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International audience; BackgroundNeuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis.MethodsALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.ResultsOverall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3–7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7–13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (

Data de publicació electrònica: 24-03-2023 Includes supplementary materials for the online appendix. Food hypersensitivity (FHS) is common, but little is known about the factors associated with severe reactions, age of onset and whether sensitization persists. This study examines the factors associated with self-reported severe food reactions, onset age and the changes in prevalence of sensitization to foods over time in an adult sample. We used data from adults taking part in the European Community Respiratory Health Survey (ECRHS) III (2010–2014) who provided information on food hypersensitivity, including symptoms, suspected culprit food and onset age (n = 4865). A subsample from six countries had serum food-specific IgE tested for 25 core foods and also in 10 years earlier (ECRHS II). We applied logistic regression and McNemar’s test for analyses. The prevalence of self-reported FHS was 13.5% at ECRHS III. Of those providing information on symptoms (n = 611), 26.4% reported severe reactions. About 80% of 1033 reported food-specific reactions (reported by 596 participants) began after age 15. History of asthma (odds ratio OR 2.12 95% confidence interval CI 1.13–3.44) and a younger age of onset of FHS (OR 1.02, 95% CI 1.01–1.03, per year) were associated with higher risks of a lifetime experience of severe food reactions. In the subsample with IgE tested in both surveys (n = 1612), the overall prevalence of sensitization to foods did not change over 10 years. Our findings support previous observations of more severe food reactions in people with asthma and that most FHS reported by this sample started after age 15. We found no evidence of changes in the prevalence of sensitization to food in adults followed for 10 years. HCYL is supported by the Medical Research Council Centre for Environment and Health. NSI is supported by the Centre for Food and Allergy Research (NHMRC Centre of Research Excellence) PhD scholarship and the Melbourne Children’s LifeCourse top-up PhD scholarship (Royal Children’s Hospital Foundation grant #2018-984). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and the Generalitat de Catalunya through the CERCA Program.

Introduction: Among allergic rhinitis (AR) symptoms, nasal obstruction particularly affects the quality of life. Antihistamines and intranasal corticosteroids are the most frequently prescribed symptomatic drugs, but their efficacy is often incomplete. Essential oils (EO) have shown an anti-inflammatory effect and potential in treating patients with AR. The aim of this study was to evaluate the effectiveness of a hypertonic EO-based nasal spray on perennial AR (PAR) symptoms. Methods: This prospective, open-label, non-randomized, multicentric trial included 43 patients with PAR sensitized to mites, not controlled for more than a year. All were treated with Puressentiel® Respiratory-Decongestant Nasal Spray for 30 days. Their usual treatment remained unchanged during the study period. Before and after treatment, each participant filled out a rhinitis questionnaire, the Allergic Rhinitis Control Test (ARCT). A nasal inspiratory peak flow (NIPF) was performed. Results: The mean ARCT was 16.4 and 20.5 at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 4.1 (p < 0.001). The proportion of patients with controlled rhinitis after 30 days of treatment was 69.8 versus 14% before treatment (p < 0.001). The mean NIPF was 86.5 L/min and 105.1 L/min at D0 and D30, respectively (p < 0.001); the mean increase between D0 and D30 was 18.5 L/min. Conclusion: A hypertonic EO-based nasal spray could be a new and natural option in the management of PAR. It could also be used as an add-on therapy when nasal symptoms are not fully controlled.

