Guidance and standard operating procedures for functional exercise testing in cystic fibrosis.

Regular exercise testing is recommended for all people with cystic fibrosis (PwCF). A range of validated tests, which integrate both strength and aerobic function, are available and increasingly being used. Together, these tests offer the ability for comprehensive exercise evaluation. Extensive research and expert consensus over recent years has enabled the adaptation and standardisation of a range of exercise tests to aid the understanding of the pathophysiology related to exercise limitation in PwCF and has led to the development of novel exercise tests which may be applied to PwCF. This article provides expert, opinion-based clinical practice guidance, along with test instructions, for a selection of commonly used valid tests which have documented clinimetric properties for PwCF. Importantly, this document also highlights previously used tests that are no longer suggested for PwCF and areas where research is mandated. This collaboration, on behalf of the European Cystic Fibrosis Society Exercise Working Group, represents expert consensus by a multidisciplinary panel of physiotherapists, exercise scientists and clinicians and aims to improve global standardisation of functional exercise testing of PwCF. In short, the standardised use of a small selection of tests performed to a high standard is advocated.

Perceptions of barriers to and facilitators of physical activity in adults with cystic fibrosis.

BACKGROUND: Physical activity (PA) is a proven therapeutic tool to increase the quality of life and life expectancy in people with cystic fibrosis (pwCF). Despite this, the PA level of pwCF is lower than recommended. OBJECTIVES: This study was conducted to identify the barriers to and facilitators of PA in adults with CF with heterogeneous severity. METHODS: Twenty adults with CF (mean age = 33.3±11.7 years, mean FEV1% = 50.55±20.4%) were recruited from two specialized centers and interviewed about the factors that limit and facilitate their PA. The collected data were transcribed, coded and analyzed using deductive and inductive methods. RESULTS: Barriers and facilitators were classified into physical, psychological and environmental dimensions. The main barriers were fatigue, breathing difficulties, lack of available facilities, negative perceptions of PA and perceived health risks. The most important facilitators were respiratory benefits, well-being, and social support. CONCLUSION: Although some barriers and facilitators were similar to those found in children with CF or adults from other vulnerable populations, others were specific to adults with CF, such as the risk of cross-contamination and transplant preparation. The comprehensive study of the barriers and facilitators in adults will enhance PA counseling for pwCF and help improve their compliance with PA recommendations.

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.

The time course of different neuromuscular adaptations to short-term downhill running training and their specific relationships with strength gains.

PURPOSE: Due to its eccentric nature, downhill running (DR) training has been suggested to promote strength gains through neuromuscular adaptations. However, it is unknown whether short-term chronic DR can elicit such adaptations. METHODS: Twelve untrained, young, healthy adults (5 women, 7 men) took part in 4 weeks' DR, comprising 10 sessions, with running speed equivalent to 60-65% maximal oxygen uptake ([Formula: see text]O2max, assessed at weeks 0 and 4). Isometric and isokinetic knee-extensor maximal voluntary torque (MVT), vastus lateralis (VL) muscle morphology/architecture (anatomical cross-sectional area, ACSA; physiological CSA, PCSA; volume; fascicle length, Lf; pennation angle, PA) and neuromuscular activation (VL EMG) were assessed at weeks 0, 2 and 4. RESULTS: MVT increased by 9.7-15.2% after 4 weeks (p < 0.01). VL EMG during isometric MVT increased by 35.6 ± 46.1% after 4 weeks (p < 0.05) and correlated with changes in isometric MVT after 2 weeks (r = 0.86, p = 0.001). VL ACSA (+2.9 ± 2.7% and +7.1 ± 3.5%) and volume (+2.5 ± 2.5% and +6.6 ± 3.2%) increased after 2 and 4 weeks, respectively (p < 0.05). PCSA (+3.8 ± 3.3%), PA (+5.8 ± 3.8%) and Lf (+2.7 ± 2.2%) increased after 4 weeks (p < 0.01). Changes in VL volume (r = 0.67, p = 0.03) and PCSA (r = 0.71, p = 0.01) correlated with changes in concentric MVT from 2 to 4 weeks. [Formula: see text]O2max (49.4 ± 6.2 vs. 49.7 ± 6.3 mL·kg-1·min-1) did not change after 4 weeks (p = 0.73). CONCLUSION: Just 4 weeks' moderate-intensity DR promoted neuromuscular adaptations in young, healthy adults, typically observed after high-intensity eccentric resistance training. Neural adaptations appeared to contribute to most of the strength gains at 2 and 4 weeks, while muscle hypertrophy seemed to contribute to MVT changes from 2 to 4 weeks only.

