Background:Bronchodilator responsiveness testing is mainly used for diagnosing asthma. We aimed to investigate whether it is associated with progression to chronic airflow obstruction over time. Methods:The multinational Burden of Obstructive Lung Disease cohort study surveyed adults, aged 40 years and above, at baseline and followed them up after a mean of 9.1 years. Recruitment took place between January 2, 2003 and December 26, 2016. Follow-up measurements were collected between January 29, 2019 and October 24, 2021. On both occasions, study participants provided information on respiratory symptoms, health status and several environmental and lifestyle exposures. They also underwent pre- and post-bronchodilator spirometry. We defined bronchodilator responsiveness at baseline using the American Thoracic Society and European Respiratory Society (ATS/ERS) 2022 definition, and the presence of chronic airflow obstruction at follow-up as a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC) less than the lower limit of normal. We used multi-level regression models to estimate the association between baseline bronchodilator responsiveness and incident chronic airflow obstruction. We stratified analyses by gender and performed a sensitivity analysis in never smokers. Findings:We analysed data from 3701 adults with 56% being women. Compared to those without bronchodilator responsiveness at baseline, those with bronchodilator responsiveness had 36% increased risk of developing chronic airflow obstruction (RR: 1.36, 95%CI 1.04, 1.80). This effect was stronger in women (RR: 1.45, 95%CI 1.09, 1.91) than men (RR: 1.07, 95%CI 0.51, 2.24). Never smokers with bronchodilator responsiveness also were at greater risk of incident chronic airflow obstruction (RR: 1.48, 95%CI 1.01, 2.20). Interpretation:Bronchodilator responsiveness appears to be a risk factor for incident chronic airflow obstruction. It is important that future studies in other large population-based cohorts replicate these findings. Funding:National Heart and Lung Institute, UK Medical Research Council, and Wellcome Trust.

BackgroundDyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function.MethodsDyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as >= 2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis.ResultsThe prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC

INTRODUCTION:Evidence of an association between breathlessness and quality of life from population-based studies is limited. We aimed to investigate the association of both physical and mental quality of life with breathlessness across several low-, middle- and high-income countries. METHODS:We analysed data from 19 714 adults (31 sites, 25 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We measured both mental and physical quality of life components using the SF-12 questionnaire, and defined breathlessness as grade ≥2 on the modified Medical Research Council scale. We used multivariable linear regression to assess the association of each quality-of-life component with breathlessness. We pooled site-specific estimates using random-effects meta-analysis. RESULTS:Both physical and mental component scores were lower in participants with breathlessness compared to those without. This association was stronger for the physical component (coefficient = -7.59; 95%CI -8.60, -6.58; I2 = 78.5%) than for the mental component (coefficient = -3.50; 95%CI -4.36, -2.63; I2 = 71.4%). The association between physical component and breathlessness was stronger in high-income countries (coefficient = -8.82; 95%CI -10.15, -7.50). Heterogeneity across sites was partly explained by sex and tobacco smoking. CONCLUSION:Quality of life is worse in people with breathlessness, but this association varies widely across the world.

BACKGROUND: For adults, prevalence estimates of food sensitization (FS) and food allergy (FA) have been obtained in a standardized manner across Europe. For children, such estimates are lacking. OBJECTIVES: To determine the prevalence of self-reported FA, FS, probable FA (symptoms plus IgE sensitization), and challenge-confirmed FA in European school-age children. METHODS: Data on self-reported FA were collected through a screening questionnaire sent to a random sample of the general population of 7- to 10-year-old children in 8 European centers in phase I of the EuroPrevall study. Data on FS and probable FA were obtained in phase II, comprising an extensive questionnaire on reactions to 24 commonly implicated foods, and serology testing. Food challenge was performed in phase III. RESULTS: Prevalence (95% CI) of self-reported FA ranged from 6.5% (5.4-7.6) in Athens to 24.6% (22.8-26.5) in Lodz; prevalence of FS ranged from 11.0% (9.7-12.3) in Reykjavik to 28.7% (26.9-30.6) in Zurich; and prevalence of probable FA ranged from 1.9% (0.8-3.5) in Reykjavik to 5.6% (3.6-8.1) in Lodz. In all centers, most food-sensitized subjects had primary (nonecross-reactive) FS. However, FS due to birch pollen related cross-reactivity was also common in Central-Northern Europe. Probable FA to milk and egg occurred frequently throughout Europe; to fish and shrimp mainly in the Mediterranean and Reykjavik. Peach, kiwi, and peanut were prominent sources of plant FA in most countries, along with notably hazelnut, apple, carrot, and celery in Central-Northern Europe and lentils and walnut in the Mediterranean. CONCLUSIONS: There are large geograhical differences in the prevalence of FS and FA in school-age children across Europe. Both primary and cross-reactive FS and FA occur frequently. (C) 2020 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Pulmonary rehabilitation (PR) is offered to patients with functional breathlessness. However, access to PR is limited. The objective of this study was to evaluate whether a 4-week education and exercise programme offered to COPD patients with Medical Research Council (MRC) dyspnoea 1-2 improves disease self-management. Patients were recruited by their GP to attend four weekly 2-h sessions provided by a multidisciplinary team. Patients completed outcome measures before and after the program. Forty-two patients entered the programme and 26 out of 42 (61.9%) completed all sessions. The Bristol COPD Knowledge Questionnaire and Patient Activation Measure improved (both p ≤ 0.001). Disease burden was not reduced according to the COPD assessment test. All patients accepted a referral for ongoing exercise. Fourteen current smokers (81.3%) accepted a referral for smoking cessation, three patients with anxiety or depression (37.5%) accepted a psychological therapies referral. The programme improved COPD disease knowledge, patient activation and stimulated referrals to further services supporting disease management. Randomised controlled trials are warranted for similar interventions for COPD patients with early stage disease.

