The Exeter Activity Unlimited statement on physical activity and exercise for cystic fibrosis: methodology and results of an international, multidisciplinary, evidence-driven expert consensus.

BACKGROUND: The roles of physical activity (PA) and exercise within the management of cystic fibrosis (CF) are recognised by their inclusion in numerous standards of care and treatment guidelines. However, information is brief, and both PA and exercise as multi-faceted behaviours require extensive stakeholder input when developing and promoting such guidelines. METHOD: On 30th June and 1st July 2021, 39 stakeholders from 11 countries, including researchers, healthcare professionals and patients participated in a virtual conference to agree an evidence-based and informed expert consensus about PA and exercise for people with CF. This consensus presents the agreement across six themes: (i) patient and system centred outcomes, (ii) health benefits, iii) measurement, (iv) prescription, (v) clinical considerations, and (vi) future directions. The consensus was achieved by a stepwise process, involving: (i) written evidence-based synopses; (ii) peer critique of synopses; (iii) oral presentation to consensus group and peer challenge of revised synopses; and (iv) anonymous voting on final proposed synopses for adoption to the consensus statement. RESULTS: The final consensus document includes 24 statements which surpassed the consensus threshold (>80% agreement) out of 30 proposed statements. CONCLUSION: This consensus can be used to support health promotion by relevant stakeholders for people with CF.

Physiological predictors of cardiorespiratory fitness in children and adolescents with cystic fibrosis without ventilatory limitation.

OBJECTIVES: [1] To investigate the cardiorespiratory fitness (CRF) levels in children and adolescents with cystic fibrosis (CF) with no ventilatory limitation (ventilatory reserve ⩾ 15%) during exercise, and [2] to assess which physiological factors are related to CRF. METHODS: A cross-sectional study design was used in 8- to 18-year-old children and adolescents with CF. Cardiopulmonary exercise testing was used to determine peak oxygen uptake normalized to body weight as a measure of CRF. Patients were defined as having 'low CRF' when CRF was less than 82%predicted. Physiological predictors used in this study were body mass index z-score, P. Aeruginosa lung infection, impaired glucose tolerance (IGT) including CF-related diabetes, CF-related liver disease, sweat chloride concentration, and self-reported physical activity. Backward likelihood ratio (LR) logistic regression analysis was used. RESULTS: Sixty children and adolescents (51.7% boys) with a median age of 15.3 years (25th-75th percentile: 12.9-17.0 years) and a mean percentage predicted forced expiratory volume in 1 second of 88.5% (±16.9) participated. Mean percentage predicted CRF (ppVO2peak/kg) was 81.4% (±12.4, range: 51%-105%). Thirty-three patients (55.0%) were classified as having 'low CRF'. The final model that best predicted low CRF included IGT (p = 0.085; Exp(B) = 6.770) and P. Aeruginosa lung infection (p = 0.095; Exp(B) = 3.945). This model was able to explain between 26.7% and 35.6% of variance. CONCLUSIONS: CRF is reduced in over half of children and adolescents with CF with normal ventilatory reserve. Glucose intolerance and P. Aeruginosa lung infection seem to be associated to low CRF in children and adolescents with CF.

Reference values for cardiopulmonary exercise testing in healthy subjects - an updated systematic review.

Introduction: Reference values for cardiopulmonary exercise testing (CPET) parameters provide the comparative basis for answering important questions concerning the normalcy of exercise responses in patients, and significantly impacts the clinical decision-making process. Areas covered: The aim of this study was to provide an updated systematic review of the literature on reference values for CPET parameters in healthy subjects across the life span. A systematic search in MEDLINE, Embase, and PEDro databases were performed for articles describing reference values for CPET published between March 2014 and February 2019. Expert opinion: Compared to the review published in 2014, more data have been published in the last five years compared to the 35 years before. However, there is still a lot of progress to be made. Quality can be further improved by performing a power analysis, a good quality assurance of equipment and methodologies, and by validating the developed reference equation in an independent (sub)sample. Methodological quality of future studies can be further improved by measuring and reporting the level of physical activity, by reporting values for different racial groups within a cohort as well as by the exclusion of smokers in the sample studied. Normal reference ranges should be well defined in consensus statements.

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.

Prevalence of severe fatigue among adults with cystic fibrosis: A single center study.

