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. 2024 Dec 2;10(6):00314-2024.
doi: 10.1183/23120541.00314-2024. eCollection 2024 Nov.

Pulmonary fibrosis in patients with autoimmune pulmonary alveolar proteinosis: a retrospective nationwide cohort study

Yoann Guirriec  1   2 , David Luque-Paz  1   3   2 , Gontran Bernard  4 , Axelle Mabo  1 , Mallorie Kerjouan  1 , Cédric Ménard  5 , Delphine Monnier  5 , Hilario Nunes  6 , Yurdagül Uzunhan  6 , Martine Reynaud-Gaubert  7 , Julien Bermudez  7 , Raphaël Borie  8   9 , Bruno Crestani  8   9 , Julie Traclet  10 , Lidwine Wémeau-Stervinou  11 , Cécile Chenivesse  11 , Emmanuel Gomez  12 , Grégoire Prévot  13 , Arnaud Bourdin  14 , Benjamin Bondue  15 , Anne Bergeron  16 , Vincent Cottin  10 , Mathieu Lederlin  4   2 , Stéphane Jouneau  1   17   2 ; OrphaLung network
Affiliations

Pulmonary fibrosis in patients with autoimmune pulmonary alveolar proteinosis: a retrospective nationwide cohort study

Yoann Guirriec et al. ERJ Open Res. .

Abstract

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease that may progress towards pulmonary fibrosis. Data about fibrosis prevalence and risk factors are lacking.

Methods: In this retrospective multicentre nationwide cohort, we included patients newly diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected from medical records using a standardised questionnaire.

Results: 61 patients were included in the final analysis. We identified 5 patients (8%) with fibrosis on initial computed tomography (CT) and 16 patients (26%) with fibrosis on final CT after a median time of 3.6 years. Dust exposure was associated with pulmonary fibrosis occurrence (OR 4.3; p=0.038). aPAP patients treated with whole-lung lavage, rituximab or granulocyte-monocyte colony-stimulating factor therapy did not have more fibrotic evolution than patients who did not receive these treatments (n=25 out of 45, 57% versus n=10 out of 16, 62%; p=0.69). All-cause mortality was significantly higher in fibrotic than in nonfibrotic cases (n=4 out of 16, 25% versus n=2 out of 45, 4.4%; p=0.036, respectively).

Conclusion: In our population, a quarter of aPAP patients progressed towards pulmonary fibrosis. Dust exposure seems to be an important factor associated with this complication. More studies are needed to analyse precisely the impact of dust exposure impact, especially silica, in patients with aPAP.

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Conflict of interest statement

Conflict of interest: C. Chenivesse declares having received grants from AstraZeneca, GlaxoSmithKline, Novartis and Santelys, personal fees from ALK-Abello, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Sanofi, and congress support from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis and Sanofi. M. Lederlin has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups and research projects over the past 5 years from AstraZeneca, Boehringer, Fresenius-Kabi and Siemens Healthcare. S. Jouneau has received fees, funding or reimbursement for national and international conferences, boards, expert or opinion groups, and research projects over the past 5 years from Actelion, AIRB, AstraZeneca, Bellorophon Therapeutics, Biogen, BMS, Boehringer, Chiesi, Fibrogen, Gilead, GSK, LVL, Mundipharma, Novartis, Olam Pharm, Pfizer, Pliant Therapeutics, Roche and Savara-Serendex. The other authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study. GM-CSF: granulocyte–monocyte colony-stimulating factor; aPAP: autoimmune pulmonary alveolar proteinosis; CT: computed tomography.
FIGURE 2
FIGURE 2
Chest computed tomography (CT) scan images of three groups. a, b) Patient without fibrosis. Diagnosis, no fibrosis (a) and 26-month follow-up, no fibrosis (b). c, d) Patient without fibrosis on initial CT and with fibrosis on final CT. Diagnosis, no fibrosis (c) and 124-month follow-up, grade 3 fibrosis (d). e, f) Patient with fibrosis on initial CT and on final CT. Diagnosis, grade 1 fibrosis (e) and 37-month follow-up, grade 1 fibrosis (f).
FIGURE 3
FIGURE 3
Kaplan–Meier curve of survival.
See this image and copyright information in PMC

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