Early interstitial lung disease in familial pulmonary fibrosis.

RATIONALE Identification of early, asymptomatic interstitial lung disease (ILD) in populations at risk of developing idiopathic pulmonary fibrosis (IPF) may improve the understanding of the natural history of IPF. OBJECTIVES To determine clinical, radiographic, physiologic, and pathologic features of asymptomatic ILD in family members of patients with familial IPF. METHODS One hundred sixty-four subjects from 18 kindreds affected with familial IPF were evaluated for ILD. Bronchoalveolar lavage fluid cells were analyzed using flow cytometry. Lung biopsies were performed in six subjects with asymptomatic ILD. MEASUREMENTS AND MAIN RESULTS High-resolution computed tomography abnormalities suggesting ILD were identified in 31 (22%) of 143 asymptomatic subjects. Subjects with asymptomatic ILD were significantly younger than subjects with known familial IPF (P < 0.001) and significantly older than related subjects without lung disease (P < 0.001). A history of smoking was identified in 45% of subjects with asymptomatic ILD and in 67% of subjects with familial IPF; these percentages were significantly higher than that of related subjects without lung disease (23%) (P = 0.02 and P < 0.001, respectively). Percentages of activated CD4(+) lymphocytes were significantly higher in bronchoalveolar lavage fluid cells from subjects with asymptomatic ILD compared with related subjects without lung disease (P < 0.001). Lung biopsies performed in subjects with asymptomatic ILD revealed diverse histologic subtypes. CONCLUSIONS Asymptomatic ILD in individuals at risk of developing familial IPF can be identified using high-resolution computed tomography scan of the chest, especially in those with a history of smoking. Lung biopsies from individuals in this cohort with early asymptomatic lung disease demonstrate various histologic subtypes of ILD.

[1]  I. Rosas,et al.  Impairment of alveolar macrophage transcription in idiopathic pulmonary fibrosis. , 2007, American journal of respiratory and critical care medicine.

[2]  Ivana V. Yang,et al.  Gene expression profiling of familial and sporadic interstitial pneumonia. , 2007, American journal of respiratory and critical care medicine.

[3]  N. Kaminski,et al.  When it comes to genes--IPF or NSIP, familial or sporadic--they're all the same. , 2007, American journal of respiratory and critical care medicine.

[4]  Fatema H. Rafiqi,et al.  Accelerated thymic maturation and autoreactive T cells in bronchopulmonary dysplasia. , 2006, American journal of respiratory and critical care medicine.

[5]  H Page McAdams,et al.  Clinical and pathologic features of familial interstitial pneumonia. , 2005, American journal of respiratory and critical care medicine.

[6]  F. Martinez,et al.  The Clinical Course of Patients with Idiopathic Pulmonary Fibrosis , 2005, Annals of Internal Medicine.

[7]  T. Hartman,et al.  Familial idiopathic pulmonary fibrosis: clinical features and outcome. , 2005, Chest.

[8]  R. Geffers,et al.  CD4 T Lymphocyte-mediated lung disease: steady state between pathological and tolerogenic immune reactions. , 2004, American journal of respiratory and critical care medicine.

[9]  G. Raghu,et al.  Inherited interstitial lung disease. , 2004, Clinics in chest medicine.

[10]  Douglas Curran-Everett,et al.  Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. , 2004, Chest.

[11]  G. Raghu,et al.  A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. , 2004, The New England journal of medicine.

[12]  R. Ross,et al.  ATS/ACCP statement on cardiopulmonary exercise testing. , 2003, American journal of respiratory and critical care medicine.

[13]  F. Martinez,et al.  American Thoracic Society/ American College of Chest Physicians ATS/ACCP Statement on Cardiopulmonary Exercise Testing , 2003 .

[14]  L. Newman,et al.  Target organ localization of memory CD4(+) T cells in patients with chronic beryllium disease. , 2002, The Journal of clinical investigation.

[15]  A. Dwyer,et al.  Hermansky-Pudlak syndrome: radiography and CT of the chest compared with pulmonary function tests and genetic studies. , 2002, AJR. American journal of roentgenology.

[16]  M. Ohtsuka,et al.  Conserved CDR 3 region of T cell receptor BV gene in lymphocytes from bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis , 2002, Clinical and experimental immunology.

[17]  T. Laitinen,et al.  Nationwide prevalence of sporadic and familial idiopathic pulmonary fibrosis: evidence of founder effect among multiplex families in Finland , 2002, Thorax.

[18]  M. Wahidi,et al.  Familial pulmonary fibrosis in the United States. , 2002, Chest.

[19]  Paul J. Friedman,et al.  American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors , 2002, American journal of respiratory and critical care medicine.

[20]  J. Tooze,et al.  Predicting survival in idiopathic pulmonary fibrosis: scoring system and survival model. , 2001, American journal of respiratory and critical care medicine.

[21]  W. Thurlbeck,et al.  Idiopathic pulmonary fibrosis: relationship between histopathologic features and mortality. , 2001, American journal of respiratory and critical care medicine.

[22]  D. Schroeder,et al.  Idiopathic pulmonary fibrosis: Impact of oxygen and colchicine, prednisone, or no therapy on survival. , 2000, American journal of respiratory and critical care medicine.

[23]  G. Laurent,et al.  Adult familial cryptogenic fibrosing alveolitis in the United Kingdom , 2000, Thorax.

[24]  W. Gahl,et al.  Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutations in HPS-1. , 2000, Chest.

[25]  K. Welsh,et al.  T‐cell receptor gene usage in patients with fibrosing alveolitis and control subjects , 1999, European journal of clinical investigation.

[26]  S. Wagenaar,et al.  Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis. , 1995, Thorax.

[27]  A. Miller,et al.  Lung function testing: selection of reference values and interpretative strategies. , 1992, The American review of respiratory disease.

[28]  D. Schwartz,et al.  Determinants of bronchoalveolar lavage cellularity in idiopathic pulmonary fibrosis. , 1991, Journal of applied physiology.

[29]  M. Schwarz,et al.  Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy. , 1987, The American review of respiratory disease.

[30]  R. Crystal,et al.  Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members. , 1986, The New England journal of medicine.

[31]  W. Roberts,et al.  Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. , 1977, The Journal of clinical investigation.