High risk of lung cancer in surfactant-related gene variant carriers.

BACKGROUND: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers. METHODS: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers. RESULTS: We identified 99 SRG adult variant carriers (SFTPA1 (n=18), SFTPA2 (n=31), SFTPC (n=24), ABCA3 (n=14) and NKX2-1 (n=12)), including 20 (20.2%) with lung cancer (SFTPA1 (n=7), SFTPA2 (n=8), SFTPC (n=3), NKX2-1 (n=2) and ABCA3 (n=0)). Among SRG variant carriers, the odds of lung cancer was associated with age (OR 1.04, 95% CI 1.01-1.08), smoking (OR 20.7, 95% CI 6.60-76.2) and SFTPA1/SFTPA2 variants (OR 3.97, 95% CI 1.39-13.2). Adenocarcinoma was the only histological type reported, with programmed death ligand-1 expression ≥1% in tumour cells in three samples. Cancer staging was localised (I/II) in eight (40%) individuals, locally advanced (III) in two (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and three received the best supportive care according to their stage and performance status. The median overall survival was 24 months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 (95% CI 7.1-44.7). CONCLUSIONS: The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular computed tomography scan follow-up should be evaluated.

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

BACKGROUND: Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. STUDY DESIGN AND METHODS: A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. RESULTS: Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). CONCLUSIONS: Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

Changes in the physical and affective dimensions of dyspnoea after a home-based pulmonary rehabilitation in fibrotic idiopathic interstitial pneumonias.

Background: Our objective was to evaluate the short-, medium- and long-term benefits of home-based pulmonary rehabilitation (PR) on the physical and affective components of dyspnoea in people with fibrotic idiopathic interstitial pneumonias (f-IIPs). Anxiety and depressive symptoms, fatigue, health-related quality of life and exercise tolerance were also assessed. Methods: Data on 166 individuals with f-IIPs who enrolled in an 8-week home-based PR programme (weekly supervised 90-min session) were retrospectively analysed. Assessments included the Dyspnoea-12 (D-12) questionnaire, Hospital Anxiety and Depression Scale, Fatigue Assessment Scale, Visual Simplified Respiratory Questionnaire and 6-min stepper test, and were performed at home at short, medium (6 months) and long (12 months) term. Results: Among the 166 individuals with f-IIPs who enrolled in PR, 75 (45%) and 91 (55%) participants had a diagnosis of idiopathic pulmonary fibrosis and fibrosing non-specific interstitial pneumonia, respectively, and 87 (52%) participants concluded a full year of follow-up. In the total group, both physical and affective components of dyspnoea were improved, at short, medium and long term, after PR. Overall, half of the participants reached the minimally important difference of 3 points of the D-12 questionnaire at the end of PR, and at the 6- and 12-month follow-ups. Anxiety and depressive symptoms, fatigue and health-related quality of life were also improved, while the short-term benefits in exercise tolerance were not maintained 1 year after PR. Conclusion: An individualised home-based PR programme resulted in short-, medium- and long-term improvements in both physical and affective components of dyspnoea assessed by the D-12 questionnaire.

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults.

BACKGROUND AND OBJECTIVE: Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults. METHODS: We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed. RESULTS: We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52-72]) and DLco was 44% ([35-50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground-glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DLCO declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DLCO , p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow-up in the ABCA3 group. CONCLUSION: SFTPC and ABCA3-associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground-glass opacities and/or cysts is frequently found in these rare conditions.

Frequency and characteristics of refractory dyspnea in idiopathic fibrosing interstitial pneumonia.

