The Impact of Exercise Intervention on Pulmonary and Physical Function in Patients With Cystic Fibrosis: A Comprehensive Systematic Review

Summary

Objective:

To evaluate the effect of various exercise interventions on lung function, specifically forced expiratory volume in 1 second (FEV₁), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP), as well as on cardiorespiratory fitness (peak oxygen uptake [VO₂peak]), and muscle strength (handgrip strength). The review also considers factors such as patient adherence, follow-up duration, and statistical significance to inform clinical practice.

Methods:

This systematic review followed preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines and was prospectively registered in international prospective register of systematic reviews. PubMed, Google Scholar, OVID, and Web of Science were systematically searched. Eligible studies were randomized controlled trials enrolling cystic fibrosis (CF) patients aged 7 or older, reporting outcomes related to pulmonary function, cardiorespiratory fitness, or muscle strength following aerobic, resistance, or mixed exercise interventions.

Results:

A total of 1,033 articles were identified through the database search. After screening and eligibility assessment, 4 randomized controlled trials involving 156 participants met the inclusion criteria. Both supervised and wearable activity tracker (WAT)-based exercise programs significantly improved VO₂peak and exercise capacity, as demonstrated by the 6-minute walk test. Home-based programs enhanced upper limb muscle strength. However, improvements in FEV₁ were inconsistent and tended to decline without ongoing training. No adverse events were reported.

Conclusion:

Structured exercise, particularly WAT based or supervised, supports better physical fitness in CF. Standardized protocols, longer-term follow-up, diverse participant inclusion, and strategies to improve adherence are needed in future research.

Introduction

Cystic fibrosis (CF) is an inherited disorder passed down in an autosomal recessive manner that affects various organ systems, especially the lungs, pancreas, and liver [1,2]. The disease is marked by the buildup of thick, sticky mucus in the airways, which is a hallmark of CF [1,2]. This abnormal mucus production leads to chronic lung infections, airway blockages, and a gradual decline in breathing ability over time [1,2]. Cystic fibrosis was once regarded mostly as a childhood illness, but improvements in diagnostics and treatment have significantly increased patient survival, resulting in more adults living with the condition [3]. Today, CF affects an estimated 100,000 people worldwide [4]. Thanks to a multidisciplinary care approach that includes both medications and nondrug therapies, CF is now considered a manageable chronic disease [4]. Among the many aspects of care, regular exercise has proven to boost muscle strength, enhance lung function, and improve overall physical health for people with CF [5].

Extensive research has investigated how exercise affects pulmonary function in individuals with CF. Many studies have focused on forced expiratory volume in 1 second (FEV₁) as a key measure for evaluating treatment effectiveness [6,7]. The FEV₁ is widely recognized as a standard benchmark for monitoring lung disease progression in CF and has a strong correlation with mortality rates among patients [8]. In addition to FEV₁, maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) are commonly used to assess respiratory muscle strength [9]. These values provide important insights into how well the respiratory muscles are functioning [9]. The link between FEV₁ and exercise varies across different studies. Notably, Kriemler et al. [10] reported in their clinical research that 6 months of regular physical activity led to a significant improvement in FEV₁ among participants. Additionally, Schneiderman et al. [11] found a link between increased physical activity and a slower decline in FEV₁ among people with CF. However, some studies suggest that exercise has only a limited effect on FEV₁ [12,13]. These studies implemented exercise programs lasting either 8 week or 12 months [12,13]. Despite these efforts, uncertainty remains regarding the optimal duration and intensity of exercise routines needed to best support pulmonary function. As a result, factors such as the length and intensity of activity could play a critical role in shaping how physical exercise affects FEV₁.

