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BackgroundAutoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking.Research questionDescribe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections.MethodsWe conducted a retrospective cohort including all patients diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected using a standardised questionnaire including demographics, comorbidities, imaging features, outcomes and microbiological data.ResultsWe included 104 patients, 2/3 were men and median age at diagnosis was 45 years. With a median follow-up of 3.4 years (IQR 1.7–6.6 years), 60 patients (58%), developed at least one infection, including 23 (22%) with opportunistic infections. Nocardiaspp was the main pathogen identified (n=10). Thirty-five (34%) patients were hospitalised due to infection. In univariate analysis, male gender was associated with opportunistic infections (p=0.04, OR=3.88; 95% CI (1.02 to 22.06)). Anti-granulocyte macrophage colony-stimulating factor antibody titre at diagnosis was significantly higher among patients who developed nocardiosis (1058 (316–1591) vs 580 (200–1190), p=0.01). Nine patients had died (9%), but only one death was related to infection.InterpretationPatients with aPAP often presented with opportunistic infections, especially nocardiosis, which highlights the importance of systematic search for slow-growing bacteria in bronchoalveolar lavage or whole lung lavage.

To assess adverse events (AEs) in relation to baseline body mass index (BMI) and the risk of malnutrition in patients with systemic sclerosis–associated interstitial lung disease (SSc–ILD) treated with nintedanib. Among patients with SSc–ILD randomized to receive nintedanib or placebo in the SENSCIS trial, we assessed AEs in subgroups by baseline BMI ≤20 kg/m2and BMI >20 kg/m2, and the risk of malnutrition using a modified version of the Malnutrition Universal Screening Tool (MUST), over 52 weeks. The AE profile of nintedanib was similar between subgroups with a baseline BMI ≤20 kg/m2(n = 61) and a baseline BMI >20 kg/m2(n = 515). In these subgroups, respectively, AEs led to treatment discontinuation in 16.7% and 15.9% of the nintedanib group and 13.5% and 8.0% of the placebo group, respectively. Based on the modified MUST, the proportions of patients who had a low risk of malnutrition at baseline and at their last assessment were 74.0% in the nintedanib group and 78.1% in the placebo group, while the proportions who were classified as at low risk at baseline but at high risk by their last assessment were 4.5% in the nintedanib group and 1.0% in the placebo group. In the SENSCIS trial, most patients with SSc–ILD remained at low risk of malnutrition over 52 weeks, but the proportion at high risk was higher in patients who received treatment with nintedanib compared to those who received placebo. Management of disease manifestations and AEs that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc–ILD.

Carriers of germline telomerase-related gene (TRG) mutations can show poor prognosis, with an increase in common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT in recipients carrying a germline TRG mutation and to identify the predictors of survival. In a multicenter cohort of LT patients, we retrospectively reviewed those carrying pathogenic TRG variations (n= 38; TERT, n= 23, TERC, n= 9, RTEL1, n= 6) between 2009 and 2018. The median age at LT was 54 years (interquartile range [IQR] 46–59); 68% were male and 71% had idiopathic pulmonary fibrosis. During the diagnosis of pulmonary fibrosis, 28 (74%) had a hematological disease, including eight with myelodysplasia. After a median follow-up of 26 months (IQR 15–46), 38 patients received LT. The overall post-LT median survival was 3.75 years (IQR 1.8-NA). The risk of death after LT was increased for patients with myelodysplasia (HR 4.1 [95% CI 1.5–11.5]) or short telomere (HR 2.2 [1.0–5.0]) before LT. After LT, all patients had anemia, 66% had thrombocytopenia, and 39% had neutropenia. Chronic lung allograft dysfunction frequency was 29% at 4 years. The present findings support the use of LT in TRG mutation carriers without myelodysplasia. Hematological evaluation should be systematically performed before LT.