BACKGROUND: With life expectancy increasing among patients with cystic fibrosis (CF), the prevalence of complications such as fatigue is also expected to increase. Our aim was to investigate the prevalence of severe fatigue among adults with CF and to identify factors associated with fatigue. METHODS: Adult patients with CF receiving treatment at a single center were invited to complete three questionnaires. We then studied the associations between fatigue and clinically measured parameters and between fatigue and patient-reported outcomes. RESULTS: A total of 77 patients (age 19-54years; 56% males; mean FEV1: 63%) completed the questionnaires (43% response rate). The prevalence of severe fatigue among these patients was 26%. The variance in fatigue was explained partially by clinically measured parameters. However, patient-reported outcomes were stronger independently associated with fatigue and included the patients' reported respiratory symptoms, emotional functioning, and social functioning. CONCLUSIONS: Fatigue is a clinically important and highly prevalent issue among adults with CF and is associated with a significant reduction in health-related quality of life and participation in society. In addition, fatigue is associated more strongly with the patient's perception of symptoms and well-being than with clinically measured parameters.

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.

Towards an individualized protocol for workload increments in cardiopulmonary exercise testing in children and adolescents with cystic fibrosis.

BACKGROUND: There is no single optimal exercise testing protocol for children and adolescents with cystic fibrosis (CF) that differs widely in age and disease status. The aim of this study was to develop a CF-specific, individualized approach to determine workload increments for a cycle ergometry testing protocol. METHODS: A total of 409 assessments consisting of maximal exercise data, anthropometric parameters, and lung function measures from 160 children and adolescents with CF were examined. 90% of the database was analyzed with backward linear regression with peak workload (W(peak)) as the dependent variable. Afterwards, we [1] used the remaining 10% of the database (model validation group) to validate the model's capacity to predict W(peak) and [2] validated the protocol's ability to provide a maximal effort within a 10±2 minute time frame in 14 adolescents with CF who were tested using this new protocol (protocol validation group). RESULTS: No significant differences were seen in W(peak) and predicted W(peak) in the model validation group or in the protocol validation group. Eight of 14 adolescents with CF in the protocol validation group performed a maximal effort, and seven of them terminated the test within the 10±2 minute time frame. Backward linear regression analysis resulted in the following equation: W(peak) (W)=-142.865+2.998×Age (years)-19.206×Sex (0=male; 1=female)+1.328×Height (cm)+23.362×FEV(1) (L) (R=.89; R(2)=.79; SEE=21). Bland-Altman analysis showed no systematic bias between the actual and predicted W(peak). CONCLUSION: We developed a CF-specific linear regression model to predict peak workload based on standard measures of anthropometry and FEV(1), which could be used to calculate individualized workload increments for a cycle ergometry testing protocol.

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.

The oxygen uptake efficiency slope in children with congenital heart disease: construct and group validity.

OBJECTIVE: The oxygen uptake efficiency slope (OUES) has been proposed as an independent and objective alternative to the peak oxygen uptake (VO(2peak)), which does not require maximal exercise. The aim of this study was to investigate the construct and group validity of the OUES in children with congenital heart disease (CHD). METHODS: Thirty-one patients with CHD, of which 16 patients (mean age ± SD 11.2 ± 2.7 years) with a Fontan repair and 15 patients (mean age ± SD 13.2 ± 3.6 years) with surgical repair of tetralogy of Fallot (ToF) completed a symptom-limited cardiopulmonary exercise test. The OUES was calculated and normalized for body surface area at three different exercise intensities: (1) using 100% of the exercise data; (2) using the first 75% of the exercise data; and (3) using exercise data up to the ventilatory threshold (VT). Furthermore, peak oxygen uptake (VO(2peak)), VT, ventilatory efficiency (V(E)/VO(2)-slope), and ventilatory drive (V(E)/VCO(2)-slope) were calculated and compared with values of 46 healthy children (mean age ± SD 12.2 ± 2.4 years). RESULTS: In all three groups, the OUES values determined at the three different exercise intensities were not significantly different from each other. Moreover, the OUES was significantly reduced in the children with CHD, with significantly lower values in the Fontan patients compared to ToF. Strong correlations were found between the OUES and both the VO(2peak) and VT in Fontan and ToF patients. DISCUSSION: The OUES provides a valid measure of cardiopulmonary fitness in children with CHD, which is independent of exercise intensity and strongly correlated with VO(2peak) and VT (construct validity). Furthermore, the OUES is capable of differentiating between healthy children and children with CHD and between Fontan and ToF patients (group validity). Therefore, the OUES may be a valid, effort-independent parameter of cardiopulmonary fitness in children with CHD.

