Impact of Cardiovascular and Metabolic Comorbidities on Long-term Outcomes of Home-based Pulmonary Rehabilitation in COPD.

Background: Cardiovascular and metabolic comorbidities in chronic obstructive pulmonary disease (COPD) are associated with higher symptoms burden. Few center-based studies have evaluated the impact of these comorbidities on short-term pulmonary rehabilitation outcomes with contrasting results. Research Question: This study aimed to determine whether cardiovascular diseases and metabolic comorbidities impacted long-term outcomes of a home-based PR program in COPD patients. Study Design and methods: Data of 419 consecutive COPD patients addressed to our pulmonary rehabilitation program between January 2010 and June 2016 were retrospectively analyzed. Our program consisted of once-weekly supervised home sessions, including therapeutic education and self-management support, with unsupervised retraining exercises and physical activities the other days for 8 weeks. Exercise capacity (6-min stepper test [6MST]), quality of life (visual simplified respiratory questionnaire), and anxiety and depression (hospital anxiety and depression scale) were assessed respectively, before (M0) and at the end (M2) of the pulmonary rehabilitation program, and at 6 (M8) and 12 months (M14) after its achievement. Results: Patients (mean age 64.1±11.2 years, 67% males, mean forced expiratory volume in one second (FEV1) 39.2±17.0% predicted) were classified as having cardiovascular comorbidities (n=195), only metabolic disorders (n=122) or none of these comorbidities (n=102). After adjustment, all outcomes appeared similar between groups at baseline and improved after pulmonary rehabilitation with a greater effect at M14 for patients with only metabolic disorders on anxiety and depression score (-5.0±0.7 vs -2.9±0.8 and -2.6±0.6, p=0.021). Quality of life and exercise capacity improvements were not significantly different between the three groups at M2 and M14. Conclusion: Cardiovascular and metabolic comorbidities do not preclude COPD patients from obtaining clinically meaningful improvements in exercise capacity, quality of life and anxiety-depression up to 1 year after a home-based pulmonary rehabilitation.

Gender Differences in Idiopathic Pulmonary Fibrosis: Are Men and Women Equal?

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF cohort (COhorte FIbrose, COFI) with a 5-year follow-up. Methods: Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a t-test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed. Results: Fifty-one (22%) females and 185 (78%) males with an average age at diagnosis of 70.1 ± 9.20 and 67.4 ± 10.9 years, respectively, were included in the cohort. Women were significantly less exposed to tobacco smoke [never n = 32 (62.7%) vs. n = 39 (21.1%), p < 0.001] and to occupational exposure [n = 7 (13.7%) vs. n = 63 (34.1%), p = 0.012]. Baseline forced vital capacity, % of predicted (FVC%) was significantly better in women compare to men (83.0% ± 25.0 v. 75.4% ± 18.7 p = 0.046). At presentation honeycombing and emphysema on CT scan were less common in women [n = 40 (78.4%) vs. n = 167 (90.3%) p = 0.041] and [n = 6 (11.8%) vs. n = 48 (25.9%) p = 0.029], respectively. During follow-up fewer women were transplanted compared to men [n = 1 (1.96%) vs. n = 20 (10.8%) p = 0.039]. Medians of survival were comparable by gender [31 months (CI 95%: 28-40) vs. 40 months (CI 95%: 33-72) p = 0.2]. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival. Conclusions: Women appear to have less advanced disease at diagnosis, maybe due to less exposure history compare to men. Disease progression and overall survival remains comparable regardless gender, but women have less access to lung transplantation.

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

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 PM2.5 (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; CI95%: 1.24-2.62, p = 0.001) and overall survival (HR: 1.49; CI95%: 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.

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

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.

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

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 versus 65.3 years), more often nonsmokers (24.7% versus 7.7%) and had a higher body mass index (28 versus 26.4 kg·m-2). They more often lived alone (50.6% versus 24.5%) and experienced social deprivation (66.7% versus 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.

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

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.

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

Mild-to-moderate haemoptysis (m-mH) is common in patients with cystic fibrosis but the risk of subsequent massive haemoptysis (MH) is not known. Allergic bronchopulmonary aspergillosis and diabetes were significant predictors of MH subsequent to m-mH. https://bit.ly/30093Hw.

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

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.

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

BACKGROUND: The prevalence of Achromobacter xylosoxidans 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 A. xylosoxidans isolation on respiratory function of adult patients with CF in the first 3 years after identification of A. xylosoxidans 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 A. xylosoxidans (Ax+) were evaluated and compared with control CF patients uninfected by A. xylosoxidans (Ax-). Respiratory function and exacerbation frequency were evaluated between 1 year prior to and 3 years after A. xylosoxidans isolation. RESULTS: Compared with the Ax- group, the Ax+ group had a lower forced expiratory volume in 1 s (FEV1) at baseline (median (interquartile range): 55.2% (50.6-59.8%) versus 73.8% (67.2-80.4%); p=0.005), a greater decline in FEV1 (±se) in the first year after A. xylosoxidans identification (-153.6±16.1 mL·year-1 versus -63.8±18.5 mL·year-1; p=0.0003), and more exacerbations in the first 3 years after A. xylosoxidans identification (9 (7-12) versus 7 (5-10); p=0.03). Ax+ patients co-colonised with Pseudomonas aeruginosa (n=27, 75%) had a greater FEV1 decline (p=0.003) and more exacerbations in the year after A. xylosoxidans identification (p=0.037) compared with patients colonised with A. xylosoxidans alone. Patients with chronic A. xylosoxidans isolation (n=23, 64%) had more exacerbations than intermittently colonised patients in the 3 years after A. xylosoxidans identification (p=0.012). CONCLUSION: A. xylosoxidans isolation is associated with a decline in respiratory function in patients with CF. Chronic A. xylosoxidans isolation and P. aeruginosa co-isolation may be markers of more severe respiratory disease in Ax+ patients.