Patients with idiopathic fibrosing interstitial pneumonias (f-IIPs) mainly suffer from dyspnea. Refractory dyspnea, defined as persistent dyspnea despite optimal treatment, could be the signal to prescribe dyspnea relievers. We aimed to examine the prevalence and characteristics of refractory dyspnea in consecutive patients with f-IIPs. Refractory dyspnea was defined by an mMRC≥3 and also by a VAS dyspnea score≥2 at rest. The sensory and affective characteristics of refractory dyspnea (mMRC≥3) and associated quality of life (QoL) anxiety and depression were compared with non-refractory dyspnea (mMRC1-2) using the Multidimensional Dyspnea Profile (MDP), King's Brief Interstitial Lung Disease (KBILD) and Hospital Anxiety and Depression scale (HADs). We included 40 patients (24 men), aged 72 [68-79], FVC of 71 % [59-86] and DLCO 47 % [40-49]. Refractory dyspnea, was found in 38 % (95%CI:23-54) when defined by mMRC≥3 and in 67 % (95%CI:50-81) using a resting VAS dyspnea score ≥2. The agreement between the two definitions was low. Patients with refractory dyspnea (mMRC≥3) were more often women (60 % vs.28 %, p = 0.046), had a lower DLCO (24 % [22-43] vs.47 % [43-51], p = 0.014) and more frequently used oxygen (60 % vs.12 %, p = 0.003); they experience more intense air hunger (5/10 [3-6] vs.2/10 [0-5], p = 0.018)). No significant differences were observed in VAS, MDP, KBILD, or HADs scores between refractory and non-refractory dyspnea patients. Our results indicate a significant frequency of refractory dyspnea in patients with f-IIPs and an association with air hunger but no impact on the affective dimension of dyspnea, anxiety, depression and QoL, suggesting that the mMRC score might not accurately identify patients distressed by their breathlessness.

Increased mortality in patients with RA-associated interstitial lung disease: data from a French administrative healthcare database.

OBJECTIVES: Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). The objectives of this study were to estimate mortality rate in patients with RA-ILD and identify factors affecting mortality. METHODS: Data from a French national claims database (Système National des Données de Santé) from 2013 to 2018 were analysed. Adults with an RA diagnosis (International Classification of Diseases (ICD)-10 codes M05, M06.0, M06.8 and M06.9) were included. ILD diagnosis was defined with ICD-10 code J84. Mortality rates were compared between patients with RA with and without ILD, using Cox proportional hazards regression, after matching 1:1 for age, sex, age at RA-ILD onset and RA duration. RESULTS: Among 173 132 patients with RA, 4330 (3%) also had ILD (RA-ILD). After matching, RA-ILD was associated with an increased mortality rate (HR 3.4, 95% CI 3.1 to 3.9). The HR for mortality was greater for: patients aged <75 years (HR 4.8, 95% CI 3.9 to 5.9) versus ≥75 years (HR 3.0, 95% CI 2.6 to 3.5); patients with ILD onset occurring before RA onset (HR 8.4, 95% CI 5.5 to 13.0) versus ILD onset occurring after RA onset (HR 2.9, 95% CI 2.6 to 3.3); and men (HR 5.2, 95% CI 4.4 to 6.2) versus women (HR 3.6, 95% CI 3.0 to 4.2). CONCLUSION: In this nationwide cohort study, RA-ILD was associated with increased mortality rate (vs in patients with RA without ILD), notably for those aged <75 years, those whose ILD preceded RA onset and men.

Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.

BACKGROUND AND AIM: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. APPROACH AND RESULTS: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001). CONCLUSIONS: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.

French recommendations for the diagnosis and management of lymphangioleiomyomatosis.

BACKGROUND: The present article is an English-language version of the French National Diagnostic and Care Protocol, a pragmatic tool to optimize and harmonize the diagnosis, care pathway, management and follow-up of lymphangioleiomyomatosis in France. METHODS: Practical recommendations were developed in accordance with the method for developing a National Diagnosis and Care Protocol for rare diseases of the Haute Autorité de Santé and following international guidelines and literature on lymphangioleiomyomatosis. It was developed by a multidisciplinary group, with the help of patient representatives and of RespiFIL, the rare disease network on respiratory diseases. RESULTS: Lymphangioleiomyomatosis is a rare lung disease characterised by a proliferation of smooth muscle cells that leads to the formation of multiple lung cysts. It occurs sporadically or as part of a genetic disease called tuberous sclerosis complex (TSC). The document addresses multiple aspects of the disease, to guide the clinicians regarding when to suspect a diagnosis of lymphangioleiomyomatosis, what to do in case of recurrent pneumothorax or angiomyolipomas, what investigations are needed to make the diagnosis of lymphangioleiomyomatosis, what the diagnostic criteria are for lymphangioleiomyomatosis, what the principles of management are, and how follow-up can be organised. Recommendations are made regarding the use of pharmaceutical specialties and treatment other than medications. CONCLUSION: These recommendations are intended to guide the diagnosis and practical management of pulmonary lymphangioleiomyomatosis.

