Publications by authors named "Benoit Wallaert"

115 Publications

Low income and outcome in idiopathic pulmonary fibrosis: An association to uncover.

Respir Med 2021 Apr 27;183:106415. Epub 2021 Apr 27.

Centre de Référence des Maladies Pulmonaires Rares (site Constitutif), AP-HP, Service de Pneumologie, Hôpital Avicenne, Bobigny, France; Université Sorbonne Paris Nord, INSERM, 1272, « Hypoxie et Poumon: Pneumopathies Fibrosantes, Modulations Ventilatoires et Circulatoires », Bobigny, France. Electronic address:

Background: Low income, a known prognostic indicator of various chronic respiratory diseases, has not been properly studied in idiopathic pulmonary fibrosis (IPF). We hypothesize that a low income has an adverse prognostic impact on IPF.

Methods: Patients were selected from the French national prospective cohort COFI. Patients' income was assessed through the median city-level income provided by the French National Institute of Statistics and Economic Studies according to their residential address. Patients were classified in two groups as "low income" vs. "higher income" depending on whether their annual income was estimated to be < or ≥18 170 €/year (the first quartile of the income distribution in the study population). The survival and progression-free survival (PFS) of the groups were compared by a log-rank test and a Cox model in multivariate analysis.

Results: 200 patients were included. The average follow-up was 33.8 ± 22.7 months. Patients in the low income group were significantly more likely to be of non-European origin (p < 0.006), and to have at least one occupational exposure (p < 0.0001), and they tended to have a higher cumulative exposure to fine particles PM (p = 0.057). After adjusting for age, gender, forced vital capacity at inclusion, geographical origin, and occupational exposure having a low-income level was a factor associated with a worse PFS (HR: 1.81; CI: 1.24-2.62, p = 0.001) and overall survival (HR: 1.49; CI: 1.0006-2.23, p = 0.049).

Conclusions: Low income appears to be a prognostic factor in IPF. IPF patients with low incomes may also be exposed more frequently to occupational exposures.
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http://dx.doi.org/10.1016/j.rmed.2021.106415DOI Listing
April 2021

Gender does not impact the short- or long-term outcomes of home-based pulmonary rehabilitation in patients with COPD.

ERJ Open Res 2020 Oct 26;6(4). Epub 2020 Oct 26.

CHU Lille, Service de Pneumologie et Immuno-Allergologie, Centre de Référence Constitutif des Maladies Pulmonaires Rares, Lille, France.

Pulmonary rehabilitation, whether performed at home or in a specialised centre, is effective in the management of COPD. As gender-related differences in COPD were previously reported, we aimed to evaluate the impact of gender on pulmonary rehabilitation outcomes in the short, medium and long term. In this retrospective observational study of 170 women and 310 men with COPD, we compared the outcomes of an 8-week home-based pulmonary rehabilitation programme including an individualised plan of retraining exercises, physical activities, therapeutic education, and psychosocial and self-management support. Exercise tolerance, anxiety, depression, and quality of life (QOL) were assessed using the 6-min stepper test (6MST), Hospital Anxiety and Depression Scale (HADS) and Visual Simplified Respiratory Questionnaire (VSRQ), respectively. Assessments were carried out before, immediately after the pulmonary rehabilitation programme (T2) and at 8 (T8) and 14 months (T14). At baseline, women were younger (mean 62.1 65.3 years), more often nonsmokers (24.7% 7.7%) and had a higher body mass index (28 26.4 kg·m). They more often lived alone (50.6% 24.5%) and experienced social deprivation (66.7% 56.4%). They had significantly lower exercise tolerance (-34 strokes, 6MST) and higher anxiety and depression (+3.2 HADS total score), but there were no between gender differences in QOL (VSRQ). Both groups showed similar improvements in all outcome measures at T2, T8 and T14 with a tendency for men to lose QOL profits over time. Despite some differences in baseline characteristics, women and men with COPD had similar short-, medium- and long-term benefits of a home-based pulmonary rehabilitation programme.
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http://dx.doi.org/10.1183/23120541.00032-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682653PMC
October 2020

Long-Term Effectiveness of a Home-Based Pulmonary Rehabilitation in Older People with Chronic Obstructive Pulmonary Disease: A Retrospective Study.

Int J Chron Obstruct Pulmon Dis 2020 15;15:2505-2514. Epub 2020 Oct 15.

FormAction Santé, Pérenchies, France.

Background: Long-term effectiveness of pulmonary rehabilitation (PR) is still uncertain in older people with severe chronic obstructive pulmonary disease (COPD). The objective was to compare the effects of home-based PR in people with COPD above and below the age of 70 years.

Methods: In this retrospective study, 480 people with COPD were recruited and divided into those ≤70 (n=341) and those >70 years of age (n=139). All participants underwent an 8 weeks of home-based PR, consisting of a weekly supervised 90-minute home session. Six-minute stepper test (6MST), timed-up and go test (TUG), Hospital Anxiety and Depression Scale, and Visual Simplified Respiratory Questionnaire (VSRQ) were assessed at baseline (M0), at 2 (M2), 8 (M8), 14 (M14) months after baseline.

Results: The older group was described by fewer current smokers (p <0.001), more long-term oxygen therapy use (p = 0.024), higher prevalence of comorbidities (p<0.001), lower 6MST score and higher TUG score (p<0.001), compared to the younger group. Both groups improved every outcome at M2 compared to baseline. At M2, 88% of people ≤70 years of age and 79% of those above 70 were considered as responders in at least one evaluated parameter (p = 0.013). Both groups maintained the benefits at M14, except for the VSRQ score and the number of responders to this outcome in the older group.

Conclusion: Regardless of the age, personalized home-based PR was effective for people with COPD in the short term. Above 70 years, an ageing effect appeared on the long-term effectiveness of quality of life benefit.
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http://dx.doi.org/10.2147/COPD.S268901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571583PMC
October 2020

Predictors of massive haemoptysis after a first episode of mild-to-moderate haemoptysis in patients with cystic fibrosis.

ERJ Open Res 2020 Jul 14;6(3). Epub 2020 Sep 14.

CHU Lille, Centre de Ressources et de Compétences de la Mucoviscidose, Service de Pneumologie et Immuno-allergologie, Hôpital Calmette, Lille, France.

https://bit.ly/30093Hw.
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http://dx.doi.org/10.1183/23120541.00382-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487340PMC
July 2020

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

Eur Respir J 2021 Feb 11;57(2). Epub 2021 Feb 11.

Dept of Rheumatology, Hôpital Avicenne, APHP, Bobigny, France.

Question Addressed By The Study: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD.

Methods: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.

Results: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001).

Answer To The Question: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.
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http://dx.doi.org/10.1183/13993003.00337-2020DOI Listing
February 2021

Impact of isolation on the respiratory function of adult patients with cystic fibrosis.

ERJ Open Res 2019 Oct 8;5(4). Epub 2019 Dec 8.