Beyond pulmonary function, assessing cardiorespiratory fitness is essential for people living with CF [14,15]. This can be measured through peak oxygen uptake (VO₂peak), which is recognized as a key marker of aerobic fitness, giving valuable insights into cardiovascular efficiency and overall physical capacity. Recent guidelines recommend using VO₂peak as a predictor of mortality in patients with CF [14,15]. Research shows that a lower VO₂peak is associated with higher mortality rates with those experiencing reduced VO₂peak facing a risk of death nearly 4.9 times greater than individuals with normal values [14,15]. It is important to consider the role of cardiorespiratory fitness when examining the benefits of exercise interventions [16]. Exercise therapy has been shown to significantly improve VO₂peak in both children and adults with CF [16].

Muscle weakness is a common symptom experienced by individuals with CF, affecting approximately 60% of patients [17,18]. This weakness may develop due to various factors, including changes in muscle metabolism, frequent hospitalizations, corticosteroid therapy, and reduced levels of physical activity [17,18,19,20]. Because of this, building muscle strength is a vital focus of exercise therapy for people living with CF [21]. One commonly used method to assess muscle strength is measuring handgrip strength [21,22]. Studies have shown that both handgrip strength and overall physical strength increase in younger patients who participate in moderate exercise, even if they do not strictly follow training programs [21]. Additionally, patients with weaker handgrip strength tend to have lower FEV₁ values, which reflect poorer respiratory function [22].

This systematic review aims to evaluate the effect of exercise interventions on pulmonary and physical function in individuals with CF. Key areas of investigation include how exercise influences muscular strength (handgrip strength), VO₂peak, and pulmonary metrics namely FEV₁, MIP, and MEP. The study also considers additional objectives, such as analyzing follow-up duration and the statistical significance of treatment effects. By providing a comprehensive assessment of the current scientific literature, this work will expand knowledge on the role of exercise in CF management and serve as a resource for future research and clinical practice. Moreover, examining the relationship between adherence to exercise programs and health outcomes in CF patients is vital. Gaining insight into factors affecting adherence can help develop strategies to boost patient participation and maximize the advantages of exercise interventions.

Methods

This systematic review was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and registered in PROSPERO [23]. A PRISMA flow diagram depicting the screening and selection process is shown in Fig. 1. No ethical approval was required due to the nature of the research. A comprehensive literature search was performed across several databases, including PubMed, Google Scholar, OVID, and Web of Science. Additional relevant articles were identified by examining the reference lists of the selected studies. Eligible studies for review were chosen based on the PICOTS framework namely: population, intervention, comparison, outcomes, timing, and setting [24].

Fig. 1.

Identification of new studies via databases and registers. n: total number.

The inclusion criteria were: i) participants were children or adults diagnosed with CF; ii) the intervention involved physical exercise, which could be aerobic, resistance, or a combination of both, iii) the comparator was either standard care, no intervention, or a placebo, iv) the study reported outcomes relating to muscle strength (handgrip strength), VO₂peak, or pulmonary function (FEV₁, MIP, MEP), (v) the study design was a randomized controlled trial (RCT), vi) and the publication was in English and released between January 2000 and October 2024. While the exclusion criteria were: i) the participants were not diagnosed with CF, or the research focused mainly on cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, ii) a physical exercise intervention was not included, or the exercise protocol was not described in sufficient detail, iii) outcomes related to pulmonary function, cardiorespiratory fitness, or muscle strength were not examined, iv) the study was not designed as an RCT, v) or the publication was a review article, case report, case series, or editorial, written in a language other than English or published before January 2000.

The screening process was performed by 2 independent reviewers (AG, MA), who simultaneously and separately examined titles and abstracts using the Rayyan web application, designed for systematic reviews [25]. All studies identified during the search were imported into Rayyan for duplicate detection, and any duplicates were eliminated after carefully checking the records. Next, 2 additional reviewers (AF, BJ) conducted concurrent assessments of full-text articles. Data extraction was carried out by 2 additional reviewers (AR, RA), who focused on key variables such as authorship, year of publication, article title, and study design. Participant demographics were noted, including the number of males and females, age range, mean age, and total sample size. For every study, details about the exercise intervention were recorded, covering the type of program (use of wearable activity trackers [WATs], home-based exercise, aerobic training, strength training), how long the intervention lasted, its intensity (moderate or self-selected), and how often sessions occurred.