Interstitial lung diseases associated with mutations of poly(A)-specific ribonuclease: A multicentre retrospective study.

BACKGROUND AND OBJECTIVE: Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations. METHODS: We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network. RESULTS: We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n = 12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n = 13), antifibrotic agents (n = 11), immunosuppressants (n = 5) and N-acetyl cysteine (n = 2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation. CONCLUSION: IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.

Interstitial pneumonia with autoimmune features: Evaluation of connective tissue disease incidence during follow-up.

OBJECTIVES: Among interstitial pneumonia with autoimmune features (IPAF) patients, identifying those at risk to develop a connective tissue disease (CTD) during the disease course is a key issue. The aim of this study was to evaluate the incidence of definite CTD diagnosis in IPAF patients during follow-up. METHODS: We performed a multicentric cohort study of interstitial lung disease (ILD) from 2010 to 2017 in pneumology and immunology departments of tertiary care centers. Patients with a known cause of ILD (including established CTD) at diagnosis were excluded. Among patients with idiopathic ILD and at least three years of follow-up, two groups (IPAF and non-IPAF) were retrospectively analyzed at time of diagnosis. RESULTS: A total of 249 patients with ILD were enrolled, including 70 IPAF and 179 non-IPAF patients. After a mean follow-up time of 77 ± 44 months, 18/70 IPAF patients (26%) had a CTD diagnosis - 9 antisynthetase syndrome, 8 systemic sclerosis and 1 overlap myositis - compared with 4/179 non-IPAF patients (2%). IPAF patients were at higher risk of CTD occurrence at 3 years of follow-up compared to non-IPAF patients (HR 10.1, 95% CI 3.1-33.1, p < 0. 01). IPAF patients progressing to CTD tended to be younger, more often female and have more frequently puffy fingers, capillaroscopy abnormalities and antisynthetase antibodies at diagnosis. CONCLUSIONS: We found that a significant proportion of IPAF patients had associated CTD diagnosis during follow-up. Prospective studies are needed to confirm baseline predictive factors of CTD occurrence in IPAF patients.

Treatment of Idiopathic Pulmonary Fibrosis with Capsule or Tablet Formulations of Pirfenidone in the Real-Life French RaDiCo-ILD Cohort.

INTRODUCTION: Pirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF. METHODS: This study was nested within the French, non-randomized, multicenter RaDiCo-ILD (Rare Disease Cohort-Interstitial Lung Diseases). Included patients with IPF received at least one dose of pirfenidone tablets or capsules from July 2017 to June 2019 in three populations: the inclusion population (patients treated at least once with pirfenidone during the study period, n = 288); the potential switch population (patients treated with pirfenidone during the switch period starting April 2018, n = 256); the newly treated population (patients who initiated pirfenidone during the study period, n = 162). Each of those last two populations included three subgroups (tablets, capsules, and substitution). RESULTS: In 288 patients treated, 162 newly initiated pirfenidone during the study period: there were no meaningful differences in the baseline characteristics with the 256 patients treated during the potential switch period. In the newly treated population, 30.3% started pirfenidone treatment with tablet formulation. In the potential switch population, 44.9% of patients shifted from capsule to tablet. Half of the patients shifted to tablet formulation within the first 10 months. The mean treatment duration was 21.5 months with a mean dose of 2106.7 mg/day; 46.5% of patients discontinued treatment, mainly because of adverse events. There were fewer discontinuations in the tablets and substitution subgroups than in the capsules-only subgroup. The most reported adverse event was skin rash (11.5%). No new adverse event was identified. CONCLUSIONS: This real-life cohort assessing the characteristics of the prescription of pirfenidone tablets and capsules suggests a good acceptability of the tablet formulation by patients with IPF. TRIAL REGISTRATION: Clinical trial registered with www.clinicaltrials.gov (NCT04238871).

