Age and Small Airway Imaging Abnormalities in Subjects with and without Airflow Obstruction in SPIROMICS

Abstract

Rationale: Aging is associated with reduced FEV 1 to FVC ratio (FEV 1 /FVC), hyperinflation, and alveolar enlargement, but little is known about how age affects small airways. Objectives: To determine if chest computed tomography (CT)assessed functional small airway would increase with age, even among asymptomatic individuals. Methods: We used parametric response mapping analysis of paired inspiratory/expiratory CTs to identify functional small airway abnormality (PRM FSA) and emphysema (PRM EMPH) in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort. Using adjusted linear regression models, we analyzed associations between PRM FSA and age in subjects with or without airflow obstruction. We subdivided participants with normal spirometry based on respiratory-related impairment (6-minute-walk distance ,350 m, modified Medical Research Council >2, chronic bronchitis, St. George's Respiratory Questionnaire .25, respiratory events requiring treatment [antibiotics and/or steroids or hospitalization] in the year before enrollment). Measurements and Main Results: Among 580 never-and eversmokers without obstruction or respiratory impairment, PRM FSA increased 2.7% per decade, ranging from 3.6% (ages 40-50 yr) to 12.7% (ages 70-80 yr). PRM EMPH increased nonsignificantly (0.1% [ages 40-50 yr] to 0.4% [ages 70-80 yr]; P = 0.34). Associations were similar among nonobstructed individuals with respiratory-related impairment. Increasing PRM FSA in subjects without airflow obstruction was associated with increased FVC (P = 0.004) but unchanged FEV 1 (P = 0.94), yielding lower FEV 1 /FVC ratios (P , 0.001). Although emphysema was also significantly associated with lower FEV 1 /FVC (P = 0.04), its contribution relative to PRM FSA in those without airflow obstruction was limited by its low burden. Conclusions: In never-and ever-smokers without airflow obstruction, aging is associated with increased FVC and CT-defined functional small airway abnormality regardless of respiratory symptoms.

Respiratory symptoms and small airway dysfunction in current and former smokers without spirometric COPD

“…Half the subjects had an abnormal MDNW or IOS measurement, and in one quarter there was an overlap in abnormal IOS and MBNW variables. The results of the study and those from previous studies using physiological tests and CT imaging biomarkers demonstrate that small airway dysfunction is commonly found in this group of current and former smokers. Interestingly, smokers without spirometric COPD following smoking cessation show sustained improvements of conductive airway dysfunction (S cond ), but not in acinar airway function (S acin ) suggesting that some abnormalities of small airway disease are reversible, possibly due to reduced inflammation or hypersecretion …”

“…The function of peripheral airways is abnormal in some smokers without COPD assessed by physiological techniques, such as multiple breath nitrogen washout (MBNW) and impulse oscillometry (IOS) . Analysis of expiratory and inspiratory computed tomography (CT) images detects increased nonemphysematous air trapping, a surrogate for functional small airways disease, in ever‐smokers with normal spirometry . However, little is known about whether small airway dysfunction assessed by physiological tests, such as MBNW or IOS are worse in symptomatic smokers without COPD compared to asymptomatic smokers.…”

“…8,9 Analysis of expiratory and inspiratory computed tomography (CT) images detects increased nonemphysematous air trapping, a surrogate for functional small airways disease, in ever-smokers with normal spirometry. [10][11][12] However, little is known about whether small airway dysfunction assessed by physiological tests, such as MBNW or IOS are worse in symptomatic smokers without COPD compared to asymptomatic smokers. In this issue of Respirology, Jetmalani et al 13 report the results of a prospective, observational study designed to determine the prevalence of respiratory symptoms (chronic bronchitis, dyspnoea, wheeze) and small airway dysfunction and their interrelationship in eighty young to middle-aged current and former smokers without spirometric COPD.…”

Quantitative analysis of hyperpolarized129Xe gas transfer MRI

“…First, our healthy reference group was not age matched to the relatively older IPF cohort. It is known that aging affects ventilation, and can reasonably be expected to similarly impair gas transfer. Therefore, future studies must also characterize gas transfer in older healthy subjects to better discriminate true disease from normal aging.…”

Computed Tomography Image Matching in Chronic Obstructive Pulmonary Disease

“…PRM-fSAD was also significantly associated with increasing age, especially in subjects without evident airflow obstruction and past smoking history. 82 Hoff and colleagues recently computed spatial relationship and local distributions of PRM-fSAD regions in COPD subjects. 78 These authors showed that the surface area of PRM-fSAD is an independent predictor of clinical outcomes in COPD.…”