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International audience; 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.

BACKGROUND: Emerging research suggests health effects in offspring after parental chemical exposures before conception. Many future mothers are exposed to potent chemicals at work, but potential offspring health effects are hardly investigated.OBJECTIVE: We sought to investigate childhood asthma in relation to mother's occupational exposure to cleaning products and disinfectants before conception.METHODS: The multicenter Respiratory Health In Northern Europe/Respiratory Health In Northern Europe, Spain and Australia generation study investigated asthma and wheeze starting at age less than 10 years in 3318 mother-offspring pairs. From an asthma-specific Job-Exposure Matrix and mothers' occupational history, we defined maternal occupational exposure to indoor cleaning agents (cleaning products/detergents and disinfectants) starting before conception, in the 2-year period around conception and pregnancy, or after birth. Never-employed mothers were excluded. Exposed groups include cleaners, health care workers, cooks, and so forth. Associations were analyzed using mixed-effects logistic regression and ordinary logistic regression with clustered robust SEs and adjustment for maternal education.RESULTS: Maternal occupational exposure to indoor cleaning starting preconception and continuing (n = 610) was associated with offspring's childhood asthma: odds ratio 1.56 (95% CI, 1.05-2.31), childhood asthma with nasal allergies: 1.77 (1.13-2.77), and childhood wheeze and/or asthma: 1.71 (95% CI, 1.19-2.44). Exposure starting around conception and pregnancy (n = 77) was associated with increased childhood wheeze and/or asthma: 2.25 (95% CI, 1.03-4.91). Exposure starting after birth was not associated with asthma outcomes (1.13 [95% CI, 0.71-1.80], 1.15 [95% CI, 0.67-1.97], 1.08 [95% CI, 0.69-1.67]).CONCLUSIONS: Mother's occupational exposure to indoor cleaning agents starting before conception, or around conception and pregnancy, was associated with more childhood asthma and wheeze in offspring. Considering potential implications for vast numbers of women in childbearing age using cleaning agents, and their children, further research is imperative.

RATIONALE: Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long-term consequences of cleaning agents on respiratory health are, however, not well described.OBJECTIVES: This study aimed to investigate long-term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction.METHODS: The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population-based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders.MEASUREMENTS AND MAIN RESULTS: As compared with women not engaged in cleaning (ΔFEV1 = -18.5 ml/yr), FEV1 declined more rapidly in women responsible for cleaning at home (-22.1; P = 0.01) and occupational cleaners (-22.4; P = 0.03). The same was found for decline in FVC (ΔFVC = -8.8 ml/yr; -13.1, P = 0.02; and -15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV1 decline (-22.0, P = 0.04; and -22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV1/FVC decline or airway obstruction.CONCLUSIONS: Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long-term respiratory health.

Objectives An employee with no prior history of allergy or asthma, experienced respiratory and flu-like symptoms during production of shrimp shell powder in a seafood savory factory in Norway. We aimed to clarify the diagnosis and to identify the cause of the symptoms by specific inhalation challenge (SIC) and by characterizing the powder's biocontaminants, particle size fractions and inflammatory potential. Methods Respiratory and immunological responses were measured the day before and after each of four challenges with 20–150 g shrimp shell powder during three consecutive days. The powder was analyzed for endotoxin, microorganisms and particle size fractions by standardized laboratory methods. Total inflammatory potential was quantified by reactive oxygen species (ROS) production in a granulocyte assay. Results The patient had elevated IgG, but not IgE, towards shrimp shell powder. 20 min challenge with 150 g shrimp shell powder induced 15% decrease in FVC, 23% decrease in FEV 1 and increased unspecific bronchial reactivity by methacholine. Neutrophils and monocytes increased 84% and 59%, respectively, and the patient experienced temperature increase and flu-like symptoms. The shrimp shell powder contained 1118 endotoxin units/g and bacteria including Bacillus cereus , and 57% respirable size fraction when aerosolized. The ROS production was higher for shrimp shell powder than for endotoxin alone. Conclusions Endotoxin and other bacterial components combined with a high fraction of respirable dust might be the cause of the symptoms. The patient's characteristics and response to SIC were best compatible with occupational asthma and organic dust toxic syndrome, while hypersensitivity pneumonitis could not be excluded.