Collecting this information enabled meaningful comparisons across various types and intensities of exercise interventions. The main outcomes evaluated in each study were pulmonary function (FEV₁), cardiorespiratory fitness (including VO₂peak and the 6 minute walk test [6MWT]), and muscle strength (handgrip strength, leg press results).

For each study, the key findings were recorded, including effect sizes, p-values, and the significance levels of the primary outcomes. Any differences in data extraction were settled through discussion between the 2 reviewers. All collected data were organized using Excel to support comprehensive analysis and synthesis across the included studies.

The risk of bias in each included study was evaluated using the Cochrane Risk of Bias Tool, which is specifically tailored for assessing RCTs [26]. The findings from this assessment are shown in Table 1. This tool was chosen for its structured approach to reviewing methodological quality across 6 key domains: i) selection bias, ii) performance bias, iii) detection bias, iv) attrition bias, v) reporting bias, and other sources of bias. Two reviewers independently completed the risk assessment for each study, resolving any disagreements through discussion or, when necessary, by involving a third reviewer. Each study's overall risk of bias was categorized as low, high, or unclear based on evaluations of these domains. Due to the small number of included studies and the diversity in available data, a meta-analysis could not be conducted because there was insufficient consistency for meaningful statistical synthesis.

Table 1.

The RoB for each study.

Authors/Year	Study type	RoB tool	Selection bias	Performance bias	Detection bias	Attrition bias	Reporting bias
Anifanti, 2022	RCT	Cochrane RoB	L	U	L	L	L
Rovedder, 2014	RCT	Cochrane RoB	L	U	L	L	L
Hommerding, 2015	RCT	Cochrane RoB	L	U	U	L	L
Kriemler, 2013	RCT	Cochrane RoB	L	U	U	L	L

RoB: risk of bias, Low risk of bias: (+) or (L), High risk of bias: (-) or (H), Unclear risk of bias: (?) or (U), RoB: risk of bias, RCT: randomized clinical trial.

Result

A total of 1,033 articles were initially identified from various databases, including Google Scholar (178), PubMed (226), OVID (200), and Web of Science (429). After duplicates were removed, 809 unique records remained. These articles were screened by title and abstract, resulting in 28 studies selected for full-text review. After in-depth assessment, 4 studies published between 2013 and 2022 met the criteria for inclusion in the final analysis. The most common reasons for exclusion were unsuitable study population, lack of relevant outcome measures, inappropriate study design, publication before January 2000, and written in a language other than English.

This analysis incorporates 4 studies, totaling 156 participants. In the study conducted by Anifanti et al. [29] there were 42 participants, 23 (54.8%) males and 19 (45.2%) females, with a mean age of 16.8 years (standard deviation (SD) = 3.6). Rovedder et al. [27] included 41 patients aged 16 or older, with a mean age of 24.73 years (SD = 7.57); this group consisted of 14 (34.1%) males and 27 (65.9%) females. Hommerding et al. [28] examined 34 individuals between 7 and 20 years old, with a mean age of 13.0 years (SD = 3.0); there were 20 (58.8%) males and 14 (41.2%) females. For the study by Kriemler et al. [10] while the mean age and gender distribution were not specified, the sample included 39 participants, all at least 12 years old.

Each study employed a distinct exercise approach. Anifanti et al. [29] implemented a moderate-intensity, WAT-based program 3 times per week for 1 year. Rovedder et al. [27] offered a 3-mo home-based aerobic and strength training program with daily sessions, although the intensity was not specified. Hommerding et al. [28] provided a 3-mo aerobic training program, which included bimonthly telephone support and required at least 2 moderately paced or self-selected sessions per week, lasting 20 min each. Kriemler et al. [10] delivered a 6 month routine of moderate-intensity aerobic and strength exercises (65% VO₂peak) 3 times per week, with sessions lasting 30 to 45 min. (Table 2).

Table 2.

The participant demographics and the implemented exercise interventions across the 4 studies.

Study ID	Total number of patients included	Mean Age in years, SD	Study design	Type of exercise intervention	Intensity
Anifanti, 2022 [29]	42 Females: 19 Males: 23	16.8 ± 3.6 years	RCT	WAT-based and ET program for 1 year	Moderate (based on steps target), 3 times per week
Rovedder, 2014 [27]	41 Females: 27 Males: 14	24.73 ± 7.57 years for 16 years old and older	RCT	Home exercise program (aerobic training and muscle strength training) for 3 months	Not specified, home based, daily
Hommerding, 2015 [28]	34 Females: 14 Males: 20	13.0 ± 3.0 years for 7-20 years old	RCT	Aerobic exercise based on verbal and written guidelines with supervision over the telephone every 2 week for 3 months	self-selected / unspecified moderate, at a minimum frequency of 2 times/week for at least 20 min
Kriemler, 2013 [10]	39 (No specific information regarding gender distribution)	NA Age range: 12 years old and older	RCT	Aerobic and strength training for 6 months	Moderate based on (ST monitored with specific exercises; AT at 65% of VO2peak initially, increasing resistance as able), 3 sessions per week (30–45 minutes each)

SD: standard deviation, RCT: randomized clinical trial, WAT: wearable activity tracker, ET: exercise training, ST: strength training, AT: aerobic training, VO₂peak: peak oxygen uptake, NA: new adult.

Participants in the study by Anifanti et al. [29] completed a yearlong fitness program using a WAT. No adverse effects were reported during the intervention, and performance on the 6MWT improved by 20% (p < 0.05). The daily number of steps was found to have a strong linear relationship with several pulmonary and functional measures, including pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE), right ventricular 4-chamber longitudinal strain (RV4CLS), right ventricular free wall longitudinal strain (RVFWLS), and 6MWT results (all p < 0.01). However, measures of pulmonary function, specifically FEV₁, MIP, and MEP, did not exhibit significant changes.

In the study by Rovedder et al. [27] participants completed a 3 month home-based exercise program that included a 1-repetition maximum (1 RM) strength test and the 6MWT. While the 6MWT results did not show significant improvement, upper limb muscle strength, particularly handgrip strength, increased notably (p = 0.011 for the left hand, p = 0.029 for the right hand). The study also assessed quality of life using a CF-specific questionnaire and the general medical outcomes study 36-item short-form health survey (SF-36) [32]. However, changes in both lung function measures and quality of life scores were not statistically significant. Hommerding et al. [28] conducted a 3 month aerobic exercise program that included activities such as swimming, walking, dancing, jogging, ball games, and skipping rope. Participants engaged in significantly more physical activity compared to others (p < 0.01), and no adverse events were reported during the intervention. However, measures of lung function, peak exercise capacity, and other clinical or physiological indicators did not show notable differences between the groups (p > 0.05). Quality of life was evaluated using age-specific questionnaires that addressed areas such as vitality, general health, social roles, weight, digestion, respiratory status, emotions, physical activity, body image, and nutrition for children aged 6–11, 12–13, and 14 years. At the outset, baseline comparisons revealed no significant differences between the groups.

In the study by Kriemler et al. [10] participants completed a 6 month program that combined aerobic and strength training, with follow-up evaluations taking place at 3, 6, 12, and 24 months. Both the aerobic training (AT) and strength training (ST) groups demonstrated significant gains in lung function (FEV₁) at the 6 month mark, with increases of 5.8% and 7.4%, when compared to the control group (p < 0.001). Furthermore, the AT group experienced a notable improvement in VO₂peak at 6 months compared to controls. However, enhancements in both FEV₁ and VO₂peak declined by 18 months if the training was not maintained. No adverse effects were observed throughout the duration of the study [10].

