Determinants of immunoglobulin G responses to respiratory syncytial virus and rhinovirus in children and adults.

Introduction: Exposure to respiratory viruses is a significant cause of morbidity and affects virus-specific antibody levels. Little is known about determinants associated with immune response to these viruses. We aimed to investigate the determinants of respiratory syncytial virus (RSV)- and rhinovirus (RV)- specific IgG responses in both children and adults. Methods: The study is based on the EGEA cohort, composed of 530 samples of children in EGEA1 (1991-95) and 1241 samples of adults in EGEA2 (2003-07). Cumulative RV-specific IgG levels (species A, B and C) and IgG levels to RSV-G protein were measured by using micro-array technoloy. Multiple linear mixed models (random effect to account for familial dependence) were performed to assess associations between age, sex, body mass index (BMI), tobacco smoke exposure and season of blood sampling with RSV-and RV-specific IgG levels. Results: In children (11.1 ± 2.8 years old, 57% boys), higher RV-specific IgG levels were associated with older age (only for RV-B), female sex and lower BMI, while only older age was associated with higher RSV-specific IgG levels. In adults (43.5 ± 16.7 years old, 48% men), younger age, female sex, lower BMI, active smoking and all seasons except summer were associated with higher RV-specific IgG levels. Older age, active smoking and all seasons except summer were associated with higher RSV-specific IgG levels. Conclusion: Personal and seasonal determinants of RSV- and RV-specific IgG levels seem to vary according to the respiratory virus type and between children and adults, suggesting different patterns of responses along the life course.

Associations between combined urban and lifestyle factors and respiratory health in European children.

INTRODUCTION: Previous studies identified some environmental and lifestyle factors independently associated with children respiratory health, but few focused on exposure mixture effects. This study aimed at identifying, in pregnancy and in childhood, combined urban and lifestyle environment profiles associated with respiratory health in children. METHODS: This study is based on the European Human Early-Life Exposome (HELIX) project, combining six birth cohorts. Associations between profiles of pregnancy (38 exposures) and childhood (84 exposures) urban and lifestyle factors, identified by clustering analysis, and respiratory health were estimated by regression models adjusted for confounders. RESULTS: Among the 1033 included children (mean ± standard-deviation (SD) age: 8.2 ± 1.6 years old, 47% girls) the mean ± SD forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were 99 ± 13% and 101 ± 14%, respectively, and 12%, 12% and 24% reported ever-asthma, wheezing and rhinitis, respectively. Four profiles of pregnancy exposures and four profiles of childhood exposures were identified. Compared to the reference childhood exposure profile (low exposures), two exposure profiles were associated with lower levels of FEV1. One profile was characterized by few natural spaces in the surroundings and high exposure to the built environment and road traffic. The second profile was characterized by high exposure to meteorological factors and low levels of all other exposures and was also associated with an increased risk of ever-asthma and wheezing. A pregnancy exposure profile characterized by high exposure levels to all risk factors, but a healthy maternal lifestyle, was associated with a lower risk of wheezing and rhinitis in children, compared to the reference pregnancy profile (low exposures). CONCLUSION: This comprehensive approach revealed pregnancy and childhood profiles of urban and lifestyle exposures associated with lung function and/or respiratory conditions in children. Our findings highlight the need to pursue the study of combined exposures to improve prevention strategies for multifactorial diseases such as asthma.

Insight into the relationship between forced vital capacity and transfer of the lungs for carbon monoxide in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Forced vital capacity (FVC) is routinely used to quantify the severity and identify the progression of idiopathic pulmonary fibrosis (IPF). Although less commonly used, lung transfer of carbon monoxide (TLCO) correlates better with the severity of IPF than does FVC. METHODS: Aiming at studying how FVC behaves in relation to TLCO, we analysed cross-sectional data from 430 IPF patients, of which 221 had at least 2 assessments (performed 2.4 ± 1.9 years apart) available for longitudinal analyses. Thresholds for identifying "abnormal" FVC and TLCO values were the statistically-defined lower limits of normal (LLN). For patients with longitudinal data, mean annual absolute declines of FVC and TLCO were calculated. RESULTS: The correlation between FVC and TLCO (%predicted) was weak (R2=0.21). FVC was "abnormal" (i.e.,

Score to Predict the Occurrence of Pneumothorax After Computed Tomography-guided Percutaneous Transthoracic Lung Biopsy.

PURPOSE: The main objective of this study was to identify risk factors for post-percutaneous transthoracic lung biopsy (PTLB) pneumothorax and to establish and validate a predictive score for pneumothorax occurrence to identify patients eligible for outpatient care. MATERIAL AND METHODS: Patients who underwent PTLB between November 1, 2012 and March 1, 2017 were retrospectively evaluated for clinical and radiologic factors potentially related to pneumothorax occurrence. Multivariate logistic regression was used to identify risk factors, and the model coefficient for each factor was used to compute a score. Then, a validation cohort was prospectively evaluated from March 2018 to October 2019. RESULTS: Among the 498 eligible patients in the study cohort, pneumothorax occurred in 124 patients (24.9%) and required drainage in 34 patients (6.8%). Pneumothorax risk factors were chronic obstructive pulmonary disease (OR 95% CI 2.28[1.18-4.43]), several passages through the pleura (OR 95% CI 7.71[1.95-30.48]), an anterior biopsy approach (OR 95% CI 6.36 3.82-10.58]), skin-to-pleura distance ≤30 mm (OR 95% CI 2.25[1.09-6.65]), and aerial effusion >10 mm (OR 95% CI 9.27 [5.16-16.65]). Among the 236 patients in the prospective validation cohort, pneumothorax occurred in 18% and 8% were drained. A negative score (<73 points) predicted a probability of pneumothorax occurrence of 7.4% and late evacuation of 2.5% (OR 95% CI respectively 0.18[0.08-0.39] and 0.15[0.04-0.55]) and suggested a reduced length of hospital stay (P=0.009). CONCLUSION: This predictive score for pneumothorax secondary to PTLB has high prognostic performance and accuracy to direct patients toward outpatient management. CLINICAL TRIALS: NCT03488043.

The exposome concept: how has it changed our understanding of environmental causes of chronic respiratory diseases?

The exposome approach can help us better understand multifactorial respiratory diseases through multidisciplinary collaboration, harmonised resources and use of sophisticated methods addressing combined exposures and longitudinal data. https://bit.ly/3Ng9MNn.

Environmental exposures in early-life and general health in childhood.

BACKGROUND: Early-life environmental exposures are suspected to be involved in the development of chronic diseases later in life. Most studies conducted so far considered single or few exposures and single-health parameter. Our study aimed to identify a childhood general health score and assess its association with a wide range of pre- and post-natal environmental exposures. METHODS: The analysis is based on 870 children (6-12 years) from six European birth cohorts participating in the Human Early-Life Exposome project. A total of 53 prenatal and 105 childhood environmental factors were considered, including lifestyle, social, urban and chemical exposures. We built a general health score by averaging three sub-scores (cardiometabolic, respiratory/allergy and mental) built from 15 health parameters. By construct, a child with a low score has a low general health status. Penalized multivariable regression through Least Absolute Shrinkage and Selection Operator (LASSO) was fitted in order to identify exposures associated with the general health score. FINDINGS: The results of LASSO show that a lower general health score was associated with maternal passive and active smoking during pregnancy and postnatal exposure to methylparaben, copper, indoor air pollutants, high intake of caffeinated drinks and few contacts with friends and family. Higher child's general health score was associated with prenatal exposure to a bluespace near residency and postnatal exposures to pets, cobalt, high intakes of vegetables and more physical activity. Against our hypotheses, postnatal exposure to organochlorine compounds and perfluorooctanoate were associated with a higher child's general health score. CONCLUSION: By using a general health score summarizing the child cardiometabolic, respiratory/allergy and mental health, this study reinforced previously suspected environmental factors associated with various child health parameters (e.g. tobacco, air pollutants) and identified new factors (e.g. pets, bluespace) warranting further investigations.

Pulmonary arterial compliance and exercise capacity after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

Objective: To determine whether changes in pulmonary vascular resistance (PVR) and changes in pulmonary artery compliance (C pa) are associated with changes in exercise capacity assessed either by changes in peak oxygen consumption (V'O2 ) or by changes in 6-min walk distance (6MWD) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA). Methods: Invasive haemodynamic parameters, peak V'O2 and 6MWD were measured within 24 h, before and after BPA (interval 3.1±2.4 months) in 34 CTEPH patients without significant cardiac and/or pulmonary comorbidities, of whom 24 received at least one pulmonary hypertension-specific treatment. C pa was calculated according to the pulse pressure method: C pa=((SV/PP)/1.76+0.1), where SV is the stroke volume and PP is the pulse pressure. The resistance-compliance (RC)-time of the pulmonary circulation was calculated as the PVR and C pa product. Results: After BPA, PVR decreased (562±234 versus 290±106 dyn·s·cm-5; p<0.001); C pa increased (0.90±0.36 versus 1.63±0.65 mL·mmHg-1; p<0.001); but RC-time did not change (0.325±0.069 versus 0.321±0.083 s; p=0.75). There were improvements in peak V'O2 (1.11±0.35 versus 1.30±0.33 L·min-1; p<0.001) and in 6MWD (393±119 versus 432±100 m; p<0.001). After adjustment for age, height, weight and gender, changes in exercise capacity, assessed either by peak V'O2 or 6MWD, were significantly associated with changes in PVR, but not with changes in C pa. Conclusions: Contrary to what has been reported in CTEPH patients undergoing pulmonary endarterectomy, in CTEPH patients undergoing BPA, changes in exercise capacity were not associated with changes in C pa.

Exposome Profiles and Asthma among French Adults.

Rationale: Although previous studies in environmental epidemiology focused on single or a few exposures, a holistic approach combining multiple preventable risk factors is needed to tackle the etiology of multifactorial diseases such as asthma. Objectives: To investigate the association between combined socioeconomic, external environment, early-life environment, and lifestyle-anthropometric factors and asthma phenotypes. Methods: A total of 20,833 adults from the French NutriNet-Santé cohort were included (mean age, 56.2 yr; SD, 13.2; 72% women). The validated asthma symptom score (continuous) and asthma control (never asthma, controlled asthma, and uncontrolled asthma) were considered. The exposome (n = 87 factors) covered four domains: socioeconomic, external environment, early-life environment, and lifestyle-anthropometric. Cluster-based analyses were performed within each exposome domain, and the identified profiles were studied in association to asthma outcomes in negative binomial (asthma symptom score) or multinomial logistic (asthma control) regression models. Measurements and Main Results: In total, 5,546 (27%) individuals had an asthma symptom score ⩾1, and 1,206 (6%) and 194 (1%) had controlled and uncontrolled asthma, respectively. Three early-life exposure profiles ("high passive smoking-own dogs," "poor birth parameters-daycare attendance-city center," or "⩾2 siblings-breastfed" compared with "farm-pet owner-molds-low passive smoking") and one lifestyle-anthropometric profile ("unhealthy diet-high smoking-overweight" compared with "healthy diet-nonsmoker-thin") were associated with more asthma symptoms and uncontrolled asthma. Conclusions: This large-scale exposome-based study revealed early-life and lifestyle exposure profiles that were at risk for asthma in adults. Our findings support the importance of multiinterventional programs for the primary and secondary prevention of asthma, including control of specific early-life risk factors and promotion of a healthy lifestyle in adulthood.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: Evaluation of haemodynamic effects, complication rates and radiation exposure over time.

BACKGROUND: In patients undergoing balloon pulmonary angioplasty (BPA) for inoperable chronic thromboembolic pulmonary hypertension (CTEPH), single-centre series from expert centres have recognized a learning curve for the magnitude of haemodynamic benefits. OBJECTIVE: To report our 7-year experience with BPA, focusing on haemodynamic effects, complication rates and radiation exposure over time. METHODS: Patients with CTEPH who were treated with BPA between May 2013 and February 2020 were analysed during the 'initial period' versus the 'recent period' (split date: March 2017). RESULTS: Among 192 patients who underwent at least one BPA procedure, 156 were included in the safety/radiation analysis and 119 were included in the efficacy analysis. During the 'recent period' versus the 'initial period', the median [interquartile range] number of procedures per patient was higher (4.5 [4.0-6.0] vs. 4.0 [3.0-4.0]; P=0.03), as was the number of dilated vessels per procedure (4.0 [3.5-5.0] vs. 3.5 [3.0-4.0]; P=0.002). Changes in haemodynamic parameters were also greater (mean pulmonary artery pressure: -22% [-31% to -14%] vs. -37% [-44% to -29%]; P=0.001; pulmonary vascular resistance: -38% [-51% to -8%] vs. -53% [-69% to -33%]; P=0.002); complication rates were similar (5.7% vs. 9.3% of procedures; P=0.38); and radiation exposure was lower (effective dose per patient: 43.9 [31.6-66.5] vs. 67.8 [47.9-101.9] mSv; P<0.001). CONCLUSION: Our analysis is consistent with a learning curve for the magnitude of haemodynamic improvements. The complication rate was low and did not change over time, but radiation exposure decreased.

Neural respiratory drive in chronic thromboembolic pulmonary hypertension: Effect of balloon pulmonary angioplasty.

Excessive ventilation (V̇E) during exercise, ascribed to heightened neural ventilatory drive and/or to increased "wasted" ventilation, is a feature of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) allows near-normalization of resting haemodynamic parameters but does not allow excess exercise hyperventilation to normalize. Neural ventilatory drive can be estimated by studying how arterial PCO2 (PaCO2), end-tidal PCO2 (PETCO2), V̇E and CO2 output (V̇CO2) change across the exercise-to-recovery transition during a cardiopulmonary exercise test. Increased "wasted" ventilation can be quantified by the physiological dead space fraction of tidal volume (VD/VT) calculated with the Enghoff simplification of the Bohr equation. These measurements were made before and after BPA in 22 CTEPH patients without significant cardiac and/or pulmonary comorbidities. Our observations suggest that before BPA, excessive hyperventilation was secondary to both heightened neural ventilatory drive and increased "wasted" ventilation; after BPA, measurements made across the exercise-to-recovery transition suggest that heightened neural ventilatory drive was no longer present.

Short- and Mid-Term Outcomes of Endovascular Stenting for the Treatment of Post-Thrombotic Syndrome due to Iliofemoral and Caval Occlusive Disease: A Multi-Centric Study from the French Society of Diagnostic and Interventional Cardiovascular Imaging (SFICV).

PURPOSE: To assess the results of endovascular treatment in a large population of patients suffering from post-thrombotic syndrome (PTS) due to iliocaval occlusive disease. METHODS: In this retrospective multi-center study, 698 patients treated by stenting for PTS in 15 French centers were analyzed. Primary, primary assisted, and secondary patency rates were assessed, and clinical efficacy was evaluated using Villalta and Chronic Venous Insufficiency Questionnaire in 20 questions (CIVIQ-20) scores. Outcomes were compared against pre-operative CT-based severity of the post-thrombotic lesions in the thigh (4 grades). RESULTS: Technical success, defined as successful recanalization and stent deployment restoring rapid anterograde flow in the targeted vessel, was obtained in 668 (95.7%) patients with a complication rate of 3.9%. After a mean follow-up of 21.0 months, primary patency, primary assisted patency, and secondary patency were achieved in 537 (80.4%), 566 (84.7%), and 616 (92.2%) of the 668 patients, respectively. Venous patency was strongly correlated to the grade of post-thrombotic changes in the thigh, with secondary patency rates of 96.0%, 92.9%, 88.4%, and 78.9%, respectively, for grades 0 to 3 (p = .0008). The mean improvements of Villalta and CIVIQ-20 scores were 7.0 ± 4.7 points (p < .0001) and 19.1 ± 14.8 points (p < .0001), respectively. CONCLUSION: Endovascular stenting as a treatment option for PTS due to chronic iliocaval venous occlusion generates a high technical success, low morbidity, high midterm patency rate, and clinical improvement. Venous patency was strongly correlated to the severity of post-thrombotic lesions in the thigh.

Exercise hyperventilation and pulmonary gas exchange in chronic thromboembolic pulmonary hypertension: Effects of balloon pulmonary angioplasty.

BACKGROUND: Excessive ventilation (V̇E) and abnormal gas exchange during exercise are features of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercise hyperventilation and gas exchange is poorly understood. METHODS: In this longitudinal observational study, symptom-limited cardiopulmonary exercise tests and carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean (SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonary comorbidities. RESULTS: Peak work rate improved by 20% after BPA whilst V̇E at peak did not change despite improved ventilatory efficiency (lower V̇E with respect to CO2 output [V̇CO2]). At the highest identical work rate pre- and post-BPA (75 (30) watts), V̇E and alveolar-arterial oxygen gradient (P(Ai-a)O2) decreased by 17% and 19% after BPA, respectively. The physiological dead space fraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO2, decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA. CONCLUSIONS: Ventilatory efficiency, physiological VD/VT, and pulmonary gas exchange improved after BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume and probably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measured before BPA and P(Ai-a)O2 measured after BPA suggests that DLCO may provide an easily accessible marker to predict the response to BPA in terms of pulmonary gas exchange.

Concurrence of 1- and 3-Min Sit-to-Stand Tests with the 6-Min Walk Test in Idiopathic Pulmonary Fibrosis.

BACKGROUND: In idiopathic pulmonary fibrosis (IPF), some physiological parameters measured during a 6-min walk test (6-MWT) impart reliable prognostic information. Sit-to-stand tests (STSTs) are field exercise tests that are easier to implement than the 6-MWT in daily practice. OBJECTIVES: The aims of the study were to test the reproducibility and compare 2 STSTs (the 1-min STST [1-STST] and the semi-paced 3-min chair rise test [3-CRT]) in IPF, and to determine if selected physiological parameters (speed of displacement and changes in pulse oxygen saturation [SpO2]) are interchangeable between the STSTs and the 6-MWT. METHODS: Thirty-three patients with stable IPF were studied in 3 French expert centers. To test reproducibility, intra-class correlations (ICCs) of parameters measured during tests performed 7-14 days apart were calculated. To test interchangeability, the agreement and correlation of physiological responses measured during STSTs and during 6-MWT were studied. RESULTS: Vertical displacements and changes in SpO2 during both STSTs were reproducible, with ICCs ranging from 0.78 [0.63-0.87] to 0.95 [0.92-0.97]. Vertical displacements during 1-STST and 3-CRT were correlated with 6-MWT distance (correlation coefficients (r) of 0.72 and 0.77, respectively; p < 0.001). Similarly, correlations were found between changes in SpO2 measured during the 2 STSTs and the 6-MWT, with coefficients ranging from 0.73 to 0.91 (p < 0.001). Distance walked and SpO2 during 6-MWT were well estimated from vertical displacement and SpO2 during the 2 STSTs, respectively. CONCLUSION: The correlations found between the 2 STSTs and the 6-MWT suggest that STSTs may be of interest to assess displacement and exercise-induced changes in SpO2 in IPF patients.

Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort.

BACKGROUND: Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class-II genomic region is a strong candidate. OBJECTIVE: To assess the association between HLA class-II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules. METHODS: The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class-II alleles. For each sIgE sensitization and HLA class-II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p-values were corrected for multiple comparisons (False Discovery Rate). RESULTS: Most of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB1*05:01, DQA1*01:01 and DRB1*01:01, respectively). CONCLUSION: Our results support the important role of HLA class-II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens.

The Exposome Approach to Decipher the Role of Multiple Environmental and Lifestyle Determinants in Asthma.

Asthma is a widespread respiratory disease caused by complex contribution from genetic, environmental and behavioral factors. For several decades, its sensitivity to environmental factors has been investigated in single exposure (or single family of exposures) studies, which might be a narrow approach to tackle the etiology of such a complex multifactorial disease. The emergence of the exposome concept, introduced by C. Wild (2005), offers an alternative to address exposure-health associations. After presenting an overview of the exposome concept, we discuss different statistical approaches used to study the exposome-health associations and review recent studies linking multiple families of exposures to asthma-related outcomes. The few studies published so far on the association between the exposome and asthma-related outcomes showed differences in terms of study design, population, exposome definition and statistical methods used, making their results difficult to compare. Regarding statistical methods, most studies applied successively univariate (Exposome-Wide Association Study (ExWAS)) and multivariate (adjusted for co-exposures) (e.g., Deletion-Substitution-Addition (DSA) algorithm) regression-based models. This latest approach makes it possible to assess associations between a large set of exposures and asthma outcomes. However, it cannot address complex interactions (i.e., of order ≥3) or mixture effects. Other approaches like cluster-based analyses, that lead to the identification of specific profiles of exposure at risk for the studied health-outcome, or mediation analyses, that allow the integration of information from intermediate biological layers, could offer a new avenue in the understanding of the environment-asthma association. European projects focusing on the exposome research have recently been launched and should provide new results to help fill the gap that currently exists in our understanding of the effect of environment on respiratory health.

Profile of exposures and lung function in adults with asthma: An exposome approach in the EGEA study.

BACKGROUND: Environmental research on multifactorial health outcomes calls for exposome approaches able to assess the joint effect of multiple exposures. OBJECTIVE: Our aim was to identify profiles of exposure to lifestyle/environmental factors associated with lung function in adults with asthma using a cluster-based approach. METHODS: We used data from 599 adults of the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) (mean age 39.0 years, 52% men) who ever had asthma. Exposures to 53 lifestyle/environmental factors were assessed by questionnaires or geographic information systems-based models. A two-step approach was developed: 1) exposome dimension reduction by selecting factors showing association with forced expiratory volume in 1 s (FEV1) (p < 0.20) in an exposome-wide association study (ExWAS), 2) clustering analysis using the supervised Bayesian Profile Regression (sBPR) to group individuals according to FEV1 level and to their profile of exposure to a reduced set of uncorrelated exposures (each paired correlation<0.70) identified in step 1. RESULTS: The ExWAS identified 21 factors showing suggestive association with FEV1 (none significant when controlling for multiple tests). The sBPR conducted on 15 uncorrelated exposures identified in step 1, revealed 3 clusters composed of 30, 115 and 454 individuals with a mean ± SD FEV1(%pred) of 79% ± 21, 90% ± 19 and 93% ± 16, respectively. Cluster 1 was composed of individuals with heavy smoking, poor diet, higher outdoor humidity and proximity to traffic, while cluster 2 and 3 included individuals with moderate/low levels of exposure to these factors. DISCUSSION: This exposome study identified a specific profile of joint lifestyle and environmental factors, associated with a low FEV1 in adults with asthma. None of the exposures revealed significant association when considered independently.

Never-smokers with occupational COPD have better exercise capacities and ventilatory efficiency than matched smokers with COPD.

Chronic obstructive pulmonary disease (COPD) in never-smokers exposed to organic dusts is still poorly characterized. Therapeutic strategies in COPD are only evaluated in smoking-related COPD. Understanding how never-smokers with COPD behave during exercise is an important prerequisite for optimal management. The objective of this study was to compare physiological parameters measured during exercise between never-smokers with COPD exposed to organic dusts and patients with smoking-related COPD matched for age, sex, and severity of airway obstruction. Healthy control subjects were also studied. Dyspnea (Borg scale), exercise tolerance, and ventilatory constraints were assessed during incremental cycle cardiopulmonary exercise testing in COPD patients at mild to moderate stages [22 exposed to organic dusts: postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z score -2.44 ± 0.72 and FEV1z score -1.45 ± 0.78; 22 with smoking-related COPD: FEV1/FVC z score -2.45 ± 0.61 and FEV1z score -1.43 ± 0.69] and 44 healthy control subjects (including 22 never-smokers). Despite the occurrence of similar significant dynamic hyperinflation, never-smoker COPD patients exposed to organic dusts had lower dyspnea ratings than those with smoking-related COPD. They also had better ventilatory efficiency, higher peak oxygen consumption and peak power output than smoking-related COPD patients, all these parameters being similar to control subjects. Differences in exercise capacity between the two COPD groups were mainly driven by better ventilatory efficiency stemming from preserved diffusion capacity. Never-smokers exposed to organic dusts with mild to moderate COPD have better exercise capacities, better ventilatory efficiency, and better diffusion capacity than matched patients with smoking-related COPD.NEW & NOTEWORTHY It is unknown whether or not never-smokers with chronic obstructive pulmonary disease (COPD) behave like their smoking counterparts during exercise. This is the first study showing that never-smokers with mild to moderate COPD [defined by a postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < lower limit of normal] have preserved exercise capacities. They also have lower exertional dyspnea than patients with smoking-related COPD. This suggests that the two COPD groups should not be managed in the same way.

Characterization of chronic obstructive pulmonary disease in dairy farmers.

BACKGROUND: Although farming is often considered a risk factor for COPD, data regarding the burden and characteristics of COPD in dairy farmers are sparse and conflicting. OBJECTIVES: To characterize COPD in dairy farmers. METHODS: 4788 subjects entered two parallel COPD screening programs, one in agricultural workers and one in general practice from 2011 to 2015. Subjects with COPD were invited to participate in the characterization phase of the study. Those who accepted were included in two subgroups: dairy farmers with COPD (DF-COPD) (n = 101) and non-farmers with COPD (NF-COPD) (n = 85). Patients with COPD were frequency-matched with subjects with normal spirometry for age, sex and tobacco smoking (pack-years and status) (DF-controls n = 98, NF-controls n = 89). All subjects from these four groups underwent lung function and exercise testing, questionnaires and blood analysis. RESULTS: The frequency of COPD in dairy farmers was 8.0% using the GOLD criterion and 6.2% using the lower limit of normal criterion and was similar in non-farming subjects (7.3% and 5.2%, respectively) although dairy farmers had lower tobacco consumption (screening phase). DF-COPD had better pulmonary function, exercise capacity and quality of life, fewer symptoms and comorbidities than NF-COPD, and higher levels of some Th2 biomarkers (MCP-2, periostin) (characterization phase). In farmers, COPD was not related to occupational exposure factors, supporting the role of host factors. CONCLUSION: COPD secondary to organic dust exposure (dairy farming) appears less severe and associated with fewer comorbidities than COPD secondary to tobacco smoking.

In Patients with Mild-to-Moderate COPD, Tobacco Smoking, and Not COPD, Is Associated with a Higher Risk of Cardiovascular Comorbidity.

Background: Comorbidities including cardiovascular diseases are very common in chronic obstructive pulmonary disease (COPD) secondary to tobacco smoking and contribute to the overall severity of the disease. In non-smoking COPD, which accounts for about 25% of COPD cases worldwide, current knowledge on the frequency and determinants of comorbidities remains scarce. The aims of the current study were to assess the frequency of major comorbidities and to evaluate their determinants in a group of non-selected patients with mild-to-moderate COPD who were exposed to organic dust (dairy farmers), to tobacco smoking, or to both, and in controls without COPD who were exposed to organic dust (dairy farmers), or to tobacco smoking, or to both, or who were without exposure. Patients and Methods: A total of 4665 subjects (2323 dairy farmers and 2342 non-farmers) including 355 patients with COPD and 4310 controls with normal spirometry were recruited through a large COPD screening program. Self-reported physician-diagnosed diseases with plausible links to COPD were recorded in this cross-sectional study. Results: Whatever the exposure, cardiovascular comorbidities were not more frequent in patients with COPD than their counterparts without airflow limitation. A higher risk of major cardiovascular comorbidities was associated with tobacco smoking and a lower risk was associated with exposure to organic dusts. Conclusion: Tobacco smoking (but not COPD) is associated with higher frequency of cardiovascular comorbidities. By contrast, being a dairy farmer exposed to organic dusts is associated with a lower frequency of the same comorbidities. This reinforces the crucial need for controlling established cardiovascular risk factors even in patients with mild-to-moderate COPD.