Rethinking physical exercise training in the modern era of cystic fibrosis: A step towards optimising short-term efficacy and long-term engagement.

Exercise is considered as an important component of the package of care delivered to people with cystic fibrosis (pwCF). However, despite the well-known short-term physiological and psychological benefits, training effects are heterogenous and the transfer of structured exercise programmes to the daily life of pwCF is challenging. Training concepts and strategies developed over the last decades must be adapted to consider the aging population of pwCF with associated comorbidities, and also a new generation of young pwCF that are healthier than ever. In the present review we propose a new framework for optimising the choice among available exercise training procedures and we provide a theoretical and scientifically justified rationale for considering and testing new exercise training modalities. We propose a multidisciplinary approach, considering various physiological, psychological and logistical factors, with the aim to increase effects of exercise training and build positive long-term exercise behaviour.

Development and validation of the Cystic Fibrosis Decisional Balance for Physical Activity scale (CF-DB-PA).

BACKGROUND: People with cystic fibrosis (pwCF) derive several physiological and psychological benefits from regular physical activity (PA), but the practice is lower than recommended. Knowledge about the facilitators of and barriers to PA at the individual level is important to act positively on PA behaviors. This study validated the Cystic Fibrosis Decisional Balance for Physical Activity scale (CF-DB-PA) for adults with CF. METHODS: French adults with CF were recruited in several specialist centres in France. The CF-DB-PA scale was validated following a quantitative study protocol comprising four stages: (1) tests of the clarity and relevance of a preliminary 44-item version and reduction analysis, (2) confirmatory factor analysis and tests of dimensionality through equation modelling analysis, (3) tests of reliability with Cronbach alphas for the internal consistency and a test-retest with a 2-to-3 week interval for temporal stability, and 4) tests of construct validity with Spearman correlations to measure the associations between each subscale and the theoretically related constructs (i.e., quality of life, PA and exercise tolerance). RESULTS: A total of 201 French adults with CF participated in the validation study. The CF-DB-PA comprises 23 items divided into two factors: facilitators of and barriers to PA. Each factor is divided into three subscales: physical, psychological and environmental. The factors (facilitators and barriers) can be used independently or combined as a whole. A general score of decisional balance for PA can also be calculated. The bi-factor model presented satisfactory adjustment indexes: χ2 (194) = 362.33; p < .001; TLI = .87; CFI = .90; RMSEA = .067. The scale showed satisfactory internal consistency (Cronbach's α = .77). The test-retest reliability was not significant for either subscale, indicating stability over time. The facilitators subscale correlated significantly with the self-reported score of PA (r = .33, p < .01) and quality of life (r = .24, p < .05). The barriers subscale correlated significantly with the self-reported scores of PA (r = - .42, p > .01), quality of life (r = - .44, p < .01), exercise tolerance (r = - .34, p < .01) and spirometry tests (r = - .30, p < .05). CONCLUSIONS: The CF-DB-PA is a reliable and valid questionnaire assessing the decisional balance for PA, the facilitators of and the barriers to PA for adults with CF in French-speaking samples.

Oxygen transport and utilisation during exercise in cystic fibrosis: contributors to exercise intolerance.

