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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., (Copyright © 2023 American Association for the Study of Liver Diseases.)

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., Competing Interests: Conflict of interest: P. Bonniaud reports grants from AstraZeneca, lecture honoraria from Sanofi and AstraZeneca, travel support from AstraZeneca, Novartis, Sanofi, Boehringer and Stallergenes, and advisory board membership with AstraZeneca, Novartis, Sanofi, GSK and Boehringer. J. Cadranel had a patent planned, received consulting fees and participated on a data safety monitoring board or advisory board for AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Daichi, Lilly, Pfizer, Novartis, MSD, Roche and Takeda. A. Cazes reports lecture honoraria and travel support from Boehringer Ingelheim. B. Crestani reports grants from Boehringer Ingelheim, consulting fees from Apellis, BMS, Boehringer Ingelheim and Sanofi, lecture honoraria from Apellis, AstraZeneca, BMS, Boehringer Ingelheim, Novartis and Sanofi, support for attending meetings or travel from AstraZeneca, BMS, Boehringer Ingelheim and Sanofi, participated on a data safety monitoring board or advisory board for Apellis, BMS, Boehringer Ingelheim and Sanofi, and had a leadership role as President of the Board of Trustees of the Fondation du Souffle. R. Epaud reports consulting fees from AstraZeneca, lecture honoraria from GSK, AstraZeneca and Menarini, travel support from GSK and AstraZeneca, and advisory board membership with AstraZeneca and Novartis. M-P. Debray reports lecture honoraria and travel support from Boehringer Ingelheim. E. Manali reports lecture honoraria from Boehringer Ingelheim, CLS Behring and Hoffman-La Roche, support for attending meetings or travel from Boehringer Ingelheim, CLS Behring, Hoffman-La Roche and Elpen, and had a leadership role as a Chair in the ERS Task Force for transition of chILD to adult care. S. Papiris reports lecture honoraria from Boehringer Ingelheim and Hoffmann-La Roche, and travel support from Boehringer Ingelheim and Elpen. N. Nathan reports grants from Legs poix de la Chancellerie des Universités 2022 (number 2022000594). C. Andréjak participated on a data safety monitoring board or advisory board for the EVER-ILD2 study (rituximab in diffuse interstitial pneumonia) and received funding via a grant from the French Research Ministry. S. Jouneau reports grants from AIRB, Boehringer Ingelheim and Roche, lecture honoraria from AIRB, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GSK, LVL, Novartis, Pfizer, Roche and Sanofi, travel support from Boehringer Ingelheim, Roche and AIRB, and advisory board participation for Boehringer Ingelheim, GSK and Sanofi. G. Beltramo reports lecture honoraria from Bristol Myers Squibb, and support for attending meetings or travel from Sanofi Aventis France and Boehringer Ingelheim France. S. Hirschi reports research grants from Agence de la Biomedécine, CSL Behring and Adiral medical assistance, lecture honoraria from Boehringer Ingelheim, travel support from CSL Behring, Boehringer Ingelheim and ISIS Medical, and received medical equipment from ISIS Medical. C. Picard reports lecture honoraria and consulting fees from Boehringer Ingelheim. G. Prévot reports honoraria for presentations and educational event from Boehringer Ingelheim, Sanofi, Jansen and MSD. G. Zalcman reports consulting fees from AstraZeneca, BMS, Pfizer and Sanofi, lecture honoraria from BMS, AstraZeneca and Sanofi, support for attending meetings or travel from AstraZeneca and BMS, and participated on a data safety monitoring board or advisory board for AstraZeneca and BMS. V. Cottin reports grants from Boehringer Ingelheim, consulting fees from AstraZeneca, Boehringer Ingelheim, Celgene/BMS, CSL Behring, Ferrer/United Therapeutics, GSK, Pliant, Pure Tech, RedX, Roche, Sanofi and Shionogi, lecture honoraria from Boehringer Ingelheim, Ferrer/United Therapeutics and Roche, support for attending meetings or travel from Boehringer Ingelheim and Roche, participated on a data safety monitoring board or advisory board for Galapagos, Galecto and GSK, and had a leadership role in an adjudication committee for Fibrogen. R. Borie reports consulting fees from Boehringer Ingelheim, Ferrer and Sanofi, lecture honoraria from Boehringer Ingelheim and Roche, travel support from Boehringer Ingelheim, Roche and Chiesi, and advisory board participation for Savara. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

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., (© 2024. The Author(s).)

