Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults

• Published in: Respirology (Carlton, Vic.) Vol. 29; no. 4; pp. 312 - 323
• Main Authors: Diesler, Rémi, Legendre, Marie, Si‐Mohamed, Salim, Brillet, Pierre‐Yves, Wemeau, Lidwine, Manali, Effrosyni D., Gagnadoux, Frédéric, Hirschi, Sandrine, Lorillon, Gwenaël, Reynaud‐Gaubert, Martine, Bironneau, Vanessa, Blanchard, Elodie, Bourdin, Arnaud, Dominique, Stéphane, Justet, Aurélien, Macey, Julie, Marchand‐Adam, Sylvain, Morisse‐Pradier, Hélène, Nunes, Hilario, Papiris, Spyros A., Traclet, Julie, Traore, Ibrahim, Crestani, Bruno, Amselem, Serge, Nathan, Nadia, Borie, Raphaël, Cottin, Vincent, Taam, Rola Abou, Bermudez, Julien, Bonniaud, Philippe, Brudon, Alexandre, Cros, Pierrick, Delestrain, Céline, Epaud, Ralph, Fouquet, Helen, Gondouin, Anne, Duverge, Alice Hadchouel, Jouneau, Stéphane, Juvin, Karine, Le Pavec, Jérôme, Meurice, Jean‐Claude, Nasser, Mouhamad, Pastre, Jean, Picard, Clément, Provost, Mathilde, Tissot, Adrien, Uzunhan, Yurdagul, Valeyre, Dominique
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-04-2024; Wiley Subscription Services, Inc; Wiley
• Subjects: ABCA3; Adult; adults; ATP-Binding Cassette Transporters - genetics; Chest; Child; Computed tomography; Cysts; fibrosing interstitial lung disease; Genetics; Human genetics; Human health and pathology; Humans; Idiopathic Pulmonary Fibrosis; interstitial lung disease; Life Sciences; Lung - diagnostic imaging; Lung diseases; Lung Diseases, Interstitial - diagnostic imaging; Lung Diseases, Interstitial - genetics; Lung transplantation; Male; Phenotypes; Pneumonia; Populations and Evolution; Pulmonary Surfactant-Associated Protein C; Pulmonology and respiratory tract; Retrospective Studies; SFTPC; surfactant; interstitial lung disease; ABCA3; SFTPC; fibrosing interstitial lung disease; surfactant; adults
• ISSN: 1323-7799; 1440-1843; 1440-1843
• DOI: 10.1111/resp.14667

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 DLCO 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 DLCO, 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.
We report the characteristics and follow‐up data of 36 adult patients in France with ILD associated variant(s) in SFTPC or ABCA3. 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.