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Background: Standard 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., Methods: In 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 features) and a NSIP pattern (defined on NSIP pathological pattern or on integration of clinicobiological data and a NSIP-like high-resolution computed tomography 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 6 months. The primary end-point was the change in percent predicted forced vital capacity (FVC) from baseline to 6 months analysed by a linear mixed model for repeated measures analysis. Secondary end-points included progression-free survival (PFS) up to 6 months and safety., Findings: Between 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 (se 1.13) in the rituximab+MMF group and -2.01 (se 1.17) in the placebo+MMF group (between-group difference 3.60, 95% CI 0.41-6.80; p=0.0273). PFS was better in the rituximab+MMF group (crude hazard ratio 0.47, 95% CI 0.23-0.96; p=0.03). Serious adverse events occurred in 26 (41%) patients of the rituximab+MMF group and in 23 (39%) of the placebo+MMF group. Nine infections were reported in the rituximab+MMF group (five bacterial infections, three viral infections, one other) and four bacterial infections in the placebo+MMF group., Interpretation: Combination of rituximab and MMF was superior to MMF alone in patients with ILD and a NSIP pattern. The use of this combination must take into consideration the risk of viral infection., Competing Interests: Conflict of interest: A. Caille reports grants from French National Research Agency, outside the submitted work. P. Bonniaud reports grants from AstraZeneca, personal fees and non-financial (reimbursement for national and international conferences) support from Roche, Boehringer Ingelheim, AstraZeneca, Novartis, Sanofi and GSK, and non-financial support (reimbursement for national and international conferences) from Chiesi and Stallergene. R. Borie has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups, and research projects over the past 3 years from Boehringer, Roche, Sanofi-Genzyme, Savara and Chiesi, outside the submitted work. J. Cadranel reports honoraria for educational events from Boehringer Ingelheim and Roche, outside the submitted work. B. Crestani has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups, and research projects over the past 3 years from BMS, Boehringer Ingelheim, Roche, Apellis, Sanofi, Novartis, AstraZeneca and Chiesi, outside the submitted work; and has also received equipment/drugs or other services from Translate Bio. M-P. Debray has received or reimbursement for national and international conferences and educational events over the past 3 years from Boehringer Ingelheim and Roche, outside the submitted work. D. Israel-Biet reports consulting fees from Boehringer Ingelheim, honoraria for educational events from Boehringer Ingelheim and Roche, payments from Galapagos as a member of an adjudication committee, and support for attending meetings and/or travel from Boehringer Ingelheim, outside the submitted work. S. Jouneau has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups, and research projects over the past 3 years from AIRB, Bellorophon Therapeutics, Biogen, Boehringer, Chiesi, Fibrogen, Galecto Biotech, Gilead, LVL, Novartis, Olam Pharm, Pfizer, Pliant Therapeutics, Roche, Sanofi-Genzyme and Savara. J-M. Naccache has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups, and research projects over the past 3 years from AstraZeneca and Boehringer Ingelheim, outside the submitted work. L. Plantier has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups, and research projects over the past 3 years from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Sanofi, Humanair and Arair, outside the submitted work. V. Valentin has received fees, funding or reimbursement for national and international conferences, and boards from Boehringer Ingelheim, outside the submitted work. L. Wémeau-Stervinou reports personal fees and non-financial (reimbursement for national and international conferences) support from Roche, Boehringer Ingelheim, Sanofi and BMS, outside the submitted work. V. Cottin reports grants, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Roche, personal fees from AstraZeneca, Boehringer Ingelheim, Celgene/BMS, MSD, CSL Behring, Galapagos, Galecto, Shionogi, Fibrogen, RedX, PureTech and Promedior, outside the submitted work. S. Marchand-Adam has received fees, funding or reimbursement for national and international conferences, and boards from Boehringer Ingelheim, Roche, BMS, Novartis, AstraZeneca, Pfizer, GSK and Chiesi, outside the submitted work. The remaining authors declare no competing interests., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Immune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-P is more often observed in patients with nonsmall cell lung cancer (NSCLC) than in those with other cancers. Likewise, it is more common in those receiving programmed cell death (PD)-1/PD-1 ligand inhibitors rather than cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors alone. The frequency of ICI-P is higher when anti-PD-1 and anti-CTLA-4 are administered concomitantly. Despite the low fatality rate (≈13%), ICI-P is the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy. Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines., Competing Interests: Conflict of interest: J. Cadranel reports grants and personal fees from AstraZeneca, Novartis and Pfizer, and personal fees from Roche, MSD and BMS, outside the submitted work. Conflict of interest: A. Canellas reports personal fees from BMS, outside the submitted work. Conflict of interest: L. Matton has nothing to disclose. Conflict of interest: M. Darrason has nothing to disclose. Conflict of interest: A. Parrot has nothing to disclose. Conflict of interest: J-M. Naccache has nothing to disclose. Conflict of interest: A. Lavolé has nothing to disclose. Conflict of interest: A-M. Ruppert has nothing to disclose. Conflict of interest: V. Fallet reports personal fees from Bristol Meyers Squib and Lilly, outside the submitted work., (Copyright ©ERS 2019.)

