ASA&#46; In 31 &#40;17&#46;3&#37;&#41; of 180 patients with AERD&#44; reactions were precipitated only by other NSAID&#44; 9 &#40;5&#37;&#41; reacted to COX-2 inhibitors&#44; and 20 &#40;11&#46;6&#37;&#41; reacted to antibiotics&#46; Clinical presentations of ASA hypersensitivity were lower respiratory in 58&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>105&#41;&#44; upper respiratory in 8&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&#44; upper and lower respiratory in 10&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>18&#41;&#44; respiratory and cutaneous in 15&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#41;&#44; and systemic type in 9&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41; of the patients &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In the comparison of patients with AERD and ASA tolerant asthma&#44; there were no significant differences in term of age&#44; gender&#44; smoking rate&#44; presence of allergic rhinitis&#44; and atopy between the groups&#46; There was no difference in asthma control levels between AERD and ASA tolerant asthma &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; The ratio of the patients with controlled&#44; partly controlled and uncontrolled asthma were 63&#46;3&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>112&#41;&#44; 23&#46;2&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>41&#41; and 13&#46;6&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41;&#44; respectively&#44; among the patients with AERD&#46; Similarly&#44; the ratio of patients with controlled&#44; partly controlled&#44; and uncontrolled asthma were 68&#37; &#40;717&#41;&#44; 21&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>227&#41; and 10&#46;4&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>110&#41;&#44; respectively&#44; among the ASA tolerant group&#46; However&#44; AERD was significantly associated with the presence of NP&#44; chronic rhinosinusitis&#47;rhinitis&#44; family history of ASA hypersensitivity&#44; hypersensitivity to COX-2 inhibitors and antibiotics&#44; the use of systemic steroid and LTRA&#44; emergency department visits and hospitalisation due to asthma during the past year &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The relationship between ASA hypersensitivity and numbers of polypectomies was statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;016&#41;&#46; The rate of three or more nasal polypectomies history was 35&#46;2&#37; in patients with AERD&#46; This rate was 16&#46;9&#37; in patients not having ASA hypersensitivity &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;008&#41;&#46; A total of 270 patients were diagnosed as having NP&#46; Of them&#44; 171 &#40;63&#46;3&#37;&#41; reported previous nasal polypectomy&#44; and 40 &#40;25&#37;&#41; had a history of more than three nasal polypectomies&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">When we compared the patients who are ASA tolerant or have AERD&#44; all were in their early thirties and there was no statistically significant difference between mean ages at the onset of chronic rhinosinusitis&#47;rhinitis&#44; allergic rhinitis&#44; NP and asthma &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Multivariate analysis indicated that family history of ASA hypersensitivity &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; OR&#58; 3&#46;746&#44; 95&#37; CI&#58; 1&#46;769&#8211;7&#46;929&#41;&#44; history of rhinosinusitis&#47;rhinitis 1&#46;713 &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;025&#44; OR&#58; 1&#46;713 95&#37; CI&#58; 1&#46;069&#8211;2&#46;746&#41; and presence of nasal polyposis &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; OR&#58; 7&#46;036&#44; 95&#37; CI&#58; 4&#46;831&#8211;10&#46;247&#41; were independent predictors for ASA hypersensitivity in patients with asthma &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">The present study demonstrated that the frequency of AERD was 13&#46;6&#37; in our country and its prevalence appeared to be affected by a family history of ASA hypersensitivity&#44; the presence of NP&#44; and chronic rhinosinusitis&#47;rhinitis&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The exact prevalence of AERD is unknown&#46; A limited number of epidemiological studies reported that the prevalence of AERD ranges from 4&#37; to 44&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;11</span></a> This difference seems to be related with the heterogeneity of the population studied&#44; as well as the methods and criteria used for determining ASA hypersensitivity&#46; A recent systematic review reported that the pooled incidence of AERD is 21&#37; &#40;95&#37; CI&#44; 14&#37; to 29&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Most studies about the prevalence of ASA hypersensitivity have been on selected populations&#44; such as patients with severe asthma or patients with required mechanical ventilation&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">4&#44;12</span></a> Very few and reliable studies have targeted the frequency of ASA hypersensitivity in unselected asthma patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;16</span></a> In a large survey of a population-based