Abstract

The majority of smokers with chronic obstructive pulmonary disease (COPD) have mild airflow limitation as determined by simple spirometry. Although small airway dysfunction is the hallmark of COPD, many studies attest to complex heterogeneous physiological impairments beyond increased airway resistance. These impairments are related to inflammation of lung parenchyma and its microvasculature, which is obscured by simple spirometry. Recent studies using advanced radiological imaging have highlighted significant structural abnormalities in smokers with relatively preserved spirometry. These important studies have generated considerable interest and have reinforced the pressing need to better understand the physiological consequences of various morphological abnormalities, and their impact on the clinical outcomes and natural history of COPD. The overarching objective of this review is to provide a concise overview of the importance and utility of cardiopulmonary exercise testing (CPET) in clinical and research settings. CPET uniquely allows evaluation of integrated abnormalities of the respiratory, cardio-circulatory, metabolic, peripheral muscle and neurosensory systems during increases in physiologic stress. This brief review examines the results of recent studies in mild COPD that have uncovered consistent derangements in pulmonary gas exchange and development of “restrictive” dynamic mechanics that together contribute to exercise intolerance. We examine the evidence that compensatory increases in inspiratory neural drive from respiratory control centers are required during exercise in mild COPD to maintain ventilation commensurate with increasing metabolic demand. The ultimate clinical consequences of this high inspiratory neural drive are earlier onset of critical respiratory mechanical constraints and increased perceived respiratory discomfort at relatively low exercise intensities.

Highlights

  • Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating inflammatory disease of the airways, alveoli, and microvasculature

  • Patients classified in the mild COPD stage by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria represent the majority of total patients with COPD, with an estimated global prevalence of 7–11% in adults over 40 years of age [1,2,3]

  • The most commonly reported symptom in patients with mild COPD is dyspnea, defined by a 2012 American Thoracic Society (ATS) statement as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity” [5]

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Summary

Frontiers in Medicine

Recent studies using advanced radiological imaging have highlighted significant structural abnormalities in smokers with relatively preserved spirometry These important studies have generated considerable interest and have reinforced the pressing need to better understand the physiological consequences of various morphological abnormalities, and their impact on the clinical outcomes and natural history of COPD. CPET uniquely allows evaluation of integrated abnormalities of the respiratory, cardio-circulatory, metabolic, peripheral muscle and neurosensory systems during increases in physiologic stress. This brief review examines the results of recent studies in mild COPD that have uncovered consistent derangements in pulmonary gas exchange and development of “restrictive” dynamic mechanics that together contribute to exercise intolerance.

INTRODUCTION
MECHANISMS OF INCREASED INSPIRATORY NEURAL DRIVE IN MILD COPD
Pulmonary Gas Exchange Abnormalities
Dynamic Respiratory Mechanics
Clinical and Therapeutic Implications
CONCLUSIONS
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