CHU Lille, Adult Cystic Fibrosis Center, Lille, France.

Background: The prevalence of lung isolation in cystic fibrosis (CF) patients has increased, but the impact on lung function is controversial. The aim of this study was to evaluate the long-term effects of isolation on respiratory function of adult patients with CF in the first 3 years after identification of isolation.

Methods: This was a case-control retrospective study performed at a single CF centre in Lille, France. Data for 36 patients with CF who had at least one sputum culture positive for () were evaluated and compared with control CF patients uninfected by (). Respiratory function and exacerbation frequency were evaluated between 1 year prior to and 3 years after isolation.

Results: Compared with the - group, the group had a lower forced expiratory volume in 1 s (FEV) at baseline (median (interquartile range): 55.2% (50.6-59.8%) 73.8% (67.2-80.4%); p=0.005), a greater decline in FEV (±se) in the first year after identification (-153.6±16.1 mL·year -63.8±18.5 mL·year; p=0.0003), and more exacerbations in the first 3 years after identification (9 (7-12) 7 (5-10); p=0.03). patients co-colonised with (n=27, 75%) had a greater FEV decline (p=0.003) and more exacerbations in the year after identification (p=0.037) compared with patients colonised with alone. Patients with chronic isolation (n=23, 64%) had more exacerbations than intermittently colonised patients in the 3 years after identification (p=0.012).

Conclusion: isolation is associated with a decline in respiratory function in patients with CF. Chronic isolation and co-isolation may be markers of more severe respiratory disease in + patients.
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http://dx.doi.org/10.1183/23120541.00051-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899338PMC
October 2019

Influence Of Socioeconomic Deprivation On Short- And Long-Term Outcomes Of Home-Based Pulmonary Rehabilitation In Patients With Chronic Obstructive Pulmonary Disease.

Int J Chron Obstruct Pulmon Dis 2019 31;14:2441-2449. Epub 2019 Oct 31.

CHU Lille, Service de Pneumologie et Immuno-Allergologie, Centre de Référence Constitutif des Maladies Pulmonaires Rares, Department of Heart and Lung Diseases, Lille F-59000, France.

Background: Pulmonary rehabilitation (PR) improves exercise tolerance and quality of life in patients with chronic obstructive pulmonary disease (COPD), regardless of disease severity. Socioeconomic deprivation has been linked to the incidence of COPD; however, little is known about its impact on PR outcomes.

Methods: In this retrospective observational study, 459 COPD patients were enrolled and dichotomized into socially deprived (n=276) and non-socially deprived (n=183) groups based on a cut-off of 30.17 in the EPICES questionnaire (Evaluation of Deprivation and Inequalities in Health Centers), which evaluates socioeconomic disadvantage. The PR program consisted of once-weekly home sessions for 8 weeks, and consisted of an individualized plan of retraining exercises, physical activities, therapeutic education, and psychosocial and motivational support. Exercise tolerance, anxiety and depression, and quality of life were assessed using the 6 min stepper test (6MST), Hospital Anxiety and Depression Scale (HADS), and Visual Simplified Respiratory Questionnaire (VSRQ). Assessments were made before the PR program (baseline) and then at 2 (T2), 8 (T8), and 14 (T14) months after baseline.

Results: Compared with the non-socially deprived group, socially deprived patients were younger, more frequently women, active smokers, and living alone, and belonged to lower socioprofessional categories. At baseline, 6MST, VSRQ, and HADS measures were lower for the socially deprived than the non-socially deprived group. At T2, T8, and T14, there were no significant between-group differences in any outcome, and the percentage of patients showing clinically important improvements was the same in both groups.

Conclusion: Home-based PR is effective for COPD patients in the short and long term, regardless of socioeconomic status.
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http://dx.doi.org/10.2147/COPD.S224348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827503PMC
April 2020

Long-term effect of home-based pulmonary rehabilitation in severe asthma.

Respir Med 2019 10 29;157:36-41. Epub 2019 Aug 29.

CHU Lille, Service de Pneumologie et Immuno-Allergologie, Centre de Référence Constitutif des Maladies Pulmonaires Rares, F-59000, Lille, France; Inserm, CNRS, Institut Pasteur de Lille, U1019, UMR 8204, CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France; Univ Lille, F-59000, Lille, France. Electronic address:

Introduction: Home-based pulmonary rehabilitation (PR) has demonstrated its effectiveness amongst patients with chronic obstructive pulmonary disease (COPD) but has never been investigated in severe asthma.

Methods: In a retrospective study, we included 28 patients with severe asthma (61.5 ± 16.2 years, FEV1: 51.4 ± 17.3%) and 164 matched COPD patients (64.3 ± 11.6 years, FEV1: 47.7 ± 15.5%) who had completed a home-based PR program and pursued at least 12 months of follow-up. The number of steps performed during a 6-min stepper test (6MST), the Hospital Anxiety and Depression (HAD) scores, and the Visual Simplified Respiratory Questionnaire score (VSRQ) were compared between baseline, the post-PR period (post-PR) and after 12 months of follow-up (M12) within each group. The evolution of the 6MST, HAD and VSRQ values between baseline, post-PR and M12 was compared between severe asthma and COPD patients.

Results: In the severe asthma group, the 6MST was higher post-PR (504 ± 150, p = 0.043) and at M12 (538 ± 163, p = 0.016) compared with baseline (450 ± 148). The VSRQ score was higher at M12 (39.0 ± 18.6, p = 0.049) but not post-PR (38.7 ± 15.8, p = 0.119) in comparison with baseline (32.2 ± 12.4). There was no difference in the HAD scores between baseline, post-PR and M12. PR outcome was not significantly different between severe asthma and COPD patients at short and long term (p > 0.05).

Conclusion: In severe asthma, home-based PR is associated with improved exercise tolerance and quality of life on a long-term basis but does not modify anxiety and depression.
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http://dx.doi.org/10.1016/j.rmed.2019.08.015DOI Listing
October 2019

Immediate Hypersensitivity to Contrast Agents: The French 5-year CIRTACI Study.

EClinicalMedicine 2018 Jul 28;1:51-61. Epub 2018 Jul 28.

Service de Pneumologie, Consultation d'Allergolo-Anesthésie, CHU Pontchaillou, Rue H. Le Guilloux, 35033 Rennes Cedex 09, France.

Background: Iodinated and gadolinium-based contrast media (ICM; GBCM) induce immediate hypersensitivity (IH) reactions. Differentiating allergic from non-allergic IH is crucial; allergy contraindicates the culprit agent for life. We studied frequency of allergic IH among ICM or GBCM reactors.

Methods: Patients were recruited in 31 hospitals between 2005 and 2009. Clinical symptoms, plasma histamine and tryptase concentrations and skin tests were recorded. Allergic IH was diagnosed by intradermal tests (IDT) with the culprit CM diluted 1:10, "potentially allergic" IH by positive IDT with pure CM, and non-allergic IH by negative IDT.