NEW FINDINGS: What is the topic of this review? This review highlights the central and peripheral mechanisms that alter oxygen transport and utilisation and thereby contribute to exercise limitation in people with cystic fibrosis, considering also viable therapeutic targets for intervention. What advances does it highlight? Although traditionally considered a respiratory condition, pathological intramuscular and cardiovascular changes in people with cystic fibrosis appear to be key determinants of exercise intolerance up until the later stages of respiratory disease. Even young, habitually active patients with normal lung function experience multisystemic abnormalities, which play a role in exercise intolerance. ABSTRACT: Cystic fibrosis (CF) is a complex condition, commonly associated with exercise limitation. The mechanisms responsible for this in CF are of interest, given that lower aerobic fitness is associated with an increased risk of being hospitalised with pulmonary exacerbation, a poorer quality of life and a poorer prognosis. Pathophysiological changes in lung function are considered central to CF, and may contribute to exercise limitation. However, it is now clear that the pathogenesis of exercise limitation in this population is multifactorial, with alterations in cardiovascular, muscle and pulmonary function contributing. Whilst some of these changes are attributable to respiratory disease per se, the CF transmembrane conductance regulator protein is also found in skeletal muscle and the vascular endothelium and can directly alter central and localised oxygen delivery, as well as the ability to effectively extract and utilise oxygen at the myocyte level. Since intense exercise poses considerable challenges to arterial oxygen content and/or blood flow and its supply to the working skeletal muscle, evaluating the exercise physiology of people with CF has helped us understand the mechanisms underlying exercise intolerance. Through several investigations over recent years, we have collectively demonstrated that people with CF exhibit reduced skeletal muscle oxygen extraction and utilisation during exercise, with a lesser contribution from haemodynamic or chronotropic mechanisms. Taken together, our findings highlight the importance of targeting mechanisms of skeletal muscle oxygen utilisation in CF to improve exercise tolerance and we offer potential therapeutic interventional strategies.

Circulating biomarkers of antioxidant status and oxidative stress in people with cystic fibrosis: A systematic review and meta-analysis.

INTRODUCTION: Oxidative stress may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to quantify CF-related redox imbalances. METHODS: Systematic searches of the Medline, CINAHL, CENTRAL and PsycINFO databases were conducted. Mean content of blood biomarkers from people with clinically-stable CF and non-CF controls were used to calculate the standardized mean difference (SMD) and 95% confidence intervals (95% CI). RESULTS: Forty-nine studies were eligible for this review including a total of 1792 people with CF and 1675 controls. Meta-analysis revealed that protein carbonyls (SMD: 1.13, 95% CI: 0.48 to 1.77), total F2-isoprostane 8-iso-prostaglandin F2α (SMD: 0.64, 95% CI: 0.23 to 1.05) and malondialdehyde (SMD: 1.34, 95% CI: 0.30 to 2.39) were significantly higher, and vitamins A (SMD: -0.66, 95% CI -1.14 to -0.17) and E (SMD: -0.74, 95% CI: -1.28 to -0.20), ß-carotene (SMD: -1.80, 95% CI: -2.92 to -0.67), lutein (SMD: -1.52, 95% CI: -1.83 to -1.20) and albumin (SMD: -0.98, 95% CI: -1.68 to -0.27) were significantly lower in the plasma or serum of people with CF versus controls. CONCLUSIONS: This systematic review and meta-analysis found good evidence for reduced antioxidant capacity and elevated oxidative stress in people with clinically-stable CF.

Fatigue in Chronic Respiratory Diseases: Theoretical Framework and Implications For Real-Life Performance and Rehabilitation.

