In a landmark study, Nixon et al., 1992 determined factors that are associated with an eight year survival rate of 109 young patients with CF. They found a significant correlation between peak oxygen uptake (VO_2peak) and survival at eight years. Thus, becoming the first study to report an association between the aerobic capacity of children, adolescents and young adults with CF and survival over an eight year period. Nixon and colleagues reported that VO_2peak was a strong predictor of survival, even after adjustment to other prognostic variables such as age, sex, lung function, bacterial colonisation and nutritional status. Patients with a high level of fitness (> 82 % predicted VO_2peak) had a 83 % chance of survival at eight years, compared to a 51 % and 28 % chance of survival for patients with medium (59-81 % predicted VO_2peak) and low fitness (< 58 % predicted VO_2peak), respectively. These data, however, do not establish a cause and effect relationship. Aerobic capacity may not be an indictor of the patient's overall health. Nevertheless, the study showed that aerobic capacity could be used as a strong predictor of survival in these patients.

A recent study by Pianosi et al., 2005, however, is the first to investigate both the utility of VO_2peak and decline of VO_2peak as a predictor of survival. Twenty-eight children aged 8 to 17 years, over a five-year period performed annual pulmonary function and maximal exercise tests to determine FEV₁ and VO_2peak. The magnitude of the change in the young patients' FEV₁ and VO_2peak over time, and survival over the subsequent 7 to 8 years were used to determine their significance as predictors of survival. Pianosi and colleagues reported that the measurement of VO_2peak from maximal exercise tests were significant predictors of patient survival. Furthermore, during the observation period a mean annual decline in VO_2peak of 2.1 mL.kg^-1.min^-1 was reported in 70 % of the patients. A dramatic increase in survival over the subsequent 7 to 8 years was seen in patients whose VO_2peak exceeded 45 mL.kg^-1.min^-1. In contrast, patients with a VO_2peak less than 32 mL.kg^-1.min^-1 showed a survival rate of 60 % over the subsequent 7 to 8 years. The FEV₁ was also reported as a significant predictor of survival. The patients' first and last measurement of FEV₁ over five years and rate of decline in FEV₁ over the time period were all significant predictors of mortality.

Previous studies investigating the prognostic value of exercise testing in young CF patients have placed much emphasis on the assessment of VO_2peak to predict outcomes such as functional capacity, disease severity and survival. Other physiological assessments derived through exercise testing have been neglected. The oxygen uptake (VO₂) kinetics during exercise and recovery, carbon dioxide (CO₂) retention, oxygen desaturation and muscle strength can all be assessed through exercise testing and may all have prognostic value. Researchers are now focusing attention on other physiological assessments derived from exercise testing that may hold prognostic significance, other than VO_2peak alone. Furthermore, researchers are using more sophisticated techniques to model the VO₂ kinetic responses from exercise in CF patients.

Hebestreit et al., 2005 has investigated the VO₂ kinetics at the onset of exercise in patients with CF. Eighteen CF patients and 15 healthy controls aged 10-33 years completed two to four transitions from low-intensity cycling at 20 W to cycling at 1.3-1.4 W.kg^-1 body weight. VO₂ data from the submaximal exercise tasks were modelled interpolated second by second, time aligned and averaged. Monoexponential equations were used to describe phase II responses. Hebestreit and colleagues reported no significant differences in the amplitude in the model of the phase II VO₂ response between the CF patients and healthy controls; however, the time constant tau was significantly prolonged in the CF patients. Thus, demonstrating a slower VO₂ kinetic response in patients with CF.

Recent work by Pouliou et al., 2001 investigated the VO₂ kinetics during early recovery from maximal exercise in adult patients with CF. Pouliou and colleagues reported that the VO₂ kinetics following maximal exercise is prolonged in adult CF patients when compared to healthy adults, and that the prolonged recovery is closely related to the Schwachman score (r = 0.81; P < 0.001), a widely accepted system of clinical evaluation to assess disease severity. The VO₂ kinetics following maximal exercise was also significantly correlated to other indexes of functional capacity such as FEV₁ (r = 0.90; P < 0.001) and VO_2peak (r = 0.81; P < 0.001). This novel approach to health assessment offers, from a clinical view, an exercise assessment that is independent from effort and physical fitness. Pouliou and colleagues used a linear regression model to evaluate the VO₂ kinetics for the first minute of the recovery period. However, no rationale was given to suggest why a linear model would fit the response. The linear model used by Pouliou et al. does not identify the slow phase of the recover period and, furthermore, may only identify 40 % of the fast phase. Assessment of the VO₂ kinetics during recovery can be used even with submaximal exercise, which is important for debilitated CF patients who cannot produce maximal exercise performances. Furthermore, data from maximal exercise testing may not be reproducible, is dependent on patient motivation and the criteria used by the clinician to terminate the test.