Findings: Among 245 skin-tested patients (ICM = 209; GBCM = 36), allergic IH to ICM was identified in 41 (19.6%) and to GBCM in 10 (27.8%). Skin cross-reactivity was observed in 11 patients with ICM (26.8%) and 5 with GBCM (50%). Allergy frequency increased with clinical severity and histamine and tryptase concentrations (p < 0.0001). Cardiovascular signs were strongly associated with allergy. Non-allergic IH was observed in 152 patients (62%) (ICM:134; GBCM:18). Severity grade was lower (p < 0.0001) and reaction delay longer (11.6 vs 5.6 min; p < 0.001). Potentially allergic IH was diagnosed in 42 patients (17.1%) (ICM:34; GBCM:8). The delay, severity grade, and mediator release were intermediate between the two other groups.

Interpretation: Allergic IH accounted for < 10% of cutaneous reactions, and > 50% of life-threatening ones. GBCM and ICM triggered comparable IH reactions in frequency and severity. Cross-reactivity was frequent, especially for GBCM. We propose considering skin testing with pure contrast agent, as it is more sensitive than the usual 1:10 dilution criteria.
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http://dx.doi.org/10.1016/j.eclinm.2018.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537532PMC
July 2018

Long-term evaluation of home-based pulmonary rehabilitation in patients with fibrotic idiopathic interstitial pneumonias.

ERJ Open Res 2019 Apr 8;5(2). Epub 2019 Apr 8.

FormAction Santé, Pérenchies, France.

Background: Few studies have examined the benefits of pulmonary rehabilitation in patients with fibrotic idiopathic pulmonary pneumonia (f-IIP). Here, we report the results of an observational study in routine clinical practice of home-based pulmonary rehabilitation for f-IIP patients.

Methods: A total of 112 consecutive patients (61 with idiopathic pulmonary fibrosis and 51 with fibrotic nonspecific interstitial pneumonitis) were enrolled, of whom 65 had mild-to-moderate disease (forced vital capacity (FVC) ≥50% predicted and diffusing capacity of the lung for carbon monoxide () ≥30% predicted) and 47 had severe disease (FVC <50% predicted and/or <30% predicted). The 2-month pulmonary rehabilitation programme consisted of a once-weekly visit with retraining, therapeutic education and psychosocial support. Patients were provided with an individualised action plan and were followed-up bimonthly for 12 months. Exercise tolerance (6-min stepper test (6MST)), mood (Hospital Anxiety and Depression Scale (HADS)) and quality of life (QoL) (Visual Simplified Respiratory Questionnaire (VSRQ)) were assessed before (T), immediately after (T), 6 months after (T) and 12 months after (T) the end of the pulmonary rehabilitation programme.

Results: 6MST strokes, HADS Anxiety score and VSRQ score were each significantly improved at T (n=101), T (n=76) and T (n=62) compared with T values. The improvements in outcomes were not influenced by disease severity or subtype. Patients who completed the study had significantly better baseline FVC and values than those who did not.

Conclusions: Home-based pulmonary rehabilitation provides long-term benefits in exercise tolerance, anxiety and QoL for patients with f-IIP. Pulmonary rehabilitation should be prescribed systematically as part of the therapeutic arsenal for these patients.
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http://dx.doi.org/10.1183/23120541.00045-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452059PMC
April 2019

Study protocol: exploring the efficacy of cyclophosphamide added to corticosteroids for treating acute exacerbation of idiopathic pulmonary fibrosis; a randomized double-blind, placebo-controlled, multi-center phase III trial (EXAFIP).

BMC Pulm Med 2019 Apr 11;19(1):75. Epub 2019 Apr 11.

Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Avicenne, Service de pneumologie, Site constitutif du centre de référence des maladies pulmonaires rares OrphaLung, EA2363, Université Paris, 13, Bobigny, France.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease, with a median survival of 2-3 years and variable natural history, characterized by gradual and progressive deterioration. Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication, associated with poor survival and a mortality > 50%. To date, no treatment has proven effective in AE-IPF, with cyclophosphamide (CYC) the only therapy suggested to be effective on survival, primarily based on retrospective series. Considering the high fatality rates of AE-IPF, evaluating the efficacy of immunosuppressive agents in a randomized controlled trial proves crucial, as the results could significantly impact treatment and prognosis of AE-IPF.

Methods: The EXAFIP study is a French national multicenter double-blind placebo-controlled randomized trial. Its primary objective is to evaluate the efficacy of CYC compared to placebo on early survival in patients treated with corticosteroids. We hypothesize that adding CYC to high-dose corticosteroids would reduce 3-month mortality in AE-IPF patients. The primary outcome is all-cause mortality rate at Month 3; secondary objectives are to evaluate the efficacy of CYC compared to placebo on overall survival at Months 6 and 12, respiratory disease-specific mortality, respiratory morbidity, and chest high-resolution computed tomography features, and to determine prognostic factors in AE-IPF and compare the safety of the two treatment arms during 6 months' follow-up.

Discussion: There is an urgent unmet clinical need for effective AE-IPF treatment. The EXAFIP study is the first large Phase III placebo-controlled randomized trial evaluating the efficacy and safety of CYC added to corticosteroids in treating AE-IPF. The results of this study could significantly impact treatment strategy and prognosis of AE-IPF.

Trial Registration: Clinical trials, NCT02460588 ; Date: June 2, 2015, prospectively; Issue date: 14/11/2017; Protocole Amendment Number: 03.
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http://dx.doi.org/10.1186/s12890-019-0830-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458697PMC
April 2019

The Long Noncoding RNA DNM3OS Is a Reservoir of FibromiRs with Major Functions in Lung Fibroblast Response to TGF-β and Pulmonary Fibrosis.

Am J Respir Crit Care Med 2019 07;200(2):184-198

2 EA 4483-IMPECS and.

Given the paucity of effective treatments for idiopathic pulmonary fibrosis (IPF), new insights into the deleterious mechanisms controlling lung fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. TGF-β (transforming growth factor-β) is the main profibrotic factor, but its inhibition is associated with severe side effects because of its pleiotropic role. To determine if downstream noncoding effectors of TGF-β in fibroblasts may represent new effective therapeutic targets whose modulation may be well tolerated. We investigated the whole noncoding fraction of TGF-β-stimulated lung fibroblast transcriptome to identify new genomic determinants of lung fibroblast differentiation into myofibroblasts. Differential expression of the long noncoding RNA (lncRNA) DNM3OS (dynamin 3 opposite strand) and its associated microRNAs (miRNAs) was validated in a murine model of pulmonary fibrosis and in IPF tissue samples. Distinct and complementary antisense oligonucleotide-based strategies aiming at interfering with DNM3OS were used to elucidate the role of DNM3OS and its associated miRNAs in IPF pathogenesis. We identified DNM3OS as a fibroblast-specific critical downstream effector of TGF-β-induced lung myofibroblast activation. Mechanistically, DNM3OS regulates this process in by giving rise to three distinct profibrotic mature miRNAs (i.e., miR-199a-5p/3p and miR-214-3p), which influence SMAD and non-SMAD components of TGF-β signaling in a multifaceted way. , we showed that interfering with DNM3OS function not only prevents lung fibrosis but also improves established pulmonary fibrosis. Pharmacological approaches aiming at interfering with the lncRNA DNM3OS may represent new effective therapeutic strategies in IPF.
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http://dx.doi.org/10.1164/rccm.201807-1237OCDOI Listing
July 2019

Daily life physical activity in patients with chronic stage IV sarcoidosis: A multicenter cohort study.

Health Sci Rep 2019 Feb 15;2(2):e109. Epub 2019 Jan 15.

Service de Pneumologie et ImmunoAllergologie, Centre de compétence des maladies rares and Univ. Lille CHU Lille Lille France.

Background And Objectives: Little is known about the consequences of chronic sarcoidosis on daily life physical activity (DL). The aim of this prospective study was to measure DL in patients with chronic sarcoidosis and to determine its relationship to clinical and functional parameters.

Methods: Fifty-three patients with chronic sarcoidosis and 28 healthy control subjects were enrolled in this multicenter prospective study. Two markers of DL (number of steps walked per day [SPD]) and total daily energy expenditure (TEE) were assessed for five consecutive days with a physical activity monitor. Pulmonary function, aerobic capacity (maximal oxygen uptake [VOmax]), exercise capacity (6-min walk test [6MWT]), and quality of life (self-reported questionnaires) were also evaluated. Comparisons of DL parameters between the two groups were performed using an analysis of covariance adjusted for age, sex, and body mass index (BMI). Relationships between DL parameters and patient characteristics were assessed in multivariable linear regression models.

Results: Patients with sarcoidosis walked significantly fewer SPD than did the control subjects (6395 ± 4119 and 11 817 ± 3600, respectively;  < 0.001 after adjustment for age, BMI, and sex). TEE was not significantly different between patients with sarcoidosis and healthy controls (median [interquartile range]: 2369 [2004-2827] and 2387 [2319-2876] kcal/day, respectively,  = 0.054 adjusted for age, BMI, and sex). SPD showed significant positive correlations with 6MWT distance (Pearson's correlation,  = 0.32, 95% confidence intervals [95%CI] = 0.06, 0.55;  = 0.019), VOmax ( = 0.44, 95%CI = 0.17, 0.65;  = 0.002), and Visual Simplified Respiratory Questionnaire score ( = 0.44, 95%CI = 0.19, 0.64;  = 0.001), and a significant negative correlation with modified Medical Research Council questionnaire score ( = -0.38, 95%CI = -0.60, -0.10;  = 0.009). TEE was significantly correlated with BMI ( = 0.38, 95%CI = 0.13, 0.59;  = 0.004), forced expiratory volume in 1 second ( = 0.55, 95%CI = 0.33, 0.71;  < 0.001), total lung capacity ( = 0.44, 95%CI = 0.18, 0.64;  = 0.001), and forced vital capacity ( = 0.56, 95%CI = 0.34, 0.72;  < 0.001). In multivariable analysis, SPD remained associated only with VOmax.

Conclusion: Patients with chronic sarcoidosis appear to have reduced DL mainly because of compromised VOmax.
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http://dx.doi.org/10.1002/hsr2.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375542PMC
February 2019

Factors associated with daily life physical activity in patients with asthma.

Health Sci Rep 2018 Oct 15;1(10):e84. Epub 2018 Aug 15.

Service de Pneumologie et ImmunoAllergologie, Centre de Référence constitutif des Maladies Pulmonaires Rares, Univ. Lille CHU Lille, Hopital Calmette Lille France.

Background And Objectives: Little is known about the consequences of asthma on daily life physical activity (DL). The aim of this study was to evaluate DL and determine its relationship to clinical and functional parameters in patients with asthma.

Methods: This was a single-center prospective study of DL conducted between May 2015 and June 2016 in northern France. Fifty-one adult patients with asthma and 36 healthy control subjects were enrolled. Four DL parameters were assessed for 5 consecutive days with a physical activity monitor: number of steps walked per day (SPD), total energy expenditure (EE, in kcal/day), EE spent in physical activity requiring ≥3 metabolic equivalents (METs), and time (min) spent in activities requiring ≥3 METs. Clinical characteristics, pulmonary function tests, 6-minute walk test, and four questionnaires (modified Medical Research Council [mMRC] for dyspnea, asthma control test [ACT], quality of life [AQLQ], and hospital anxiety and depression scale [HADS]), were evaluated. Comparisons of DL parameters between the two groups were performed using an analysis of covariance adjusted for age, sex, and body mass index (BMI). Relationships between DL parameters and patient characteristics were assessed in multivariable linear regression models.

Results: Compared with patients with mild/moderate asthma, those with severe asthma had lower mean (± standard deviation) forced expiratory volume in 1 s (FEV) (66 ± 24 vs 94 ± 15% predicted,  < 0.001), ACT score (16.7 ± 4.5 vs 19.8 ± 4.2,  = 0.015), and AQLQ score (157 ± 40 vs 184 ± 33,  = 0.012). There were no significant differences between the two groups in SPD (6560 ± 3915 vs 8546 ± 3431; adjusted  = 0.95), EE in physical activity requiring ≥3 METs (620 ± 360 vs 660 ± 140 kcal/day;  = 0.86), time spent in activities requiring EE ≥3 (120 ± 54 vs 121 ± 32 min/day;  = 0.69), or total EE (2606 ± 570 vs 2666 ± 551 kcal/day;  = 0.80). These four DL measures showed strong inter-parameter correlations in patients with asthma ( = 0.37-0.95, all  < 0.01). All four parameters were lower in the patients with asthma group than in the control group: SPD, 7651 ± 3755 vs 11704 ± 4054 (adjusted  < 0.001); EE in activities requiring ≥3 METs, 642 ± 360 vs 852 ± 374 kcal/day (adjusted  = 0.041); time spent in activities requiring ≥3 EE, 120 ± 73 vs 189 ± 85 min (adjusted  = 0.005); and total EE, 2639 ± 555 vs 2746 ± 449 kcal/day (adjusted  = 0.007). In the patients with asthma group, the number of SPD correlated with age, FEV, mMRC score, 6-minute walk test distance, and HADS scores, but not with BMI or ACT test score. Using multivariate analysis, the number of SPD was associated with only age, anxiety, and FEV, whereas total EE was associated with mMRC score and BMI.

Conclusion: Age, anxiety, and FEV were significantly associated with the number of SPD in patients with asthma. Addressing anxiety should be further studied as way to attempt to increase physical activity in patients with asthma.
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http://dx.doi.org/10.1002/hsr2.84DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266451PMC
October 2018

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.

N Engl J Med 2018 12 20;379(23):2209-2219. Epub 2018 Oct 20.

From Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bichat-Claude Bernard, Departments of Rheumatology (P.-A.J., E.E., S. Ottaviani, P.D.), Genetics (C.K., C. Boileau), Pulmonology A (R.B., B.C.), Pulmonology B (G.T.), and Radiology (M.-P.D.), Département Hospitalo-Universitaire Fibrose Inflammation Remodelage, INSERM Unité Mixte de Recherche (UMR) 1152, Université Paris Diderot (P.-A.J., C.K., R.B., G.T., B.C., P.D.), Arthritis Recherche et Développement (P.-A.J.), AP-HP, Hôpital Lariboisière, Service de Rhumatologie (A. Frazier, P.R.), INSERM, UMR 1132 (P.R.), AP-HP, Hôpital Cochin, Service de Rhumatologie A, and INSERM, Unité 1016, UMR 8104 (Y.A.), AP-HP, Hôpital Tenon, Service de Pneumologie (H.L.), AP-HP, Service de Pneumologie Pédiatrique et Centre de Référence des Maladies Respiratoires Rares, and INSERM UMR S933 (N.N., S.A., A.C.), and AP-HP, Département de Génétique, Hôpital Trousseau (S.A.), Paris, Centre Hospitalier Régional Universitaire (CHRU) de Lille, Service de Pneumologie et Immuno-Allergologie, Centre de Compétence des Maladies Pulmonaires Rares, Fédératif Hospitalo-Universitaire Immune-Mediated Inflammatory Diseases and Targeted Therapies (L.W.-S., B.W.), and Centre Hospitalier Universitaire (CHU) de Lille, Service de Rhumatologie (R.-M.F.), Lille, the Departments of Pulmonology (H.N., D.V.) and Rheumatology (N.S.-K., M.-C.B.), Hôpital Avicenne, AP-HP, INSERM UMR 1125 (N.S.-K., M.-C.B.), and Université Paris 13, Sorbonne Paris Cité (N.S.-K., M.-C.B.), Bobigny, the Department of Pulmonology, CHRU Tours, Tours (S.M.-A.), CHRU de Strasbourg, Service de Rhumatologie, Hôpital de Hautepierre, INSERM UMR S1109, and Laboratoire d'Immuno-Rhumatologie Moléculaire, Centre de Recherche en Histoire des Idées, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg (J. Sibilia), Service de Pneumologie (C.D.) and Service de Rhumatologie (C.R., T.S.), CHU de Bordeaux, and ImmunoConcEpT, Centre National de la Recherche Scientifique UMR 5164 (C.R., T.S.), Bordeaux, CHU Clermont-Ferrand, Service de Rhumatologie, Institut National de la Recherche Agronomique (INRA), UMR 1019, Unité de Nutrition Humaine, Centre de Recherche en Nutrition Humaine Auvergne, Clermont-Ferrand (M.S.), and Hospices Civils de Lyon, Hôpital Louis Pradel, Centre National de Référence des Maladies Pulmonaires Rares, and INRA, UMR 754, Université Claude Bernard Lyon 1, Lyon, (V.C.) - all in France; the Departments of Medicine (J.S.L., E.D., K.D., A.D.W., A. Fischer, M.I.S., M.H., D.A.S.) and Immunology and Microbiology (D.A.S.), University of Colorado School of Medicine, Aurora, and the Departments of Biomedical Research (T.F.) and Medicine (J.J. Solomon), National Jewish Health, Denver - both in Colorado; the Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba (H.F., S. Oka, N.T.), and the Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara (H.F., S. Oka, S.T.) - both in Japan; the Department of Epidemiology, Harvard T.H. Chan School of Public Health (S.G.), and the Department of Medicine, Brigham and Women's Hospital (T.D., I.O.R.), Boston, and the Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge (S.G.) - all in Massachusetts; the Interstitial Lung Disease and Rheumatology Unit (J.R.-S., M.I.G.-P., M.M., I.B.-R.) and the HLA Laboratory (R.F.-V., E.A.-O.), Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City; the 2nd Pulmonary Medicine Department (E.M., S.A.P.) and the Rheumatology and Clinical Immunology Unit, 4th Department of Internal Medicine (T.K., D.B.), University Hospital of Athens "Attikon," National and Kapodistrian University of Athens, Athens, and the Department of Respiratory Medicine and the Laboratory of Molecular and Cellular Pneumonology, Faculty of Medicine, University of Crete, Crete (K.A.) - both in Greece; St. Antonius ILD Center of Excellence, St. Antonius Ziekenhuis, Nieuwegein, the Netherlands (C.H.M.M., J.V., Y.A.M., J.C.G.); the Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China (Y.W.); the Divisions of Pulmonary and Critical Care Medicine (J.H.R.) and Rheumatology (E.L.M.), Mayo Clinic College of Medicine and Science, Rochester, MN; the Colton Center for Autoimmunity, New York University School of Medicine, New York (T.B.N.); the Department of Medicine, McGill University, Montreal (D.A.); the Department of Medicine, University of California, San Francisco, San Francisco (A.G., P.W.); and Data Tecnica International, Glen Echo, and the Laboratory of Neurogenetics, National Institute on Aging, Bethesda - both in Maryland (C. Blauwendraat, M.A.N.).

Background: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA.

Methods: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls.

Results: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone.

Conclusions: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).
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http://dx.doi.org/10.1056/NEJMoa1801562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371965PMC
December 2018

The 1-minute sit-to-stand test to detect exercise-induced oxygen desaturation in patients with interstitial lung disease.

Ther Adv Respir Dis 2018 Jan-Dec;12:1753466618793028

CHU Lille, Service de Pneumologie et Immuno-Allergologie, Centre de Compétence des Maladies Pulmonaires Rares, Lille F-59000, France.

Background: Although the 6-min walk test (6MWT) is the gold standard for assessing exercise-induced impairment of gas exchange, it cannot easily be performed in a clinical office environment. The aim of this study was to compare the 1-min sit-to-stand test (1STST) with the 6MWT for the ability to assess exercise-induced oxygen desaturation in patients with interstitial lung diseases (ILDs).

Methods: A total of 107 patients were enrolled and classified into three groups: sarcoidosis, fibrotic idiopathic interstitial pneumonia (f-IIP), and other forms of ILD. The 6MWT and 1STST were performed on the same day, and pulmonary function tests, pulse oxygen saturation (SpO), and dyspnea and fatigue (modified Borg scale) were assessed. SpO desaturation was evaluated by intraclass correlation coefficient (ICC), Bland-Altman analysis, and kappa (κ) coefficient in the whole population and the patient subgroups.

Results: The SpO nadir during the 1STST and 6MWT showed good consistency [mean ± standard deviation: 92.5% ± 5% and 90% ± 7%, respectively; ICC 0.77, 95% confidence interval (CI) 0.71-0.83] and correlated strongly ( r = 0.9, p < 0.0001). The frequency of patients with oxygen desaturation ⩾4% was also consistent for the two exercise tests ( κ = 0.68, 95% CI 0.54-0.82). The number of repetitions in the 1STST correlated with the 6MWT distance ( r = 0.5, p < 0.0001), but the dyspnea scores were higher during the 1STST than the 6MWT ( p < 0.0001). These findings did not differ for the three patient subgroups.

Conclusion: The 1STST can measure exercise-induced desaturation in ILD patients and could be used as an alternative test to the 6MWT in office practice.
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http://dx.doi.org/10.1177/1753466618793028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088463PMC
January 2019

Cardiorespiratory adaptation during 6-Minute Walk Test in fibrotic idiopathic interstitial pneumonia patients who did or did not respond to pulmonary rehabilitation.

Eur J Phys Rehabil Med 2019 Feb 14;55(1):103-112. Epub 2018 Jun 14.

Competence Center for Rare Pulmonary Diseases, Department of Immuno-Allergology and Respiratory Diseases, Lille University Hospital, University of Lille, Lille, France.

Background: Pulmonary rehabilitation (PR) improves performance in the 6-min walk test (6MWT) in a subset of patients with fibrotic idiopathic interstitial pneumonia (f-IIP); however, a large proportion of patients does not respond to PR.

Aim: To investigate the effects of a PR program on cardiorespiratory responses during a 6MWT and to identify the characteristics of patients who do not show improved performance after PR.

Design: An observational study.

Setting: Patients were recruited from the Competence Centre for Rare Pulmonary Diseases at Lille University Hospital, France and completed an 8-week home-based PR program.

Population: A total of 19 patients with f-IIP; 12 with idiopathic pulmonary fibrosis (IPF) and 7 with fibrotic non-specific interstitial pneumonia.

Methods: Patients underwent spirometry and completed a 6MWT before and after an 8-week PR program. Gas exchange, heart rate, and pulse O2 saturation were measured continuously during the 6MWT. Quality of life, dyspnea, and anxiety/depression were assessed using the Short-Form 36 (SF-36), the baseline/transition dyspnea index (BDI/TDI), and the Hospital Anxiety and Depression Scale (HADS) questionnaires.

Results: Patients who did and did not improve the distance walked in the 6MWT by at least 30 m after PR were classified as responders (N.=9) and non-responders (N.=10), respectively. O2 uptake, ventilation rate, and distance covered during the 6MWT were significantly improved only in the responder group (P<0.05). Changes in SF-36, BDI/TDI, and HADS scores did not differ significantly between responders and non-responders. The non-responder group contained significantly more patients with IPF (P<0.05) and experienced greater arterial oxygen desaturation during the 6MWT compared with the responder group.

Conclusions: Failure to improve performance in the 6MWT after PR was associated with a diagnosis of IPF, non-improvement in gas exchange, and greater arterial oxygen desaturation.

Clinical Rehabilitation Impact: Most f-IIP patients who did not respond to PR were diagnosed with IPF and displayed greater hypoxemia during exercise. Clinical practitioners should seek to determine why patients fail to improve exercise performance after PR and propose an alternative exercise regimen to these patients.
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http://dx.doi.org/10.23736/S1973-9087.18.05093-1DOI Listing
February 2019

The immediate effects of a single autogenic drainage session on ventilatory mechanics in adult subjects with cystic fibrosis.

PLoS One 2018 29;13(3):e0195154. Epub 2018 Mar 29.

CHU-Lille, Centre de Ressource et de Compétence pour la Mucoviscidose, Service de Pneumologie et Immuno-allergologie, Hôpital Calmette and Univ. Lille, Lille, France.

Introduction: The aim of this study was to gain insight into the physiological changes occurring in subjects with cystic fibrosis (CF) after autogenic drainage (AD). Changes in respiratory system resistance (Rrs), reactance (Xrs), and spirometry were analyzed in adult CF subjects after a single AD physiotherapy session.

Methods: This prospective observational study was conducted during the annual check-up of adult CF subjects in stable condition. Spirometry and Rrs and Xrs measurements using the forced oscillations technique at 5, 11, and 19 hertz (Hz) were performed before and 30 min after a 20-min AD session. Control CF subjects were tested at baseline and 50 min without AD. Results are expressed as mean ± standard deviation or median [interquartile range].

Results: Thirty subjects were included in the physiotherapy group (age 29 [25-34] years, forced expiratory volume in 1 s (FEV1) 40.3 [30.1-57.9]% predicted) and 11 in the control group (age 31 [28.5-36.5] years, FEV1 43.6 [31.1-51.9] % predicted). No significant changes in any parameter were observed in the control group. AD modestly but significantly increased the forced vital capacity (FVC) and FEV1 (p<0.001). Inspiratory resistance was also significantly improved by AD: Rrs5 from 5.74±2.39 to 5.24±2.17 cmH2O/L/s, p<0.05; Rrs11 from 4.83±1.98 to 4.32±1.7 cmH2O/L/s, p = 0.003; and Rrs19 from 4.18 [3.46-5.07] to 3.86 [2.76-4.98] cmH2O/L/s, p<0.001. In contrast, AD had no significant effects on frequency dependence of resistance (Rrs5-Rrs19) or expiratory resistance. Inspiratory Xrs5, but not ΔXrs5 (expiratory-inspiratory Xrs), was improved by AD (p<0.05). Moderate correlations were detected between the improvement in FEV1 and FVC and inspiratory resistance (r = 0.53, p = 0.005 and r = 0.44, p = 0.02, respectively).

Conclusion: A single session of AD improved inspiratory airway resistance, except in the distal airways. The forced oscillations technique provides a new tool for understanding the pathophysiological effects of airway clearance physiotherapy in CF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195154PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875810PMC
July 2018

Phenotypes of organ involvement in sarcoidosis.

Eur Respir J 2018 01 25;51(1). Epub 2018 Jan 25.

University College Dublin, Dublin, Ireland.

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.
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http://dx.doi.org/10.1183/13993003.00991-2017DOI Listing
January 2018

Real-life feasibility and effectiveness of home-based pulmonary rehabilitation in chronic obstructive pulmonary disease requiring medical equipment.

Int J Chron Obstruct Pulmon Dis 2017 12;12:3549-3556. Epub 2017 Dec 12.

FormAction Santé, Pérenchies, France.

Background: Pulmonary rehabilitation (PR) is a key treatment of chronic obstructive pulmonary disease (COPD) but studies are still needed to identify the most pertinent criteria to personalize this intervention and improve its efficacy.

Objective: This real-life retrospective study compared the effects of home-based PR on exercise tolerance, anxiety, depression, and health-related quality of life (HRQoL) in COPD patients, according to their medical equipment.

Methods: Exercise tolerance, anxiety, depression, and HRQoL were evaluated in 109 patients equipped with long-term oxygen therapy (LTOT), 84 patients with noninvasive ventilation (NIV), 25 patients with continuous positive airway pressure (CPAP), and 80 patients with no equipment (NE), before, just after, and 6 and 12 months after PR.

Results: At baseline, the body mass index in the CPAP and NIV groups was higher (<0.05) than in the other two groups, and the forced expiratory volume in 1 second was lower in the LTOT and NIV groups (<0.001). All parameters improved after PR in the four groups (<0.05), but for exercise tolerance, only the 6-minute stepper test showed maintained improvement after 6 and 12 months, whereas the 10 times sit-to-stand and timed up-and-go tests were only improved just after PR. At every time point, exercise tolerance was lower in the LTOT group (<0.05), with a similar trend in the NIV group.

Conclusion: Despite differences in the medical equipment to treat COPD, home-based PR showed comparable feasibility, safety, and efficacy in all equipment-based groups. Medical equipment should therefore not be a barrier to home-based PR.
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http://dx.doi.org/10.2147/COPD.S150827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732556PMC
September 2018

Allergies and Exercise-Induced Bronchoconstriction in a Youth Academy and Reserve Professional Soccer Team.

Clin J Sport Med 2017 Sep;27(5):450-456

*Department of Sport Sciences and Physical Education, University of Lille, EA7369, URePSSS Unité de Recherche Pluridisciplinaire Sport, Santé, Société, Lille, France;†LOSC Lille, Research Department, Lille, France; and‡CHU Lille, Service de Pneumologie et immuno-allergologie, Hôpital Calmette et Université de Lille 2, France.

Objectives: A high prevalence of respiratory allergies and exercise-induced bronchoconstriction (EIB) has been reported among endurance athletes. This study was designed to analyze the frequency of sensitization to respiratory allergens and EIB in young soccer players.

Design: Prospective cohort design.

Setting: Youth academy and reserve professional soccer team during the seasons 2012 to 2013 and 2013 to 2014.

Participants: Eighty-five soccer players (mean age: 20 ± 4 years) participated.

Intervention: Players underwent skin prick tests (SPTs) during the seasons 2012 to 2013 and 2013 to 2014. Spirometry and a eucapnic voluntary hyperpnea test were performed on soccer players during the first season 2012 to 2013 (n = 51) to detect EIB. Two self-administered questionnaires on respiratory history and allergic symptoms (European Community Respiratory Health Survey and Allergy Questionnaire for Athletes) were also distributed during both seasons (n = 59).

Main Outcome Measures: The number of positive SPTs, exercise-induced respiratory symptoms, presence of asthma, airway obstruction, and EIB.

Results: Forty-nine percent of players were sensitized to at least one respiratory allergen, 33% reported an allergic disease, 1 player presented airway obstruction at rest, and 16% presented EIB. Factors predictive of EIB were self-reported exercise-induced symptoms and sensitization to at least 5 allergens.

Conclusions: Questioning players about exercise-induced respiratory symptoms and allergies as well as spirometry at the time of the inclusion medical checkup would improve management of respiratory health of soccer players and would constitute inexpensive preliminary screening to select players requiring indirect bronchial provocation test or SPTs.

Clinical Relevance: This study showed that despite low frequencies, EIB and allergies are underdiagnosed and undertreated in young soccer players.
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http://dx.doi.org/10.1097/JSM.0000000000000393DOI Listing
September 2017

Role of atmospheric pollution on the natural history of idiopathic pulmonary fibrosis.

Thorax 2018 02 10;73(2):145-150. Epub 2017 Aug 10.

EPAR, Université Pierre et Marie, Paris, France.

Introduction: Idiopathic pulmonary fibrosis (IPF) has an unpredictable course corresponding to various profiles: stability, physiological disease progression and rapid decline. A minority of patients experience acute exacerbations (AEs). A recent study suggested that ozone and nitrogen dioxide might contribute to the occurrence of AE. We hypothesised that outdoor air pollution might influence the natural history of IPF.

Methods: Patients were selected from the French cohort COhorte FIbrose (COFI), a national multicentre longitudinal prospective cohort of IPF (n=192). Air pollutant levels were assigned to each patient from the air quality monitoring station closest to the patient's geocoded residence. Cox proportional hazards model was used to evaluate the impact of air pollution on AE, disease progression and death.

Results: Onset of AEs was significantly associated with an increased mean level of ozone in the six preceding weeks, with an HR of 1.47 (95% CI 1.13 to 1.92) per 10 µg/m (p=0.005). Cumulative levels of exposure to particulate matter PM and PM were above WHO recommendations in 34% and 100% of patients, respectively. Mortality was significantly associated with increased levels of exposure to PM (HR=2.01, 95% CI 1.07 to 3.77) per 10 µg/m (p=0.03), and PM (HR=7.93, 95% CI 2.93 to 21.33) per 10 µg/m (p<0.001).

Conclusion: This study suggests that air pollution has a negative impact on IPF outcomes, corroborating the role of ozone on AEs and establishing, for the first time, the potential role of long-term exposure to PM and PM on overall mortality.
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http://dx.doi.org/10.1136/thoraxjnl-2017-209967DOI Listing
February 2018

Fungal and Bacterial Diversity of Airway Microbiota in Adults with Cystic Fibrosis: Concordance Between Conventional Methods and Ultra-Deep Sequencing, and Their Practical use in the Clinical Laboratory.

Mycopathologia 2018 Feb 1;183(1):171-183. Epub 2017 Aug 1.

Service de Pneumologie, CHRU de Lille, Lille, France.

Given the complexity of the airway microbiota in the respiratory tract of cystic fibrosis (CF) patients, it seems crucial to compile the most exhaustive and exact list of the microbial communities inhabiting CF airways. The aim of the present study was to compare the bacterial and fungal diversity of sputa from adult CF patients during non-exacerbation period by culture-based and molecular methods, and ultra-deep-sequencing (UDS). Sputum samples from four CF patients were cultured and analysed by DNA extractions followed by terminal restriction fragment length polymorphism analysis through resolution of bacterial ribosomal gene (rDNA) fragments, and cloning plus sequencing of part of fungal rRNA genes. These approaches were compared with UDS method targeting 16S rDNA gene and the internal transcribed spacer (ITS) 2 region of rDNA. A total of 27 bacterial and 18 fungal genera were detected from the four patients. Five (18%) and 3 (16%) genera were detected by culture for bacteria and fungi, respectively, 9 (33%) and 3 (16%) by first generation sequencing (FGS) methods, and 26 (96%) and 18 (100%) by UDS. The mean number of genera detected by UDS per patient was statistically higher than by culture or FGS methods. Patients with severe airway disease as assessed by standard spirometry exhibited a reduced fungal and bacterial diversity. UDS approach evaluates more extensively the diversity of fungal and bacterial flora compared with cultures. However, it currently remains difficult to routinely use UDS mainly because of the lack of standardization, and the current cost of this method.
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http://dx.doi.org/10.1007/s11046-017-0185-xDOI Listing
February 2018

Toward the Standardization of Mycological Examination of Sputum Samples in Cystic Fibrosis: Results from a French Multicenter Prospective Study.