While Rovedder et al. [27] observed increases in muscle strength, both Anifanti et al. [10] and Kriemler et al. [29] reported significant improvements in exercise capacity and lung function. In contrast, the findings from Hommerding et al. [28] did not show meaningful enhancements in any measured outcomes Table 3.

Table 3.

The statistical significance and outcome of the 4 studies.

Study ID	Statistical significance	Outcomes	Recommendation
Anifanti, 2022	Significant linear correlation between the number of steps per day recorded and the PASP (p < 0.01), TAPSE (p < 0.001), RV4CLS (p < 0.001) and RVFWLS (p < 0.001). Significant linear correlation between the number of steps recorded and the 6-MWT results at the end of the study (p < 0.01).	6MWT: Significant improvement, with a 20% increase in distance walked for the intervention group (p < 0.05).	Regular exercise therapy is recommended as an essential part of CF treatment.
Rovedder, 2014	Significant increase in upper limb muscle strength in the exercise group (p < 0.05).	Significant increase in muscle strength in upper limbs compared with the control group on the 1 RM test (p = 0.011 for the left upper limb and p = 0.029 for the right upper limb). No significant change in quality of life.	The study suggests that future research should consider including VO2max measurements (through a cardiopulmonary force test) to assess aerobic capacity more accurately. Also encourages further exploration of home-based exercise programs, particularly those that are remotely supervised, despite the modest benefits observed.
Hommerding, 2015	Group 1 showed a significant increase in physical exercise practice compared to Group 2 (p < 0.01). No significant differences in lung function and maximum exercise capacity between groups (p > 0.05).	After 3 months, there was a significant increase in physical exercise practice reported by subjects in group 1 compared with subjects in group 2. No significant change in quality of life.	The study recommends that more comprehensive guidelines for exercise intensity and frequency should be incorporated in future interventions and a longer or more intense intervention may improve patient's quality of life and physiological outcomes.
Kriemler, 2013	FEV1 significantly improved in both training groups compared to the control group at 6 months (p < 0.001) and VO2peak was a statistically significant improvement in the AT group compared to the control group at 6 months; however, diminished effects were observed by 18 months without continued training.	Significant improvement in both intervention groups after 6 months: AT group: FEV1 increased by +5.8%. ST group: FEV1 increased by +7.4%.	The study suggests that continuing a partially supervised physical activity program can be easily implemented in routine CF care to ensure persistent and meaningful changes in activity behavior and physical health.

PASP: pulmonary artery systolic pressure, TAPSE: tricuspid annular plane systolic excursion, RV4CLS: right ventricular 4-chamber longitudinal strain, RVFWLS: right ventricular free wall longitudinal strain, 6-MWT: 6 minute walk test, FEV1: forced expiratory volume in 1 second, VO2peak: peak oxygen uptake, AT: aerobic training, RM: repetition maximum, ST: strength maximum, CF: cystic fibrosis.

Overall, results from the 6MWT and VO₂peak indicated that exercise interventions, especially those using WATs or supervised routines, boosted exercise capacity. Changes in pulmonary function, particularly FEV₁, varied between studies. Home-based and strength training programs were linked to increased muscular strength, notably in the upper limbs. Quality of life improvements were modest, with some progress in areas such as social role, but there were no major advancements across all categories or among all groups of participants.