Background: Lung health might be influenced by oral bacteria through micro-aspiration and transfer of inflammatory mediators from the oral mucosa. Aim: To describe the association between oral bacteria and lung function in a healthy population from Bergen, Norway. Methods: Samples of gingival fluid were collected concurrently with spirometry in 288 adults (52% males, median age 28 years) from the RHINESSA study, Bergen centre. Bacterial DNA from the 16S rRNA gene were isolated from gingival fluid, sequenced by Illumina® and assigned bacterial taxonomy by the Human Oral Microbiome Database. Differential abundance in the gingival microbiome by FEV1 and FVC percent predicted was evaluated by the Analysis of Composition of Microbiomes methodology with 5% False Discovery Rate, adjusting for weight, education, smoking and asthma medication. Results: We identified 148 bacteria genera in the gingival fluid samples. 12 genera, accounting for 4.5% of the total gingiva microbiota, showed increased relative abundance with lower FEV1. The main contributors were Rothia spp. (2.4%) and Enterococcus spp. (1.2%). Among the 12 genera associated with FEV1, 6 genera (0.8% of the gingiva bacterial community) were also associated with lower FVC, with Propionibacterium spp. (0.6%) as the main contributor. Additionally 6 genera were associated with lower FVC; these contributed to Conclusion: High levels of Rothia, Propionibacterium and Enterococcus genera were associated with lower lung function, FEV1 in particular. Rothia species are implicated in lung disease and with periodontitis, while Propionibacterium and Enterococcus include known cariogenic pathogens. Thus, the main contributors to lower lung function are known oral or lung pathogens.

Objective: A fish-processing worker reporting symptoms consistent with HP during slaughtering of salmon was referred to our clinic. The 42 year old man, never smoker, no history of allergy or respiratory disease, reported job-related symptoms for the last 3 years (dyspnoe, coughing, flu-like symptoms and fever). The symptoms started 3-4 hours after start of work shift. He felt better next morning and during weekends. The last year he had had recurrent episodes of pneumonia. Aim: By the use of specific inhalation challenge (SIC), we aimed to describe the patient´s respiratory, clinical and immunological responses after inhalation of salmon proteins. Method: SIC is a method for diagnosing occupational asthma and a modified version of the protocol is used for diagnosing hypersensitivity pneumonitis (HP). The challenge with salmon proteins was conducted in a provocation chamber (13 m3) with the patient manually filleting salmon (20 min). Results: At baseline there was a tendency of low diffusion capacity for carbon monoxide (DLCO 74% of predicted), lung function verging a restrictive pattern (FVC 80% of predicted), and no specific IgEs towards fish allergens. In response to SIC, he got flu-like symptoms, further decrease in FVC (12.5%) and DLCO (11%), increase in neutrophils (12%) and decrease in lymphocytes (23%), as compared to pre-test values. Next day the patient was asymptomatic, and FVC and DLCO were normalized to pre-test values. Conclusion: The patient’s response to salmon proteins was compatible with HP according to Munoz X et al [Curr Opin Allergy Clin Immunol. 2013;13:151-8]. A better awareness of etiological factors of HP other than birds and mold is needed.