BACKGROUND: According to the community-based EuroPrevall surveys, prevalence of self-reported food allergy (FA) in adults across Europe ranges from 2% to 37% for any food and 1% to 19% for 24 selected foods. OBJECTIVE: To determine the prevalence of probable FA (symptoms plus specific IgE-sensitization) and challenge-confirmed FA in European adults, along with symptoms and causative foods. METHODS: In phase I of the EuroPrevall project, a screening questionnaire was sent to a random sample of the general adult population in 8 European centers. Phase II consisted of an extensive questionnaire on reactions to 24 preselected commonly implicated foods, and measurement of specific IgE levels. Multiple imputation was performed to estimate missing symptom and serology information for nonresponders. In the final phase, subjects with probable FA were invited for double-blind placebo-controlled food challenge. RESULTS: Prevalence of probable FA in adults in Athens, Reykjavik, Utrecht, Lodz, Madrid, and Zurich was respectively 0.3%, 1.4%, 2.1%, 2.8%, 3.3%, and 5.6%. Oral allergy symptoms were reported most frequently (81.6%), followed by skin symptoms (38.2%) and rhinoconjunctivitis (29.5%). Hazelnut, peach, and apple were the most common causative foods in Lodz, Utrecht, and Zurich. Peach was also among the top 3 causative foods in Athens and Madrid. Shrimp and fish allergies were relatively common in Madrid and Reykjavik. Of the 55 food challenges performed, 72.8% were classified as positive. CONCLUSIONS: FA shows substantial geographical variation in prevalence and causative foods across Europe. Although probable FA is less common than self-reported FA, prevalence still reaches almost 6% in parts of Europe. (C) 2019 American Academy of Allergy, Asthma & Immunology

Background Around 16 000 people in the UK work with laboratory animals with 75% of procedures being carried out on mice. Historical data, based largely on work with rats, suggest 15% develop IgE sensitisation to laboratory animal proteins and 10% clinical symptoms of laboratory animal allergy (LAA). The main risk factor for LAA is exposure to respirable aeroallergens. In recent years, conventional open cages have been replaced by individually ventilated cages (IVC) and while lower ambient aeroallergen levels are reported, the impact on LAA incidence is unknown. Methods We surveyed laboratory animal workers at seven UK research institutions. Participants completed a questionnaire about work practices, underwent skin prick testing (to common aeroallergens and mouse epithelium) and had bloods taken for measurement of specific IgE to mouse epithelium and urine. We compared airborne Mus m 1 (the major mouse allergen) levels and the prevalence of sensitisation to mouse proteins in IVC-only and open cage units. Results 750 individuals were recruited (response rate 85%); primary analyses were performed on data from 216 participants with <3 years' exposure to mice. Prevalence of sensitisation to mice was lower in IVC units compared with conventional cage units (2.4% (n=2) vs 9.8% (n=13); p=0.052). In IVCs the prevalence of sensitisation varied from 0% to 9.5%. Aeroallergen levels were generally lower in the IVC units. Mask usage for tasks associated with high allergen exposure (handling mice or soiled bedding) and mask 'fit' testing was more common in IVC units where prevalence of sensitisation was low or zero. Prevalence of atopy to common aeroallergens did not vary significantly between units (figure 1). Conclusions In contemporary practice, the prevalence of sensitisation to mouse proteins is generally low and significantly so in those who have worked only in IVC units. The variation in sensitisation in IVC units was not fully explained by lower aeroallergen levels but also appears related to use of respiratory protective equipment, perhaps a proxy for a proactive approach to occupational health and safety. Our results suggest that LAA is now largely preventable using a combined approach of allergen control measures with IVCs and adherence to 'good practice'.

