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. 2024 Dec 18;25(1):433.
doi: 10.1186/s12931-024-03063-y.

Diagnostic and prognostic implications of family history of fibrotic interstitial lung diseases

D Duminy-Luppi  1   2 , A Alcaide-Aldeano  3   4 , L Planas-Cerezales  5   6 , G Bermudo  7   8   6 , V Vicens-Zygmunt  7   8   6 , P Luburich  9   6 , B Del Río-Carrero  9 , R Llatjós  10   6 , L Pijuan  10 , I Escobar  11 , F Rivas  11 , A Montes-Worboys  7   6 , Y Gutiérrez-Rodríguez  7 , D Rodríguez-Plaza  7 , A Padró-Miquel  12 , A Esteve-Garcia  12 , B Fernández-Varas  13 , C Flores  6   14   15   16 , M Fuentes  7   8 , J Dorca  3 , S Santos  3   7   8   6 , R Perona  13   17   18 , A Günther  19 , J Shull  8 , M Molina-Molina  20   21   22
Affiliations

Diagnostic and prognostic implications of family history of fibrotic interstitial lung diseases

D Duminy-Luppi et al. Respir Res. .

Abstract

Background: Patients with familial fibrotic interstitial lung disease (ILD) experience worse survival than patients with sporadic disease. Current guidelines do not consider family aggregation or genetic information in the diagnostic algorithm for idiopathic pulmonary fibrosis or other fibrotic ILDs. Better characterizing familial cases could help in diagnostic and treatment decision-making.

Methods: This retrospective cohort study included 222 patients with fibrotic ILD (104 familial and 118 sporadic) from Bellvitge University Hospital. Clinical, radiological, pulmonary functional tests (PFT), and histological evaluations were performed at diagnosis and follow-up. Telomere shortening and disease-associated variants (DAVs) in telomerase-related genes were analysed in familial patients and sporadic patients with telomeric clinical signs. Primary outcomes were the presence of a UIP histological pattern and disease progression.

Results: Patients with idiopathic pulmonary fibrosis (IPF) (52%), fibrotic hypersensitivity pneumonitis (23%), and other fibrotic ILDs (25%) were included. 42% of patients underwent lung biopsy. Patients with family aggregation were younger and less frequently associated comorbidities, male sex, and smoking history. However, usual interstitial pneumonia (UIP) was more frequent on pathology (p = 0.005; OR 3.37), especially in patients with indeterminate or non-UIP radiological patterns. Despite similar PFT results at diagnosis, familial patients were more likely to present with progressive disease (p = 0.001; OR 3.75). Carrying a DAV increased the risk of fibrotic progression in familial and sporadic patients (p = 0.029, OR 5.01).

Discussion: Familial patients diagnosed with different fibrotic ILDs were more likely to exhibit a histological UIP pattern and disease progression than sporadic patients, independent of radiological findings and pulmonary function at diagnosis.

Conclusion: Considering the diagnostic likelihood of the histological UIP pattern and disease outcome, the presence of family aggregation would be useful in the decision making of multidisciplinary committees.

Keywords: Biopsy; Disease Progression; Family; Fibrosis; Idiopathic pulmonary fibrosis; Lung; Lung diseases, interstitial; Prognosis; Retrospective studies; Telomere Shortening.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The Ethics Committee of HUB approved the study (PR307/16), and all patients provided written informed consent before inclusion, including written informed consent for genetic testing if needed. Consent for publication: Not applicable. Clinical trial number: Not applicable. Competing interests: MMM has received grants for research purposes and fees for scientific advice outside this work from Boehringer Ing, Ferrer, Roche, Veracyte and Chiesi. The other authors of this work have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Flow chart of grouping based on final diagnosis IPF: idiopathic pulmonary fibrosis, fHP: fibrotic hypersensitivity pneumonitis, uILD: unclassifiable interstitial lung disease, CPFE: combined pulmonary fibrosis and emphysema, SRIF: smoking-related interstitial fibrosis, CTD-ILD: connective tissue disease associated interstitial lung disease. Other include ANCA-associated vasculitis, cocaine-induced pulmonary fibrosis, stage IV sarcoidosis, fibrotic non-specific interstitial pneumonia, radiotherapy induced pulmonary-fibrosis, interstitial pneumonia with autoimmune features and pleuroparenchymal fibroelastosis
Fig. 2
Fig. 2
Estimated marginal means of the probability of progressive disease Estimated marginal means of the probability of progressive disease according to familial vs. sporadic and carrying a disease-associated gene variant yes/no based on the binomial logistic regression model, with 95% confidence intervals of the probability and the numeric values. SE standard error 95% CI 95% confidence interval
See this image and copyright information in PMC

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