Reply to: “Ventilatory efficiency in athletes, asthma and obesity”: different ventilatory phenotypes during exercise in obesity?

Reply to N. Borasio and co-workers:

We thank N. Borasio and co-workers for their correspondence bringing attention to their recent publications [1, 2]. The ventilatory response to exercise in patients with obesity is clearly an area of interest, as their original research articles [1, 2], along with others [3], have been published after our review article “Ventilatory efficiency in athletes, asthma and obesity” [4] was first submitted for publication.

Ventilatory efficiency after bariatric surgery: recent findings by Borasio et al. [2] in patients with a baseline body mass index of 43.6±5.3 kg·m⁻² show that the minute ventilation (Vʹ_E)–carbon dioxide production (Vʹ_CO2) slope was reduced following sleeve gastrectomy, while the submaximal partial pressure of end-tidal carbon dioxide (P_ETCO2) at anaerobic threshold and Vʹ_E/Vʹ_CO2 at the respiratory compensation point (i.e. nadir) were unchanged. The Vʹ_E/Vʹ_CO2 ratio at peak exercise was not specifically reported, but can be calculated using Vʹ_E, Vʹ_CO2 and respiratory exchange ratio data reported in the published tables [2]. Using these data, the Vʹ_E/Vʹ_CO2 ratio at peak exercise appears slightly reduced after sleeve gastrectomy as compared to baseline (30.5 versus 29.1).

In their correspondence letter, the authors state that the Vʹ_E/Vʹ_CO2 ratio at peak exercise may be used as a clinical marker to better understand the underlying mechanisms of exercise intolerance. While we agree that Vʹ_E/Vʹ_CO2 ratio at peak exercise may be useful when evaluating responses following interventions like bariatric surgery, we want to clarify that it is not an appropriate evaluation of ventilatory efficiency, due to the instability of arterial carbon dioxide tension (P_CO2) (and P_ETCO2) at peak exercise, largely due to respiratory compensation at heavy metabolic demands [5–7]. To our knowledge, the prognostic utility of Vʹ_E/Vʹ_CO2 in this disease population has not been established.

Combined obesity and obstructive sleep apnoea (OSA): N. Borasio and co-workers bring up the important point that there is limited research on the ventilatory response to exercise in patients with obesity and OSA and propose that OSA can contribute to further worsening exercise tolerance in obesity. Their recently published work found that patients with concomitant obesity and OSA show evidence of blunted Vʹ_E and higher P_ETCO2 at peak exercise, as compared to those without OSA and individuals with OSA receiving night-time nasal continuous positive airway pressure treatment [1]. These data are suggestive of mechanical constraint; however, additional work is required to determine the precise mechanism behind these responses.

In their correspondence, the authors suggest evaluating ΔP_ETCO2 (calculated as the difference between the maximum value obtained during exercise versus the value at peak exercise) and proposed that a threshold value may be a predictor of OSA in patients with morbid obesity. We are cautious to use P_ETCO2 as a clinical marker because of a lack of accuracy and suggest that temperature corrected arterial P_CO2 is preferred in evaluating alveolar ventilation as P_ETCO2 is prone to errors [5–7]. Specifically, P_ETCO2 may be higher than alveolar and arterial P_CO2 in health and obesity [8, 9], since during exercise more carbon dioxide diffuses into the alveoli as lung volumes decrease during a continued exhalation. Therefore, expiratory P_CO2 increases toward mixed-venous P_CO2 faster during exercise than at rest [5–7].

We thank N. Borasio and co-workers for bringing attention to their interesting work [1, 2]. We look forward to future studies evaluating the ventilatory response to exercise in patients with obesity and various comorbidities.