2 Regular exercise training may improve pulmonary function, increase aerobic and anaerobic capacity, strengthen ventila- tory muscles, and help airway sputum clearance, the latter probably due to enhanced ventilation and vibrations during exercise, leading to mechanical airway clearance [7, 8, 11, 15– 19]. Furthermore, it is suspected that moderate intensity exercise blocks the amiloride-sensitive sodium channels of the respiratory epithelium, thus resulting in lower mucus viscosity, simplifying mucus expectoration [20]. Moreover, higher activity levels and peak V˙O2 are positively related to survival in CF [21–23]. Types of training (aerobic versus anaerobic) may have diﬀerent eﬀects on improvement in exercise tolerance [13], but most training studies so far have focused on endurance training, observing improvements in pulmonary function, peak V˙ O2, breathlessness, and quality of life [11, 18, 19, 24]. Exercise training including anaerobic (strength) exercises can improve muscle strength and muscle size, resulting in weight gain [16, 19, 25]. Therefore, a com- prehensive training programme should include a variety of sports activities, adapted to the special needs and preferences of each individual. However, the eﬀects of training most likely depend on the training methods, as improvements may only persist with continuous training in the long term. The aim of this paper is to provide a focused update on aerobic and anaerobic responses to exercise and habitual physical activity exclusive to children and adolescents with CF. This paper will help to strengthen the rationale for the initiation of further clinical trials examining the eﬀects of regular exercise on overall health in the paediatric CF population. 2. Method of Review All relevant studies for this paper were identiﬁed using electronic search of Medline and PubMed databases. A bibliography search of all accessed publications was also performed. Key descriptors were cystic ﬁbrosis, training, rehabilitation, aerobic ﬁtness, children, and adolescents. The selection of studies presented in the paper was based upon the agreement by all four authors. We include studies of subjects with CF, independently of their disease severity, and type of exercise training (aerobic training; anaerobic training; combination of aerobic and anaerobic training, as well as inspiratory muscle training). 2.1. Physiological Responses to Exercise in Children and Adolescents with Cystic Fibrosis. Physical activity is a fun- damental part of the growth and development of children. