Association between ventilation inhomogeneity, small airway abnormality and exercise intolerance in patients with COPD

Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality, representing a significant socioeconomic impact and a major public health problem. Its global impact continues to rise due to the continued exposure to risk factors and the aging of the population. Spirometry is essential for diagnostic confirmation, but because it focuses on the stratification of airway obstruction severity - by the analysis of forced expiratory volume in the first second (FEV1) -, it has little correlation with patient-centered outcomes such as dyspnea, exercise tolerance, health-related quality of life (HRQoL), and mortality. In order to elucidate the common ventilatory limitations in the COPD patient, interest in the use of the single breath nitrogen washout test (N2SBW) has increased. N2SBW detects poor distribution of pulmonary ventilation and small airway disease, even when other lung function tests (PFTs) still bring values within normal range. On the other hand, the cardiopulmonary exercise test (CPET) promotes the integrated evaluation of cardiorespiratory responses to exercise by analyzing metabolic, ventilatory and cardiovascular responses during dynamic exercise, thus having an important diagnostic and prognostic potential in patients with COPD. Objective: To evaluate the contribution of N2SBW in predicting HRQoL and tolerance during CPET in patients with COPD. Methods: In this cross-sectional quantitative study 31 patients were included. The patients underwent clinical evaluation, modified Medical Research Council (m-MRC) dyspnea scale, and the HRQoL questionnaires including COPD assessment test (CAT) score, 36-Item Short Form Health Survey (SF36), and St. George’s Respiratory Questionnaire (SGRQ). They were also submitted to PFTs, including spirometry, body plethysmography, and N2SBW. Finally, they were evaluated for their functional capacity and exercise tolerance during CPET. Results: Sixteen men and 15 women were evaluated. The mean age was 67.5 ± 9.9 years, while the smoking load was 50.9 ± 26.2 pack-years. It was observed that the greater the inomogeneity in ventilation measured by the phase III slope of the nitrogen washout test in single breathing (SIIIN2), the lower the oxygen consumption (peak VO2) and breathing reserve measured in the exercise peak due to negative correlations between the variables (r = -0.681, P < 0.0001; r = -0.799, P < 0.0001, respectively). It was also verified that the higher the SIIIN2 there will be a greater negative impact on the HRQoL evaluated through the CAT (r = 0.591, P <0.0005) and physical component summary measured by SF36 (r = -0.475, P <0.007). Conclusion: The observed correlation between the ventilation inomogeneity and exercise intolerance indicates that N2SBW should be explored as a complementary tool in the evaluation of patients with COPD.