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: 97.9/10 5 and incidence: 19.4/10 5 /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 30.2/10 5 for sarcoidosis, 12.1/10 5 for CTDs-ILDs and 8.2/10 5 for IPF. The prevalence of fibrotic idiopathic interstitial pneumonias, merging IPF, nonspecific interstitial pneumonia and cases registered with code J84.1 was 16.34/10 5 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., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing of TERT/TERC genes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis.We retrospectively analysed all the genetic diagnoses made between 2007-2014 in patients with pulmonary fibrosis. We evaluated the prevalence of TERT/TERC disease-associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival.237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested for TERT/TERC DAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence of TERT/TERC DAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2% versus 16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40-60 years. Transplant-free survival was lower with than without TERT/TERC DAV (4.2 versus 7.2 years; p=0.046).TERT/TERC DAV were associated with specific clinical and biological features and reduced transplant-free survival., (Copyright ©ERS 2016.)

The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis 20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis. Clinical examination showed more frequent crackles in patients than controls (45% versus 1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80% versus 42%, respectively; p=0.004) as well as bronchiectasis (65% versus 23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean ± sd 1.6 ± 1.1 versus 5.3 ± 4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30% versus 0%, respectively) and resulted from common variable immunodeficiency complications. ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.

The objectives of this study were to compare the survival of sarcoid patients with pulmonary fibrosis with that of the general population and to determine the causes of death and the incidence of evolutive complications. This retrospective cohort included 142 sarcoid patients in radiographic stage IV (74 males; mean ± SD age 48.1 ± 12 yrs). Their survival was compared with that of the general French population, matched for the year and age at diagnosis of stage IV disease, sex and length of follow-up. Expected survival probabilities were calculated year-by-year on the basis of probabilities provided by official demographic data for France. Survival curves were based on the Kaplan-Meier method and compared using the log-rank test. During the follow-up period (7.1 ± 4.8 yrs), pulmonary hypertension (PH) was observed in 29.7% of cases and aspergilloma in 11.3%. Long-term oxygen therapy was required in 12%. Survival was 84.1% at 10 yrs, which was worse than for the general population (p = 0.013). 16 (11.3%) patients died from the following causes: refractory PH (n = 5), chronic respiratory insufficiency (n = 4), acute respiratory insufficiency (n = 2), haemoptysis due to aspergilloma (n = 1), heart sarcoidosis (n = 1), nocardiosis (n = 1) and unknown causes (n = 2). Survival is significantly decreased in stage IV patients. 75% of fatalities are directly attributable to respiratory causes.

Chronic beryllium disease (CBD) is a granulomatous disorder that affects the lung after exposure to beryllium. The present study reports short- and long-term evolution of granulomatous and fibrotic components in eight patients with severe CBD receiving corticosteroid therapy. Eight patients with confirmed CBD were studied at baseline, after initial corticosteroid treatment (4-12 months), at relapse and at the final visit. Beryllium exposure, Glu(69) (HLA-DPB1 genes coding for glutamate at position beta69) polymorphism, symptoms, pulmonary function tests (PFT), serum angiotensin-converting enzyme (SACE) and high-resolution computed tomography (HRCT) quantification of pulmonary lesions were analysed. The CBD patients were observed for a median (range) of 69 (20-180) months. After stopping beryllium exposure, corticosteroids improved symptoms and PFT (vital capacity +26%, diffusing capacity of the lung for carbon monoxide +15%), and decreased SACE level and active lesion HRCT score. In total, 18 clinical relapses occurred after the treatment was tapered and these were associated with SACE and active lesion HRCT score impairment. At the final visit, corticosteroids had completely stabilised all parameters including both HRCT scores of active lesions and fibrotic lesions in six out of eight patients. Corticosteroids were beneficial in chronic beryllium disease. They were effective in suppressing granulomatosis lesions in all cases and in stopping the evolution to pulmonary fibrosis in six out of eight patients.