H.J. Hulzebos

Chronic infection and inflammation affect exercise capacity in cystic fibrosis

Pulmonary function and nutritional status are important determinants of exercise capacity in patients with cystic fibrosis (CF). Studies investigating the effects of determinants, such as genotype or infection and inflammation, are scarce and have never been analysed in a multivariate longitudinal model. A prospective longitudinal cohort study was performed to evaluate whether genotype, chronic inflammation and infection were associated with changes in exercise capacity. Furthermore, we investigated whether exercise capacity can predict clinical outcome. 504 exercise tests of 149 adolescents with CF were evaluated. Maximal oxygen uptake corrected for body mass % predicted declined 20% during adolescence, and was associated with immunoglobulin (Ig)G levels and chronic Pseudomonas aeruginosa infection. A lower exercise capacity was associated with a higher mortality, steeper decline in pulmonary function and greater increase in IgG levels. Since a decline in exercise capacity during adolescence was negatively associated with IgG levels and chronic P. aeruginosa infection, these data emphasise the importance of prevention and treatment of chronic inflammation and infections in patients with CF. Furthermore, a lower exercise capacity was associated with a higher mortality rate, steeper decline in pulmonary function and higher increase in IgG levels with increasing age in adolescents with CF. This stresses the value of regular exercise testing for assessing prognosis in adolescents with CF.

Chronic inflammation and infection associate with a lower exercise training response in cystic fibrosis adolescents

Considerable heterogeneity among training-induced effects is observed in patients with cystic fibrosis (CF). We previously showed that longitudinal changes in exercise capacity in adolescents with CF were negatively associated with Pseudomonas aeruginosa (P. aeruginosa) colonization and total immunoglobulin G (IgG) levels, independent of age, pulmonary function and bodyweight. This is the first study investigating whether chronic inflammation and infection also associate with the exercise training response in adolescents with CF. Participants performed a home-based exercise training program for 12 weeks. Pulmonary function, anthropometrics, exercise capacity, markers of inflammation and P. aeruginosa colonization status were measured at baseline. Exercise training-induced changes in pulmonary function and exercise capacity were compared between patients with a low and high inflammation-infection status. Participants with CF with high total IgG levels and P. aeruginosa colonization improved significantly less from the exercise training program, with regard to maximal oxygen consumption. These observations support the hypothesis that chronic systemic inflammation and infection leads to devastating effects on skeletal muscles, hampering skeletal muscle tissue to improve from regular physical exercise. Data further suggest that patients with CF should preferentially be encouraged to engage in regular physical exercise when inflammation and infection status is low (e.g. at a young age).

Effect of Long-Term Voluntary Exercise Wheel Running on Susceptibility to Bacterial Pulmonary Infections in a Mouse Model

Regular moderate exercise has been suggested to exert anti-inflammatory effects and improve immune effector functions, resulting in reduced disease incidence and viral infection susceptibility. Whether regular exercise also affects bacterial infection susceptibility is unknown. The aim of this study was to investigate whether regular voluntary exercise wheel running prior to a pulmonary infection with bacteria (P. aeruginosa) affects lung bacteriology, sickness severity and phagocyte immune function in mice. Balb/c mice were randomly placed in a cage with or without a running wheel. After 28 days, mice were intranasally infected with P. aeruginosa. Our study showed that regular exercise resulted in a higher sickness severity score and bacterial (P. aeruginosa) loads in the lungs. The phagocytic capacity of monocytes and neutrophils from spleen and lungs was not affected. Although regular moderate exercise has many health benefits, healthy mice showed increased bacterial (P. aeruginosa) load and symptoms, after regular voluntary exercise, with perseverance of the phagocytic capacity of monocytes and neutrophils. Whether patients, suffering from bacterial infectious diseases, should be encouraged to engage in exercise and physical activities with caution requires further research.

Paediatric exercise testing in clinics and classrooms: a comparative review of different assessments

non-clinical setting in large population based studies. The steep ramp test and the 20 m shuttle run test are valid and reliable non-sophisticated alternatives for predicting aerobic capacity in children and adolescents in those studies. Nevertheless, prediction equations used to estimate aerobic capacity reached during cardiopulmonary exercise testing from steep ramp test or 20 m shuttle run test performance should be interpreted with caution. Additionally, these non-sophisticated tests should not be used as a substitute for performing regular cardiopulmonary exercise testing, as they are less accurate and do not provide diagnostic or prognostic information.