BACKGROUND:Most studies on the relationship between helminth infections and atopic disorders have been conducted in (sub)tropical developing countries where exposure to multiple parasites and lifestyle can confound the relationship. We aimed to study the relationship between infection with the fish-borne helminth Opishorchis felineus and specific IgE, skin prick testing, and atopic symptoms in Western Siberia, with lifestyle and hygiene standards of a developed country.METHODS:Schoolchildren aged 7-11 years were sampled from one urban and two rural regions. Skin prick tests (SPT) and specific IgE (sIgE) against food and aeroallergens were measured, and data on allergic symptoms and on demographic and socioeconomic factors were collected by questionnaire. Diagnosis of opisthorchiasis was based on PCR performed on stool samples.RESULTS:Of the 732 children included, 34.9% had opisthorchiasis. The sensitization to any allergen when estimated by positive SPT was 12.8%, while much higher, 24.0%, when measured by sIgE. Atopic symptoms in the past year (flexural eczema and/or rhinoconjunctivitis) were reported in 12.4% of the children. SPT was positively related to flexural eczema and rhinoconjunctivitis, but not to wheezing. Opisthorchiasis showed association with lower SPT response, as well as borderline association with low IgE reactivity to any allergen. However, the effect of opisthorchiasis on SPT response was not mediated by IgE, suggesting that opisthorchiasis influences SPT response through another mechanism. Opisthorchiasis also showed borderline association with lower atopic symptoms.CONCLUSIONS:There is a negative association between a chronic helminth infection and skin prick test reactivity even in a developed country.

BACKGROUND:Data are lacking regarding the prevalence of food sensitization and probable food allergy among general population in India. We report the prevalence of sensitization and probable food allergy to 24 common foods among adults from general population in Karnataka, South India. METHODOLOGY:The study was conducted in two stages: a screening study and a case-control study. A total of 11 791 adults in age group 20-54 were randomly sampled from general population in South India and answered a screening questionnaire. A total of 588 subjects (236 cases and 352 controls) participated in the case-control study involving a detailed questionnaire and specific IgE estimation for 24 common foods. RESULTS:A high level of sensitization (26.5%) was observed for most of the foods in the general population, higher than that observed among adults in Europe, except for those foods that cross-react with birch pollen. Most of the sensitization was observed in subjects who had total IgE above the median IgE level. A high level of cross-reactivity was observed among different pollens and foods and among foods. The prevalence of probable food allergy (self-reports of adverse symptoms after the consumption of food and specific IgE to the same food) was 1.2%, which was mainly accounted for cow's milk (0.5%) and apple (0.5%). CONCLUSION:Very high levels of sensitization were observed for most foods, including those not commonly consumed in the general population. For the levels of sensitization, the prevalence of probable food allergy was low. This disassociation needs to be further explored in future studies.

RATIONALE:There is conflicting evidence on whether patients with asthma experience an accelerated decline in lung function with age. We examined the association between postbronchodilator lung function, asthma, chronic rhinosinusitis (CRS), and atopy with age using a large European sample. METHODS:In 17 centers in 11 European countries, case-control studies were nested within representative cross-sectional surveys of adults aged less than 75 years. Representative samples of participants with asthma, CRS or both and controls were assessed for postbronchodilator ventilatory function, smoking history, atopy, and treatment. Multiple regression was used to assess the interactive effects of age and diagnostic group on decline in postbronchodilator ventilatory function. RESULTS:A total of 3337 participants provided adequate data (778 with asthma, 399 with CRS, 244 with both asthma and CRS and 1916 controls who had neither asthma nor CRS). Participants with asthma had lower FEV1 /FVC (-4.09% (95% CI: -5.02, -3.15, P < 0.001) and a steeper slope of FEV1 /FVC against age (-0.14%/annum [95%CI: -0.19, -0.08]) equivalent to smoking 1-2 packs of cigarettes per day. Those with atopy had a slope equivalent to controls. CONCLUSIONS:People with asthma have a steeper decline in postbronchodilator lung function with age, but neither CRS nor atopy alone were associated with such decline.

