Extensive phenotyping of individuals at risk for familial interstitial pneumonia reveals clues to the pathogenesis of interstitial lung disease
| Autor: | John A. Worrell, Dong Sheng Cheng, Cheryl Markin, John A. Phillips, Eric S. White, Joyce E. Johnson, Steve D. Groshong, Jason M. Pritchett, Brittany R. Jones, Jae-Woo Lee, Donald F. Zoz, Rinat Zaynagetdinov, Lisa Lancaster, Peter F. Crossno, Lisa R. Young, Leena Choi, Pierre P. Massion, Otis B. Rickman, Mark P. Steele, Jonathan A. Kropski, Vasiliy V. Polosukhin, James E. Loyd, Joseph F. Solus, Melinda E. McConaha, Joy D. Cogan, William Lawson, Amber L. Degryse, Timothy S. Blackwell, Jonathan D. Kurtis, Lorraine B. Ware, Linda A. Gleaves, Errine T. Garnett, Frank B. McMahon, Daphne B. Mitchell |
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| Rok vydání: | 2014 |
| Předmět: |
Lung Diseases
Male Pathology bronchoscopy Biopsy Respiratory System Critical Care and Intensive Care Medicine Medical and Health Sciences Bronchoalveolar Lavage Gene Frequency 2.1 Biological and endogenous factors Medicine Viral Prospective Studies Aetiology Tomography Lung Herpesviridae telomere screening and diagnosis medicine.diagnostic_test Interstitial lung disease respiratory system Middle Aged Mucin-5B X-Ray Computed Detection medicine.anatomical_structure Phenotype Pneumonia & Influenza Respiratory biomarker Biomarker (medicine) Original Article Female medicine.symptom Pulmonary and Respiratory Medicine Adult Genetic Markers medicine.medical_specialty Asymptomatic Rare Diseases Genetic Clinical Research Bronchoscopy Genetics Humans Polymorphism alveolar epithelial cell Idiopathic interstitial pneumonia Aged Polymorphism Genetic business.industry Prevention Case-control study Editorials DNA Pneumonia medicine.disease 4.1 Discovery and preclinical testing of markers and technologies respiratory tract diseases IPF Bronchoalveolar lavage Case-Control Studies Asymptomatic Diseases DNA Viral Interstitial business Lung Diseases Interstitial Tomography X-Ray Computed Biomarkers Blood sampling |
| Zdroj: | American journal of respiratory and critical care medicine, vol 191, iss 4 |
| ISSN: | 1535-4970 |
| Popis: | Rationale: Asymptomatic relatives of patients with familial interstitial pneumonia (FIP), the inherited form of idiopathic interstitial pneumonia, carry increased risk for developing interstitial lung disease. Objectives: Studying these at-risk individuals provides a unique opportunity to investigate early stages of FIP pathogenesis and develop predictive models of disease onset. Methods: Seventy-five asymptomatic first-degree relatives of FIP patients (mean age, 50.8 yr) underwent blood sampling and high-resolution chest computed tomography (HRCT) scanning in an ongoing cohort study; 72 consented to bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies. Twenty-seven healthy individuals were used as control subjects. Measurements and Main Results: Eleven of 75 at-risk subjects (14%) had evidence of interstitial changes by HRCT, whereas 35.2% had abnormalities on transbronchial biopsies. No differences were noted in inflammatory cells in BAL between at-risk individuals and control subjects. At-risk subjects had increased herpesvirus DNA in cell-free BAL and evidence of herpesvirus antigen expression in alveolar epithelial cells (AECs), which correlated with expression of endoplasmic reticulum stress markers in AECs. Peripheral blood mononuclear cell and AEC telomere length were shorter in at-risk individuals than healthy control subjects. The minor allele frequency of the Muc5B rs35705950 promoter polymorphism was increased in at-risk subjects. Levels of several plasma biomarkers differed between at-risk subjects and control subjects, and correlated with abnormal HRCT scans. Conclusions: Evidence of lung parenchymal remodeling and epithelial dysfunction was identified in asymptomatic individuals at risk for FIP. Together, these findings offer new insights into the early pathogenesis of idiopathic interstitial pneumonia and provide an ongoing opportunity to characterize presymptomatic abnormalities that predict progression to clinical disease. |
| Databáze: | OpenAIRE |
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