Susan K. Mathai M.D.

Posted December 15th 2019

MUC5B variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis.

Susan K. Mathai, M.D.
Susan K. Mathai, M.D.

Mathai, S. K., S. Humphries, J. A. Kropski, T. S. Blackwell, J. Powers, A. D. Walts, C. Markin, J. Woodward, J. H. Chung, K. K. Brown, M. P. Steele, J. E. Loyd, M. I. Schwarz, T. Fingerlin, I. V. Yang, D. A. Lynch and D. A. Schwartz (2019). “MUC5B variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis.” Thorax 74(12): 1131-1139.

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BACKGROUND: Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT. METHODS: First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in MUC5B and TERT was performed. FINDINGS: In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95% CI 0.72 to 0.89) and 86% sensitivity (95% CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex. INTERPRETATION: PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities.


Posted October 15th 2019

Muc5b Variant Is Associated with Visually and Quantitatively Detected Preclinical Pulmonary Fibrosis.

Susan K. Mathai, M.D.

Susan K. Mathai, M.D.

Mathai, S. K., S. Humphries, J. A. Kropski, T. S. Blackwell, J. Powers, A. D. Walts, C. Markin, J. Woodward, J. H. Chung, K. K. Brown, M. P. Steele, J. E. Loyd, M. I. Schwarz, T. Fingerlin, I. V. Yang, D. A. Lynch and D. A. Schwartz (2019). “Muc5b Variant Is Associated with Visually and Quantitatively Detected Preclinical Pulmonary Fibrosis.” Thorax Sep 26. [Epub ahead of print].

Full text of this article.

BACKGROUND: Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT. METHODS: First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in MUC5B and TERT was performed. FINDINGS: In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95% CI 0.72 to 0.89) and 86% sensitivity (95% CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex. INTERPRETATION: PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities.


Posted July 15th 2019

Translational research in pulmonary fibrosis.

Susan K. Mathai, M.D.

Susan K. Mathai, M.D.

Mathai, S. K. and D. A. Schwartz (2019). “Translational research in pulmonary fibrosis.” Transl Res 209: 1-13.

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Pulmonary fibrosis refers to the development of diffuse parenchymal abnormalities in the lung that cause dyspnea, cough, hypoxemia, and impair gas exchange, ultimately leading to respiratory failure. Though pulmonary fibrosis can be caused by a variety of underlying etiologies, ranging from genetic defects to autoimmune diseases to environmental exposures, once fibrosis develops it is irreversible and most often progressive, such that fibrosis of the lung is one of the leading indications for lung transplantation. This review aims to provide a concise summary of the recent advances in our understanding of the genetics and genomics of pulmonary fibrosis, idiopathic pulmonary fibrosis in particular, and how these recent discoveries may be changing the clinical approach to diagnosing and treating patients with fibrotic interstitial lung disease.