Gas cooking indoors and respiratory symptoms in the ECRHS cohort.

BACKGROUND: Gas cooking is an important source of indoor air pollutants, and there is some limited evidence that it might adversely be associated with respiratory health. Using repeated cross-sectional data from the multi-centre international European Community Respiratory Health Survey, we assessed whether adults using gas cookers have increased risk of respiratory symptoms compared to those using electric cookers and tested whether there was effect modification by a priori selected factors. METHODS: Data on respiratory symptoms and gas cooking were collected from participants at 26-55 and 38-67 years (median time between examinations 11.4 years) from interviewer-led questionnaires. Repeated associations between gas cooking (versus electric) and respiratory symptoms were estimated using multivariable mixed-effects logistic regression models adjusted for age, sex, study arm, smoking status, education level, and included random intercepts for participants within study centres. Analyses were repeated using a 3-level variable for type of cooker and gas source. Effect modification by ventilation habits, cooking duration, sex, age atopy, asthma, and study arm were examined. RESULTS: The sample included 4337 adults (43.7% males) from 19 centres in 9 countries. Gas cooking increased the risk of "shortness of breath whilst at rest" (OR = 1.38; 95%CI: 1.06-1.79) and "wheeze with breathlessness" (1.32; 1.00-1.74). For several other symptoms, effect estimates were larger in those who used both gas hobs and ovens, had a bottled gas source and cooked for over 60 min per day. Stratifying results by sex and age found stronger associations in females and younger adults. CONCLUSION: This multi-centre international study, using repeat data, suggested using gas cookers in the home was more strongly associated than electric cookers with certain respiratory symptoms in adults. As gas cooking is common, these results may play an important role in population respiratory health.

SNPs inFAM13AandIL2RBgenes are associated with FeNO in adult subjects with asthma.

Nitric oxide has different roles in asthma as both an endogenous modulator of airway function and a pro-inflammatory mediator. Fractional exhaled nitric oxide (FeNO) is a reliable, quantitative, non-invasive, simple, and safe biomarker for assessing airways inflammation in asthma. Previous genome-wide and genetic association studies have shown that different genes and single nucleotide polymorphisms (SNPs) are linked to FeNO. We aimed at identifying SNPs in candidate genes or gene regions that are associated with FeNO in asthma. We evaluated 264 asthma cases (median age 42.8 years, female 47.7%) who had been identified in the general adult population within the Gene Environment Interactions in Respiratory Diseases survey in Verona (Italy; 2008-2010). Two hundred and twenty-one tag-SNPs, which are representative of 50 candidate genes, were genotyped by a custom GoldenGate Genotyping Assay. A two-step association analysis was performed without assuming ana priorigenetic model: step (1) a machine learning technique [gradient boosting machine (GBM)] was used to select the 15 SNPs with the highest variable importance measure; step (2) the GBM-selected SNPs were jointly tested in a linear regression model with natural log-transformed FeNO as the normally distributed outcome and with age, sex, and the SNPs as covariates. We replicated our results within an independent sample of 296 patients from the European Community Respiratory Health Survey III. We found that SNP rs987314 in family with sequence similarity 13 member A (FAM13A) and SNP rs3218258 in interleukin 2 receptor subunit beta (IL2RB) gene regions are significantly associated with FeNO in adult subjects with asthma. These genes are involved in different mechanisms that affect smooth muscle constriction and endothelial barrier function responses (FAM13A), or in immune response processes (IL2RB). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with this biomarker of airways inflammation.

IL18 Gene Polymorphism Is Associated with Total IgE in Adult Subjects with Asthma.