Javadpour et al., 2005 recently examined CO₂ retention during exercise testing, and discovered it had an association with a rapid decline in lung function. Children with CF aged 11 to 15 years performed annual pulmonary function and exercise testing over a three-year period. CO₂ retention was defined as a rise of > 5 mm Hg end tidal CO₂ from the first work rate until the peak work rate, and a failure to reduce end CO₂ after the peak work rate by 3 mm Hg by the termination of exercise. Using this definition of CO₂ retention Javadpour and colleagues reported that children with CF who were found to have CO₂ retention on exercise testing showed a faster rate of decline in FEV₁ when compared to those who did not retain CO₂. The decline in FEV₁ between patients who retained CO₂ and patients who showed no CO₂ retention during exercise over a 12 month period was reported as -3.2 % (SD 1.1) and -2.3 % (SD 0.9), respectively. After 24 months the decline was reported as -6.3 % (SD 1.3) and -1.8 % (SD 1.1), respectively. Finally, after 36 months the decline in FEV₁ was -5.3 % (SD 1.2) and -2.6 % (SD 1.1), respectively. Both patients who retained CO₂ during exercise and those who showed no CO₂ retention started the study with similar baseline FEV₁, 62 % and 64 % predicted, respectively. The overall decline in FEV₁ was, however, 14.8 % (SD 2.1) and 6.7 % (SD 1. 8), respectively. The study suggests that children with CF with a similar degree of pulmonary disease as measured by FEV₁, if found to have CO₂ retention on exercise testing, will have a greater decline in FEV₁ over a three year period than children with CF who do not retain CO₂. This shows the identification of CO₂ retention during exercise can be an additional prognostic marker of disease progression in children with CF. Furthermore, as FEV₁ is closely associated with survival in this patient group, CO₂ retention during exercise testing will help identify those patients who may require more intensive therapy to prevent this increased rate in pulmonary decline.

Aerobic fitness is associated with prolonged survival and quality of life. Therefore, most studies investigating the potential of exercise programmes have assessed the effects of aerobic training. In one training study, however, Selvadurai et al., 2002 compared the effects of both aerobic and strength training. CF inpatients aged 8 to 16 years were randomly allocated into an aerobic or strength training group, and exercised five times a week for 3 weeks. Selvadurai and colleagues reported that children who received aerobic training had significantly better VO_2peak, activity levels and quality of life than children in the strength- training group. Children in the strength-training group when compared to the aerobic training group, however, had better weight gain (total mass, as well as fat-free mass), lung function and leg strength, which all have a high correlation with health status. The findings of this study support the proposition that a combination of aerobic and strength training may be the best training programme for young CF patients. Future studies assessing the potential of exercise programmes should assess the combination of different exercises to optimise training programmes for young CF patients.

Klijn et al., 2004 are the first authors to conduct a high intensity anaerobic training programme for children with CF. The authors suggest that children may be more suited to high intensity anaerobic training, as children's natural activity patterns are characterised by very short vigorous bouts of physical activity, interspersed with varying levels of low to moderate intensities. In a randomised, controlled study 11 children with CF participated in a 12-week anaerobic training programme. The children trained two days per week, with each session lasting 30 to 45 minutes. The training consisted of anaerobic activities lasting 20 to 30 seconds. The control group consisting of 9 young CF patients were asked not to change their normal daily activities. Participants of the exercise programme showed significant improvements in both anaerobic and aerobic performance and quality of life as measured by a disease specific health-related quality of life questionnaire. Children in the control group showed no improvements in any measured parameters. This study also identified the benefits of including different exercises into training programmes designed for children with CF. Furthermore, the inclusion of different types of exercises adds variation to training, which may help to improve adherence.

A later study by Orenstein et al., 2004 also supports the suggestion of incorporating both aerobic and anaerobic exercises into training programmes to optimise the functional capacity of the young CF patient. During a one-year randomised controlled trial, 67 young patients with CF, aged 8 to 18 years, participated in either an aerobic or upper-body strength-training programme. All children were asked to exercise at least three times per week for 12 consecutive months. Each patient in the aerobic training group was given a stair stepping machine and instructed to exercise five minutes per session, gradually increasing to 30 minutes per session. Young patients in the upper-body strength group were given a weight resistance machine, which they used to perform bicep curls, lateral pull-downs and bench presses. The exercises were individually tailored to each patient's strength, and the exercises increased gradually by the number of sets and repetitions as well as by the amount of resistance per bout over the year. Contrary to previous studies, Orenstein and colleagues reported that aerobic training did not, however, produce greater fitness or greater pulmonary function than strength training. Furthermore, both types of training increased upper-body strength and physical work capacity.