Systemic Pulmonary Events Associated with Myelodysplastic Syndromes: A Retrospective Multicentre Study.

Although pulmonary events are considered to be frequently associated with malignant haemopathies, they have been sparsely studied in the specific context of myelodysplastic syndromes (MDS). We aimed to describe their different types, their relative proportions and their relative effects on overall survival (OS). We conducted a multicentre retrospective cohort study. Patients with MDS (diagnosed according to the 2016 WHO classification) and pulmonary events were included. The inclusion period was 1 January 2007 to 31 December 2017 and patients were monitored until August 2019. Fifty-five hospitalized patients were included in the analysis. They had 113 separate pulmonary events. Thirteen patients (23.6%) had a systemic autoimmune disease associated with MDS. Median age at diagnosis of MDS was 77 years. Median time to onset of pulmonary events was 13 months. Pulmonary events comprised: 70 infectious diseases (62%); 27 interstitial lung diseases (23.9%), including 13 non-specific interstitial pneumonias and seven secondary organizing pneumonias or respiratory bronchiolitis-interstitial lung diseases; 10 pleural effusions (8.8%), including four cases of chronic organizing pleuritis with exudative effusion; and six pulmonary hypertensions (5.3%). The median OS of the cohort was 29 months after MDS diagnosis but OS was only 10 months after a pulmonary event. The OS was similar to that of the general myelodysplastic population. However, the occurrence of a pulmonary event appeared to be either an accelerating factor of death or an indicator for the worsening of the underlying MDS in our study. More than a third of pulmonary events were non-infectious and could be systemic manifestations of MDS.

Filamin A Mutations: A New Cause of Unexplained Emphysema in Adults?

Emphysema is a chronic respiratory disorder characterized by destruction of alveoli, usually due to cigarette smoking or exposure to noxious particles or gases. Dysfunction of proteins that are involved in lung development and maintenance, such as alpha-1 antitrypsin, also contributes to emphysema. Filamin A (FLNA) is an actin-binding protein involved in cytoskeleton reorganization. Mutations in the FLNA gene classically lead to abnormal neuronal migration and connective and vascular tissue anomalies. Pulmonary manifestations consist of a wide range of pulmonary disorders that occur during infancy. We report the first familial case of emphysema in non- and very low-smoking adults who carry a loss-of-function mutation of the FLNA gene. The identification of this new risk factor for emphysema encourages (1) screening, prevention and monitoring of pulmonary disorders in patients with FLNA mutation and (2) screening for FLNA mutation in patients with early-onset emphysema that is associated with low-smoking or vascular or connective tissue anomalies.

Efficacy and safety of rituximab in patients with chronic hypersensitivity pneumonitis (cHP): A retrospective, multicentric, observational study.

BACKGROUND: There are chronic forms of hypersensitivity pneumonitis (cHP) that can progress to pulmonary fibrosis. There is no recommended treatment for patients whose respiratory condition continues to deteriorate in spite of antigen avoidance. Whether rituximab may be beneficial to patients with cHP is unknown. The aim of this study was to describe the course of 20 patients with cHP under rituximab therapy. METHODS: This retrospective study was conducted from November 2018 to July 2019 in 7 French university hospitals. Forced Vital Capacity (FVC) was measured 6 months before rituximab therapy onset (M - 6), at rituximab onset (M0), and 6 months later (M+6). RESULTS: FVC decreased significantly in the 6 months preceding the introduction of rituximab (65% [44; 112%] at M - 6 versus 59% [39; 102%] at M0; p = 0.0001), but it did not differ significantly from that at 6 months after the introduction of rituximab (61% [38; 99%]). The decline in FVC between M0 and M+6 (-3% [-15; +19%]) was significantly less than between M - 6 and M0 (-8% [-21; 0%]) (p = 0.0002). Between M0 (37% [16; 73%]) and M + 6 (45% [15; 70%]), the median DLCO remained stable (p = 0.12). DLCO improved at M+6 in 5 of the 8 patients (63%) for whom a DLCO value was available at M+6 improved their DLCO. CONCLUSION: Rituximab seems well tolerated, and may lead to stabilization or improvement of lung function in some patients.

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.