Introduction MicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome. Method Using specific culture conditions, we differentiated immature human monocyte-derived DCs into DC1, DC2, and DCreg subsets (supporting the differentiation of TH1, TH2 or regulatory T cells, respectively). Profiling of miRNA expression was performed in these DC subpopulations using microarrays. Levels of miRNAs specific for polarized DCs were then evaluated in a cohort of 58 patients with allergic rhinitis and 25 non-allergic controls, as well as in samples from 30 subjects treated with sublingual grass pollen tablets or placebo for four months. Results We successfully identified 16 miRNAs differentially regulated between immature DCs, DC1, DC2, and DCreg cells. In allergic rhinoconjunctivitis patients, the expression of two of those miRNAs (miR-132 and miR-155), was down-regulated compared to non-allergic individuals. However, the levels of these miRNAs were not significantly modified following four months of grass pollen immunotherapy. Conclusions Studying polarized DCs and clinical samples from subjects with or without allergic rhinoconjunctivitis, we demonstrated that the expression of two miRNAs linked to effector DCs (i.e., DC1 and/or DC2 cells), was reduced in the blood of patients with allergic rhinoconjunctivitis. Nevertheless, these miRNAs did not represent relevant biomarkers to predict or follow-up AIT efficacy.

Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking.

Background: Nitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO2 on inflammation without allergen exposure is poorly studied. Objectives: We investigated whether repeated peaks of NO2, at various realistic concentrations, induce changes in airway inflammation in asthmatics. Methods: Nineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO2, 600 ppb NO2, or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three series of exposures were separated by 2 weeks. The inflammatory response in sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the first exposure, and compared with baseline values measured twice 10–30 days before the first exposure. Results: Compared with baseline measurements, the percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb NO2 (p = 0.003) but did not change significantly after exposure to 200 ppb. The slope of the association between the percentage of eosinophils and NO2 exposure level was significant (p = 0.04). Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO2 (p = 0.001). Lung function, which was assessed daily, was not affected by NO2 exposure. Conclusions: We observed that repeated peak exposures of NO2 performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner. Citation: Ezratty V, Guillossou G, Neukirch C, Dehoux M, Koscielny S, Bonay M, Cabanes PA, Samet JM, Mure P, Ropert L, Tokarek S, Lambrozo J, Aubier M. 2014. Repeated nitrogen dioxide exposures and eosinophilic airway inflammation in asthmatics: a randomized crossover study. Environ Health Perspect 122:850–855; http://dx.doi.org/10.1289/ehp.1307240

Background Neuromuscular blocking agents (NMBA) are responsible for most immediate hypersensitivity reactions during anesthesia, as a result of the presence of a quaternary ammonium ion. The aim of this study was to evaluate the diagnostic performance of a commercial immunoglobulin E (IgE) test (quaternary ammonium morphine [QAM]) for diagnosing sensitivity to NMBA. Methods We tested 168 patients exposed to NMBAs during anesthesia. Of those patients, 54 had an uneventful procedure and 114 had immediate hypersensitivity reactions, and 57 patients had positive skin tests to the administered NMBA, whereas 57 had negative skin tests. Specific IgE concentrations determined with the QAM method based on a morphine solid phase were compared with those obtained with a recommended experimental method with a choline solid phase. Results For the QAM test, a 0.35 kUA/l positivity cutoff was chosen from the receiver operating characteristics curve. QAM-specific IgE was found in 84.2% of skin test-positive reactors (80.7% with the recommended method; no significant difference), and binding was inhibited by the culprit NMBA in 80% of cases. The frequency of QAM-specific IgE positivity was significantly higher in skin test-negative reactors (24.6%) than in controls (9.3%), suggesting NMBA sensitivity. Conclusion Sensitivity of the QAM test (84.2%), together with its simplicity and suitability for routine laboratory use, makes it a valuable tool, in conjunction with skin tests, for diagnosing NMBA sensitivity in patients who react after NMBA injection. The QAM test is of particular interest when skin tests are not available or not reliable or give results poorly compatible with mediator release or clinical features.