The aim was to evaluate susceptibility of oropharyngeal contamination with various bronchoscopic sampling techniques. 67 patients with obstructive lung disease and 58 control subjects underwent bronchoscopy with small-volume lavage (SVL) through the working channel, protected bronchoalveolar lavage (PBAL) and bilateral protected specimen brush (PSB) sampling. Subjects also provided an oral wash (OW) sample, and negative control samples were gathered for each bronchoscopy procedure. DNA encoding bacterial 16S ribosomal RNA was sequenced and bioinformatically processed to cluster into operational taxonomic units (OTU), assign taxonomy and obtain measures of diversity. The proportion of Proteobacteria increased, whereas Firmicutes diminished in the order OW, SVL, PBAL, PSB (p, Protected bronchoscopic sampling is most suitable for identification of a distinct airway microbiome http://ow.ly/qIIy30eqB9M

Introduction: Occupational and regular cleaning at home is associated with excess risk of asthma and respiratory symptoms, but little is known about long term effects on lung function decline. Aim: To study whether occupational cleaning and/or cleaning at home causes accelerated lung function decline. Methods: Lung function (FVC and FEV 1 ) was measured in the ECRHS multicentre population-based study in 1992-94 and at two follow-ups in 1998-02 and 2010-12. In ECRHS II 3462 women responded to the questions “since the last survey, have you been the person doing the cleaning and/or washing in your home?” and “since the last survey, have you worked as a cleaner?” respectively. Decline in FVC and FEV 1 between ECRHS I and III was analysed by mixed effect models adjusted for FEV 1 , age and height at baseline, number of years between each follow-up, BMI at each survey, pack years at last survey, age at completed education, social class and centre. Results: Between the first and last survey, women not working as cleaners or doing the cleaning at home had an adjusted mean decline in FVC and FEV 1 of 19.5 (95% CI [15.4-23.6]) and 29.6 [26.8-32.3] ml/yr, respectively. Women cleaning at home had an adjusted mean decline in FVC and FEV 1 of 24.6 [23.4-25.5] and 33.6 [32.9-34.3] ml/yr, whereas the decline in occupational cleaners was 27.6 [24.2-31.0] and 34.6 [32.2-36.7] ml/yr, respectively. Lung function decline was significantly more rapid in both groups of cleaners as compared to the reference group (p Conclusion: Women who work as cleaners and/or regularly clean their home had accelerated lung function decline and are thus at increased risk for the development of obstructive and/or restrictive lung disease.

Introduction: We examined the degree of contamination of the airway microbiome with different bronchoscopic sampling techniques. Methods: We collected oral wash (OW), protected specimen brushes (PSB), protected broncho-alveolar lavage (PBAL), and small-volume lavage (SVL) using the suction canal on the bronchoscope, in 16 COPD patients and 8 controls. Together with negative control samples (NCS) we performed paired-end sequencing of the V3-V4 region of 16S rRNA on a Illumina MiSeq. We performed analyses of α- and β-diversity after removing all operational taxonomic units (OTUs) in the NCS, using QIIME. Results: NCS OTUs accounted for 80% of all sequences, and we retained 2.5 million sequences from 144 samples distributed in 803 OTUs for analyses. Bonferroni-corrected, Wilcoxon matched-pairs test indicated that OW samples were more α-diverse (phylogenetic distance) than the PBAL and PSB samples, but not compared to the SVL. Also the first fraction of the PBAL was more α-diverse than the second (p In principle coordinates analysis of β-diversity (UniFrac distance), all respiratory tract samples clustered differently from the OW samples, the overlap was larger for SVL and PBAL samples than for PSB (Figure 1). Thus, SVL samples were more similar to OW than the protected samples, indicating contamination. Conclusions: We need protected sampling techniques (PSB and PBAL) to avoid contaminated samples of the airway microbiome.

Background: Several ongoing studies on the low-biomass airway microbiome may be hampered with an hithereto unestimated contamination by laboratory processing. Methods: We collected negative control samples (NCS), oral wash (OW), small volume lavage, protected specimen brushes and bronchoalveolar lavage (PSB, PBAL) in 16 subjects with COPD and 8 controls. We sequenced the V3-V4 region of the 16S rRNA on an Illumina MiSeq. Bioinformatic analyses were performed with QIIME. We estimated operational taxonomic units (OTUs) seen in NCS and compared the effect of keeping (1) or removing (2) NCS OTUs from the airway samples. Results: We were left with 10.5 and 2.5 million sequences and 803 and 777 OTUs using approach (1) and (2), respectively. Ralstonia dominated airway samples in approach (1). whereas the taxonomic distribution was more heterogeneous in approach (2) (Figure1). The impact of keeping NCS contaminants was also evident in principle coordinate analyses of β-diversity (Figure 2). Conclusion: Contamination from sample handling and sequencing steps is likely to influence the composition of airway microbiota, and needs to be addressed in future studies.

BACKGROUND: Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception.METHODS: In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family.RESULTS: Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries.CONCLUSIONS: Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations.

Background: The employees in a seafood savory factory experienced fever, chill, and respiratory problems while producing shrimpshell powder. They had no specific IgE towards shrimp and no problems when working with powder from whole shrimp. Aim: The aim of the study was to identify the cause of the symptoms associated with shrimpshell powder. Methods: Standardized laboratory methods were used to measure the concentration of endotoxin and size fractions of the powder, as well as the total inflammatory potential with a granulocyte assay that quantifies reactive oxygen species (ROS). One worker had a specific inhalation challenge (SIC) with respiratory and immunological responses measured before (Day 0 ), and after each of the 4 challenges with 20-150 g shrimpshell powder (maximum 20 minutes exposure). Results: The shrimpshell powder contained 1118 endotoxin units/gram and the aerosol consisted of 90%, 86% and 57% inhalable, thoracic and respirable size fractions, respectively. The ROS production of the cells as a response to the inhalable fraction of the shrimp shell powder was significantly higher than with fish powder (control). The ROS production profiles were similar for shrimpshell powder and endotoxin stimulation. After challenge with 150 g shrimp shell powder, the worker had a 23% decrease in FEV 1 compared to baseline (Day 0 ). The neutrophils and monocytes increased 84% and 59%, respectively, from Day 0 to after the last challenge (Day 3 ). Conclusion: The SIC resulted in >20% decrease in FEV 1, which could be bronchoconstriction due to endotoxin and the high levels of respirable dust. Also considering the flu-like symptoms and the increase in monocytes, this may indicate organic dust toxic syndrome.

Background : Recent methodological developments, in particular new sequencing methods for bacterial RNA/DNA, have shown that microorganisms reside in airways that do not suffer from acute infection and that respiratory microbiota might vary according to airways disease status. We aim to establish high-quality sampling methods for lower airways microbiota as well as describe the respiratory microbiome in subjects with and without chronic obstructive pulmonary disease (COPD) and to relate the microbiome to disease development, progression, and the host immune system. Methods : The Bergen COPD microbiome study (MicroCOPD) is a longitudinal study aiming to collect data from 200 subjects with COPD as well as 150 individuals without COPD. At baseline, subjects go through a bronchoscopy in which protected specimen brushes, small-volume lavage, bronchoalveolar lavage, and bronchial biopsies provide a unique chance to analyze the microbiota and the host immune system status. These variables will be related to baseline clinical parameters (lung function, smoking status, exacerbation frequency, arterial blood gases, comorbidities, and medications) as well as follow-up parameters (lung function changes, exacerbation frequency, mortality, and more). Results : Per date more than 150 bronchoscopies have been performed, equally distributed between cases and controls, with a very low complication frequency. Conclusions : MicroCOPD will provide unique data on a large material, with insight on a new field of respiratory research. Keywords : COPD; control subjects; bronchoscopy; biopsies; microbiome; inflammation; remodeling Citation : European Clinical Respiratory Journal 2014, 1: 26196 - http://dx.doi.org/10.3402/ecrj.v1.26196 (Published: 29 December 2014) Responsible Editor : Christer Janson, Uppsala University, Sweden.