random sample &#40;<span class="elsevierStyleItalic">n</span>&#58; 4300&#41; in Finland&#44; the prevalence of ASA hypersensitivity was 1&#46;2&#37; using a postal questionnaire but it was higher in patients with doctor-diagnosed asthma &#40;8&#46;8&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In an Austrian postal questionnaire survey&#44; the prevalence of physician diagnosed-AERD was 10&#8211;11&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> More recently&#44; in the largest random selected population study from Poland &#40;<span class="elsevierStyleItalic">n</span>&#58; 12&#44;971&#41;&#44; hypersensitivity to ASA&#47;NSAIDs was observed in 12&#46;9&#37; of asthmatics via interview of subjects by medical students and nurses&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> We also worked with an unselected outpatient asthma population&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The use of history alone in the assessment of ASA hypersensitivity among asthma patients has been associated with underestimation or overestimation of the real prevalence of AERD&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">4&#44;17</span></a> A recent systematic review reported that history alone resulted in a much lower prevalence &#40;2&#46;7&#37;&#41; compared to the pooled incidence of AERD as 21&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a> Lack of awareness of the patients&#44; who are hypersensitive to ASA&#44; or patients with asthma having been advised to avoid ASA may all contribute to the underdiagnosis of ASA hypersensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Furthermore&#44; a recent review<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a> showed that analyses based on the use of a questionnaire in doctor-diagnosed asthma resulted in a higher number of positive results for AERD &#40;11&#8211;24&#37;&#41; than those based on the retrospective analysis of medical records &#40;2&#8211;3&#37;&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">When ASA provocation is performed&#44; the prevalence of AERD can be as high as 21&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">4&#44;12&#44;17</span></a> However&#44; because of the potential for severe reactions&#44; provocation tests are not a usual method used for studies of AERD&#46; ASA provocation could be done in five centres in our trial&#46; Since it was not systematically used in all patients in the study&#44; we did not separately evaluate the prevalence of AERD in these centres&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The typical patient with AERD is an adult who develops rhinosinusitis in the third-fourth decade of life&#46; The typical clinical picture is completed with the addition of asthma and ASA hypersensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> In our trial&#44; the mean ages of the patients at the onset of rhinosinusitis&#44; NP&#44; asthma&#44; and ASA hypersensitivity were around the third decade&#44; and the order of development of AERD was similar to that previously indicated&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">It is well known that AERD patients suffer from a more severe phenotype of persistent asthma than average with higher medication requirements&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;19</span></a> Supporting this&#44; our patients with AERD were associated with a higher rate of systemic steroid and LTRA use in addition to ICS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>LABA when compared to ASA tolerant patients&#46; Similarly&#44; as reported previously&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> a high rate of emergency room visit&#47;hospitalisation was associated with ASA hypersensitivity in our group&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Several risk factors have been supposed for AERD including atopy&#44; persistent rhinosinusitis and NP&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> The role of atopy as a risk factor is controversial<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;23&#44;24</span></a>&#46; In this trial&#44; the atopy rate of the whole group was significantly higher than that of the general adult population in Turkey &#40;47&#37; vs&#46; 25&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> but it seems to be related with the presence of asthma rather than ASA hypersensitivity since the atopy ratio was not different in AERD than in ASA tolerant asthma&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The prevalence of ASA hypersensitivity in patients with NP has been found to be 20&#8211;40&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;26&#44;27</span></a> Consistently&#44; in our study&#44; the presence of NP was a significant and independent risk factor for AERD&#46; Moreover&#44; NP has a high tendency for recurrence&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Likewise&#44; there was a statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;016&#41; relationship between ASA hypersensitivity and the number of polypectomies in our patients&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Cross-sensitivity to NSAIDs is a well-known feature of ASA