The allergic asthma phenotype is characterized by a T helper type 2 (Th2) immune response, based on Immunoglobulin E (IgE)-mediated type 1 hypersensitivity reactions. Total IgE is the sum of all IgE types produced by the human body and is used as a biomarker of inflammation in asthma. We analysed data collected in 143 asthma cases (median age 42.1 years) from the general Italian population (GEIRD survey; 2008-2010) to identify single nucleotide polymorphisms (SNPs) in candidate genes that are associated with total IgE in adult subjects with asthma. These patients reported respiratory symptoms in response to perennial allergens and provided data on 166 SNPs tagging 50 candidate genes or gene regions. Replication of the statistically significant results was performed in 842 asthma cases from other European countries (ECRHS II survey; 1998-2002). SNP rs549908 in interleukin 18 (IL18) gene was significantly associated with total IgE in GEIRD, and this result was replicated in ECRHS II. SNP rs1063320 in the human leukocyte antigen G (HLA-G) gene was identified in GEIRD, but this association was not replicated in ECRHS II. Further investigating IL18 and its biological pathways could be important for developing new therapeutic targets, due to its involvement in inflammatory response processes.

Occupational Exposure of Forest Workers to the Urticating Setae of the Pine Processionary Moth Thaumetopoea pityocampa.

The larvae of the pine processionary moth are a threat to public health because they produce detachable setae that are about 200 µm long and 6 µm wide, reaching a total number of up to 1 million per mature individual. The setae are intended to be released to protect the larvae from predators but become a public health issue when in contact with humans and warm-blooded animals. Symptoms associated with the setae are typically urticaria and local swelling erythema, although edema of the skin, conjunctivitis or respiratory mucosa may occur. Occupational exposure concerns mainly forest workers but also farmers and gardeners. In the present study, we quantify the exposure to the setae of forest workers in a district of Northern Italy. The pine processionary moth represents a real case of occupational exposure as the urticating setae produced by the larvae caused symptoms in most forest workers directly in contact with the infested trees. In addition, the urticating setae were detected on the body of the chainsaw operators and in the surroundings of the felled trees during the operations. The non-exposed workers of the same agency did not report symptoms, with only one exception, likely linked to a non-occupational exposure. As the risk is not immediately perceived by the workers because direct contact with the larvae is unlikely, a campaign of information to workers and the general population living nearby infested forestry areas about the risk associated with airborne exposure is recommended. This becomes especially important in the areas of recent expansion of the insect, where people are inexperienced.

Six-minute walk distance in healthy subjects: reference standards from a general population sample.

INTRODUCTION: The 6-min walking distance (6MWD) test is a useful tool to obtain a measure of functional exercise capacity. However, reference equations have been mainly based on selected populations or small samples. The purpose of this study was to determine the reference equations to predict the 6MWD in a large Italian population sample of healthy adults of a wide age range. METHODS: In the frame of the multi case-control population-based study Gene Environment Interaction in Respiratory Diseases (GEIRD), we studied 530 healthy subjects: 287 females ranging 21-76 and 243 males ranging 21-78 years of age. We measured 6MWD, demographic and anthropometric data and collected the reported physical activity. A multiple linear regression model for the 6MWD included age, age2, height, weight and physical activity for both sex equations. The two-way interaction age-height and age-weight and the quadratic terms of weight and height were also tested for inclusion separately in each model. RESULTS: The mean ± SD for 6MWD was 581.4 ± 66.5 m (range 383-800 m) for females and 608.7 ± 80.1 m (range 410-875 m) for males. The reference equations were 6MWD = 8.10*age + 1.61*heightcm-0.99*weightkg + 22.58*active-0.10*age2 + 222.55 for females (R squared = 0.238) and 6MWD = 26.80*age + 8.46*heightcm-0.45*weightkg-2.54*active-0.06*age2-0.13*age*heightcm-890.18 for males (R squared = 0.159), where "active" is 1 when the subject is physically active, 0 otherwise. CONCLUSION: This study is the first to describe the 6MWD in a large population sample of young, middle aged and elderly healthy Caucasian subjects, and to determine reference equations. These findings will help to improve the evaluation of Italian and European patients with diseases influencing their functional capacity.

Natural pollen exposure increases in a dose-dependent way Fraction of exhaled Nitric Oxide (FeNO) levels in patients sensitized to one or more pollen species.

