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BackgroundStandard of care for interstitial lung disease (ILD) with a nonspecific interstitial pneumonia (NSIP) pattern proposes mycophenolate mofetil (MMF) as one of the first step therapies while rituximab is used as rescue therapy.MethodsIn a randomised, double blind, two-parallel group, placebo-controlled trial (NCT02990286), patients with connective tissue disease-associated ILD or idiopathic interstitial pneumonia (with or without autoimmune feature) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinico-biological data and a NSIP-like HRCT pattern) were randomly assigned in a 1:1 ratio to receive rituximab (1000 mg) or placebo on day 1 and day 15 in addition to MMF (2 g daily) for six months. The primary endpoint was the change in percent of predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary endpoints included progression-free survival (PFS) up to 6 months and safety.FindingsBetween January 2017 and January 2019, 122 randomised patients received at least one dose of rituximab (n=63) or placebo (n=59). The least-squares mean change from baseline to 6 months in FVC (% predicted) was +1.60 (se1.13) in the rituximab+MMF group and −2.01 (se1.17) in the placebo+MMF group (between-group difference, 3.60 [95% CI 0.41 to 6.80]; p=0.0273). PFS was better in the rituximab+MMF group (crude HR 0.47 [95%CI 0.23 to 0.96]; p=0.03). Serious adverse events occurred in 26 patients of the rituximab+MMF group (41%) and in 23 of the placebo+MMF group (39%). Nine infections were reported in the rituximab+MMF group (five bacterial infections, 3 viral infections, 1 other) and four bacterial infections in the placebo+MMF group.InterpretationCombination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must consider the risk of viral infection.

Genetic predisposition to pulmonary fibrosis has been confirmed by the discovery of several gene mutations that cause pulmonary fibrosis. Although genetic sequencing of familial pulmonary fibrosis (FPF) cases is embedded in routine clinical practice in several countries, many centres have yet to incorporate genetic sequencing within interstitial lung disease (ILD) services and proper international consensus has not yet been established. An international and multidisciplinary expert Task Force (pulmonologists, geneticists, paediatrician, pathologist, genetic counsellor, patient representative and librarian) reviewed the literature between 1945 and 2022, and reached consensus for all of the following questions: 1) Which patients may benefit from genetic sequencing and clinical counselling? 2) What is known of the natural history of FPF? 3) Which genes are usually tested? 4) What is the evidence for telomere length measurement? 5) What is the role of common genetic variants (polymorphisms) in the diagnostic workup? 6) What are the optimal treatment options for FPF? 7) Which family members are eligible for genetic sequencing? 8) Which clinical screening and follow-up parameters may be considered in family members? Through a robust review of the literature, the Task Force offers a statement on genetic sequencing, clinical management and screening of patients with FPF and their relatives. This proposal may serve as a basis for a prospective evaluation and future international recommendations.