BACKGROUND: Cross-sectional studies have reported a lower prevalence of sensitization in older adults, but few longitudinal studies have examined whether this is an aging or a year-of-birth cohort effect. OBJECTIVE: We sought to assess changes in sensitization and total IgE levels in a cohort of European adults as they aged over a 20-year period. METHODS: Levels of serum specific IgE to common aeroallergens (house dust mite, cat, and grass) and total IgE levels were measured in 3206 adults from 25 centers in the European Community Respiratory Health Survey on 3 occasions over 20 years. Changes in sensitization and total IgE levels were analyzed by using regression analysis corrected for potential differences in laboratory equipment and by using inverse sampling probability weights to account for nonresponse. RESULTS: Over the 20-year follow-up, the prevalence of sensitization to at least 1 of the 3 allergens decreased from 29.4% to 24.8% (-4.6%; 95% CI, -7.0% to -2.1%). The prevalence of sensitization to house dust mite (-4.3%; 95% CI, -6.0% to -2.6%) and cat (-2.1%; 95% CI, -3.6% to -0.7%) decreased more than sensitization to grass (-0.6%; 95% CI, -2.5% to 1.3%). Age-specific prevalence of sensitization to house dust mite and cat did not differ between year-of-birth cohorts, but sensitization to grass was most prevalent in the most recent ones. Overall, total IgE levels decreased significantly (geometric mean ratio, 0.63; 95% CI, 0.58-0.68) at all ages in all year-of-birth cohorts. CONCLUSION: Aging was associated with lower levels of sensitization, especially to house dust mite and cat, after the age of 20 years. Amaral receives research funding from the Medical Research Council. M. J. Abramson receives research support from E.H.Walters & M.Abramson, Pfizer, and Boehringer Ingelheim and receives consulting fees from AstraZeneca and travel support from Boehringer Ingelheim and Sanofi. P. Demoly receives consulting fees from ALK-Abell o, Circassia, Stallergenes, Allergopharma, Chiesi, Thermo Fisher Scientific, Medam Menarini, AstraZeneca, Pierre Fabra Mediacament, and DBV. R. Jogi receives research support from the Estonian Research Council and receives consulting and lecture fees from Boehringer, Novartis, and GlaxoSmithKline and travel support from GlaxoSmithKline and Boehringer. C. Neukirch receives consulting fees and travel support from ALKAbell o and Stallergenes. D. Nowak receives speaker fees from Mundipharma. I. Pin receives lecture fees from Novartis and MSD and travel support from GlaxoSmithKline, TEVA, and Novartis. R. van Ree receives consulting fees from HAL Allergy BV and speaker fees from Thermo Fisher Scientific. J.-P. Zock receives research support from FIS, Health Institute Carlos III, and the Spanish Ministry of Health. P. G. J. Burney serves on the Novartis Advisory Board. D. L. Jarvis receives research support from the Medical Research Council

Formaldehyde is a well-known airborne contaminant causing eye, nose, and throat irritation as well as airway irritation and slight neuropsychologic changes (Hester and Harrison 1998; Samet et al. 1988). The major indoor sources of formaldehyde are off-gassing from urea–formaldehyde foam insulation, particle board, paneling, plywood, some carpets and furniture, and, to a lesser extent, tobacco smoke and indoor combustion sources. Indoor concentrations of formaldehyde can vary between different countries (Sakai et al. 2004). In a Japanese study, formaldehyde concentrations ranged between 91.25 and 290 μg/m3 (Minami et al. 2002), whereas in the United Kingdom, the highest level measured in 876 homes was much lower (median = 24 μg/m3) (Brown et al. 2002). Indoor formaldehyde concentrations measured in mobile homes in the United States ranged from nondetectable values to 575 μg/m3 (Liu et al. 1991). Indoor concentrations generally exceed those outdoors, and studies on formaldehyde levels in homes have demonstrated higher formaldehyde concentrations in newer compared with older dwellings, with higher levels in buildings built after 1970 (Gilbert et al. 2005). Formaldehyde is an etiologic factor in occupational asthma. However, although formaldehyde may cause asthma in some individuals, this occurs relatively rarely (Nordman et al. 1985; Paustenbach et al. 1997). Whether nonoccupational exposure to formaldehyde is related to asthma is still subject to discussion (Delfino 2002; Institute of Medicine 2000). In murine models, formaldehyde exposure has been shown to enhance the allergic eosinophilic airway inflammation in sensitized mice (Sadakane et al. 2002). In a part of the European Community Respiratory Health Survey, asthma prevalence was greater for newly painted homes, consistent with greater differences in formaldehyde exposure (Wieslander et al. 1997). A relationship between physician-diagnosed asthma and indoor concentration of formaldehyde was reported even at low levels of exposure in children (Rumchev et al. 2002). Franklin et al. (2000) reported that exposure to formaldehyde in homes could produce a subclinical inflammatory response in the airways of healthy children. A possible association between exposure to formaldehyde and allergic sensitization to common aeroallergens has been suggested by another cross-sectional study in children (Garrett et al. 1999). Human exposure studies can provide valuable data for assessing more specifically the acute effects of air pollutants, particularly the airway response to allergen (Sandstrom 1995). The hypothesis that formaldehyde enhances asthmatic response to allergen has not yet been investigated in controlled conditions in humans. To test this hypothesis, we carried out this controlled human study to investigate the effect of a short exposure to 500 μg/m3 formaldehyde on asthmatic response to inhaled allergen.

