Tetsuro Araki1,2, Rachel K Putman3, Hiroto Hatabu1,2, Wei Gao4,5, Josée Dupuis4,5, Jeanne C Latourelle6,7, Mizuki Nishino2,8, Oscar E Zazueta3, Sila Kurugol8, James C Ross8,9, Raúl San José Estépar2,8, David A Schwartz10, Ivan O Rosas3, George R Washko3, George T O'Connor4,11, Gary M Hunninghake1,3. 1. 1 Center for Pulmonary Functional Imaging. 2. 2 Department of Radiology. 3. 3 Pulmonary and Critical Care Division. 4. 4 The NHLBI's Framingham Heart Study, Boston, Massachusetts. 5. 5 Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts. 6. 6 Department of Medicine and. 7. 7 Department of Neurology, Boston University, Boston, Massachusetts. 8. 8 Surgical Planning Laboratory, Department of Radiology, and. 9. 9 Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts. 10. 10 Pulmonary Center, Department of Medicine, University of Colorado, Denver, Colorado; and. 11. 11 Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
Abstract
RATIONALE: The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated. OBJECTIVES: To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study. METHODS: ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (and Cox) models were used to assess the association between ILA progression and pulmonary function decline (and mortality). MEASUREMENTS AND MAIN RESULTS: During the follow-up period 660 (35%) participants did not have ILA on either CT scan, 37 (2%) had stable to improving ILA, and 118 (6%) had ILA with progression (the remaining participants without ILA were noted to be indeterminate on at least one CT scan). Increasing age and increasing copies of the MUC5B promoter polymorphism were associated with ILA progression. After adjustment for covariates, ILA progression was associated with a greater FVC decline when compared with participants without ILA (20 ml; SE, ±6 ml; P = 0.0005) and with those with ILA without progression (25 ml; SE, ±11 ml; P = 0.03). Over a median follow-up time of approximately 4 years, after adjustment, ILA progression was associated with an increase in the risk of death (hazard ratio, 3.9; 95% confidence interval, 1.3-10.9; P = 0.01) when compared with those without ILA. CONCLUSIONS: These findings demonstrate that ILA progression in the Framingham Heart Study is associated with an increased rate of pulmonary function decline and increased risk of death.
RATIONALE: The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated. OBJECTIVES: To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study. METHODS: ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (and Cox) models were used to assess the association between ILA progression and pulmonary function decline (and mortality). MEASUREMENTS AND MAIN RESULTS: During the follow-up period 660 (35%) participants did not have ILA on either CT scan, 37 (2%) had stable to improving ILA, and 118 (6%) had ILA with progression (the remaining participants without ILA were noted to be indeterminate on at least one CT scan). Increasing age and increasing copies of the MUC5B promoter polymorphism were associated with ILA progression. After adjustment for covariates, ILA progression was associated with a greater FVC decline when compared with participants without ILA (20 ml; SE, ±6 ml; P = 0.0005) and with those with ILA without progression (25 ml; SE, ±11 ml; P = 0.03). Over a median follow-up time of approximately 4 years, after adjustment, ILA progression was associated with an increase in the risk of death (hazard ratio, 3.9; 95% confidence interval, 1.3-10.9; P = 0.01) when compared with those without ILA. CONCLUSIONS: These findings demonstrate that ILA progression in the Framingham Heart Study is associated with an increased rate of pulmonary function decline and increased risk of death.
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