Relationship between daily physical activity and aerobic fitness in adults with cystic fibrosis

In cystic fibrosis (CF) peak oxygen uptake (V’O ₂, _peak), maximal work rate (Work _max) and ventilatory equivalents for oxygen uptake (V’E/V’O ₂) measured during incremental cardiopulmonary exercise testing (CPET) are significant predictors of mortality [ 1, 2]. Recently, data obtained in children with CF suggest that aerobic fitness is also associated with lower risk of hospitalization [ 3]. Although peak exercise tolerance is reduced in CF [ 4], some studies have shown that aerobic exercise capacity increases with physical training programs [ 4- 6].

The best clinical practice to investigate aerobic fitness includes measurements obtained during CPET, however there are still many difficulties associated with its use in clinical practice [ 7]. In particular, maximal exercise tests require the subject to make maximal efforts, rendering such tests highly dependent on motivation. Submaximal exercise related data (also known as lactate threshold-LT measures) is an alternative index of aerobic fitness, information that is directly relevant to a patient’s ability to carry out the tasks of daily living and may be useful in the clinical environment in patients who may not be able or willing to provide a maximal effort, especially when maximal exercise tolerance is limited by ventilatory factors [ 7]. Despite some studies highlighting the use of exercise testing in CF [ 8, 9] and CF guidelines recommending an annual assessment [ 10], CPET remains underutilised [ 11]. This is due in part to its expense and the lack of adequately trained staff [ 11] as well as patient’s dislike of the test itself [ 9]. So, to investigate this further, different methods of quantifying exercise capacity in CF are required. Modalities that are not excessively stressful to patients are particularly favorable. Field tests, such as shuttle tests, timed walking and step tests are reasonable surrogates for incremental CPET [ 11, 12] and they have the added value of being more reflective of usual physical activity patterns [ 13]. It has not been investigated in adults with CF whether objective measurements of physical activity (PA) could be added among the CPET surrogates.

Physiological responses to submaximal CPET reflect daily PA at different intensities in a healthy population [ 14], however no information is currently available in clinically stable adults with CF. To date, the relationship between formal CPET parameters at submaximal workloads and daily activity levels in CF has not been well established. Thus, the possibility that measuring habitual PA by a portable accelerometer could be used to assess the CF aerobic state is worthy of further investigation.

As survival in CF continues to improve a better understanding of the relationship between lifestyle in adulthood and habitual daily PA is important. Few studies have compared daily PA in adult CF patients and healthy subjects. The CF population examined by Troosters et al. [ 15] spent less time in moderately intense PA compared with healthy controls. Conversely, our recent study demonstrated that the time spent in daily PA at different intensities was similar in adults with CF and age-matched healthy controls [ 16]. Similarly, Rasekaba et al. showed that moderate or vigorous habitual PA measured using a validated questionnaire was similar between CF adults and controls [ 17]. So, it remains unclear whether CF adults have different habitual activities compared with healthy peers and in order to clarify the discrepancies in the current literature further studies are needed. Moreover, despite our knowledge about the beneficial effects of a supervised exercise intervention on submaximal and maximal oxygen uptake in CF [ 18, 19], there have been no studies examining the relationship between habitual daily PA and submaximal fitness in CF.

Therefore the purpose of this study was twofold. First, we aimed to examine the relationship between daily PA and aerobic fitness both at submaximal and maximal levels in clinically stable adults with CF. Specifically, we were interested in evaluating PA as a surrogate of CPET in the assessment of exercise capacity in CF. In addition to this primary aim, we wished to compare both daily PA levels and responses to CPET of adult CF patients and healthy controls. In analyzing the possible positive effect of habitual PA in CF, we sought to evaluate the parameters obtained at submaximal level of exercise in CF and in healthy control peers.