BACKGROUND: Co-exposures and polysensitization to several pollen species are very common in real life practice. However, little information exists on allergic symptoms and airway inflammation related to natural pollen exposure in large general population samples. OBJECTIVE: To assess the combined effect of sensitization and/or exposure to one or more pollen species on Fraction of exhaled Nitric Oxide (FeNO) levels. METHODS: Within Gene Environment Interactions in Respiratory Diseases (GEIRD) multicase-control study, 1070 adults from the general population of Verona, Italy, underwent a clinical evaluation including standardized interview, spirometry, skin prick test to inhalants and FeNO measurement. Pollen exposure was assumed, when the mean pollen concentration in the previous week was above the cutoff established by the Italian Aerobiological Monitoring Network. RESULTS: Subjects sensitized to one or more pollen species were respectively 15.5% and 29.6%. FeNO levels were directly related to the number of both pollen species around and pollen-related sensitizations. Median FeNO levels were directly related to number of pollen species around and pollen sensitization. FeNO levels increased from 15.4 ppb (p. 25-p. 75 = 9.9-21.0) outside the pollen season to 17.5 ppb (11.2-30.5) when there were ≥3 pollen species around. Likewise FeNO levels rose from 14.8 ppb (10.0-22.3) in not sensitized subjects, to 16.7 (10.1-25.0) in monosensitized and further to 20.4 (12.3-40.6) in poly-sensitized. According to multivariable quantile regression, median FeNO was 17.9 ppb higher (p. 25-p. 75 = 12.5-23.3) for subjects sensitized and exposed to more than one pollen species, compared to subjects who were neither sensitized nor exposed. Differences in FEV1/FVC between groups were less pronounced (-2.0%, -4.1 to 0.1). Median FeNO level was 15.1 ppb (p. 25-p. 75 = 10.0-23.2) in subjects without pollen-related symptoms, 17.8 ppb (12.1-40.2) in those with nasal symptoms only, and 22.7 ppb (14.7-43.0) in those with asthma-like symptoms (p < 0.001). CONCLUSION AND CLINICAL RELEVANCE: Airways inflammation, evaluated by FeNO, increases in dose-dependent manner from subjects monosensitized to pollen species to those poly-sensitized, especially when asthma-like symptoms on pollen exposure are also reported. This should be considered by allergists during natural pollen seasons when evaluating both pulmonary function and airways inflammation.

Glucose/Ribitol Dehydrogenase and 16.9 kDa Class I Heat Shock Protein 1 as Novel Wheat Allergens in Baker's Respiratory Allergy.

Wheat allergens are responsible for symptoms in 60-70% of bakers with work-related allergy, and knowledge, at the molecular level, of this disorder is progressively accumulating. The aim of the present study is to investigate the panel of wheat IgE positivity in allergic Italian bakers, evaluating a possible contribution of novel wheat allergens included in the water/salt soluble fraction. The water/salt-soluble wheat flour proteins from the Italian wheat cultivar Bolero were separated by using 1-DE and 2-DE gel electrophoresis. IgE-binding proteins were detected using the pooled sera of 26 wheat allergic bakers by immunoblotting and directly recognized in Coomassie stained gel. After a preparative electrophoretic step, two enriched fractions were furtherly separated in 2-DE allowing for detection, by Coomassie, of three different proteins in the range of 21-27 kDa that were recognized by the pooled baker's IgE. Recovered spots were analyzed by nanoHPLC Chip tandem mass spectrometry (MS/MS). The immunodetected spots in 2D were subjected to mass spectrometry (MS) analysis identifying two new allergenic proteins: a glucose/ribitol dehydrogenase and a 16.9 kDa class I heat shock protein 1. Mass spectrometer testing of flour proteins of the wheat cultivars utilized by allergic bakers improves the identification of until now unknown occupational wheat allergens.

Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitization.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant. OBJECTIVE: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study. METHODS: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made. RESULTS: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without. CONCLUSIONS & CLINICAL RELEVANCE: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis.

Fractional exhaled nitric oxide levels in relation to work-related respiratory burden and sensitization to wheat flour and multigrain in bakers.