Grading of recommendations assessment, development and evaluation (GRADE) assessment of exercise interventions in cystic fibrosis. The RCT by Anifanti et al. [29] examined a long-term WAT-based exercise program for individuals with CF, resulting in a moderate level of evidence certainty. This rating was influenced mainly by the study's small sample size and concerns about bias, though no issues with indirectness were identified, and publication bias was considered a possibility. Similarly, Kriemler et al. [10] studied supervised exercise training effects on FEV₁ in CF patients and received a moderate certainty classification. Limitations included a relatively small cohort, some risk of bias, imprecision in results, and a low likelihood of publication bias. Conversely, Rovedder et al. [27] conducted an RCT on an exercise intervention in CF, but due to methodological weaknesses and insufficient data across key GRADE domains such as the risk of bias, inconsistency, indirectness, imprecision, the certainty of evidence could not be established for this study. Finally, Hommerding et al. [28] evaluated an educational physical activity program in CF. Like Rovedder et al. [27], the available evidence was inadequate for a comprehensive GRADE assessment, making it impossible to assign a certainty rating from this review (Table 4).

Table 4.

Certainty of evidence (using the GRADE technique).

Study	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Certainty
Anifanti et al. 2022, [29]	RCT	Some concerns	Some	None	Some	Possible	Moderate
Rovedder et al. 2014, [27]	RCT	Not assessable	Not assessable	Not assessable	Not assessable	Unknown	Cannot grade
Hommerding et al. 2015, [28]	RCT	Not assessable	Not assessable	Not assessable	Not assessable	Unknown	Cannot grade
Kriemler et al. 2013, [10]	RCT	Some concerns	Minimal	None	Some	Low	Moderate

GRADE: grading of recommendations assessment, development and evaluation, RCT: randomized clinical trial.

Discussion

Our systematic review set out to assess how different exercise interventions affect exercise capacity, lung function, muscle strength, and quality of life for individuals with CF. The findings revealed that structured exercise programs, especially those incorporating WATs or involving supervision, produced notable improvements in physical fitness, demonstrated by better 6MWT distances and higher VO₂peak values within certain groups.

For example, Anifanti et al's. [29] WAT-based regimen resulted in a 20% increase in 6MWT distance for the intervention group (p < 0.05). Similarly, the study by Kriemler et al. [10], which included aerobic and strength training, showed gains in lung function: FEV₁ rose by 5.8% in the aerobic group and 7.4% in the strength training group at 6 months (p < 0.001). However, these pulmonary improvements diminished when the exercise routines were discontinued. While Rovedder et al's. [27] home-centered program boosted handgrip strength, no significant changes were noted in the 6MWT, pulmonary function, or quality of life. Importantly, none of these exercise programs led to adverse side effects. While exercise interventions consistently improved physical performance, their long-term effects on lung function and quality of life were variable. Overall, the evidence suggests supervised or WAT-based exercise can enhance physical fitness in CF patients, though benefits for pulmonary function and quality of life remain inconsistent.

Exercise interventions play a vital part in the management of CF, delivering a variety of clinically meaningful benefits [1,2,10]. Research consistently shows that structured exercise programs can improve pulmonary function, boost cardiorespiratory fitness, and increase muscle strength, all of which are key factors influencing overall health and disease outlook in CF [2,7,10,14,15]. Beyond physiological gains, regular exercise supports a better quality of life by fostering physical independence, psychological wellness, and greater social participation [7,10,13]. To achieve the greatest benefit, it is important to tailor exercise prescriptions to fit each patient's needs, considering disease progression, baseline abilities, and personal preferences [10,14]. Individualized exercise plans may promote lasting improvements in lung function and physical capacity and can help lower the frequency of pulmonary exacerbations and hospital admissions [1,2,9,15]. Altogether, these findings highlight the value of integrating personalized, evidence-based exercise interventions into standard CF care as a central part of multidisciplinary management [1,10]. Both aerobic and resistance training are advised for individuals with CF to help combat muscle wasting and support cardiovascular health. Given the variability in patient responses, regular evaluations and modifications of exercise routines are important to achieve optimal outcomes. Working closely with physiotherapists ensures that exercise interventions remain safe and effective. Incorporating consistent exercise as part of CF management has the potential to slow disease progression and enhance long-term patient outcomes [30,31].

