Cystic fibrosis (CF) is an autosomal recessive disorder involving multiple body systems, mainly the respiratory, gastrointestinal, endocrine, and reproductive systems. Epidemiologic studies report an incidence of 1 in every 2,381 live births, mainly affecting Northern Europeans.

CF arises from a defective transmembrane conductance regulator gene (CFTR) which is responsible for ion transport, so exocrine glands and pulmonary epithelia are affected. The liquid on the airway surface is reduced, causing increased viscosity, mucus clogging, inflammation, irreversible damage to airway epithelia, and consequent bronchiectasis, which eventually leads to respiratory failure. Modern immunomodulator and potentiator therapy have greatly enhanced the life expectancy of these patients. In this scenario, rehabilitation aims to maintain respiratory health and optimize quality of life (QoL). Airway clearance is managed through a great variety of techniques, such as postural drainage and percussion (PD&P), autogenic drainage (AD), and active cycle of breathing technique (ACBT). Respiratory health maintenance also can be aided by devices that use oscillation or positive expiratory pressure (PEP). Currently, the effectiveness of exercise to increase airway clearance has not been investigated, while physical activity and exercise can improve function and endurance and decrease exacerbations and hospital admissions.

This review investigated the effectiveness and the occurrence of adverse events of exercise compared to usual airway clearance techniques (ACTs) in people with CF.

This review is important for

People with cystic fibrosis, their loved ones/caregivers, health professionals caring for this population, general practitioners, researchers, and policymakers.

Outcomes of this review

This is a new Cochrane Systematic Review (CSR), published in 2022. The outcomes analyzed were lung function, exercise capacity, quality of life, adverse events, patients’ preference and adherence, sputum weight, number of hospital admissions caused by exacerbations, and necessity of antibiotics. The CSR included four randomized controlled trials (RCTs). The trials were published and/or registered up to February 15, 2022, with 86 participants. There wasn’t enough evidence to support exercise as a replacement for other methods of airway clearance. No data were available to assess the quality of life or the need for extra antibiotic treatment. The trials were too heterogeneous to allow a combination of results.

The authors were uncertain whether exercise compared to active cycle of breathing technique (ACBT) improved FEV1 or was preferred by the patients, as the evidence is very low. No adverse events occurred, and exercise produced less sputum. Similarly, the authors were uncertain whether exercise together with postural drainage and percussion (PD&P) improved FEV1 compared to PD&P only, as the certainty of the evidence was very low. No difference in exercise capacity, duration of hospitalization, or sputum volume was reported, and no adverse events were reported (very low-certainty evidence). On the other hand, exercise compared to underwater positive expiratory pressure (uPEP) showed no adverse events, no increase in sputum, and a greater patient satisfaction with the exercise albeit being more fatiguing (very low-certainty evidence). No data were available for pulmonary function, quality of life, and exercise capacity.

These results must be interpreted with caution because:

(i) The low number of participants yielded imprecise results. (ii) The authors were mostly able to find studies that compared exercise to a control group that underwent both exercise and another ACT; therefore, it was not an ideal control. (iii) Most of the studies examined only a short-term intervention. (iv) No study defined the baseline severity of lung disease, making it difficult to generalize the results to the general CF population. (v) Results on hospital admissions had low applicability, validity, and significance since baseline characteristics and previous admissions were not reported. (vi) Significant time has passed since some of the studies were conducted, and today the history of CF has drastically changed. (vii) No data were reported on adherence to the intervention in the medium term. (viii) All trials had an unclear risk of bias for all domains. Furthermore, the (ix) blinding of personnel and patients was not possible for the nature of the intervention itself. (x) Two studies have not comprised any data on the baseline characteristics of their participants. (xi) Only one trial reported on the quality of life and did so without using a validated questionnaire. (xii) No study carried out a power calculation. (xiii) The data were heterogeneous. And finally, (xiv) numerical data analyses were not possible for most outcomes.

Author’s conclusion of the review

The number of trials was not sufficient to draw any conclusion about whether or not exercise is as effective as ACT and thus can be used as an alternative treatment. Moreover, the diverse design of the studies did not allow for meta-analysis of results. Insufficient evidence was available to assess the effectiveness of exercise in sputum clearance or for respiratory health, even though it increases aerobic capacity and has a positive effect on lung function and quality of life.

In conclusion, the authors were uncertain whether exercise was effective per se as an ACT as the evidence is very low.

Therefore, further studies are needed to allow any proper conclusion to be drawn.

Future recommendations

The authors recommended that large-scale studies are needed, particularly to find out (a) the long-term effects of the intervention, and (b) if exercise could be non-inferior to standard ACT in terms of forced expiratory volume in one second (FEV1) or lung clearance index. (c) They might focus on individual outcomes, like improvement in quality of life, assessed by the Cystic Fibrosis Questionnaire or the St George’s Respiratory Questionnaire. (d) Authors suggest that cross-over trial designs could offer the possibility to recruit a larger pool of patients, but they tend to be short in duration or use insufficient washout periods. Moreover, they tend to suffer from dropouts due to exacerbations. (e) Studies should also consider the many genetic variations to the conductance regulator to be able to apply the results to the CF population. (f) The authors suggest that all recruited patients should be tested genetically or via sweat test and should be stable for a fixed period. Further studies also should accurately (g) gather patients’ baseline characteristics, (h) note who is taking modulator therapy, and (i) consider other predictors such as height, weight, and body mass index (BMI). (j) To improve adherence, the exercises should be selected by the patients among a wide range that is equally capable of achieving a high heart rate. (k) The authors recommend that cardiopulmonary exercise should be carried out as gold standard guidelines at 70% to 80% of maximal heart rate or peak oxygen uptake, even if it may actually negatively impact individuals’ needs and enjoyment and, consequently, their long-term adherence. (l) Research might also examine the effects of different types of training and the optimal combination of exercise programs to optimize CF patients’ global health.

Robin Kuruvila Sentinella