The Global Allergy and Asthma European Network (GALEN rhinosinusitis cohort: a large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common yet under-recognised chronic inflammatory disease of the nose and paranasal sinuses that is classified according to the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. METHODS: This paper reports the methodology and descriptive results of the Global Allergy and Asthma European Network (GALEN) rhinosinusitis cohort. We established a large CRS cohort within the GALEN consortium (European FP6 research initiative) to identify inflammatory endotypes, the natural disease course, and its impact on health-related quality of life (HRQoL). Detailed information on the impact of CRS on HRQoL, comorbidity incidence, objective disease measures, and medical and surgical treatments were collected. RESULTS: This multicentre cross-sectional case-control study recruited 935 adults (869 eligible for analysis: 237 CRSsNP; 445 CRSwNP; 187 controls [reference group]). Comorbidities such as asthma, allergy, eczema, food allergy, urticaria, and chronic obstructive pulmonary disease were significantly more frequent in CRS patients. Nasal corticosteroids, antibiotics, and oral corticosteroids were the most common treatments. Significantly more CRSwNP patients reported previous sinonasal surgery. CONCLUSIONS: This study provides detailed information that facilitates studying CRS and its main phenotypes. However, patient distribution of this study does not necessarily reflect disease distribution in the general population.

The GALEN rhinosinusitis cohort: chronic rhinosinusitis with nasal polyps affects health-related quality of life.

BACKGROUND: Chronic rhinosinusitis (CRS) significantly affects health-related quality of life (HRQoL). Few multinational observational studies have evaluated the impact of CRS with nasal polyps (CRSwNP) on patients’ HRQoL. This study aimed to assess HRQoL outcomes (including analyses by disease severity and impact of comorbidities and refractory disease) in CRSwNP patients from a large European database. METHODOLOGY: Data were analysed from the Global Allergy and Asthma European Network (GALEN) Rhinosinusitis Cohort, including sociodemographic data, patient-reported disease severity (visual analogue scale), and scores on the 36-Item ShortForm Health Survey (SF-36) questionnaire. Differences in mean SF-36 scores were evaluated between patients with CRSwNP and population norms and between subgroups of interest (disease severity, comorbidity, and refractory disease, defined by a history of sinonasal surgery). RESULTS: Patients with CRSwNP (N = 445) had significantly lower mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores vs population norms, demonstrating that CRSwNP negatively affects HRQoL. The presence of comorbidities affected HRQoL, as shown by significant differences in PCS scores in patients with asthma or non-steroidal antiinflammatory drug-exacerbated respiratory disease, compared with patients without asthma. Patients with moderate-to-severe disease had significantly lower PCS scores than patients with mild disease. Severe disease had a significant impact on MCS score. History of surgery had a clinically meaningful negative effect on HRQoL compared with no history of surgery. CONCLUSIONS: CRSwNP patients have significantly lower HRQoL compared with population norms. The impact is greater in patients with greater disease severity, comorbidities, or refractory disease.

Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA2 LEN) survey.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. METHODS: The GA2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. RESULTS: The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis. CONCLUSION: Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.

Staphylococcal enterotoxin sensitization in a community-based population: a potential role in adult-onset asthma.

BACKGROUND: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. OBJECTIVE: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. METHODS: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. RESULTS: Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. CONCLUSIONS AND CLINICAL RELEVANCE: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.

Staphylococcus aureus enterotoxin-specific IgE is associated with asthma in the general population: a GA(2)LEN study.

BACKGROUND: Specific IgE to Staphylococcus aureus enterotoxins (SE-IgE) has been associated with asthma. In the general population, we aimed to determine the prevalence of and risk factors for serum SE-IgE and to examine the association with asthma. METHODS: A postal questionnaire was sent to a random sample of adults in 19 centers across Europe. A random sample of respondents was invited for clinical examination upon which they answered a questionnaire, underwent skin prick tests (SPTs) for common aeroallergens, and provided blood for measurement of total IgE and SE-IgE. Risks were analyzed within centers using weighted logistic regression, and overall estimates calculated using fixed-effects meta-analysis. RESULTS: 2908 subjects were included in this analysis. Prevalence of positive SE-IgE was 29.3%; no significant geographic variation was observed. In contrast to positive skin prick tests, SE-IgE was more common in smokers (<15 pack-year: OR 1.11, P = 0.079, ≥15 pack-year: OR 1.70, P < 0.001), and prevalence did not decrease in older age-groups or in those with many siblings. Total IgE concentrations were higher in those with positive SE-IgE than in those with positive SPT. SE-IgE was associated with asthma (OR 2.10, 95% confidence interval [1.60-2.76], P = 0.001) in a concentration-dependent manner. This effect was independent of SPT result and homogeneous across all centers. CONCLUSIONS: We report for the first time that SE-IgE is common in the general population throughout Europe and that its risk factors differ from those of IgE against aeroallergens. This is the first study to show that SE-IgE is significantly and independently associated with asthma in the general population.

Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe.