Fatigue is a primary disabling symptom in chronic respiratory diseases (CRD) with major clinical implications. However, fatigue is not yet sufficiently explored and is still poorly understood in CRD, making this symptom underdiagnosed and undertreated in these populations. Fatigue is a dynamic phenomenon, particularly in such evolving diseases punctuated by acute events which can, alone or in combination, modulate the degree of fatigue experienced by the patients. This review supports a comprehensive inter-disciplinary approach of CRD-related fatigue and emphasizes the need to consider both its performance and perceived components. Most studies in CRD evaluated perceived fatigue as a trait characteristic using multidimensional scales, providing precious information about its prevalence and clinical impact. However, these scales are not adapted to understand the complex dynamics of fatigue in real-life settings and should be augmented with ecological assessment of fatigue. The state level of fatigue must also be considered during physical tasks as severe fatigue can emerge rapidly during exercise. CRD patients exhibit alterations in both peripheral and central nervous systems and these abnormalities can be exacerbated during exercise. Laboratory tests are necessary to provide mechanistic insights into how and why fatigue develops during exercise in CRD. A better knowledge of the neurophysiological mechanisms underlying perceived and performance fatigability and their influence on real-life performance will enable the development of new individualized countermeasures. This review aims first to shed light on the terminology of fatigue and then critically considers the contemporary models of fatigue and their relevance in the particular context of CRD. This article then briefly reports the prevalence and clinical consequences of fatigue in CRD and discusses the strengths and weaknesses of various fatigue scales. This review also provides several arguments to select the ideal test of performance fatigability in CRD and to translate the mechanistic laboratory findings into the clinical practice and real-world performance. Finally, this article discusses the dose-response relationship to training and the feasibility and validity of using the fatigue produced during exercise training sessions in CRD to optimize exercise training efficiency. Methodological concerns, examples of applications in selected diseases and avenues for future research are also provided.

Overall and differentiated sensory responses to cardiopulmonary exercise test in patients with cystic fibrosis: kinetics and ability to predict peak oxygen uptake.

PURPOSE: We evaluated the validity of predicting peak oxygen uptake ([Formula: see text]O2peak) from submaximal ratings of perceived exertion (RPE) during incremental cardiopulmonary exercise test (CPET) in patients with cystic fibrosis (CF) and compared the predictive accuracy between overall and differentiated RPE scores. METHODS: Thirty-five adults with CF (FEV1 = 58 ± 23%) performed a CPET on cycle ergometer with gas exchange measurements. Leg, chest and overall RPE were collected every minute throughout the test. Linear regressions between [Formula: see text]O2 and RPE ≤ 15 were extrapolated to maximal theoretical RPE (i.e. RPE18 and RPE19) to predict [Formula: see text]O2peak. Agreements between measured and all predicted [Formula: see text]O2peak were tested using Bland-Altman Plots, for the whole group and for subjects presenting significant exercise intolerance (n = 24). RESULTS: Leg, chest and overall RPE increased similarly with exercise intensity. No differences were found between predicted [Formula: see text]O2peak and measured [Formula: see text]O2peak with RPE18 as maximal RPE, for both overall and differentiated RPE (P range 0.94-0.98). Ranges for Pearson correlations and limits of agreements were 0.88-0.91 and 380-461 mL min-1 for the whole group and 0.92-0.94 and 269-365 mL min-1 for subjects with significant exercise intolerance. The greatest association and narrowest limits of agreements were obtained from chest RPE scores. CONCLUSIONS: Submaximal RPE scores obtained during CPET can provide acceptable estimate of [Formula: see text]O2peak in adults with CF, particularly in those having significant exercise intolerance. Future studies should assess whether the prediction can be improved, particularly by encouraging the regular use of RPE scales during physical activities/exercise rehabilitations sessions.

Peripheral muscle abnormalities in cystic fibrosis: Etiology, clinical implications and response to therapeutic interventions.