Is static hyperinflation a limiting factor during exercise in adolescents with cystic fibrosis?

Increased work of breathing is considered to be a limiting factor in patients with cystic fibrosis (CF) performing aerobic exercise. We hypothesized that adolescents with CF and with static hyperinflation are more prone to a ventilatorily limited exercise capacity than non-static hyperinflated adolescents with CF. Exercise data of 119 adolescents with CF [range 12-18 years], stratified for static hyperinflation, defined as ratio of residual volume to total lung capacity (RV/TLC) > 30%, were obtained during a progressive bicycle ergometer test with gas analysis and analyzed for ventilatory limitation. Static hyperinflation showed a significant, though weak association (Φ 0.38; P < 0.001) with a ventilatorily limited exercise capacity (breathing reserve index at maximal effort >0.70; FEV(1) < 80% predicted and reduced exercise capacity, defined as VO(2peak) < 85% predicted). Analysis of association for increasing degrees of hyperinflation showed an increase to Φ 0.49 (P < 0.001) for RV/TLC > 50%. In adolescents with static hyperinflation, peak work rate (W(peak) ; 3.1 ± 0.7 W/kg (75.1 ± 17.3% of predicted), peak oxygen uptake (VO(2peak) /kg (ml/min/kg); 39.2 ± 9.2 ml/min/kg (91.0 ± 20.3% of predicted), peak heart rate (HR(peak) ; 176 ± 19 beats/min) were significantly (P < 0.05) decreased when compared with non-static hyperinflated adolescents (W(peak) 3.5 ± 0.5 W/kg (81.4 ± 10.0% of predicted)); VO(2peak) /kg (ml/min/kg); 43.1 ± 7.5 ml/min/kg (98.0 ± 15.1% of predicted); and HR(peak) 185 ± 14 beats/min). Additionally, no difference was found in the degree of association of FEV(1) (%) and RV/TLC (%) with VO(2peak) /kg(pred) and W(peak) /kg(Pred) , but we found the RV/TLC (%) to be a slightly stronger predictor of VO(2peak) /kg(pred) and W(peak) /kg(Pred) than FEV(1) (%). These results indicate that the presence of static hyperinflation in adolescents with CF by itself does not strongly influence ventilatory constraints during exercise and that static hyperinflation is only a slightly stronger predictor of W(peak) /kg(Pred) and VO(2peak) /kg(Pred) than airflow obstruction (FEV(1) (%)).

High-intensity interval training in an adolescent with cystic fibrosis: a physiological perspective.

Nutritional, musculoskeletal, and/or ventilatory status can lead to a decreased exercise capacity in children with cystic fibrosis (CF). Exercise training is already part of the usual care; however, the "optimal" intensity and volume of exercise training to improve exercise capacity is still unknown. Six weeks of high-intensity interval training (HIT) for a patient with CF with a ventilatory limitation was evaluated by a cardiopulmonary exercise test (CPET). Peak oxygen uptake and peak workload increased 19% and 16%, respectively, and there was a rise in peak ventilation from 50 L/min to 75 L/min, with an increase in both breathing depth and respiratory rate. A relative short period of HIT resulted in a significant increase in exercise capacity. In patients with CF, HIT might be an effective and efficient training regimen, especially in CF patients with a ventilatory limitation. Further research is necessary to investigate whether HIT is a better alternative than traditional aerobic training programs especially in ventilatory limited patients with CF.

Feasibility and preliminary effectiveness of preoperative therapeutic exercise in patients with cancer: a pragmatic study.