The study population comprised 30 patients with CF and 15 controls. Baseline characteristics, pulmonary function and daily physical activity data for both groups are shown in Table  1. There were no significant differences in terms of age, sex and body mass index (BMI) between the groups. Of the CF group, 83.3% (n = 25) had pancreatic insufficiency and 43.3% (n = 13) were homozygous for the mutation F508del (all remaining patients were compound heterozygous F508del with the exception of one patient who had an unidentified second mutation). One patient had CF-related diabetes and all patients had chronic pulmonary infection ( Pseudomonas aeruginosa, n = 26; Staphylococcus aureus, n = 3, Burkholderia cenocepacia complex, n = 1) . Smoking history was negative for all patients and controls.

The main finding of this study is that daily PA, particularly of moderate intensity or greater, correlated with measurements of exercise fitness, including V’O ₂ uptake and work rate at LT. Additionally, clinically stable adults with CF and healthy controls have similar daily PA levels and they presented with a V’O ₂ response to CPET and a V’O ₂ at LT comparable to healthy controls.

To our knowledge, this study is the first to investigate the relationship between submaximal exercise data and PA in clinically stable adults with CF and mild to moderate lung disease. The LT is an excellent submaximal index of aerobic performance, information that is directly relevant to a patient’s ability to carry out the tasks of daily living and allows determination of the optimum training intensity in a given individual [ 7]. We demonstrate that in this clinically stable CF population submaximal CPET indices of aerobic performance are objectively associated with measurements of daily PA. When the relationship between habitual PA and CPET responses was explored in the CF group, there appeared to be significant associations. It was found that PA at moderate and vigorous intensity was closely related to LT parameters, namely V’O ₂ and work rate. Similarly, moderate and vigorous PA was related to VO _2,peak and to maximal workloads suggesting that daily PA might play an important role in maintaining aerobic fitness in clinically stable adults with CF. In addition, we postulate that early changes in daily habitual PA may indicate a decline in exercise capacity and therefore may be a sensitive marker of early change in a patient’s disease status. The use of accelerometers has received increasing interest in chronic respiratory diseases [ 32] and several studies have validated its use in CF [ 29, 30]. So, the possibility of monitoring the CF state of aerobic fitness by measuring habitual physical activity with a portable accelerometer offers obvious advantages.

There are only few studies in which PA levels were objectively assessed and compared with exercise capacity in an adult CF population. The largest study of Hebestreit et al. identified that high levels of PA were associated with high aerobic capacity, but the results were obtained recruiting a CF group aged from 12 to 40 years with a mean age of 20 years [ 33]. Troosters et al. confirmed the relationship between PA and VO _2,peak in 20 CF patients with a mean age of 25 years [ 15]. In keeping with that, we confirm in our study the possible role of PA above moderate intensity in the maintenance of better exercise fitness in an older CF population. This is important since it is generally acknowledged that PA at moderate intensity has an important long-term protective effect on health [ 34] and, as recently shown in CF, prevents muscle strength deterioration after a hospital admission [ 35].

In this study, the adults with CF were able to accomplish their activities of daily living as much as healthy controls with no differences in terms of PA intensity levels between the two groups. We speculate that these results might follow our clinical practice in terms of patient education to enhance PA levels by explaining all the benefits associated with an active lifestyle. Using the same motion sensor for PA monitoring and the same METS levels, our findings were comparable to those of Ward et al. [ 36] who investigated 24 adults with CF after one month post-discharge, for the mean time spent doing mild and vigorous PA (mild: 159 minutes in our study vs. 163 min in Ward’s study; vigorous: 1 min vs. 3 min in Ward’s study) despite moderate PA being lower in our study (13 vs. 43 min). Moreover, our findings are comparable to those of Troosters et al. [ 15] for the number of steps (9160 vs. 9398), times spent in mild and moderate PA (13 minutes in our study vs. 14.8 reported by Troosters et al.). Vigorous PA was greater in Troosters’s study (1 min vs. 4.2). In this latter study the CF population demonstrated step number and PA at mild and vigorous intensity that was not significantly different to healthy subjects, whereas only activities at moderate intensity were reduced in patients with CF [ 15]. Conversely in our study, we found no differences between CF and controls in any of the PA variables measured. These results could be explained by different PA levels of the healthy control group, especially because our population seems to be more sedentary than Troosters’s control group. In fact, despite similar mild PA and number of steps (10591 in our study vs. 10281 in Troosters’s study), PA at moderate and vigorous intensity were lower (moderate PA 11 min in our study vs. 34 min and vigorous PA 1 min in our study vs. 9 min in Troosters’s study). It is possible that differences in PA results may reflect cultural differences, subjects’ motivation to participate in the study, a small sample size or a sampling error. However, with the use of a subjective method (a questionnaire) in a large CF population, new insights into the adult CF patients’ PA habits have been highlighted, showing similarities in moderate and vigorous habitual PA to control groups [ 17]. Larger studies may be needed to objectively confirm if adults with CF can achieve PA levels similar to the general population.