Peripheral muscle dysfunction is an important systemic consequence of cystic fibrosis (CF) with major clinical implications, such as exercise intolerance and reduced quality of life. Evidence is now accumulating that lack of physical activity is unlikely to be the sole explanation for peripheral muscle dysfunction of patients with CF. Particularly, the demonstration of CFTR expression in both murine and human skeletal muscle suggests the potential implication of intrinsic CF-related factors. By combining data from both human and animal models, this review describes CF peripheral muscle abnormalities and critically reviews the advances in understanding the impact of the underlying mechanisms. We also describe how peripheral muscles respond to intervention in this population. Methodological concerns and directions for future research are also considered. Peripheral muscle atrophy and weakness is prevalent in patients with CF and associated with reduced aerobic and anaerobic performances. Further investigations are however needed to confirm alterations in peripheral muscle endurance and fatigability. Physical inactivity is probably the major contributor of peripheral muscle abnormalities in patients with CF with mild-to-moderate phenotypes. However, the relative influence of additional factors (e.g. inflammation, metabolic abnormalities) probably increases with disease severity making specific and individualized interventions necessary in severe patients. Exercise training is the most effective intervention to address peripheral muscle dysfunction but other strategies, such as neuromuscular electrical stimulation and nutritional or hormonal supplementation may be of interest in some patients. Investigations are needed to determine whether pharmacological interventions such as CFTR modulators are effective to address this condition. To better elucidate the etiology of peripheral muscle dysfunction in CF, future studies should combine measurements at the cellular level with indices of muscle function and monitor physical activity levels to account for its potential effects on muscle function.

The 1-Minute Sit-to-Stand Test in Adults With Cystic Fibrosis: Correlations With Cardiopulmonary Exercise Test, 6-Minute Walk Test, and Quadriceps Strength.

BACKGROUND: Exercise testing is part of the regular assessment of patients with cystic fibrosis (CF). We aimed to evaluate (1) the convergent validity of the 1-min sit-to-stand (STS) test in CF by investigating its relationships with peak oxygen uptake (peak V̇O2 ), quadriceps strength, and quality of life and (2) to compare these associations with those of the 6-min walk test (6MWT). METHODS: Twenty-five adults with CF (FEV1 = 59 ± 24%) performed the STS test, the 6MWT, quadriceps strength assessment, and cardiopulmonary exercise test (CPET). Physical activity level, quality of life, and self-esteem were assessed by questionnaires. RESULTS: STS repetitions, 6-min walk distance, quadriceps strength, and peak V̇O2 were, respectively, 71 ± 12, 90 ± 10, 93 ± 29, and 62 ± 16% of predicted. The STS test had moderate associations with peak V̇O2 (r = 0.56, P = .004), quadriceps strength (r = 0.52, P = .008), and some questionnaire items (eg, perceived physical strength, r = 0.67, P < .001) only when repetitions were expressed as a product of body weight. Overall, these associations were weaker than those obtained from 6-min walk distance × weight. Oxygen desaturation during the STS test was strongly associated with oxygen desaturation during CPET (r = 0.80, P < .001). Peak heart rate was lower during the STS test as compared with CPET (P < .001) and the 6MWT (P = .009). CONCLUSIONS: The STS test cannot be used as a replacement for CPET to accurately assess peak exercise capacity in CF. The STS test may have utility in detecting patients with CF who may exhibit a high level of oxygen desaturation during heavy exercise. Further studies should identify the factors contributing to STS performance to confirm the potential interest of STS repetitions × body weight outcome as a useful submaximal exercise parameter in CF.

Physiological Responses of the Modified Shuttle Test in Adults With Cystic Fibrosis.

PURPOSE: The modified shuttle test (MST) is increasingly used in clinical practice to assess functional capacity in patients with cystic fibrosis (CF). The purpose of this study was to evaluate the physiological responses of the MST in adults with CF as compared with the gold standard cardiopulmonary exercise test (CPET). METHODS: Participants performed an MST and a CPET on a cycle ergometer in random order. Oxygen (O2) uptake ((Equation is included in full-text article.)O2), carbon dioxide (CO2) retention (end-tidal PCO2; PETCO2), minute ventilation, heart rate, and peripheral O2 saturation (SpO2) were continuously monitored. Whole blood lactate, dyspnea, and leg discomfort were recorded immediately after both exercises. RESULTS: Twenty patients with CF (aged 33 ± 8 years; forced expiratory volume in 1 second = 48% ± 17%) completed both tests. Peak values for (Equation is included in full-text article.)O2 (27 ± 7 vs 24 ± 6 mL/kg/min), heart rate (169 ± 19 vs 163 ± 16 bpm), end PETCO2 (42 ± 7 vs 39 ± 8 mm Hg), and O2 desaturation (end SpO2, 86% ± 7% vs 90% ± 6%) were significantly higher during the MST than during the CPET (all Ps < .05). Leg discomfort and whole blood lactate were significantly higher after the CPET (both Ps < .05). Thirty-five percent and 40% of patients showed significant O2 desaturation and CO2 retention, respectively, during the MST, which was not detected during the CPET. A strong relationship was found between MST peak (Equation is included in full-text article.)O2 and body weight walking distance product (r = 0.90; P < .01). CONCLUSIONS: The MST may provide a strong indicator of exercise tolerance in adults with CF as indicated by high peak (Equation is included in full-text article.)O2 values. In clinical practice, body weight walking distance should be considered as the primary outcome. This test is also better than cycle ergometry CPET for detecting O2 desaturation and CO2 retention, further emphasizing its clinical interest.