hypersensitivity<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> and in our study 63&#46;5&#37; of patients with AERD also reported reactions to other COX-1 inhibitors&#46; COX-2 inhibitors are generally considered safe in AERD&#44; but some cutaneous and systemic reactions have been reported with them&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> In our trial a few &#40;5&#37;&#41; AERD patients had a history of reaction to COX-2 inhibitors&#59; unfortunately we do not have data about the type of reaction to these drugs&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Drug reactions can aggregate in families&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Familial aggregation of ASA hypersensitivity was reported by 10&#46;2&#37; of our patients with AERD&#46; As far as we know&#44; there are no data regarding familial aggregation of ASA hypersensitivity with the exception of a multicentre study in which the family history of hypersensitivity to ASA has been reported by 6&#37; of the families&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> As a limitation of our study&#44; we did not confirm ASA hypersensitivity in family members&#46; Individuals with a history of ASA hypersensitivity may be more likely to remember ASA hypersensitivity in family members or inadvertent interviewer bias could have influenced the results&#46; A recent study evaluating familial aggregation of ASA-induced urticaria demonstrated LTC4S&#41;-444C alleles aggregations in family members&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Contrary to studies genetic background of AERD&#44;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#8211;34</span></a> there is no genetic study regarding familial aggregation of AERD&#46; It would be interesting to see if there is any inheritance pattern in such patients&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Another limitation of our study is the diagnosis of ASA hypersensitivity&#44; which was mainly based on a detailed history&#46; However&#44; all patients were both recruited from centres&#44; which specialise in allergy&#47;pulmonology&#44; and were also evaluated by specialists&#46; A significant correlation between a history of ASA hypersensitivity and the result of oral challenge has been previously demonstrated&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#44;36</span></a> Therefore&#44; despite this limitation&#44; this questionnaire-based study provides nationwide data regarding the prevalence of AERD in our country for the first time&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion&#44; this nationwide survey showed that AERD is highly prevalent among our adult asthmatics and its prevalence seems to be affected by family history of ASA hypersensitivity&#44; presence of NP&#44; chronic rhinosinusitis and&#47;or rhinitis&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest&#46; There is no financial support&#46;</p></span></span>"
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              "titulo" => "Statistics"
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    "fechaRecibido" => "2011-03-01"
    "fechaAceptado" => "2011-05-02"
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            2 => "Asthma"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">There are no country-based data focused on aspirin &#40;ASA&#41;-exacerbated respiratory disease &#40;AERD&#41; in Turkey&#46;</p> <span class="elsevierStyleSectionTitle">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To assess the prevalence of AERD in adult patients with asthma&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A structured questionnaire was administered via face-to-face interview by a specialist in pulmonology&#47;allergy at seven centres across Turkey&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 1344 asthma patients &#40;F&#47;M&#58; 1081&#47;263&#58; 80&#46;5&#37;&#47;19&#46;5&#37;&#44; mean age&#58; 45&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;2 years&#41; were enrolled&#46; Atopy rate was 47&#37;&#46; Prevalence of allergic rhinitis&#44; chronic rhinosinusitis&#47;rhinitis&#44; and nasal polyposis &#40;NP&#41; were 49&#37;&#44; 69&#37; and 20&#37;&#44; respectively&#46; Of 270 patients with NP&#44; 171 &#40;63&#46;3&#37;&#41; reported previous nasal polypectomy and 40 &#40;25&#37;&#41; had a history of more than three nasal polypectomies&#46; Aspirin hypersensitivity was diagnosed in 180 &#40;13&#46;6&#37;&#41; asthmatic patients&#44; with a reliable history in 145 &#40;80&#46;5&#37;&#41;&#44; and oral ASA provocation test in 35 &#40;19&#46;5&#37;&#41; patients&#46; Clinical presentations of ASA hypersensitivity were respiratory in 76&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>137&#41;&#44; respiratory&#47;cutaneous in 15&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#41;&#44; and systemic in 9&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41; of the patients&#46; Multivariate analysis indicated that a family history of ASA hypersensitivity &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;001&#44; OR&#58; 3&#46;746&#44; 95&#37; CI&#58; 1&#46;769&#8211;7&#46;929&#41;&#44; history of chronic rhinosinusitis&#47;rhinitis &#40;<span class="elsevierStyleItalic">p</span>&#58; 0&#46;025&#44; OR&#58; 1&#46;713&#44; 95&#37; CI&#58; 1&#46;069&#8211;2&#46;746&#41; and presence of NP &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#44; OR&#58; 7&#46;036&#44; 95&#37; CI&#58; 4&#46;831&#8211;10&#46;247&#41; were independent predictors for AERD&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">This cross-sectional survey showed that AERD is highly prevalent among adult asthmatics and its prevalence seems to be affected by family history of ASA hypersensitivity&#44; history of rhinosinusitis and presence of NP&#46;</p>"