Mycopathologia 2018 Feb 26;183(1):101-117. Epub 2017 Jul 26.

CRCM adulte, Centre Hospitalier Universitaire de Lille, Université de Lille 2, Lille, France.

Fungal respiratory colonization of cystic fibrosis (CF) patients emerges as a new concern; however, the heterogeneity of mycological protocols limits investigations. We first aimed at setting up an efficient standardized protocol for mycological analysis of CF sputa that was assessed during a prospective, multicenter study: "MucoFong" program (PHRC-06/1902). Sputa from 243 CF patients from seven centers in France were collected over a 15-month period and submitted to a standardized protocol based on 6 semi-selective media. After mucolytic pretreatment, sputa were plated in parallel on cycloheximide-enriched (ACT37), erythritol-enriched (ERY37), benomyl dichloran-rose bengal (BENO37) and chromogenic (CAN37) media incubated at 37 °C and on Sabouraud-chloramphenicol (SAB27) and erythritol-enriched (ERY27) media incubated at 20-27 °C. Each plate was checked twice a week during 3 weeks. Fungi were conventionally identified; time for detection of fungal growth was noted for each species. Fungal prevalences and media performances were assessed; an optimal combination of media was determined using the Chi-squared automatic interaction detector method. At least one fungal species was isolated from 81% of sputa. Candida albicans was the most prevalent species (58.8%), followed by Aspergillus fumigatus (35.4%). Cultivation on CAN37, SAB27, ACT37 and ERY27 during 16 days provided an optimal combination, detecting C. albicans, A. fumigatus, Scedosporium apiospermum complex and Exophiala spp. with sensitivities of 96.5, 98.8, 100 and 100%. Combination of these four culture media is recommended to ensure the growth of key fungal pathogens in CF respiratory specimens. The use of such consensual protocol is of major interest for merging results from future epidemiological studies.
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http://dx.doi.org/10.1007/s11046-017-0173-1DOI Listing
February 2018

Relationships between heart rate target determined in different exercise testing in COPD patients to prescribed with individualized exercise training.

Int J Chron Obstruct Pulmon Dis 2017 16;12:1483-1489. Epub 2017 May 16.

Centre Hospitalier Béthune, Service de Pneumologie et d'Allergologie, Rue Delbecque, Beuvry.

Background: It has been scientifically proven that pulmonary rehabilitation improves exercise tolerance and facilitates the carrying out of daily physical activities. To optimize the physical and physiological benefits, it is necessary to individualize the training intensity for each patient. The aim of this study is to compare the heart rate (HR) responses to three exercise modalities measuring aerobic fitness in chronic obstructive pulmonary disease patients, in order to easily prescribe individual target HRs for endurance training.

Patients And Method: Fifty COPD patients (mean age: 60.1±8.5 years) were included in the study. Each patient carried out a cardiopulmonary exercise test, a 6-minute walk test (6MWT) and a 6-minute stepper test (6MST). During these tests, HR was recorded continuously. After the cardiopulmonary exercise test, the HR was noted at the ventilatory threshold (VT) and at the end of the two exercise field tests (6MWT and 6MST). The values of the HR during the last 3 minutes of both field tests were averaged (6MWT and 6MST). Finally, the HR at 60% of the HR reserve was calculated with the values of the HR measured during 6MWT and 6MST (HRr, HRr).

Results: The HRs measured during the 6MST were significantly higher than those measured during the 6MWT. The HRr was not significantly different from 6MWT and 6MWT HR (=0.51; =0.48). A significant correlation was observed between 6MWT and 6MWT (=0.58). The 6MWT and 6MWT HR were correlated with HRr (=0.68 and =0.62). The VT could be determined in 28 patients. The HR was not different from 6MWT, 6MWT, and HRr (=0.57, =0.41 and =0.88) and was correlated to 6MWT, 6MWT, and HRr (=0.45, =0.40, =0.48).

Conclusion: An individualized target HR for endurance training can be prescribed from the HR measured during routine tests, such as 6MWT or 6MST.
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http://dx.doi.org/10.2147/COPD.S129889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5439969PMC
March 2018

Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis.

Eur Respir J 2017 05 11;49(5). Epub 2017 May 11.

APHP, Hôpital Bichat, Service de Rhumatologie, DHU FIRE, Paris, France.

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the , , or coding regions The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of , , or mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10). Telomeres were shorter in RA-ILD patients with a , or mutation than in controls (p=2.87×10).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.
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http://dx.doi.org/10.1183/13993003.02314-2016DOI Listing
May 2017

Specific Polysaccharide Antibody Deficiency Revealed by Severe Bacterial Infections in Adulthood: A Report on 11 Cases.

Clin Infect Dis 2017 Jul;65(2):328-331

CHU Lille, Institut d'Immunologie.

We report on 11 cases of specific polysaccharide antibody deficiency (SPAD) revealed in adulthood by severe infections with encapsulated bacteria. Given that immunoglobulin replacement therapy can effectively prevent the recurrence of bacterial infections in this context, SPAD should be considered once other antibody deficiencies have been ruled out.
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http://dx.doi.org/10.1093/cid/cix284DOI Listing
July 2017

Efficacy of Whole-Lung Lavage in Pulmonary Alveolar Proteinosis: A Multicenter International Study of GELF.

Respiration 2017 21;93(3):198-206. Epub 2017 Jan 21.

Department of Pulmonology, University Hospital of Saint-Étienne, France.

Background: New therapies have emerged in the treatment of pulmonary alveolar proteinosis (PAP) and, therefore, there is a real need to evaluate the efficacy of whole-lung lavage (WLL) in this rare disease.

Objectives: The aim of this study was to assess the efficacy of WLL in patients with PAP.

Methods: We included 33 patients from 12 centers, which are members of the French-Speaking Thoracic Endoscopy Group, for analysis. Data collection concerned patients and disease characteristics, pulmonary function tests (PFTs) and technical information on the procedure.

Results: The median age of the patients was 44 years (range 13-77). There were 23 (71.9%) patients with respiratory insufficiency at presentation. All patients underwent WLL by general anesthesia and selective lung ventilation, except 1 who underwent awake flexible bronchoscopy. We noted differences in the technique, as 12 (36.36%) patients had percussion during the procedure and only 4 (12.1%) patients underwent 2-lung lavage during 1 anesthesia. A median of 12 L was used to perform WLL (1.0-40 L). Complications occurred in 11 (33.3%) patients, and 18 (56.25%) of them relapsed in a median period of 16.9 months. No significant changes were found in any PFT parameters studied, except for PaO2, which was significantly improved by 6.375 mm Hg (p = 0.0213) after the procedure compared to before.

Conclusions: Although the application of the WLL technique was variable, overall, it significantly improved patients' short-term respiratory condition by improving PaO2. However, a long-term effect needs to be confirmed, as many of our patients relapsed.
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http://dx.doi.org/10.1159/000455179DOI Listing
September 2017