Skeletal muscle contractility and fatigability in adults with cystic fibrosis.

BACKGROUND: Recent discovery of cystic fibrosis transmembrane conductance regulator expression in human skeletal muscle suggests that CF patients may have intrinsic skeletal muscle abnormalities potentially leading to functional impairments. The aim of the present study was to determine whether CF patients with mild to moderate lung disease have altered skeletal muscle contractility and greater muscle fatigability compared to healthy controls. METHODS: Thirty adults (15 CF and 15 controls) performed a quadriceps neuromuscular evaluation using single and paired femoral nerve magnetic stimulations. Electromyographic and mechanical parameters during voluntary and magnetically-evoked contractions were recorded at rest, during and after a fatiguing isometric task. Quadriceps cross-sectional area was determined by magnetic resonance imaging. RESULTS: Some indexes of muscle contractility tended to be reduced at rest in CF compared to controls (e.g., mechanical response to doublets stimulation at 100 Hz: 74±30 Nm vs. 97±28 Nm, P=0.06) but all tendencies disappeared when expressed relative to quadriceps cross-sectional area (P>0.5 for all parameters). CF and controls had similar alterations in muscle contractility with fatigue, similar endurance and post exercise recovery. CONCLUSIONS: We found similar skeletal muscle endurance and fatigability in CF adults and controls and only trends for reduced muscle strength in CF which disappeared when normalized to muscle cross-sectional area. These results indicate small quantitative (reduced muscle mass) rather than qualitative (intrinsic skeletal muscle abnormalities) muscle alterations in CF with mild to moderate lung disease.

Use of the peak heart rate reached during six-minute walk test to predict individualized training intensity in patients with cystic fibrosis: validity and reliability.

OBJECTIVE: To determine whether the peak heart rate reached during a six-minute walk test (HR(6peak)) can be used to predict the heart rate determined at the gas exchange threshold (HR(GET)) during a maximal cardiopulmonary exercise test (CPET) in patients with cystic fibrosis (CF). To assess the test-retest reliability of HR(6peak). DESIGN: Case-control and reliability study. SETTING: CF unit. PARTICIPANTS: Adults with CF (n=23) and age-matched sedentary subjects (control group, n=17). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Six-minute walk test, HR(6peak), CPET, and HR(GET). RESULTS: HR(GET) and HR(6peak) were not significantly different and were highly correlated in both groups (CF, r=.91, P<.01; controls, r=.81, P<.01). The mean differences (HR(6peak)-HR(GET)) for patients with CF and control subjects were, respectively, -0.9 beats.min(-1) (bpm) and -0.1 bpm, with neither significantly different from 0. The limits of agreements were +/-11 bpm and +/-18 bpm, respectively. HR(6peak) demonstrated excellent relative reliability (intraclass correlation coefficient=.93) and was associated with low variability (standard error of measurement=4.9 bpm) in patients with CF. CONCLUSIONS: HR(6peak) is valid and demonstrates satisfactory test-retest reliability in patients with CF. These results might suggest the use of HR(6peak) as a simple alternative method to individualize exercise prescriptions in this population. Further studies are needed in a larger cohort of patients to confirm these preliminary findings.