Our study demonstrated that, despite reduced exercise tolerance, CF patients produced V’O ₂ responses comparable to healthy controls and reached their LT at a work rate and O ₂ uptake similar to that of healthy controls. This is important if we consider that the V’O ₂ at which lactate starts to increase closely reflects the fitness of an individual and can increase with a training program [ 18]. The novelty of the present study was that we observed these CPET responses in a group of adults with CF who were not engaged in specific home-based exercise training. They were generally active as part of their daily lifestyle, as evidenced by the similar levels of daily PA between CF and healthy controls. The benefits of an exercise program in CF have been largely established by Cerny et al. [ 37] and Gruber et al. [ 18]. The results were obtained during hospitalization for pulmonary exacerbations or during an in-patient rehabilitation course. In both studies, CF patients were under supervision and received several medical interventions (i.e., i.v. antibiotics, nutritional supplement, airway clearance therapy, psychological counseling), therefore making it difficult to ascertain which of the above-mentioned factors were responsible for the greatest effect of the observed changes. Moreover, in a previous study, well-nourished female athletes with CF and normal pulmonary function tests reached the LT at a level of exercise intensity equivalent to that of healthy subjects, suggesting similar muscle conditioning [ 38]. In this sense, the similarity observed in our study between CF and healthy subjects for exercise parameters measured at LT and their correlation with PA in CF population, made us assume that habitual PA may positively affect the submaximal exercise parameters in adult CF.

Finally, our measurements at peak exercise revealed that CF patients’ peak symptom-limited V’O ₂ was reduced by 24% of the predicted normal value and that there were no differences between the CF and the healthy group in the V’O ₂/work rate slopes which were within the normal range. The present study focused on the role of daily physical activity; other factors which may contribute to the reduced exercise tolerance in CF patients were not investigated in detail.

We recognize limitations of the present study. Firstly, this study involved a relatively small number of participants, the majority of which were male, so this limits its generalizability. Secondly, our healthy controls are disease-free but possibly sedentary, even if they were recruited from staff and colleagues of our hospital and they were physiotherapists, students and doctors. Unfortunately, it was technically difficult to recruit a different control group at the time we conducted the study. Further research including a bigger population both for CF patients and for healthy control is needed to highlight potential differences in habitual PA and to better characterize their lifestyle. Finally, CPET variables have been reported to predict survival in CF [ 1, 2] but whether this holds true or not for PA is unknown. Further studies are needed to evaluate the influence of regular PA on this and other important clinical outcomes in CF.

Daily PA positively correlated with aerobic capacity in adults with CF and mild to moderate lung function impairment and was similar to healthy controls. We have also shown that V’O ₂ profile and the V’O ₂ at LT were comparable between healthy controls and patients with CF. These data suggest daily PA could be considered a valuable tool in the assessment of aerobic fitness in adult CF population. Measuring PA is straightforward and could easily be integrated into interventional exercise trials. Further studies are required to determine if PA measurements are sensitive enough to detect early pathophysiological changes in CF exercise capacity, in order to consider them as a simple and practical method for monitoring the disease status.