BACKGROUND: Work-related lower airway symptoms (WR-LAS), rhinitis (WRR), and asthma (WRA) are very common among bakers, due to airborne exposure to wheat flour and multigrain. Limited data is available regarding fractional exhaled nitric oxide (FeNO) in bakers in relation to respiratory burden and occupational sensitization in a real-life situation. OBJECTIVE: To analyze FeNO levels in relation to WRR, WR-LAS, and WRA with regard to allergic sensitization to occupational allergen in bakers. METHODS: Cross-sectional, observational study of 174 bakers employed in traditional small bakeries in the Verona District. Subjects did FeNO measurements, spirometry, methacholine challenge, and skin prick test to common inhalant aeroallergens and bakeries occupational allergens. RESULTS: FeNO levels were higher in subjects sensitized to occupational allergens compared with bakers not sensitized to occupational allergens (22.8 ppb (18.9, 27.6) vs. 12.0 ppb (9.9, 14.5), p < 0.05). FeNO levels were higher in bakers with WRR and occupational sensitization (25.4 (20.6, 31.3)) than in bakers with WRR without occupational sensitization compared and bakers without respiratory burden (13.4 (9.6, 18.6) and 11.9 (9.8, 14.5), both p < 0.001). Similar findings were found for WR-LAS with regard to the same categories (31.2 (24.1, 40.4) vs 13.3 (11.4, 15.6) and 15.3 (8.5, 27.5), p < 0.001 and p = 0.005). Bakers with WRA, with or without occupational allergic sensitization, had higher levels of FeNO than bakers without respiratory burden (both p ≤ 0.001). These findings were consistent after adjustments for gender, age, height, weight, smoking, and sensitization to common inhalant aeroallergens and lung function. CONCLUSIONS: WRR and lower airway symptoms in bakers sensitized to occupational allergens relate to increased FeNO. Our study suggests that FeNO is associated with work-related allergic inflammation in occupational sensitized bakers, but future studies are needed to assess how FeNO should be integrated in the diagnostic work-up of occupational disease in bakers.

Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. OBJECTIVES: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. METHODS: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. RESULTS: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. CONCLUSIONS: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.

Gastritis and gastroesophageal reflux disease are strongly associated with non-allergic nasal disorders.

BACKGROUND: Gastroesophageal reflux disease (GERD) has been reported to be significantly associated with chronic rhinosinusitis, but the strength of the association is still debated. AIMS: To evaluate the strength of the association between gastritis/GERD and non-allergic rhinitis (NAR)/allergic rhinitis (AR)/sinusitis. METHODS: We investigated 2887 subjects aged 20-84 years, who underwent a clinical visit in seven Italian centres (Ancona, Palermo, Pavia, Terni, Sassari, Torino, Verona) within the study on Gene Environment Interactions in Respiratory Diseases, a population-based multicase-control study between 2008 and 2014. Subjects were asked if they had doctor-diagnosed "gastritis or stomach ulcer (confirmed by gastroscopy)" or "gastroesophageal reflux disease, hiatal hernia or esophagitis". The association between NAR/AR/sinusitis and either gastritis or GERD was evaluated through relative risk ratios (RRR) by multinomial logistic regression. RESULTS: The prevalence of gastritis/GERD increased from subjects without nasal disturbances (22.8% = 323/1414) to subjects with AR (25.8% = 152/590) and further to subjects with NAR (36.7% = 69/188) or sinusitis (39.9% = 276/691). When adjusting for centre, sex, age, education level, BMI, smoking habits and alcohol intake, the combination of gastritis and GERD was associated with a four-fold increase in the risk of NAR (RRR = 3.80, 95% CI 2.56-5.62) and sinusitis (RRR = 3.70, 2.62-5.23) with respect to controls, and with a much smaller increase in the risk of AR (RRR = 1.79, 1.37-2.35).. CONCLUSION: The study confirmed the association between gastritis/GERD and nasal disturbances, which is stronger for NAR and sinusitis than for AR.

