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. 2024 Apr;202(2):151-156.
doi: 10.1007/s00408-024-00685-3. Epub 2024 Mar 10.

Genetic Testing Goes Beyond Imaging and Histological Evaluation in Pleuroparenchymal Fibroelastosis

Ghadah Alrehaili  1 , Jennifer Kemppainen  2   3 , Sanjay Kalra  1 , Filippo Pinto E Vairo  2   3 , Teng Moua  1 , Eunhee S Yi  4 , Alejandro Ferrer  5 , Mrinal M Patnaik  5 , Eva M Carmona  6
Affiliations

Genetic Testing Goes Beyond Imaging and Histological Evaluation in Pleuroparenchymal Fibroelastosis

Ghadah Alrehaili et al. Lung. 2024 Apr.

Abstract

Background: Lung biopsy remains the gold standard in the diagnosis of fibrotic interstitial lung disease (F-ILD), but there is a growing appreciation of the role of pathogenic gene variants in telomere and surfactant protein genes, especially in familial pulmonary fibrosis (FPF). Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that can coexist with different patterns of F-ILD, including FPF. It can be progressive and often leads to respiratory failure and death. This study tested the hypothesis that genetic testing goes beyond radiological and histological findings in PPFE and other F-ILD further informing clinical decision-making for patients and affected family members by identifying pathological gene variants in telomere and surfactant protein genes.

Methods: This is a retrospective review of 70 patients with F-ILD in the setting of FPF or premature lung fibrosis. Six out of 70 patients were diagnosed with PPFE based on radiological or histological characteristics. All patients underwent telomere length evaluation in peripheral blood by Flow-FISH or genetic testing using a customized exome-based panel that included telomere and surfactant protein genes associated with lung fibrosis.

Results: Herein, we identified six individuals where radiographic or histopathological analyses of PPFE were linked with telomere biology disorders (TBD) or variants in surfactant protein genes. Each case involved individuals with either personal early-onset lung fibrosis or a family history of the disease. Assessments of telomere length and genetic testing offered insights beyond traditional radiological and histopathological evaluations.

Conclusion: Detecting anomalies in TBD-related or surfactant protein genes can significantly refine the diagnosis and treatment strategies for individuals with PPFE and other F-ILD.

Keywords: Lung genetics; Pleuroparenchymal fibroelastosis (PPFE); Pulmonary fibrosis; SFTPA2; Surfactant protein disorders; Telomere biology disorders.

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Conflict of interest statement

Ghadah Alrehaili, Jennifer Kemppainen, Sanjay Kalra, Filippo Pinto e Vairo, Teng Moua, Eunhee S. Yi and Alejandro Ferrer declare no competing interests. Mrinal M. Patnaik has received research funding from StemLine, Kura, Epigenetix, and Polaris and is currently on the advisory board for Center for Therapeutic Intervention (CTI). Eva M. Carmona reports providing consultation to Boehringer Ingelheim for sarcoidosis. This is unrelated to the submitted work.

Figures

Fig. 1
Fig. 1
Pedigree of patient with a SFTPA2 pathogenic variant (NM_001098668.4: c.532 G > A—p.(Val178Met)) and histological features. Multiple family members were affected with F-ILD and lung cancer, as shown. Pedigree also shows the 40X H&E lung tissue histology of proband (A) and proband’s cousin (B)
See this image and copyright information in PMC

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