DISCUSSION
The present study further explored physiological responses of aerobic fitness in children and adolescents with CRD. The main findings have shown that CF patients presented lower ventilatory efficiency, lower BR and reduced lung function. In spite of that, a good exercise capacity was achieved, meaning no difference in VO2peak when compared with healthy controls. On the other hand, the asthma group was not able to reach a cardiorespiratory capacity comparable to the healthy group. These data may contribute to a better understanding of different factors influencing aerobic fitness, helping to develop more efficient strategies for monitoring and treatment of patients with CRD.
The effects of asthma on the exercise capacity of children and adolescents are still controversial. Patients in the asthma group reported BR and ventilatory efficiency at peak exercise comparable to the healthy controls but failed to achieve good exercise capacity. The results presented here agree with previous studies showing a decrease in VO2peak 8–10, although there is also evidence reporting no differences 6,7. For children and adolescents with CF, we have described maintenance of exercise capacity, contrary to evidence reporting reduced levels compared to healthy controls 11. Interestingly, this effect was seen even though CF patients presented lower BR and poor ventilatory efficiency both at VT1 and peak exercise. Although the reasons for these differences are not fully comprehended, we hypothesize that physical conditioning may play a role to explain the maintenance of VO2peak in patients with CF. A recent systematic review and meta-analysis concluded that CF children and adolescents have similar moderate-to-vigorous physical activity and sedentary time as healthy controls 29. European Cystic Fibrosis Society states that physical activity and exercise must be integral to the overall physiotherapy management suggested for every individual with CF, irrespective of age and disease severity 30. As an active lifestyle is considered part of standard care, CF patients participate in a wide range of physical activities and sports. One study demonstrates that 22,7% of school children with CF reported participating in three or more (un)structured physical activities or sports compared to 4,4% of healthy children 31. On the other hand, although physical activity and exercise should be encouraged in children and adolescents with asthma 32, a lower active lifestyle compared to their peers has been reported33. The decrease in physical activity reduces the stimuli to improve muscular and cardiorespiratory fitness, producing a progressive and sustained deconditioning 13. A recent study reported that physical deconditioning is the only significant determinant of reduced exercise capacity in asthma, irrespective of asthma diagnosis, BMI, ventilatory limitation or presence of EIB in children and adolescents with controlled mild-to-moderate asthma34. Taken together, we believe that the most likely hypothesis for the reduced exercise capacity in asthmatics compared to patients with CF is physical deconditioning.
The influence of lung function on exercise capacity in children and adolescents with asthma and CF is also still a matter of debate. Although FEV1is an important clinical parameter, according to our results, it does not influence the VO2peak achieved, at least for patients with mild-to-moderate impairments. In asthmatic children and adolescents, previous studies reported no significant correlations between FEV1 and exercise capacity 13, while others found a positive correlation 14. For children and adolescents with CF, some studies found a positive correlation between FEV1 and exercise capacity, while others reported that VO2peak could be preserved until FEV1 falls below the predicted 60%35.
In our study, comparisons between asthmatic and healthy controls revealed no differences in BR, which seems to be in accordance with previous evidence 6,7. Santuz et al. reported that BR was comparable among asthmatic and healthy individuals6, as well as Moraes et al. described no significant differences between children and adolescents with both mild-to-moderate and mild-persistent asthma as compared to healthy peers7. On the other hand, our results have shown the patients with CF presented lower BR than the healthy and asthmatic groups. The reduced BR found for the CF group indicates that these patients require higher ventilatory demands during exertion, confirming evidence that reported reduced BR at peak exercise11,22. Ronen Bar-Yoseph et al. observed low BR in 49% of patients with CF11, while Borel et al. found a reduced BR for patients with CF when compared to healthy children 22. It is also important to highlight that MVV was estimated using the FEV1 36. Although this is a widely used method, it is also subjected to underestimation of true ventilatory capacity in obstructive diseases with low FEV1, which may have influenced the present results 37.
Ventilatory efficiency has also been considered an important component of aerobic fitness in CRD 7,38. Our results have shown that, both at VT1 and peak exercise, an increase in VE/VO2 and VE/VCO2 was found for the CF group, which was previously described 38. Moorcroft et al. have also described differences in the VE/VO2 between patients with CF who survived or not 39. Several factors may explain lower ventilatory efficiency in patients with CF. As exercise ventilatory demand increases, progressive expiratory airflow obstruction and increasing flow resistance occur, leading to dynamic hyperinflation. In addition, ventilatory efficiency is also reduced by increased dead space ventilation, even in mildly affected CF patients 16. Regarding the asthma group, patients have shown an increase in VE/VO2 and VE/VCO2 at VT1, but not at peak exercise. These results are consistent with those reported by a previous study 7. There is scarce evidence on possible factors explaining lower ventilatory efficiency at VT1for asthmatics, although an obstructive origin may be the most likely. In addition, the role of inflammatory mediators could also be important, as there is evidence correlating exercise-induced sputum histamine levels with low arterial oxygen partial pressure 40.
The present study presents limitations, including the lack of measures of the degree of airway inflammation, such as exhaled nitric oxide fraction, sputum analysis, or exhaled breath condensate, as these measures could correlate with the outcome measures and help us to understand the main mechanisms involved in exercise intolerance. In addition, our study did not evaluate participants’ daily levels of physical activity, which prevented us from further discussion on the topic. On the other hand, although indirect estimation of MVV is likely the optimal test in pediatric patients 36, it may underestimate the true ventilatory capacity in obstructive diseases where a low FEV1 is present.
In conclusion, the findings of the present study provide evidence on aerobic fitness and its related determinants in children and adolescents with CRD. Patients with CF achieved good exercise capacity despite low ventilatory efficiency, low BR, and reduced lung function. However, asthmatics presented reduced cardiorespiratory capacity and normal ventilatory efficiency at peak exercise, although there were differences in the ventilatory threshold, when compared to healthy peers, highlighting the different mechanisms implicated in determining aerobic fitness in CRD. These results may contribute to a better understanding of the influence of CRD on exercise capacity, providing data to support exercise practice aiming to improve physical conditioning, and emphasizing the importance of routine evaluation of BR and ventilatory efficiency as part of CPET outcomes.