      ]
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Reactions types of ASA hypersensitivity&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#41; &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SEM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">45&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1081 &#40;80&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Current smoker&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">119 &#40;9&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Emergency care admission due to asthma in the last year&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">187 &#40;13&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hospitalisation due to asthma in the last year&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">96 &#40;7&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Presence of atopy&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">613 &#40;47&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Patients who were on ICS &#43; LABA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">927 &#40;68&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Patients who were on only ICS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">44 &#40;3&#46;27&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Patients who were on only LTRA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">28 &#40;2&#46;08&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Patients who were on ICS&#43;LABA&#43; LTRA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">315 &#40;23&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Systemic CS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">50 &#40;3&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">657 &#40;49&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">599 &#40;44&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chronic rhinosinusitis and&#47;or rhinitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">923 &#40;69&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nasal polyps&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">270 &#40;20&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">History of drug hypersensitivity&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ASA&#47;NSAIDs hypersensitivity&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">180 &#40;13&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hypersensitivity to antibiotics&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">67 &#40;5&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">6 &#40;0&#46;004&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Family history of ASA hypersensitivity&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">42 &#40;3&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">ASA&#58; aspirin&#59; NSAIDs&#58; nonsteroidal anti-inflammatory drugs&#59; LTRA&#58; leukotriene receptor antagonist&#59; COX&#58; cyclooxygenase&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">AIA patients<span class="elsevierStyleItalic">n</span>&#58; 180&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Patients with ASA tolerance<span class="elsevierStyleItalic">n</span>&#58; 1104&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#40;years &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SEM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns<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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female gender&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">147 &#40;81&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">883 &#40;79&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Current smoker&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;7&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98 &#40;9&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Presence of allergic rhinitis&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93 &#40;52&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">543 &#40;49&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Presence of atopy&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 &#40;44&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">519 &#40;48&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Presence of nasal polyps&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98 &#40;54&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">155 &#40;14&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Presence of chronic rhinosinusitis&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">107 &#40;59&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">464 &#40;42&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Family history of ASA hypersensitivity&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;10&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;2&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other NSAIDs hypersensitivity&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">108 &#40;63&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypersensitivity to COX-2 inhibitors <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;5&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypersensitivity to antibiotics&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;11&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;3&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use of systemic corticosteroids&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;7&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;3&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#61;0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Use of LTRA&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76 &#40;42&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">283 &#40;25&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Admission to emergency care unit due to asthma&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52 &#40;28&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">135 &#40;12&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospitalisation due to asthma&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;15&#46;0&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69 &#40;6&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#61;0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;3 nasal polypectomies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;35&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;16&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#61;0&#46;008&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Mean age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Chronic rhinosinusitis&#47;rhinitis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">32&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">32&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;713 &#91;1&#46;069&#8211;2&#46;746&#93;&nbsp;\t\t\t\t\t\t\n
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                      "titulo" => "Adverse reactions to nonsteroidal anti-inflammatory drugs"
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2011.05.015

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	7	2	9
2024 October	26	10	36
2024 September	17	19	36
2024 August	22	12	34
2024 July	29	9	38
2024 June	21	10	31
2024 May	21	2	23
2024 April	21	11	32
2024 March	24	7	31
2024 February	18	13	31
2024 January	16	6	22
2023 December	22	8	30
2023 November	20	10	30
2023 October	29	23	52
2023 September	18	5	23
2023 August	17	18	35
2023 July	28	18	46
2023 June	17	8	25
2023 May	20	13	33
2023 April	26	19	45
2023 March	22	11	33
2023 February	28	19	47
2023 January	30	10	40
2022 December	17	7	24
2022 November	18	9	27
2022 October	15	23	38
2022 September	18	17	35
2022 August	18	24	42
2022 July	15	12	27
2022 June	16	14	30
2022 May	16	11	27
2022 April	21	20	41
2022 March	13	15	28
2022 February	16	10	26
2022 January	21	11	32
2021 December	22	31	53
2021 November	26	12	38
2021 October	30	16	46
2021 September	33	18	51
2021 August	25	11	36
2021 July	22	11	33
2021 June	54	14	68
2021 May	12	12	24
2021 April	28	7	35
2021 March	32	34	66
2021 February	11	13	24
2021 January	11	17	28
2020 December	0	2	2
2020 November	0	3	3
2020 October	0	2	2
2020 September	0	2	2
2020 August	0	2	2
2020 July	0	1	1
2020 June	0	2	2
2020 May	0	3	3
2020 April	0	5	5
2020 March	0	3	3
2020 February	0	9	9
2020 January	0	9	9
2019 December	0	5	5
2019 August	0	5	5
2019 July	0	2	2
2019 June	0	5	5
2019 May	0	8	8
2019 April	0	6	6
2019 February	0	3	3
2019 January	0	1	1
2018 December	0	6	6
2018 February	90	6	96
2018 January	40	3	43
2017 December	97	6	103
2017 November	29	2	31
2017 October	9	1	10
2017 September	10	6	16
2017 August	10	4	14
2017 July	11	4	15
2017 June	12	16	28
2017 May	13	4	17
2017 April	11	6	17
2017 March	7	23	30
2017 February	6	2	8
2017 January	2	1	3
2016 December	6	3	9
2016 November	8	7	15
2016 October	21	3	24
2016 September	23	8	31
2016 August	9	5	14
2016 July	3	7	10
2016 June	11	2	13
2016 May	8	9	17
2016 April	11	8	19
2016 March	5	7	12
2016 February	11	10	21
2016 January	10	16	26
2015 December	17	6	23
2015 November	8	5	13
2015 October	17	9	26
2015 September	10	9	19
2015 August	8	3	11
2015 July	6	3	9
2015 June	4	4	8
2015 May	8	2	10
2015 April	8	6	14
2015 March	16	4	20
2015 February	6	2	8
2015 January	21	5	26
2014 December	33	5	38
2014 November	16	5	21
2014 October	28	9	37
2014 September	28	3	31
2014 August	26	4	30
2014 July	18	3	21
2014 June	24	1	25
2014 May	16	3	19
2014 April	4	1	5
2014 March	44	12	56
2014 February	34	12	46
2014 January	37	6	43
2013 December	31	5	36
2013 November	33	6	39
2013 October	43	12	55
2013 September	36	8	44
2013 August	59	9	68
2013 July	38	8	46
2013 June	15	1	16
2013 May	29	8	37
2013 April	37	10	47
2013 March	28	6	34
2013 February	20	6	26
2013 January	13	2	15
2012 December	11	5	16
2012 November	2	2	4
2012 October	1	2	3
2012 September	3	1	4
2012 June	400	0	400

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