The authors have presented a paper on the relationship between lung function and cardiovascular risk factors in young subjects. While the subject is of interest and worthy of further studies, there are several points that need to be amended. Major Compulsory Revisions: 1) There are numerous factual errors related to the numerical analyses in the manuscript that must be corrected. For example: p2, row 38 "...FVC bLLN 7%..". 7% is among males only and should read 4.7%. 2) Page 8, row 175: "As expected, men had higher lung function than women". Clearly incorrect. I presume the authors mean that men had larger lung volumes as compared to women. In continuation on row 175: "Over 7% of men had lung obstruction as indicated by FVC bLLN". First, the term is airway obstruction. Second, using FVC alone is not a correct manner of establishing airway obstruction. 3) Page 8, row 181-183: " a consistent trend for a lower FVC with higher tertiles of LDL and TGs in men only". However, among the whole sample association between FVC and LDL was statistically significant, p=0.03. 4) Page 8, row 185-186: "...elevated levels of HOMA-IR had lower levels of FEV1 and FVC levels in the whole sample, as well as per gender (the association being weaker in females). The association between HOMA-IR and FEV1 in women is not statistically significant (p=0.43), which should be clearly stated. Subsequently the same conclusion should be drawn from the association between metabolic syndrome and FEV1 in females, where the association was not, as stated, weaker but not statustically significant.

BACKGROUND:Complaints of 'food allergy' are increasing. Standardized surveys of IgE sensitization to foods are still uncommon and multicountry surveys are rare. We have assessed IgE sensitization to food-associated allergens in different regions of Europe using a common protocol. METHODS:Participants from general populations aged 20-54 years in eight European centres (Zurich, Madrid, Utrecht, Lodz, Sophia, Athens, Reykjavik and Vilnius) were asked whether they had allergic symptoms associated with specific foods. Weighted samples of those with and without allergic symptoms then completed a longer questionnaire and donated serum for IgE analysis by ImmunoCAP for 24 foods, 6 aeroallergens and, by allergen microarray, for 48 individual food proteins. RESULTS:The prevalence of IgE sensitization to foods ranged from 23.6% to 6.6%. The least common IgE sensitizations were to fish (0.2%), milk (0.8%) and egg (0.9%), and the most common were to hazelnut (9.3%), peach (7.9%) and apple (6.5%). The order of prevalence of IgE sensitization against different foods was similar in each centre and correlated with the prevalence of the pollen-associated allergens Bet v 1 and Bet v 2 (r = 0.86). IgE sensitization to plant allergen components unrelated to pollen allergens was more evenly distributed and independent of pollen IgE sensitization (r = -0.10). The most common foods containing allergens not cross-reacting with pollens were sesame, shrimp and hazelnut. DISCUSSION:IgE sensitization to foods is common, but varies widely and is predominantly related to IgE sensitization to pollen allergens. IgE sensitization to food allergens not cross-reacting with pollens is rare and more evenly distributed.

BACKGROUND:The epidemiological surveys in children and adults of the EU-funded multidisciplinary Integrated Project EuroPrevall, launched in June 2005, were designed to estimate the currently unknown prevalence of food allergy and exposure to known or suspected risk factors for food allergy across Europe. We describe the protocol for the epidemiological surveys in children and adults. This protocol provides specific instructions on the sampling strategy, the use of questionnaires, and collection of blood samples for immunological analyses.METHODS:The surveys were performed as multi-centre, cross-sectional studies in general populations. Case-control studies were nested within these surveys. The studies in children aged 7-10 years and adults aged 20-54 years were undertaken in eight centres representing different social and climatic regions in Europe.RESULTS:After a community-based survey collecting basic information on adverse reactions to foods, all those stating they had experienced such reactions, as well as of a random sample of those stating 'no reactions' to foods, completed a detailed questionnaire on potential risks and exposures. Also a blood sample was taken to allow serological analysis to establish patterns of food and aeroallergen sensitization. We also included a questionnaire to schools on their preparedness for dealing with food allergy amongst pupils. Subjects reporting adverse reactions to foods and sensitized to the same food(s) were called in for a full clinical evaluation that included a double blind placebo controlled food challenge (DBPCFC), following a protocol which is described in detail elsewhere.CONCLUSIONS:The outcome of these studies will help to improve our understanding of several important aspects of food allergies in the European Community, providing for more well-informed policies and effective measures of disease prevention, diagnosis and management.