Background: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Its use has been associated with hypersensitivity pneumonitis and diffuse lung disease. Whether MTX exposure increases the risk of interstitial lung disease (ILD) in patients with RA is disputed. Objectives: We aimed to evaluate the association of antecedent MTX use with development of RA-ILD. Methods: Through a case-control study design with derivation and international validation samples, we examined the association of MTX exposure with ILD in 482 patients with RA-ILD and 741 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. Results: Analysis of the derivation sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25 to 0.92; P=0.028), which was confirmed in the validation samples (pooled adjusted OR, 0.39; 95% CI, 0.23 to 0.68; P Conclusion: Our results suggest that MTX is not a risk factor for RA-ILD and support a possible disease modifying effect of MTX on development of RA-ILD. Disclosure of Interests: Pierre-Antoine Juge: None declared, Joyce S. Lee Consultant of: Celgene, Genentech, Boehringer Ingelheim, Jessica Lau: None declared, Leticia Kawano: None declared, Jorge Rojas-Serrano: None declared, Marco Sebastiani: None declared, Gouri Koduri: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Karina Bonfiglioli Consultant of: Roche, Abbvie, Pfizer, Janssen and BMS, Marcio Sawamura: None declared, Ronaldo Kairalla: None declared, Lorenzo Cavagna: None declared, Emanuele Bozzalla Cassione: None declared, Andreina Manfredi: None declared, Mayra Mejia: None declared, Pedro Rodriguez Henriquez: None declared, Montserrat I. Gonzalez-Perez: None declared, Ramces Falfan-Valencia: None declared, Ivette Buendia-Roldan: None declared, Glora Perez-Rubio: None declared, Esther Ebstein Consultant of: BMS, Employee of: BMS, Steven Gazal: None declared, Raphael Borie Consultant of: Roche, Boehringer Ingelheim, Sebastien Ottaviani: None declared, Caroline Kannengiesser: None declared, Benoit Wallaert Consultant of: Roche, Boehringer Ingelheim, Yurdagul Uzunhan Consultant of: Roche, Boehringer Ingelheim,, Hilario Nunes: None declared, Dominique Valeyre Consultant of: Astra Zeneca, Roche, Boehringer Ingelheim, Nathalie Saidenberg Kermanac’h: None declared, marie-Christophe Boissier: None declared, Lidwine Wemeau Stervinou Consultant of: Roche, Janssen, BMS, Boehringer Ingelheim, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Sylvain Marchand-Adam Consultant of: Roche, Novartis, Boehringer Ingelheim, Pascal Richette: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi, Claire Dromer: None declared, Marie-Elise Truchetet: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thierry Schaeverbeke: None declared, Huguette Liote: None declared, Gabriel Thabut Employee of: Astra Zeneca, Kevin Deane Grant/research support from: Janssen, Consultant of: Inova, ThermoFisher, Janseen, BMS and Microdrop, Joshua Solomon: None declared, Tracy Doyle: None declared, Jay H. Ryu: None declared, Ivan O. Rosas Consultant of: Boehringer Ingelheim, Gerentech, Three Lakes Partners, V. Michael Holers Grant/research support from: Janssen, Celgene, and BMS, Catherine Boileau: None declared, Marie-Pierre Debray: None declared, Raphael Porcher: None declared, David A. Schwartz Consultant of: NuMedii, Robert Vassallo Shareholder of: Pfizer, BMS, SunPharma, Bruno Crestani Shareholder of: Apellis, Boehringer Inghelheim, Medillune, Roche, Consultant of: Boehringer Ingelhiem, Astra Zeneca, Roche, Sanofi, Philippe Dieude: None declared

Light chain deposition disease (LCDD) is a rare disease resulting from non-amyloid immunoglobulin (Ig) light chain deposition in tissue. In systemic LCDD, plasma cell dyscrasia is common and renal involvement is almost always present, sometimes with damage to other organ systems (cardiac, hepatic and neurological systems). LCDD can be limited to the lungs, presenting as multiple cystic lung disease, nodules or bronchiectasis. Cystic lung related to LCDD (CL-LCDD) was recently described in patients referred for lung transplantation to treat end-stage multiple cystic lung disease [1]. In the reported cases, blood and bone marrow examinations did not reveal clonal plasma cell proliferation. Here we report the first case of CL-LCDD revealing a B-cell extrapulmonary lymphoproliferative disorder and the results of treatment for the underlying haematological disease with autologous peripheral blood stem cell transplantation during the CL-LCDD. Despite respiratory insufficiency, lung transplantation was actually not considered because of the underlying disease. We report a case of CL-LCDD that was treated with autologous peripheral blood stem cell transplantation

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients.This was a retrospective study of the French national cohort of adult patients (≥16 years old) with CGD.Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%).Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary.

Asbestosis is a fibrosing interstitial pneumonitis, which can develop following occupational asbestos exposure and a lengthy latency period [1]. Even after strict regulations on the asbestos industry, an estimated 3400 individuals worldwide died as a consequence of asbestosis in 2017 [2]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr Platenburg has nothing to disclose. Conflict of interest: Dr Wiertz has nothing to disclose. Conflict of interest: Dr van der Vis has nothing to disclose. Conflict of interest: Dr Crestani has nothing to disclose. Conflict of interest: Dr Borie reports grants and personal fees from Roche, grants and personal fees from Boerhinger Ingelheim, outside the submitted work. Conflict of interest: Philippe Dieude Conflict of interest: Dr Kannengiesser has nothing to disclose. Conflict of interest: D. Burgers reports grants from MSD, other from Roche, other from AstraZeneca, other from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr Grutters has nothing to disclose. Conflict of interest: Dr van Moorsel has nothing to disclose.