Effects of Respiratory Disorders on Smoking Cessation and Re-Initiation in an Italian Cohort Study.

The present study aims to prospectively assess the influence of respiratory disorders on smoking cessation and re-initiation. Three population-based Italian cohorts answered a questionnaire on respiratory health and smoking habits during 1998-2001 and after a mean follow-up (SD) of 9.1 (0.8) years. Out of 1874 current smokers and 1166 ex-smokers at baseline, 965 (51.5%) and 735 (63.0%) reported their smoking status at follow-up. From current smokers, 312 had stopped smoking at follow-up, while 86 ex-smokers had resumed smoking. People reporting asthma at baseline were more likely to stop smoking than the other subjects (48.6% vs. 31.7%), while people reporting allergic rhinitis or chronic cough/phlegm had a higher probability to resume smoking (16.7% vs. 10.5% and 20.7% vs. 10.4%, respectively). In the multivariable logistic model, smoking relapse strongly decreased with increasing abstinence duration in people without chronic cough/phlegm (OR for ≥7.5 years vs. <7.5 years = 0.23, 95% CI 0.20-0.27), while no effect was detected in people with chronic cough/phlegm (p for interaction = 0.039). Smoking cessation was enhanced in asthmatic subjects, while people with allergic rhinitis or chronic cough/phlegm were at higher risk to resume smoking. Chronic cough/phlegm blunted the decrease in smoking resumption associated with longer abstinence duration.

Exposure to additives or multigrain flour is associated with high risk of work-related allergic symptoms among bakers.

OBJECTIVES: Wheat flour exposure in bakers can elicit respiratory and skin symptoms. Scarce data are available on the prevalence of such conditions in bakers. We investigated the prevalence of work-related rhinitis, asthma-like symptoms and dermatitis in bakers according to job task and type of allergens involved. METHODS: Of the 229 traditional bakeries in Verona area who were invited to participate in a cross-sectional survey, 211 (92%) accepted; 727 employees in these bakeries answered a modified version of a questionnaire on job tasks; allergen exposure within the bakery; and work-related nasal, asthma-like and skin symptoms during 2010-2014. Determinants of work-related nasal, asthma-like or skin disorders were separately evaluated using different logistic models. RESULTS: The prevalence of work-related nasal and asthma-like symptoms was, respectively, 15.1% and 4.2% in bakery shop assistants, increasing to 25.7% and 9.5% in bakers using only wheat flour, and further to 31.8% and 13.6% in bakers using flour and additives, and then to 34.1% and 18.2% in bakers using flour with additives and multigrain (p<0.001). The risk of work-related asthma-like symptoms was more than doubled in bakers using additives without or with multigrain than in shop assistants (OR 2.3, 95% CI 1.0 to 5.5 and OR 3.4, 95% CI 1.1 to 10.8, respectively). Making bread with additives alone or with multigrain significantly increased the risk of work-related nasal symptoms in shop assistants, while the risk of skin symptoms was not significantly affected. CONCLUSIONS: Bakers using additives alone or with multigrain are at a high risk of experiencing nasal and asthma-like symptoms.

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

Biomarkers of Oxidative Stress and Inflammation in Chronic Airway Diseases.

