Rationale: The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.Objectives: We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV 1 decline.Methods: We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV 1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRM emph ) and functional small airways disease (PRM fSAD ), a measure of nonemphysematous air trapping.Measurements and Main Results: Mean (SD) rate of FEV 1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8), respectively (trend test for grades 1-4; P , 0.001). In multivariable linear regression, for participants without airflow obstruction, PRM fSAD but not PRM emph was associated with FEV 1 decline (P , 0.001). In GOLD 1-4 participants, both PRM fSAD and PRM emph were associated with FEV 1 decline (P , 0.001 and P = 0.001, respectively). Based on the model, the proportional contribution of the two CT metrics to FEV 1 decline, relative to each other, was 87% versus 13% and 68% versus 32% for PRM fSAD and PRM emph in GOLD 1/2 and 3/4, respectively.Conclusions: CT-assessed functional small airway disease and emphysema are associated with FEV 1 decline, but the association with functional small airway disease has greatest importance in mildto-moderate stage chronic obstructive pulmonary disease where the rate of FEV 1 decline is the greatest.Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

The composite physiologic index(CPI) was derived to represent the extent of fibrosis on high resolution computed tomography, adjusting for emphysema in patients with idiopathic pulmonary fibrosis(IPF). We hypothesized longitudinal change in CPI would better predict mortality than forced expiratory volume in 1 second(FEV1), forced vital capacity(FVC), or diffusing capacity for carbon monoxide(DLCO) in all patients with IPF, and especially in those with combined pulmonary fibrosis and emphysema(CPFE). Cox proportional hazard models were performed on pulmonary function data from IPF patients at baseline (n=321), 6 months (n=211) and 12 months (n=144). Presence of CPFE was determined by high resolution computed tomography. A 5 point increase in CPI over 12 months predicted subsequent mortality (HR 2.1, p=0.004). At 12 months, a 10% relative decline in FVC, a 15% relative decline in DLCO or an absolute increase in CPI of 5 points all discriminated median survival by 2.1 to 2.2 years versus patients with lesser change. Half our cohort had CPFE. In patients with moderate/severe emphysema, only a 10% decline in FEV1 predicted mortality (HR 3.7, p=0.046). In IPF, a 5 point increase in CPI over 12 months predicts mortality similarly to relative declines of 10% in FVC or 15% in DLCO. For CPFE patients, change in FEV1 was the best predictor of mortality.

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Information from TBB, when combined with clinical and HRCT data, may provide enough information to make a confident and accurate diagnosis in approximately 20% to 30% of patients with ILD.

Three prognostically distinct, radiologically defined phenotypes are identified among patients with HP. The importance of pursuing a specific diagnosis (eg, HP vs IPF) among patients with non-honeycomb fibrosis is highlighted. When radiologic honeycombing is present, invasive diagnostic testing directed at determining the diagnosis may be of limited value given a uniformly poor prognosis.