In a large subset of patients with asthma, blood eosinophilia is common, as a marker of T helper 2 cell (Th2) inflammation. Hypereosinophilia (HE), defined by blood eosinophil count >1500/mm3, is rare, observed in 0.3% of asthmatic patients [1]. Classically, in the context of uncontrolled asthma and HE, allergic bronchopulmonary aspergillosis, vasculitis or parasitic infection must be investigated [2]. Asthma is also a feature of HE related to various haematological disorders, although respiratory manifestations are rarely isolated in this setting [2]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Tabeze has nothing to disclose. Conflict of interest: Dr. Marchand-Adam has nothing to disclose. Conflict of interest: Dr. BORIE reports grants and personal fees from Boerhinger ingelheim, grants and personal fees from Roche, outside the submitted work. Conflict of interest: Dr. JUSTET has nothing to disclose. Conflict of interest: Dr. DOMBRET has nothing to disclose. Conflict of interest: Dr. CRESTANI reports grants and personal fees from Boerhinger ingelheim, grants and personal fees from Roche, grants from Apellis, personal fees from Astra Zeneca, grants from Medimmune, personal fees from Sanofi, outside the submitted work. Conflict of interest: Dr. TAILLE reports personal fees and other from Astra Zeneca, personal fees and other from Boeringher, personal fees from Chiesi, grants, personal fees and other from GSK, personal fees and other from Novartis, personal fees from Teva, personal fees and other from ALK, other from Sanofi, outside the submitted work. Conflict of interest: Dr. Dupin has nothing to disclose.

To the Editors: Amyloidosis is characterised by the deposition of insoluble protein fibrils in organs and tissues, which leads to organ dysfunction. Amyloidosis is classified according to the composition and localisation of fibrils. The most frequent amyloidosis is immunoglobulin (Ig)-light-chain (AL) amyloidosis. In systemic AL amyloidosis, the fibrils are derived from circulating monoclonal light chains that are usually produced by intramedullary clonal plasma cells. Localised AL amyloidosis is most often identified in upper respiratory, urogenital and gastrointestinal tracts, in the skin and in the orbit. In such circumstances, the amyloidogenic light chains are produced by a subtle clone of lymphoplasma cells localised near the amyloid deposits [1]. Characterising the associated clonal cells is often not possible because of their low number. Tracheobronchial amyloidosis is a rare form of localised amyloidosis [1,2]. To our knowledge, local B-cell clonal expansion has never been consistently demonstrated in tracheobronchial amyloidosis. We present the first case of tracheobronchial amyloidosis with molecular demonstration of localised tracheobronchial B-cell clonal proliferation and the results of targeted B-cell therapy with rituximab. A 41-yr-old female complained of persistent cough and expectoration for 1 yr. She was a 10-pack-yr active smoker. The physical examination was unremarkable. Lung function tests revealed an obstructive pattern, with a forced expiratory volume in 1 s of 1,880 mL (66%) and vital capacity of 3,420 mL (102%) without reversibility. Thorax computed tomography (CT) revealed a thickening of the trachea and primary bronchi without sparing the posterior tracheal wall (fig. 1a). Bronchoscopy confirmed a diffuse infiltration of the mucosa from the beginning of the trachea to the beginning of the tertiary bronchi, without sparing the …

The objective of the study was to estimate the prevalence and incidence of interstitial lung diseases (ILDs) in Seine-Saint-Denis, a multi-ethnic county of Greater Paris, France. Patients with ILDs were identified between January and December 2012 by using several sources; all potentially involved medical specialists from public and private hospitals, community-based pulmonologists and general practitioners, and the Social Security system. Diagnoses were validated centrally by an expert multidisciplinary discussion. 1170 ILD cases were reported (crude overall prevalence: 97.9/105 and incidence: 19.4/105/year). In the 848 reviewed cases, the most prevalent diagnoses were sarcoidosis (42.6%), connective tissue diseases associated ILDs (CTDs-ILDs) (16%), idiopathic pulmonary fibrosis (IPF) (11.6%), and occupational ILDs (5.0%), which corresponded to a crude prevalence of 30.2/105 for sarcoidosis, 12.1/105 for CTDs-ILDs and 8.2/105 for IPF. The prevalence of fibrotic idiopathic interstitial pneumonias, merging IPF, nonspecific interstitial pneumonia and cases registered with code J84.1 was 16.34/105. An adjusted multinomial model demonstrated an increased risk of sarcoidosis in North Africans and Afro-Caribbeans and of CTDs-ILDs in Afro-Caribbeans, compared to that in Europeans. This study, with a comprehensive recruitment and stringent diagnostic criteria, emphasises the importance of secondary ILDs, particularly CTDs-ILDs and the relatively low prevalence of IPF, and confirms that sarcoidosis is a rare disease in France., ILD prevalence reaches 97.9/100000, with a fairly low prevalence of IPF and a high contribution of secondary ILDs http://ow.ly/vLXq30bssKR

Pulmonary alveolar proteinosis may occur after lung transplantation and may be a cause of respiratory deterioration http://ow.ly/tlrl307KlKY