BACKGROUND: The prevalence of asthma and its association with chronic rhinosinusitis (CRS) have not been widely studied in population-based epidemiological surveys. METHODS: The Global Allergy and Asthma Network of Excellence (GA(2) LEN) conducted a postal questionnaire in representative samples of adults living in Europe to assess the presence of asthma and CRS defined by the European Position Paper on Rhinosinusitis and Nasal Polyps. The prevalence of self-reported current asthma by age group was determined. The association of asthma with CRS in each participating centre was assessed using logistic regression analyses, controlling for age, sex and smoking, and the effect estimates were combined using standard methods of meta-analysis. RESULTS: Over 52,000 adults aged 18-75 years and living in 19 centres in 12 countries took part. In most centres, and overall, the reported prevalence of asthma was lower in older adults (adjusted OR for 65-74 years compared with 15-24 years: 0.72; 95% CI: 0.63-0.81). In all centres, there was a strong association of asthma with CRS (adjusted OR: 3.47; 95% CI: 3.20-3.76) at all ages. The association with asthma was stronger in those reporting both CRS and allergic rhinitis (adjusted OR: 11.85; 95% CI: 10.57-13.17). CRS in the absence of nasal allergies was positively associated with late-onset asthma. CONCLUSION: Geographical variation in the prevalence of self-reported asthma was observed across Europe, but overall, self-reported asthma was more common in young adults, women and smokers. In all age groups, men and women, and irrespective of smoking behaviour, asthma was also associated with CRS.

Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis--a GA² LEN study.

BACKGROUND: The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA(2) LEN European survey. METHODS: On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chance-corrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. RESULTS: There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers (-3.0%, 95% CI: -5.0 to -1.0%, I(2) = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. CONCLUSION: Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS.

Chronic rhinosinusitis in Europe--an underestimated disease. A GA²LEN study.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common health problem, with significant medical costs and impact on general health. Even so, prevalence figures for Europe are unavailable. In this study, conducted by the GA²LEN network of excellence, the European Position Paper on Rhinosinusitis and nasal Polyps (EP³OS) diagnostic criteria are applied to estimate variation in the prevalence of Chronic rhinosinusitis (CRS) for Europe. METHOD: A postal questionnaire was sent to a random sample of adults aged 15-75 years in 19 centres in Europe. Participants reported symptoms of CRS, and doctor diagnosed CRS, allergic rhinitis, age, gender and smoking history. Definition of CRS was based on the EP³OS diagnostic criteria: the presence of more than two of the symptoms: (i) nasal blockage, (ii) nasal discharge, (iii) facial pain/pressure or (iv) reduction in sense of smell, for >12 weeks in the past year--with at least one symptom being nasal blockage or discharge. RESULTS: Information was obtained from 57,128 responders living in 19 centres in 12 countries. The overall prevalence of CRS by EP³OS criteria was 10.9% (range 6.9-27.1). CRS was more common in smokers than in nonsmokers (OR 1.7: 95% CI 1.6-1.9). The prevalence of self-reported physician-diagnosed CRS within centres was highly correlated with the prevalence of EP³OS-diagnosed CRS. CONCLUSION: This is the first European international multicentre prevalence study of CRS. In this multicentre survey of adults in Europe, about one in ten participants had CRS with marked geographical variation. Smoking was associated with having CRS in all parts of Europe.

Rhinosinusitis and asthma: a link for asthma severity.

The term rhinosinusitis describes an inflammation of the mucosal lining of the nose and sinuses; however, recent evidence points to the need to differentiate patients with chronic rhinosinusitis without nasal polyps from those with nasal polyps. Asthma comorbidity is especially common in nasal polyp disease and may be associated with aspirin-exacerbated respiratory disease. Of interest, asthma comorbidity is uncommon in some parts of the world but common in others. A further analysis of the inflammatory patterns also revealed that nasal polyps do not represent one single entity; interleukin (IL)-5-positive nasal polyps can be differentiated from IL-5-negative forms by different inflammatory patterns (predominance of eosinophils vs neutrophils). Staphylococcus aureus superantigens frequently colonize IL-5-positive nasal polyps and may amplify the eosinophilic inflammation, induce a polyclonal local IgE formation, and increase the risk of asthma comorbidity. Recent findings in severe asthma patients confirm the role of superantigens in lower airway disease.

Return to work after spinal cord injury.

OBJECTIVE: To describe predictors of return to work after spinal cord injury (SCI), in particular the physical intensity of the pre-injury job. STUDY DESIGN: Survey. SETTING: Patients' home. METHODS: We interviewed 234 persons with a spinal cord injury (SCI) between 18 and 65 years of age and who were gainfully employed at the time of the injury. Possible predictors were tested with logistic regression analyses. RESULTS: After the SCI, only 37% of the persons were gainfully employed. People with heavy and strenuous physical work pre-injury regained work in only 25%, respectively 21%. Being male (Odds Ratio (OR) 3.70), light to moderate physical job pre-injury (OR 3.16), high Barthel Index (OR 2.76), high educational level (OR 2.12) and education post-injury (OR 2.14) were significant predictors for returning to gainful work after injury. Many unemployed persons thought they were capable of working. CONCLUSIONS: Only a minority returned to gainful employment after SCI even to a physically less demanding job. In addition to intensive inpatient re-education, long-term support in job seeking is very important, including switching to a less demanding job.