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.

French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2021 update. Full-length version.

BACKGROUND: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS: Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.

Digestive-tract sarcoidosis: French nationwide case-control study of 25 cases.

Digestive tract sarcoidosis (DTS) is rare and case-series are lacking. In this retrospective case-control study, we aimed to compare the characteristics, outcome, and treatment of patients with DTS, nondigestive tract sarcoidosis (NDTS), and Crohn disease.We included cases of confirmed sarcoidosis, symptomatic digestive tract involvement, and noncaseating granuloma in any digestive tract. Each case was compared with 2 controls with sarcoidoisis without digestive tract involvement and 4 with Crohn disease.We compared 25 cases of DTS to 50 controls with NDTS and 100 controls with Crohn disease. The major digestive clinical features were abdominal pain (56%), weight loss (52%), nausea/vomiting (48%), diarrhea (32%), and digestive bleeding (28%). On endoscopy of DTS, macroscopic lesions were observed in the esophagus (9%), stomach (78%), duodenum (9%), colon, (25%) and rectum (19%). As compared with NDTS, DTS was associated with weight loss (odds ratio [OR] 5.8; 95% confidence interval [CI] 1.44-23.3) and the absence of thoracic adenopathy (OR 5.0; 95% CI 1.03-25). As compared with Crohn disease, DTS was associated with Afro-Caribbean origin (OR 27; 95% CI 3.6-204) and the absence of ileum or colon macroscopic lesions (OR 62.5; 95% CI 10.3-500). On the last follow-up, patients with DTS showed no need for surgery (versus 31% for patients with Crohn disease; P = 0.0013), and clinical digestive remission was frequent (76% vs. 35% for patients with Crohn disease; P = 0.0002).The differential diagnosis with Crohn disease could be an issue with DTS. Nevertheless, the 2 diseases often have different clinical presentation and outcome.

Intravenous Immunoglobulin as an Immunomodulating Agent in Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A French Nationwide Study of Ninety-Two Patients.

OBJECTIVE: Intravenous immunoglobulin (IVIG) represents a therapeutic alternative in antineutrophil cytoplasmic antibody-associated vasculitides (AAV), but its efficacy has been evaluated in only 2 small prospective trials. The aim of this study was to evaluate the efficacy and safety of IVIG in patients with AAV. METHODS: We conducted a nationwide retrospective study of patients who received IVIG as immunomodulatory therapy for AAV. RESULTS: A total of 92 patients (mean age 51 years) presenting with either granulomatosis with polyangiitis (Wegener's) (68%), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (22%), or microscopic polyangiitis (10%) received at least 1 course of IVIG. Antineutrophil cytoplasmic antibodies were present in 72% during the flare that required IVIG, as determined by immunofluorescence assay. IVIG was initiated because of relapsing disease in 83% of cases. IVIG was given for a median of 6 months (range 1-156 months) and in combination with corticosteroids in 21% of the patients or with other immunosuppressive agents in 77%. Efficacy of IVIG was assessed in the entire population and in a subset of 34 patients with unmodified background therapy. Remission rates at 6 months were 56% in the entire population and 58% in the unmodified background therapy group. Refractory disease and treatment failure at 6 months were observed in 7% and 18% in the whole population and 3% and 21% in the unmodified background therapy group, respectively. Adverse events (AEs) occurred in 33%, including serious AEs in 12% and AEs leading to discontinuation of IVIG in 7%. CONCLUSION: This large study shows the clinical benefit of IVIG as adjunctive therapy, with an acceptable tolerance profile, and thus supports its use in AAV patients with refractory or relapsing disease.

Lung cancer among women in France. Analysis of the 904 French women with lung cancer included in the KBP-2000-CPHG study of the French College of General Hospital-based Pneumologists (CPHG).

As the incidence of primary lung cancer in women seems to be increasing in parallel with that of smoking, we conducted an exhaustive epidemiological study in 137 hospitals in 2000. We identified 904 women with proven primary lung cancer (mean age 63.9 years), many of whom have never smoked (32.3%), particularly in cases of adenocarcinoma (43.4%). Small cell cancer accounted for 16.1% of cases. Adenocarcinomas were the most frequent (45.3%) of the non-small cell lung cancer (NSCLC), followed by squamous cell (23.4%), large cell (11.6%) and bronchoalveolar (1.9%) carcinomas. About one third (32.2%) of NSCLC were stage III and 48.1% were stage IV. Over half of all adenocarcinomas were stage IV. According to multivariate analysis, adenocarcinoma is related to less smoking and younger age. In conclusion, many women affected by lung cancer have never smoked. Adenocarcinoma appears to be the most frequent form and more often at a metastatic stage.