C-reactive protein (CRP), a marker of systemic inflammation, is a powerful predictor of adverse cardiovascular events. Respiratory impairment is also associated with cardiovascular risk. Although some studies have found an inverse relationship between lung function and markers of systemic inflammation, only one study has reported a relationship between lung function and CRP levels. In contrast, little is known about the relationship between bronchial hyperresponsiveness (BHR) and systemic inflammation. The association between lung function and CRP and between BHR and CRP has been investigated.As part of the European Community Respiratory Health Survey follow up study serum CRP levels, forced expiratory volume in 1 second (FEV(1)), and BHR to methacholine (/=20% decrease in FEV(1) to4 mg methacholine) were measured in 259 adults aged 28-56 years free of cardiovascular disease or respiratory infection.Mean (SD) FEV(1) (adjusted for age, sex, height, and smoking status) was lower in subjects with a high CRP level (high tertile) (3.29 (0.44) l/s v 3.50 (0.44) l/s; p0.001) and BHR was more frequent (41.9% v 24.9%; p = 0.005) than in subjects with lower CRP levels (low+middle tertiles). Similar results were obtained when the potential confounding factors were taken into account. Similar patterns of results were found in non-smokers and in non-asthmatic subjects.Increased CRP levels are strongly and independently associated with respiratory impairment and more frequent BHR. These results suggest that both respiratory impairment and BHR are associated with a systemic inflammatory process.

Background— Respiratory alterations have been associated with subsequent coronary heart diseases in numerous population-based studies. The underlying mechanisms remain largely unknown. The objective of this study was to examine the association between bronchial hyperresponsiveness (BHR) to methacholine (which reflects local inflammation in the bronchus) and common carotid intima-media thickness (CCA-IMT). Methods and Results— As part of the European Community Respiratory Health Survey follow-up, in Paris Center, we assessed BHR to methacholine (≥20% decrease in FEV1 for a maximum methacholine dose of 4 mg) and measured CCA-IMT by ultrasonography in 255 adults free of cardiovascular diseases aged 29 to 56 years (123 men, 132 women; mean age 44.5 years, 43.5% never smokers). In men, CCA-IMT mean value was higher in subjects with BHR than in those without (0.68±0.11 versus 0.62±0.09 mm, P =0.002). No association was found in women. Multivariate analysis confirmed the independent association between BHR and CCA-IMT in men (adjusted odds ratio for a 0.10-mm increase in CCA-IMT=2.1, 95% confidence interval: 1.1 to 4.3; P =0.02). These results remained similar after exclusion of asthmatic subjects (n=11). In each strata of smoking status (nonsmoker, ex-smoker, and current smokers), CCA-IMT mean values tended to be higher in subjects with BHR than in those without, although the difference between the 2 groups was more pronounced in current smokers. Conclusions— The results of the present study suggest that BHR is independently associated with CCA-IMT in men. The interrelationships between cardiovascular and respiratory alterations should be further investigated.