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 DL CO 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 DL CO , 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., (© 2024 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

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., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Competing interests: PA-J has received grant/research support from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Medac, Novartis, Roche Chugai and Societe Francaise de Rhumatologie; and consultancy fees from Bristol Myers Squibb. LW has received consultancy fees from Boehringer Ingelheim, Bristol Myers Squibb, Roche and Sanofi. SO has received consultancy fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Roche-Chugai, SOBI and UCB. GD has received consultancy fees from Bristol Myers Squibb. JZ and VV-M are employees of and shareholders in Bristol Myers Squibb. R-MF has received speakers bureau fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Medac, Merck Sharp & Dohme, Novartis, Pfizer and Roche-Chugai; and grant/research support from Amgen, Janssen, Novartis and Pfizer. BC has received consultancy fees from Apellis, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Roche and Sanofi; and grant/research support from Boehringer Ingelheim, Bristol Myers Squibb and Roche. PD has received consultancy fees from Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Eli Lilly, Medac, Novartis, Pfizer and Sanofi; and grant/research support from Bristol Myers Squibb, GlaxoSmithKline and Pfizer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of Competing Interest Vincent COTTIN has no conflict of interest to disclose in relation with the content of the manuscript. Elodie BLANCHARD has no conflict of interest to disclose in relation with the content of the manuscript. Mallorie KERJOUAN declares research fees paid by Pfizer and Novartis to her institution. Romain LAZOR has no conflict of interest to disclose in relation with the content of the manuscript. Martine REYNAUD-GAUBERT has no conflict of interest to disclose in relation with the content of the manuscript. Romain LAZOR has no conflict of interest to disclose in relation with the content of the manuscript. Camille TAILLE declares consulting fees paid to her by Novartis. Yurdagül UZUNHAN has no conflict of interest to disclose in relation with the content of the manuscript. Lidwine WEMEAU has no conflict of interest to disclose in relation with the content of the manuscript. Claire ANDREJAK has no conflict of interest to disclose in relation with the content of the manuscript. Dany BAUD has no conflict of interest to disclose in relation with the content of the manuscript. Philippe BONNIAUD has no conflict of interest to disclose in relation with the content of the manuscript. Pierre-Yves BRILLET has no conflict of interest to disclose in relation with the content of the manuscript. Alain CALENDER has no conflict of interest to disclose in relation with the content of the manuscript. Lara CHALABREYSSE has no conflict of interest to disclose in relation with the content of the manuscript. Isabelle COURT-FORTUNE has no conflict of interest to disclose in relation with the content of the manuscript. Nicolas DESBAILLETS has no conflict of interest to disclose in relation with the content of the manuscript. Gilbert FERRETTI has no conflict of interest to disclose in relation with the content of the manuscript. Anne GUILLEMOT has no conflict of interest to disclose in relation with the content of the manuscript. Laurane HARDELIN has no conflict of interest to disclose in relation with the content of the manuscript. Marianne KAMBOUCHNER has no conflict of interest to disclose in relation with the content of the manuscript. Violette LECLERC (deceased). Mathieu LEDERLIN has no conflict of interest to disclose in relation with the content of the manuscript. Marie-Claire MALINGE has no conflict of interest to disclose in relation with the content of the manuscript. Alain MANCEL has no conflict of interest to disclose in relation with the content of the manuscript. Sylvain MARCHAND-ADAM declares consulting fees paid by Novartis. Jean-Michel MAURY has no conflict of interest to disclose in relation with the content of the manuscript. Jean-Marc NACCACHE has no conflict of interest to disclose in relation with the content of the manuscript. Mouhamad NASSER has no conflict of interest to disclose in relation with the content of the manuscript. Hilario NUNES has no conflict of interest to disclose in relation with the content of the manuscript. Gaële PAGNOUX has no conflict of interest to disclose in relation with the content of the manuscript. Grégoire PRÉVOT has no conflict of interest to disclose in relation with the content of the manuscript. Christine ROUSSET-JABLONSKI has no conflict of interest to disclose in relation with the content of the manuscript. Olivier ROUVIERE has no conflict of interest to disclose in relation with the content of the manuscript. Salim SI-MOHAMED has no conflict of interest to disclose in relation with the content of the manuscript. Renaud TOURAINE has no conflict of interest to disclose in relation with the content of the manuscript. Julie TRACLET has no conflict of interest to disclose in relation with the content of the manuscript. Ségolène TURQUIER has no conflict of interest to disclose in relation with the content of the manuscript. Stéphane VAGNARELLI has no conflict of interest to disclose in relation with the content of the manuscript. Kaïs AHMAD has no conflict of interest to disclose in relation with the content of the manuscript., (Copyright © 2023 SPLF and Elsevier Masson SAS. All rights reserved.)

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., (© 2022 Asian Pacific Society of Respirology.)