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

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 ±â€¯16.2 years, FEV1: 51.4 ±â€¯17.3%) and 164 matched COPD patients (64.3 ±â€¯11.6 years, FEV1: 47.7 ±â€¯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 ±â€¯150, p = 0.043) and at M12 (538 ±â€¯163, p = 0.016) compared with baseline (450 ±â€¯148). The VSRQ score was higher at M12 (39.0 ±â€¯18.6, p = 0.049) but not post-PR (38.7 ±â€¯15.8, p = 0.119) in comparison with baseline (32.2 ±â€¯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.

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).

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.

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

Rationale: 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-ß (transforming growth factor-ß) is the main profibrotic factor, but its inhibition is associated with severe side effects because of its pleiotropic role. Objectives: To determine if downstream noncoding effectors of TGF-ß in fibroblasts may represent new effective therapeutic targets whose modulation may be well tolerated. Methods: We investigated the whole noncoding fraction of TGF-ß-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. Measurements and Main Results: We identified DNM3OS as a fibroblast-specific critical downstream effector of TGF-ß-induced lung myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans 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-ß signaling in a multifaceted way. In vivo, we showed that interfering with DNM3OS function not only prevents lung fibrosis but also improves established pulmonary fibrosis. Conclusions: Pharmacological approaches aiming at interfering with the lncRNA DNM3OS may represent new effective therapeutic strategies in IPF.

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

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 (D LCO) ≥30% predicted) and 47 had severe disease (FVC <50% predicted and/or D LCO <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 (T0), immediately after (T2), 6 months after (T8) and 12 months after (T14) the end of the pulmonary rehabilitation programme. RESULTS: 6MST strokes, HADS Anxiety score and VSRQ score were each significantly improved at T2 (n=101), T8 (n=76) and T14 (n=62) compared with T0 values. The improvements in outcomes were not influenced by disease severity or subtype. Patients who completed the study had significantly better baseline FVC and D LCO 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.

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

BACKGROUND AND OBJECTIVES: Little is known about the consequences of chronic sarcoidosis on daily life physical activity (DLPA). The aim of this prospective study was to measure DLPA 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 DLPA (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 [VO2max]), exercise capacity (6-min walk test [6MWT]), and quality of life (self-reported questionnaires) were also evaluated. Comparisons of DLPA parameters between the two groups were performed using an analysis of covariance adjusted for age, sex, and body mass index (BMI). Relationships between DLPA 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; P < 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, P = 0.054 adjusted for age, BMI, and sex). SPD showed significant positive correlations with 6MWT distance (Pearson's correlation, r = 0.32, 95% confidence intervals [95%CI] = 0.06, 0.55; P = 0.019), VO2max (r = 0.44, 95%CI = 0.17, 0.65; P = 0.002), and Visual Simplified Respiratory Questionnaire score (r = 0.44, 95%CI = 0.19, 0.64; P = 0.001), and a significant negative correlation with modified Medical Research Council questionnaire score (r = -0.38, 95%CI = -0.60, -0.10; P = 0.009). TEE was significantly correlated with BMI (r = 0.38, 95%CI = 0.13, 0.59; P = 0.004), forced expiratory volume in 1 second (r = 0.55, 95%CI = 0.33, 0.71; P < 0.001), total lung capacity (r = 0.44, 95%CI = 0.18, 0.64; P = 0.001), and forced vital capacity (r = 0.56, 95%CI = 0.34, 0.72; P < 0.001). In multivariable analysis, SPD remained associated only with VO2max. CONCLUSION: Patients with chronic sarcoidosis appear to have reduced DLPA mainly because of compromised VO2max.

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

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.

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.

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=9.7×10-17). 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=4.7×10-35) 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=1.3×10-49). 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=7.4×10-5), 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=2.5×10-6). 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.).

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

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 (SpO2), and dyspnea and fatigue (modified Borg scale) were assessed. SpO2 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 SpO2 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.

Effects of pulmonary rehabilitation on daily life physical activity of fibrotic idiopathic interstitial pneumonia patients.

Fibrotic idiopathic interstitial pneumonia patients derived benefit from a pulmonary rehabilitation programme in terms of exercise tolerance, anxiety, depression and quality of life without increasing their daily life physical activity http://ow.ly/WV7U30kgNkU.

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

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.