Jason Stockhausen and Jennifer Zurawka, respiratory therapists from VA Pittsburgh Healthcare System’s H.J. Heinz III campus, demonstrate pulmonary function testing with spirometry. VA photo
SAN FRANCISCO — Abnormal lung volumes representing air-trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes can be identified by abnormal lung volumes representing air-trapping. Still, exactly how lung volumes evolve in early COPD with airflow obstruction development has remained less clear.
The general understanding of COPD has been that as airflow obstruction progresses, the retention of air in the lung (air trapping) and over-inflation of the lungs due to trapped air (hyperinflation) worsen and a decrease occurs in vital capacity (VC)—the amount of air that the lungs can expel after having been filled—and inspiratory capacity (IC)—the maximum volume of air that can be inspired after reaching the end of a normal, quiet expiration.
More recent studies have suggested, however, that, in early disease, the development of spirometric COPD occurs from an increase in forced VC (FVC)—the maximum amount of air that can be forcibly exhaled from the lungs after fully inhaling—while airflow obstruction (as measured by forced expiratory volume in 1 second, FEV1) remains unaffected. This finding is contrary to the current conventional wisdom.
Mehrdad Arjomandi, MD
For Mehrdad Arjomandi, MD, a pulmonologist with the San Francisco VA Healthcare system, this finding prompted an interest to more precisely investigate how the lung volumes change during the development and progression of spirometric disease, as it remains unclear how underlying obstructive pathology might contribute to an increased FVC in early COPD.
To do this, Arjomandi and colleagues first examined the differences in lung volumes by conducting cross-sectional analyses of patients with differing severity of COPD. Second, they examined the longitudinal changes in lung volumes in smokers with preserved spirometry to determine whether the changes in lung volume mirrored the cross-sectional differences that they observed at baseline.
For these analyses, the study team used the plethysmographic lung volume measurements from the pulmonary function test results available for 71,356 patients in the VA electronic health records and lung volumes measurements derived from thoracic computerized tomography (CT) scans of 7,969 patients available in the National Institute of Health (NIH)-funded research cohorts of COPD Genetic Epidemiology (COPDGene) and Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) (2,552 patients).1
Lung volumes from all three cohorts showed similar patterns of distributions and longitudinal changes with worsening airflow obstruction, they reported in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. “The distributions for total lung capacity (TLC), vital capacity (VC), and inspiratory capacity (IC) and their patterns of change were nonlinear and included different phases,” they wrote. “When stratified by airflow obstruction using GOLD stages, patients with GOLD-1 (mild) COPD had larger lung volumes (TLC, VC, IC) compared to patients with GOLD-0 (smokers with preserved spirometry) or GOLD-2 (moderate) disease. In longitudinal follow-up of baseline GOLD-0 patients who progressed to spirometric COPD, those with initially higher TLC and VC developed mild obstruction (GOLD-1) while those with initially lower TLC and VC developed moderate obstruction (GOLD-2).”
The study did not provide any mechanistic explanation for the observed pattern of lung volumes changes, the authors wrote, noting that it also is possible that different disease mechanisms might underlie progression from GOLD-0 to GOLD-1 vs. to GOLD-2 disease.
While several pathological factors have been described to contribute to changes in lung volumes in COPD, it is unclear whether these pathological factors begin to affect the lungs concurrently or sequentially, and whether they affect all at-risk populations in a similar manner.
“The biphasic pattern that we observed in this analysis suggests that different pathologies may develop or become important at different stages of the disease in different at-risk individuals,” they wrote. “For example, the higher baseline TLC and VC in those progressing from GOLD-0 to GOLD-1 may be due to a disproportionately higher rate of loss of lung elastance in the setting of a relatively lower burden of small airway disease, resulting in lung expansion with lesser air trapping (an “emphysematous” phenotype). Conversely, the lower baseline and subsequent decline in TLC, VC, and IC values among those progressing to GOLD-2 may be due to a higher burden of small airway disease in the presence of a slower loss of lung elastance, resulting in more air trapping with relatively lesser thoracic expansion in the early stages of disease progression (a “small airway” phenotype).”
Disruption of connective tissue is also recognized as a potential mechanism, they added. However, lung connective tissue is organized into an extremely complex three-dimensional network, they noted, and it is reasonable to speculate that disruption of different portions of the network by similar mechanisms could have very disparate effects.
The researchers said further research with quantification of various pathologic mechanisms can lead to a better understanding of the nature and sequence of the pathologies that contribute to the observed nonlinear lung volume changes with spirometric disease progression in COPD. “By understanding these mechanisms, we may be able to better apply prognostic biomarkers and design targeted therapy for the different stages of COPD,” they concluded.
- Arjomandi M, Zeng S, Chen J, Bhatt SP, et. al. and the COPDGene and SPIROMICS Investigators. Changes in Lung Volumes with Spirometric Disease Progression in COPD. Chronic Obstr Pulm Dis. 2023 May 16. doi: 10.15326/jcopdf.2022.0363. Epub ahead of print. PMID: 37199719.