A Possible Alternative Exercise Test for Youths with Cystic Fibrosis: The Steep Ramp Test

PURPOSE The steep ramp test (SRT) can be used to provide an indication of exercise capacity when gas exchange measurements are not possible. This study evaluated the clinical usefulness of the SRT in adolescents with cystic fibrosis (CF) and compared the physiological responses of the SRT with the standard cardiopulmonary exercise test (CPET). METHODS Forty patients with CF (17 boys and 23 girls; mean ± SD age, 14.7 ± 1.7 years; forced expiratory volume in 1 s, 86% ± 18% of predicted) performed an SRT and a CPET with respiratory gas analysis in a randomized balanced design. Peak work rate (WRpeak), HRpeak, peak minute ventilation (V˙Epeak), and peak oxygen uptake (V˙O2peak) were the main outcome measures. RESULTS Patients with CF attained values for absolute and relative WRpeak during the SRT of 82% ± 14% and 92% ± 14% of predicted. Nutritional status and degree of airway obstruction did not influence SRT performance. Significantly higher values were attained for WRpeak during the SRT compared with those during the CPET (252 ± 60 vs 174 ± 46 W; P < 0.001), whereas significantly lower values were achieved for HRpeak (168 ± 14 vs 182 ± 12 bpm; P < 0.001), V˙Epeak (59.2 ± 19.5 vs 72.0 ± 20.2 L·min(-1); P = 0.006), and V˙O2peak (36.9 ± 7.5 vs 41.5 ± 7.6 mL·kg(-1)·min(-1); P = 0.008). A strong correlation between WRpeak attained at the SRT and the V˙O2peak achieved during the CPET was found (r = 0.822, P < 0.001). CONCLUSIONS The SRT seems to be a quick, convenient, and low-cost exercise test that is well-tolerated in patients with CF with mild-to-moderate airway obstruction. It provides an indication of exercise capacity and can potentially be used when exercise testing using gas exchange measurements is not possible.

Validation of the Modified Shuttle Test to Predict Peak Oxygen Uptake in Youth Asthma Patients Under Regular Treatment

Background: Oxygen uptake (VO2) evaluations by cardiopulmonary exercise test is expensive and time-consuming. Estimating VO2 based on a field test would be an alternative. Objective: To develop and validate an equation to predict VO2peak based on the modified shuttle test (MST). Methods: Cross sectional study, with 97 children and adolescents with asthma. Participants were divided in two groups: the equation group (EG), to construct the equation model of VO2peak, and the cross-validation group (VG). Each subject performed the MST twice using a portable gas analyzer. The peak VO2peak during MST was used in the equation model. The patients’ height, weight, gender, and distance walked (DW) during MST were tested as independent variables. Results: The final model [-0.457 + (gender × 0.139) + (weight × 0.025) + (DW × 0.002)] explained 87% of VO2peak variation. The VO2peak predicted was similar to VO2peak measured by gas analyzer (1.9 ± 0.5 L/min and 2.0 ± 0.5 L/min, respectively) (p = 0.67), and presented significant ICC 0.91 (IC95% 0.77 to 0.96); p < 0.001. The Bland–Altman analysis showed low bias (-0.15 L/min) and limits of agreement (-0.65 to 0.35 L/min). There was no difference in DW between EG (760 ± 209 m) and VG (731 ± 180 m), p = 0.51. Conclusion: The developed equation adequately predicts VO2peak in pediatric patients with asthma.

Mechanisms of Exercise Limitation in Cystic Fibrosis: A Literature Update of Involved Mechanisms

Abstract Patients with Cystic Fibrosis (CF) are known to have a reduced exercise tolerance. To date, however, there is no (scientific) consensus about the exact physiological mechanisms leading to a reduced exercise capacity in these patients, and to what extent each mechanism contributes to exercise limitation. Moreover, it is still unknown at which point of the disease process the different exercise-limiting mechanisms come into play. An up-to-date (literature) overview of the determinants known to play a role in the reduced exercise capacity might be helpful for (1) understanding the underlying (physiological) mechanisms, and (2) for providing and indicating appropriate therapeutic interventions such as exercise training in patients with CF.