Quality of life has been found to be impaired both in patients with asthma and in patients with allergic rhinitis, but the relative burden of these diseases has not been investigated. We analyzed answers to the SF-36 questionnaire from 850 subjects recruited in two French centers participating in the European Community Respiratory Health Survey, a population-based study of young adults. Both asthma and allergic rhinitis were associated with an impairment in quality of life. However, 78% of asthmatics also had allergic rhinitis. Subjects with allergic rhinitis but not asthma (n = 240) were more likely than subjects with neither asthma nor rhinitis (n = 349) to report problems with social activities, difficulties with daily activities as a result of emotional problems, and poorer mental well-being. Patients with both asthma and allergic rhinitis (n = 76) experienced more physical limitations than patients with allergic rhinitis alone, but no difference was found between these two groups for concepts related to social/mental health. As asthma was not found to further impair the quality of life in subjects with allergic rhinitis for concepts related to mental disability and well-being, and as subjects with asthma often also suffer from allergic rhinitis, further studies on quality of life in asthma should ensure that the impairment in quality of life attributed to asthma could not result from concomitant allergic rhinitis.

It has been recognized recently that theophylline possesses anti-inflammatory effects that could be of clinical interest in patients with airway inflammatory diseases such as asthma and allergic rhinitis (AR). The aim of the present study was to explore the effect of theophylline on the nasal eosinophilic inflammatory response following allergen challenge in patients with AR. Fourteen subjects suffering from seasonal rhinitis with an early reaction after nasal allergen provocation were challenged outside the pollen season after pretreatment for 3 weeks with placebo or slow-release theophylline (Euphylong in a randomized double-blind, cross-over study. Nasal blocking index (NBI), nasal airway resistance and symptoms were recorded before, and 1 and 5 h after challenge; additionally, nasal lavage fluid was collected before, as well as 1 and 5 h after challenge. Eosinophil cationic protein (ECP) was measured in the lavage as well as the number of eosinophils before, and 1 h and 5 h after allergen challenge. After 3 weeks of treatment, baseline concentrations of ECP in nasal lavage amounted to 826+/-329 ng x L(-1) (placebo) and 936+/-351 ng x L(-1) (theophylline). The ECP levels did not increase during the early phase response. Five hours after challenge, ECP in the placebo group increased markedly (p

A 35-year-old patient received omalizumab (300 mg twice a month) for 2 years for a severe atopic keratoconjunctivitis (AKC) in order to reduce the risk for steroid-induced keratitis. After 4 months, quality of life and ocular symptoms improved, and the use of oral steroids was strongly reduced. The treatment was well tolerated. This observation suggests that omalizumab may be a good option for the treatment of severe AKC, especially to avoid side effects of immunosuppressive treatments, as suggested for other allergic diseases. Specific trials should be designed for allergic eye diseases.

An association between impaired lower respiratory function and cardiovascular risk factors, such as hypertension, is often reported but it is unknown whether there is a relationship between upper airway disorders and cardiovascular risk factors, despite evidence that upper and lower respiratory tract disorders are closely linked. Our objective was to assess whether rhinitis is associated with arterial blood pressure and hypertension. In a population-based study of 330 adults aged 28-56 years, as part of the European Community Respiratory Health Survey, rhinitis was assessed by means of a questionnaire, and cardiovascular data were obtained using a questionnaire and by measuring blood pressure. Systolic blood pressure (SBP) was higher in men with rhinitis than in men without rhinitis (130.6 +/- 12.7 mm Hg versus 123.5 +/- 13.9 mm Hg; p = 0.002), and it was still the case after adjustment for cardiovascular and respiratory confounding factors. Hypertension was more frequent in men with rhinitis than in men without rhinitis, even after multivariate adjustment (odds ratio = 2.6, 95% confidence interval = [1.14-5.91]). The observation of SBP levels according to whether men have no rhinitis, seasonal rhinitis, or perennial rhinitis was compatible with a dose-response relationship (p for trend = 0.02). In conclusion, rhinitis is strongly associated with SBP and hypertension in men. Blood pressure should be regularly checked in men with rhinitis.

