Excess ventilation and ventilatory constraints during exercise in patients with chronic obstructive pulmonary disease

https://doi.org/10.1016/j.resp.2014.03.002Get rights and content

Highlights

  • Excess ventilation and ventilatory constraints occur in COPD during exercise.

  • VE/VCO2 slope and intercept give complementary information on ventilatory response.

  • Excess ventilation and ventilatory constraints analysis may define COPD phenotypes.

Abstract

We assessed the relationship between minute ventilation/carbon dioxide output (VE/VCO2) and ventilatory constraints during an incremental cardiopulmonary exercise testing (CPET) in patients with chronic obstructive pulmonary disease (COPD).

Slope and intercept of the VE/VCO2 linear relationship, the ratios of inspiratory capacity/total lung capacity (IC/TLC) and of tidal volume (VT) over vital capacity (VTpeak/VC) and IC (VTpeak/IC) and over forced expiratory volume at 1st second (VTpeak/FEV1) at peak of exercise were measured in 52 COPD patients during a CPET. The difference peak-rest in end-tidal pressure of CO2 (PETCO2) was also measured.

VE/VCO2 intercept showed a negative correlation with IC/TLC peak (p < 0.01) and a positive one with VTpeak/FEV1 (p < 0.01) and with PETCO2 peak-rest (p < 0.01). VE/VCO2 slope was negatively related to VTpeak/VC, VTpeak/IC and VTpeak/FEV1 (all correlations p < 0.05) and to PETCO2 peak-rest (p < 0.01).

In COPD, VE/VCO2 slope and intercept provide complementary information on the ventilatory limitation to exercise, as assessed by changes in the end-expiratory lung volume and in tidal volume excursion.

Introduction

An excess in exercise ventilation for a given metabolic rate may occur in patients with chronic obstructive pulmonary disease (COPD). The minute ventilation (VE) to the carbon dioxide output (VCO2) ratio, also known as ventilatory equivalent for CO2 (VE/VCO2) (Wasserman et al., 1994), may be increased in patients with COPD during exercise, as compared to control subjects (O’Donnell et al., 2001, Paoletti et al., 2011). In addition, in COPD patients the slope of the VE/VCO2 linear relationship was found to be negatively related to the peak oxygen uptake (VO2peak) during a rapidly incremental cardiopulmonary exercise testing (CPET) (Caviedes et al., 2012, Teopompi et al., 2013). Interestingly, the VE/VCO2 slope values were found to be decreased in patients with more severe emphysema, by indicating a relationship between VE/VCO2 slope and ventilatory limitation (Paoletti et al., 2011). Furthermore, even the intercept of the VE/VCO2 relationship has the potential for understanding the ventilatory response to exercise in patients with chronic cardiopulmonary disabling conditions (Agostoni et al., 2011, Teopompi et al., 2013).

Patients with COPD experience ventilatory constraints on exertion. In these patients, the development of dynamic hyperinflation limits exercise capacity and plays a key role in the perception of exertional breathlessness (O’Donnell, 2008). Indeed, COPD patients while exercising, may breathe in before achieving a full exhalation and, accordingly, trap air within the lungs with each further breath with serious mechanical and sensory consequences. Notably, dynamic lung hyperinflation may progressively restrict the tidal volume excursion and exercise ventilation can increase only by quickening the breathing frequency, thereby inducing a further hyperinflation in a vicious circle. Furthermore, in COPD patients dynamic hyperinflation may be associated with a poor cardiovascular response to exercise (Tzani et al., 2011).

Up to now, no study has been specifically aimed to assess the relationship between the excess in exercise ventilation for a given metabolic rate and the ventilatory limitation in COPD patients. The aim of the present study was, therefore, to measure in a cohort of COPD patients the VE/VCO2 value, both in terms of slope and in terms of intercept, and to ascertain whether or not these parameters may be related to the development of dynamic hyperinflation and to the tidal volume constraints. We hypothesized that the VE/VCO2 slope and intercept values might be differently associated to the ventilatory constraints during exercise in COPD patients.

Section snippets

Patients

We consecutively enrolled over a 9-month period, from January 2013 to September 2013, patients affected by COPD, who were admitted to a pulmonary rehabilitation program. COPD was diagnosed according to the GOLD criteria (Pauwels et al., 2001) and patients with moderate to severe airflow obstruction, i.e. forced expiratory volume in 1 s/vital capacity ratio (FEV1/VC) < 70% and FEV1  80% of predicted value, were included. Eligibility criteria of patients were (1) ex-smoking habit; (2) no long-term

Results

Fifty-six stable COPD patients, aged between 42 and 75 years were studied. According to the GOLD classification (Pauwels et al., 2001) 29 patients were moderate, 18 severe and 5 very severe. At study entry, patients were receiving regular therapy with inhaled steroids (60%), long-acting beta2-agonists (62%) and tiotropium (51%). All of them were ex-smokers.

Patients completed the exercise test without any complication and no patient was excluded because of poor motivation. In addition, no

Discussion

The main finding of this study is that in COPD patients intercept and slope values of the VE/VCO2 linear relationship are differently associated to the indices of ventilatory limitation during exercise. Notably, the VE/VCO2 intercept value increased as more as the dynamic hyperinflation was severe, as expressed by the reduction in IC/TLC during exercise. Furthermore, the VE/VCO2 intercept values were positively related to the corresponding values of VTpeak/FEV1 ratio, which may be considered as

Conflict of interest

This work had no conflict of interest and no extramural funding was used to support the study.

Authors’ contributions

E.T. served as the primary author. She developed the study protocol, participated in the patients recruitment and statistical analysis and drafted the manuscript and she is the guarantor of the entire manuscript. P.T. and M.A. participated in the design of the study and helped to patients recruitment. M.R.G. helped to patients recruitment. E.M. participated in the coordination of the study. A.C. developed the study protocol, interpreted study data, contributed to and reviewed drafts of the

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