This study encountered several limitations that affect how its findings can be interpreted and generalized. The overall sample size was small because only 4 studies were included, and the exercise protocols differed in type, intensity, and duration, making direct comparisons and consistent conclusions challenging [16,17]. In addition, inconsistencies in reporting key outcome measures, including FEV₁ for lung function, VO₂peak for cardiorespiratory fitness, and various indices of muscle strength, made it harder to achieve reliable and comparable results across the studies [17].

Short follow-up periods in several studies restricted the evaluation of longer-term benefits offered by exercise intervention, while small sample sizes further reduced the statistical power of the results [17,18]. Some studies targeted specific age groups, limiting how broadly the findings apply to the wider CF population [16,18]. Due to the limited and heterogeneous nature of the data, performing a meaningful meta-analysis was not possible [16,18].

Long-term research with extended follow-up periods is crucial for determining whether the benefits gained from exercise interventions in CF can be sustained over time [19,21,22]. Standardizing exercise protocols is also essential to allow for more reliable comparisons across studies and to strengthen the evidence base [16,19]. Expanding participant demographics by including a wider age range and varying disease severity will improve the generalizability of future findings [16,20,22]. Consistent and standardized reporting of outcomes, such as pulmonary function, cardiovascular fitness, and muscle strength, will help ensure that the effects of exercise interventions are thoroughly and accurately understood [16,19,22]. Exploring patient adherence strategies and understanding factors that drive engagement in physical activity will be key to maximizing the effectiveness of exercise programs [16,22]. Further studies should investigate the possible synergistic effects of combining exercise interventions with pharmacological treatments [19,22]. Additionally, integrating advanced outcome measures such as VO₂peak and muscle strength assessments can offer a more comprehensive view of the advantages of exercise in the management of CF [13,16,19].

Study limitation

Our systematic review has notable methodological constraints that must be acknowledged. The inclusion of only 4 RCTs with 156 total participants limits statistical power and generalizability of our conclusions. Considerable heterogeneity was observed across the included studies regarding intervention modality (WAT-based programs, home-based aerobic exercise, supervised combined training, educational interventions), treatment duration (3–12 months), and outcome assessment tools, which prevented data pooling and precluded meta-analysis. Additionally, most studies employed relatively short follow-up periods (3-12 months, with 1 extending to 24 months), limiting our ability to evaluate long-term sustainability of benefits in this chronic, progressive disease. Participant variability in age groups and disease severity further restricts the applicability of findings across the broader CF population. These limitations underscore the necessity for larger, multicenter randomized trials with standardized intervention protocols and extended follow-up durations to establish evidence-based exercise guidelines for CF management.

In conclusion, this systematic review underscores the positive effect of structured exercise programs, including WAT-based and supervised interventions, on physical fitness and aspects of pulmonary function in people living with CF. Consistent improvements were also observed in cardiorespiratory fitness and muscle strength. Still, the evidence base was limited by small sample sizes, short follow-up durations, and considerable variation in exercise protocols among studies. For future research, there is a clear need to standardize exercise regimens, implement longer-term follow-up, and include participants across a broader age range and disease severity to enhance generalizability. Developing stronger strategies to promote patient adherence and investigating how exercise works alongside pharmacological treatments will be essential to achieve optimal outcomes in CF management. Altogether, the findings highlight structured exercise as a promising, necessary component of multidisciplinary CF care, though further research is needed to strengthen and expand the evidence base.

Acknowledgement

The authors would like to thank ProofreadingPal LCC for the English language editing.

Disclosure

Authors have no conflicts of interest and the work was not supported or funded by any drug company. Authors declare that this article was not presented in conference proceedings. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The manuscript was prepared by the authors. No artificial intelligence tools were used to generate the text, figures, or tables, or to collect or analyze the data. The authors are fully responsible for the content and accuracy of the work. Data is available upon reasonable request.