Carriers of germline telomerase‐related gene (TRG) mutations can show poor prognosis, with an increase in common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT in recipients carrying a germline TRG mutation and to identify the predictors of survival. In a multicenter cohort of LT patients, we retrospectively reviewed those carrying pathogenic TRG variations (n= 38; TERT, n= 23, TERC, n= 9, RTEL1, n= 6) between 2009 and 2018. The median age at LT was 54 years (interquartile range [IQR] 46–59); 68% were male and 71% had idiopathic pulmonary fibrosis. During the diagnosis of pulmonary fibrosis, 28 (74%) had a hematological disease, including eight with myelodysplasia. After a median follow‐up of 26 months (IQR 15–46), 38 patients received LT. The overall post‐LT median survival was 3.75 years (IQR 1.8‐NA). The risk of death after LT was increased for patients with myelodysplasia (HR 4.1 [95% CI 1.5–11.5]) or short telomere (HR 2.2 [1.0–5.0]) before LT. After LT, all patients had anemia, 66% had thrombocytopenia, and 39% had neutropenia. Chronic lung allograft dysfunction frequency was 29% at 4 years. The present findings support the use of LT in TRG mutation carriers without myelodysplasia. Hematological evaluation should be systematically performed before LT. Among patients with telomerase‐related gene mutations who undergo lung transplantation for idiopathic pulmonary fibrosis, pre‐transplant myelodysolasia is associated with reduced post‐transplant survival.

The soluble form of the membrane hemoglobin scavenger receptor CD163 (sCD163), released by shedding, is a strong marker for macrophage activation. Serum sCD163 levels rise in several acute inflammatory states and some fibrosing diseases. Monocyte-derived macrophages (MoDM) differentiated by macrophage colony-stimulating factor (M-MoDM) contribute to the pathophysiology of idiopathic pulmonary fibrosis (IPF), an irreversible and rapidly fatal interstitial lung disease. Since M-MoDM express high membrane CD163 levels, we thus postulated that sCD163 could be a relevant biomarker for macrophage activation in IPF. We found that M-MoDM constitutively released higher amounts of sCD163 (49.5 ± 24.5 ng/ml) than monocytes (0.45 ± 0.32 ng/ml) or MoDM differentiated with granulocyte macrophage-stimulating factor (2.24 ± 0.98 ng/ml). The basal production of sCD163 by M-MoDM was increased following stimulation with lipopolysaccharide (123.4 ± 54.9 ng/ml) or ATP (168.9 ± 41.8 ng/ml). The sCD163 release was controlled by metalloproteases but not through ADAM17 activation. Moreover, CD163-positive macrophages and sCD163 were detected in pulmonary tissues and alveolar fluids of Caucasian patients with IPF, respectively. IPF alveolar macrophages constitutively secreted sCD163 amounts (67.6 ± 44.6 ng/µg RNA) which were significantly higher than those released by alveolar macrophages isolated from controls (19.2 ± 7.6 ng/µg RNA) or patients with other interstitial lung disease (31.5 ± 16.6 ng/µg RNA). However, the concentrations of sCD163 in blood serum collected from 155 patients with IPF did not correlate with the severity of their disease. In conclusion, our results show that M-MoDM constituted a pertinent model to study the regulation of sCD163 production. Yet, serum sCD163 values could not provide a prognostic biomarker for IPF in our cohort.

Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Blood signatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classify undetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could be detected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosed radiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening.

A hallmark of idiopathic pulmonary fibrosis is the excess accumulation of extracellular matrix in the lungs. Degradation of extracellular matrix generates free-circulating protein fragments called neoepitopes. The aim of the INMARK trial was to investigate changes in neoepitopes as predictors of disease progression in patients with idiopathic pulmonary fibrosis and the effect of nintedanib on these biomarkers.

Objective.To investigate the uncommon co-occurrence of antisynthetase syndrome (AS) and sarcoidosis.Methods.From 2000 to 2015, patients with sarcoidosis were extracted from a retrospective multicentric cohort of 352 patients with AS.Results.Ten patients (2.8%; 6 men, 8 whites, 5 smokers, median age 50 yrs) had both AS and sarcoidosis. Most of the time, sarcoidosis and AS occurred simultaneously (n = 7). Antibody testing revealed anti-Jo1 (n = 5), anti-PL12 (n = 4), or anti-PL7 (n = 1). Finally, no patient had a worsening of muscular condition, 5 patients presented respiratory deterioration, 3 remained stable, and 2 showed improvement.Conclusion.Sarcoidosis may be underdiagnosed in patients with AS.

In complicated parapneumonic effusion (CPPE), antibiotics and evacuation of the infected pleural fluid are mandatory. The first-line evacuation treatment is still controversial. The aim of this article is to highlight the usefulness of repeated therapeutic thoracentesis (RTT) as a first-line treatment.

La Société de pneumologie de langue française définie l’exacerbation aiguë de bronchopneumopathie chronique obstructivecomme une majoration des symptômes respiratoires au-delà des variations quotidiennes (en pratique, d’une durée ≥ 48 h ou justifiant une modification thérapeutique).