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)., (© 2021. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

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., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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 (T 0 ), immediately after (T 2 ), 6 months after (T 8 ) and 12 months after (T 14 ) the end of the pulmonary rehabilitation programme., Results: 6MST strokes, HADS Anxiety score and VSRQ score were each significantly improved at T 2 (n=101), T 8 (n=76) and T 14 (n=62) compared with T 0 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., Competing Interests: Conflict of interest: B. Wallaert reports personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: L. Duthoit has nothing to disclose. Conflict of interest: E. Drumez has nothing to disclose. Conflict of interest: H. Behal has nothing to disclose. Conflict of interest: L. Wemeau reports personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: C. Chenivesse has nothing to disclose. Conflict of interest: J-M. Grosbois reports that FormAction Santé received financial support from Adair, France Oxygène, Homeperf, LVL Medical, Orkyn, Santélys, Santeo, SOS Oxygène, Sysmed, VitalAire and ARS Hauts de France, during the conduct of the study.

Background and Objectives: Little is known about the consequences of chronic sarcoidosis on daily life physical activity (DL PA ). The aim of this prospective study was to measure DL PA 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 PA (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 [VO 2 max]), exercise capacity (6-min walk test [6MWT]), and quality of life (self-reported questionnaires) were also evaluated. Comparisons of DL PA parameters between the two groups were performed using an analysis of covariance adjusted for age, sex, and body mass index (BMI). Relationships between DL PA 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), VO 2 max ( 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 VO 2 max., Conclusion: Patients with chronic sarcoidosis appear to have reduced DL PA mainly because of compromised VO 2 max.

Objective: The aim of this study was to determine the frequency and characteristics of antisynthetase syndrome (ASS) revealed by polyarthritis., Methods: First we conducted a retrospective single-centre study to assess the frequency of ASS patients who presented with polyarthritis without pulmonary and/or muscle symptoms. Secondly, we conducted a larger, multicentre study in order to describe the clinical characteristics of these patients. Exclusion criteria were the presence of RF, the presence of ACPA and overlap with another CTD., Results: In the single-centre study, polyarthritis was the first manifestation in 12 of 45 ASS patients (27%). An additional 28 patients were collected for the multicentre study, resulting in a total population of 40 ASS patients who presented with polyarthritis. The mean delay from polyarthritis onset to ASS diagnosis was 27 months (s.d. 40). Pulmonary and muscle symptoms were uncommon at ASS diagnosis (40% and 32.5%, respectively) and were dramatically delayed [mean delay after polyarthritis onset of 41 months (s.d. 53) and 21 months (s.d. 14), respectively]. Mechanic's hands and cutaneous signs of DM occurred in 25% and 22.5%, respectively, with a mean delay of 10 months (s.d. 10) and 31 months (s.d. 21), respectively. When present (32%), RP was the earliest non-articular manifestation [mean delay 3 months (s.d. 23) after polyarthritis onset]. On HEp-2 cells, antinuclear and/or cytoplasmic fluorescence was found in 70% of cases, with specificity for various anti-aminoacyl tRNA synthetase (anti-ARS) antibodies., Conclusion: ASS may be revealed by polyarthritis. To decrease the delay in diagnosis of ASS, pulmonary and muscle symptoms and anti-ARS antibodies might usefully be searched for in seronegative polyarthritis patients, especially in those with RP., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The six-minute stepper test (6MST) is a new test for evaluating exercise tolerance. Unlike the six-minute walk test (6MWT) it can be carried out in a limited space. The aim of this study was to compare the 6MST and the 6MWT in patients with various diffuse interstitial lung disease (ILD). 6MWT and 6MST were performed the same day in 84 patients with various ILD. The covered distance during 6MWT was compared to the number of steps during the 6MST. We also compared heart rate, oxygen saturation, dyspnoea and leg tiredness on a Borg scale. All the patients successfully completed the tests, and tolerance was considered good. The number of steps completed in the 6MST was strongly correlated with the distance walked in the 6MWT (r2 = 0.5; p < 0.0001). Oxygen desaturation was less frequent and less severe (p < 0.0001), heart rate was higher (p < 0.0001) and dyspnoea and leg tiredness were more marked (p < 0.0001) in the 6MST than in the 6MWT. The 6MST is feasible for patients with ILD. It is a simple, safe, mobile test that is cheap and easy to carry out in all structures.