The aim of this pilot study is to determine the feasibility and preliminary effectiveness of an individually designed preoperative therapeutic exercise program (PreTEP), in patients recently diagnosed with cancer and awaiting elective surgery. The purpose is to improve their physical fitness levels during this waiting period with the intention of decreasing postoperative morbidity. A preexperimental pilot study was performed at the University Medical Center Utrecht, The Netherlands. Thirty-nine patients diagnosed with cancer, scheduled for elective abdominal/thoracic surgery, were referred to a multidisciplinary preoperative screening. Fifteen patients (38%) participated in PreTEP. Participants were satisfied and motivated during the period of training (on average 5 weeks) in which they attended 84% of the sessions. Cardiorespiratory fitness (A strand-test) and muscle strength (Handheld Dynamometry) increased significantly, from 25 to 33 mL/kg/min, respectively (p<0.01; 95% confidence interval [CI]=-0.011 to -0.004) and from 894 Newton (N) to 961N (p<0.01; 95% CI=-94.53 to -39.0). No adverse events occurred during the training period. PreTEP was shown to be feasible, safe, and well-tolerated and appreciated by participants. Despite the relatively short period of training, physical fitness improved in all participants.

Oxygen uptake to work rate slope in children with a heart, lung or muscle disease.

The purposes of this study were all to determine if DeltaVO2/DeltaWR is dependent on age, body mass, height and fitness and if DeltaVO2/DeltaWR could discriminate between healthy children and children with a chronic disease that limits O2 delivery or utilization. Four groups were included: muscle disease (Juvenile Dermatomyositis; JDM; n=12), lung disease (Cystic Fibrosis; CF; n=13), Congenital Heart Disease (CHD; (n=13), and healthy children (n=44). All children performed a cardiopulmonary exercise test on a cycle ergometer with respiratory gas analysis. The DeltaVO2/DeltaWR was determined by linear regression using data from unloaded cycling to peak exercise. No associations were found between the DeltaVO2/DeltaWR and age, body mass and height in healthy children. DeltaVO2/DeltaWR was significantly correlated with VO2peak/kg (r=0.44; p<0.01). Children with JDM had lower DeltaVO2/DeltaWR values than healthy children (p=0.02), and DeltaVO2/DeltaWR tended to be lower in CHD and higher in CF (p=0.09 and p=0.08, respectively). DeltaVO2/DeltaWR may be more sensitive for conditions that are characterized by local hypo perfusion (as in JDM), than for conditions that are characterized by impaired oxygen delivery (i. e. CF or CHD).

Exercise prescription for patients with a Fontan circulation: current evidence and future directions.

It is well documented that children with a Fontan circulation have a reduced exercise capacity. One of the modalities to improve exercise capacity might be exercise training. We performed a systematic literature review on the effects of exercise training in patients with a Fontan circulation. Six published studies were included that reported on the effects of exercise training in 40 patients. All studies had a small sample size and/or did not include a control group.Based on the six published studies we can conclude that children who have undergone a Fontan operation and who are in a stable haemodynamic condition can safely participate in an exercise training programme and that exercise training results in an improved exercise capacity. However, more research is needed to establish the optimal exercise mode, dose-response relation, and the effects of exercise training on cardiac function, peripheral muscle function, physical activity, and health-related quality of life. (Neth Heart J 2007;15:142-7.).

Does physical training increase insulin sensitivity in chronic heart failure patients?

To determine the effect of training on insulin sensitivity (IS) and how this relates to peak V(.)O(2) (peak oxygen uptake) in CHF (chronic heart failure), 77 CHF patients (New York Heart Association class, II/III; men/women, 59/18; age, 60+/-9 years; body mass index, 26.7+/-3.9 kg/m(2); left ventricular ejection fraction, 26.9+/-8.1%; expressed as means+/-S.D.) participated in the study. Patients were randomly assigned to a training or control group (TrG or CG respectively). Sixty-one patients completed the study. Patients participated in training (combined strength and endurance exercises) four times per week, two times supervised and two times at home. Before and after intervention, anthropometry, IS (euglycaemic hyperinsulinaemic clamp) and peak V(.)O(2) (incremental cycle ergometry) were assessed. Intervention did not affect IS significantly, even though IS increased by 20% in TrG and 11% in CG (not significant). Peak V(.)O(2) increased as a result of training (6% increase in TrG; 2% decrease in CG; P <0.05). In both groups (TrG and CG), the change in IS correlated positively with the change in peak V(.)O(2) ( r =0.30, P <0.05). Training resulted in an increase in peak V(.)O(2), but not in IS. Whether physical training actually increases IS in CHF patients remains unclear.