Background Delayed hypersensitivity to betalactam drugs is one of the most frequently suspected drug allergies. However, it is sometimes difficult to diagnose. Drug challenges are the diagnostic gold standard, but they are costly and complex to organize. In vitro testing could thus represent a valid alternative. The existence of amoxicillin-specific T cells have long been demonstrated, however few studies have compared the diagnostic performances of the different methods aiming at detecting them, and there is currently no available test validated for diagnostic purpose. In this context, we started a prospective study to establish the relevance of such in vitro tests in delayed hypersensitivity to amoxicillin.

The association of impaired pulmonary function with cardiovascular morbidity and mortality has been reported in several prospective studies. The nature of this association and the mechanisms underlying it are unknown. Both atherosclerosis and central arterial stiffness might be involved. We recently reported, in a 4-yr longitudinal study, that reduced lung function predicts the development of carotid atherosclerotic plaques. In the present study, we report the associations of aortic stiffness with lung function measurements. One hundred and ninety-four men, aged 30 to 70 yr and free of coronary heart disease, who volunteered for a standard health examination were included. FEV(1) and FVC were used to assess lung function. Aortic stiffness was estimated from the carotid-femoral pulse-wave velocity (PWV), which increases proportionally with an increase in aortic stiffness. PWV was significantly and negatively associated with FEV(1) and FVC (partial correlation coefficients adjusted for age and height: -0.27 [p0.001] and -0.24 [p0.001], respectively). For every 1 SD increase in PWV (2.5 m/s), FEV(1) decreased by 195.2 +/- 50.1 ml (p0.001) in an age- and height-adjusted analysis. The corresponding decrease in FVC was 190.4 +/- 55.0 ml (p0.001). Further adjustment for cardiovascular risk factors (weight, smoking habits, hypercholesterolemia, diabetes, and hypertension) did not markedly alter these results. In addition, negative associations of PWV with lung function measurements were observed within each category of cardiovascular risk factors. This study suggests that reduced pulmonary function is independently associated with aortic stiffness in men. The interrelations between pulmonary and vascular alterations should be thoroughly investigated.

Objective: To assess whether the severity of asthma is associated with sensitisation to airborne moulds rather than to other seasonal or perennial allergens. Design: Multicentre epidemiological survey in 30 centres. Setting: European Community respiratory health survey. Participants: 1132 adults aged 20-44 years with current asthma and with skin prick test results. Main outcome measure: Severity of asthma according to score based on forced expiratory volume in one second, number of asthma attacks, hospital admissions for breathing problems, and use of corticosteroids in past 12 months. Results: The frequency of sensitisation to moulds ( Alternaria alternata or Cladosporium herbarum , or both) increased significantly with increasing asthma severity (odds ratio 2.34 (95% confidence interval 1.56 to 3.52) for either for severe v mild asthma). This association existed in all of the study areas (gathered into regions), although there were differences in the frequency of sensitisation. There was no association between asthma severity and sensitisation to pollens or cats. Sensitisation to Dermatophagoides pteronyssinus was also positively associated with severity. In multivariable logistic regressions including sensitisation to moulds, pollens, D pteronyssinus , and cats simultaneously, the odds ratios for sensitisation to moulds were 1.48 (0.97 to 2.26) for moderate v mild asthma and 2.16 (1.37 to 3.35) for severe v mild asthma (P Conclusions: Sensitisation to moulds is a powerful risk factor for severe asthma in adults. This should be taken into account in primary prevention, management, and patients9 education.