The effect of therapy on the modification of a functional parameter is an elegant method for assessing the causal relationship between functional abnormalities and symptoms. We report an analysis of the effects of thromboendarterectomy for post-embolic pulmonary arterial hypertension on exercise functional parameters. A patient (62 years) had post-embolic pulmonary hypertension documented by pulmonary angiography and right heart catheterization (PAP mean: 48 mmHg). Cardiopulmonary exercise testing demonstrated a decreased aerobic capacity (59% predicted), significant hyperventilation (VE/VO(2) at peak 82) and a dead space to tidal volume ratio (VD/Vt) increased at rest (0.55) and remaining high at peak exercise (0.48). Thromboendarterectomy was performed and led to a dramatic improvement in dyspnoea (NYHA class II to I), a gradual improvement in aerobic capacity, and a significant decrease of VD/Vt (0.26) and hyperventilation (VE/VO(2) at peak: 38) on exercise. This observation illustrates the fact that an increase in the physiological dead space on exercise is associated with significant hyperventilation and consequently dyspnoea of effort., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: The association between interstitial pneumonia and hepatopulmonary syndrome (HPS) has rarely been described., Observation: We report the cases of two patients, 62 and 64 years old, who presented with idiopathic interstitial pneumonia (IIP) and severe, disproportionate hypoxemia, PaO(2) 42 and 47 mmHg, respectively. This hypoxemia lead to search for associated disease. The diagnosis of right-to-left shunt was established by the 99mTc-MAA perfusion lung imaging. A contrast cardiac echography confirmed the intrapulmonary shunt. Both patients were found to have hepatic cirrhosis, classed as Child Grade A6 and C10. In this context of chronic hepatopathy, the diagnosis of SHP associated with IIP was established. Liver transplantation, the only way to cure the lung consequences of the HPS, was planned., Conclusion: These two cases highlight the importance of searching for right-to-left shunt in patients who have lung disease with severe disproportionate hypoxemia. Liver transplantation is the only way to cure the lung consequences of the hepathopathy. The rare association between ILD and HPS raises problems when deciding to go forward to transplantation in the absence of a histological diagnosis of the lung disease and where the prognosis of the lung disease is unclear., (Copyright © 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Among the large number of technics proposed to cure effort urinary incontinence in women, two types of operation are usually considered: --indirect cervico-cystopexy or colopexy (Marshall-Marchietti-Krantz operation or its derivatives); --operations of catapult type or suspension of the bladder neck, e.g. Goebell-Stoeckel's operation. The latter was chosen exclusively by us over the last ten years. We have thus grouped together 85 cases of effort urinary incontinence operated and followed up for a period of 1 to 11 years. At five years, this operation gave 82.85% good results and a delay of two years seemed to us the minimum necessary to assess these results. We noted 6 failures (7.05%) and 4 relapses (4.7%). Suspension of the bladder neck is often disputed and even denigrated. Some authors consider it is the best operation available especially in cases of relapse of effort incontinence [21]. Its technical difficulty has been reproached. Our objective thus double: --describe our technic of musculo-aponeurotic suspension of the bladder neck; --give our results emphasising the long term results. We thus hope to prove that this operation maintains its place in the treatment of effort incontinence.

Renal angiomyolipomas are benign mesenchymal tumours. Whether isolated or associated with phacomatosis, they are histologically identical, but it is often difficult to distinguish an isolated angiomyolipoma from renal cancer. When it is combined with phacomatosis, it is frequently bilateral and can provoke retroperitoneal haemorrhages. These peculiarities qualify the therapeutical management which would a priori be conservative in the case of a benign tumour.

Renal angiomyolipoma is a benign mesenchymatous tumour. Whether isolated or associated with phacomatoses, they are histologically identical and the hypothesis which suggests that isolated angiomyolipomas represent a forme fruste or tuberose sclerosis is attractive. The tumour is benign and resembles a carcinoma clincally and radiologically, to such an extent as to lead to confusion. Improved knowledge and more detailed study of radiological documents should avoid their always being, in the words of R. Couvelaire" a constant operative or histological surprise". However whilst there remains no doubt as to its benign nature, the association of true malignant tumours is possible and even seems frequent, which takes us back to the starting point and, given the difficulty of the pre-operative differential diagnosis with a carcinoma; we prefer to opt for extended nephrectomy when operation is indicated.

Secondary tumours of the kidney are relatively common. Found at autopsy in approximately 4 per cent of patients dying of malignant disease, they are clinically latent in most instances. Thus in a total series of 295 malignant tumours of the kidney, only 8 were metastases. The primary tumour is most often a bronchial carcinoma, this being confirmed in our series (5 cases). This is followed, in order of decreasing frequency, the breast, stomach, pancreas and stomach. Two of the 8 cases were rarities: a renal metastasis from a meningoblastoma and a metastasis from one tumour to another, a carcinoma of the ovary metastasising to a hypernephroma. The pathogenesis of these secondary tumours leads to the consideration of 2 modes of spread: haematogenous and lymphatic. They present no special clinical features. Intravenous pyelogram reveals the appearances of a malignant tumour mass. Angiography is more informative, the results reflecting the histological nature of the primary tumour. The latter being most frequently a carcinoma, the arteriographic image is one of hypovascularisation, thus differing from a hypernephroma with its rich vascularisation and resembling an infiltrating pelvi-calyceal carcinoma. Histopathological examination is not always conclusive itself. Nephrectomy is effectively only justified if the primary tumour has been or can be successfully treated in the absence of other metastases.