La Société de pneumologie de langue française définie l’exacerbation aiguë de bronchopneumopathie chronique obstructivecomme une majoration des symptômes respiratoires au-delà des variations quotidiennes (en pratique, d’une durée ≥ 48 h ou justifiant une modification thérapeutique).

ABSTRACTPneumocystis jiroveciipneumonia (PCP) is a life-threatening infection in immunocompromised patients. Quantitative real-time PCR (qPCR) is more sensitive than microscopic examination for the detection of P. jiroveciibut also detects colonized patients. Hence, its positive predictive value (PPV) needs evaluation. In this 4-year prospective observational study, all immunocompromised patients with acute respiratory symptoms who were investigated for PCP were included, totaling 659 patients (814 bronchoalveolar lavage fluid samples). Patients with negative microscopy but positive qPCR were classified through medical chart review as having retained PCP, possible PCP, or colonization, and their clinical outcomes were compared to those of patients with microscopically proven PCP. Overall, 119 patients were included for analysis, of whom 35, 41, and 43 were classified as having retained PCP, possible PCP, and colonization, respectively. The 35 patients with retained PCP had clinical findings similar to those with microscopically proven PCP but lower fungal loads (P< 0.001) and were mainly non-HIV-infected patients (P< 0.05). Although the mean amplification threshold was higher in colonized patients, it was not possible to determine a discriminant qPCR cutoff. The PPV of qPCR in patients with negative microscopy were 29.4% and 63.8% when considering retained PCP and retained plus possible PCP, respectively. Patients with possible PCP had a higher mortality rate than patients with retained PCP or colonization (63% versus 3% and 16%, respectively); patients who died had not received co-trimoxazole. In conclusion, qPCR is a useful tool to diagnose PCP in non-HIV patients, and treatment might be better targeted through a multicomponent algorithm including both clinical/radiological parameters and qPCR results.

The drug 131I-labeled lipiodol is used as internal radiotherapy for unresectable hepatocellular carcinoma. Although the drug was considered safe during preapproval studies, we observed several cases of interstitial pneumonia following its administration.

The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population.

Patients with advanced-stage non-small cell lung cancer (NSCLC) whose tumors harbor an anaplastic lymphoma kinase (ALK) gene rearrangement benefit from treatment with multiple ALK inhibitors (ALKi). Approximately 30% of tumor biopsies contain insufficient tissue for successful ALKmolecular characterization. This study evaluated the added value of analyzing circulating tumor cells (CTCs) as a surrogate to ALKtissue analysis and as a function of the response to ALKi.

Les éleveurs laitiers-bovins présentent une incidence plus élevée de symptômes respiratoires et de maladies bronchopulmonaires que la population générale. Un facteur de risque important serait l’exposition professionnelle à divers aérocontaminants d’origine biologique et chimique. Les paramètres de l’activité professionnelle déterminant les niveaux d’exposition à ces contaminants restent cependant mal connus. Cette connaissance est nécessaire à la fois pour identifier des mesures de prévention mais aussi dans le cadre d’études épidémiologiques futures. Dans ce contexte, nous nous sommes attachés à rechercher les déterminants professionnels de l’exposition aux bioaérosols thoraciques (poussières organiques, endotoxines, bactéries et moisissures), à l’ammoniac et à l’acétaldéhyde.

Les télomérases sont les enzymes assurant la synthèse des télomères, séquences d’ADN essentiels dans la protection des chromosomes. Les mutations des télomérases sont responsables, entre autres, d’anomalies hématologiques, pulmonaires (fibrose pulmonaire idiopathique) et hépatiques. Il n’y a que peu de données dans la littérature concernant les résultats des transplantations pulmonaires chez ces patients mutés.

Nous rapportons ici la première observation d’un cas de leucoencéphalopathie multifocale progressive (LEMP) associée à une silicose pulmonaire chez un patient sans traitement immunosuppresseur.

Les cas d’asthmes induits par les anti-TNF-α sont rares, et il n’a jamais été décrit de tentative de réintroduction d’une molécule de même classe.

Le cancer du pancréas est une néoplasie souvent diagnostiquée au stade métastatique et au pronostic sombre. Les lésions secondaires pulmonaires, pléiomorphes, sont souvent présentes au diagnostic et peuvent faire découvrir une maladie par ailleurs asymptomatique.