INTRODUCTION: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory and oxidative stress biomarkers in patients with chronic bronchitis, current asthma and past asthma in the frame of a population-based study. METHODS: For this purpose, data collected from the Gene Environment Interactions in Respiratory Diseases (GEIRD) Study, an Italian multicentre, multicase-control study, was evaluated. Cases and controls were identified through a two-stage screening process of individuals aged 20-65 years from the general population. Out of 16,569 subjects selected from the general population in the first stage of the survey, 2259 participated in the clinical evaluation. Oxidative stress biomarkers such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-isoprostane and glutathione and inflammatory biomarkers such as Fractional Exhaled Nitric Oxide (FENO) and white blood cells were evaluated in 1878 subjects. RESULTS: Current asthmatics presented higher levels of FENO (23.05 ppm), leucocytes (6770 n/µL), basophils (30.75 n/µL) and eosinophils (177.80 n/µL), while subjects with chronic bronchitis showed higher levels of GSH (0.29 mg/mL) and lymphocytes (2101.6 n/µL). The multivariable multinomial logistic regression confirmed high levels of leucocytes (RRR = 1.33), basophils (RRR = 1.48), eosinophils (RRR = 2.39), lymphocytes (RRR = 1.26) and FENO (RRR = 1.42) in subjects with current asthma. Subjects with past asthma had a statistically significant higher level of eosinophils (RRR = 1.78) with respect to controls. Subjects with chronic bronchitis were characterized by increased levels of eosinophils (RRR = 2.15), lymphocytes (RRR = 1.58), GSH (RRR = 2.23) and 8-isoprostane (RRR = 1.23). CONCLUSION: In our study, current asthmatics show a greater expression of the inflammatory profile compared to subjects who have had asthma in the past and chronic bronchitis. On the other hand, chronic bronchitis subjects showed a higher rate of expression of oxidative stress biomarkers compared to asthmatic subjects. In particular, inflammatory markers such as circulating inflammatory cells and FENO seem to be more specific for current asthma, while oxidative stress biomarkers such as glutathione and 8-isoprostane appear to be more specific and applicable to patients with chronic bronchitis.

Effects of smoking bans on passive smoking exposure at work and at home. The European Community respiratory health survey.

This longitudinal study investigated whether smoking bans influence passive smoking at work and/or at home in the same subjects. Passive smoking at work and/or at home was investigated in random population samples (European Community Respiratory Health Survey) in 1990-1995, with follow-up interviews in 1998-2003 and 2010-2014. National smoking bans were classified as partial (restricted to public workplaces) or global (extended to private workplaces). Multivariable analysis was accomplished by three-level logistic regression models, where level-1, level-2, and level-3 units were, respectively, questionnaire responses, subjects, and centers. Passive smoking at work was reported by 31.9% in 1990-1995, 17.5% in 1998-2003, and 2.5% in 2010-2014. Concurrently, passive smoking at home decreased from 28.9% to 18.2% and 8.8%. When controlling for sex, age, education, smoking status, and ECHRS wave, the odds of passive smoking at work was markedly reduced after global smoking bans (OR = 0.45, 95% CI 0.25-0.81), particularly among non-smokers, while the protective effect of global smoking bans on passive smoking at home was only detected in non-smokers. Smoking bans both in public and private workplaces were effective in reducing passive smoking at work in Europe. However, given the inefficacy of smoking bans in current smokers' dwellings, better strategies are needed to avoid smoking indoors.

Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III.

INTRODUCTION: The fractional exhaled nitric oxide (FE NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FE NO as a reliable biomarker, it is important to investigate factors that influence FE NO in healthy individuals. Men have higher levels of FE NO than women, but it is unclear whether determinants of FE NO differ by sex. OBJECTIVE: To identify determinants of FE NO in men and women without lung diseases. METHOD: Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease. RESULTS: Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3-67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FE NO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = <0.001 higher FE NO, compared with the lowest age quartile. Height was related to 8% higher FE NO level in men (P < 0.001) and 5% higher FE NO levels in women (P = 0.008). Men who smoked had 37% lower FE NO levels and women had 30% lower levels compared with never-smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FE NO levels compared with non-sensitized subjects 26% and 29%, P < 0.001 for both. CONCLUSION AND CLINICAL RELEVANCE: Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FE NO started increasing at lower age in women than in men, suggesting that interpretation of FE NO levels in adults aged over 50 years should take into account age and sex.

Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: the European Community Respiratory Health Survey.

OBJECTIVES: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. METHODS: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. RESULTS: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. CONCLUSIONS: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.

Second-hand smoke exposure in adulthood and lower respiratory health during 20 year follow up in the European Community Respiratory Health Survey.

BACKGROUND: Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. METHODS: We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. RESULTS: Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (ß: - 49 ml; 95%-CI: -132, 35 for FEV1 and ß: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. CONCLUSION: Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes.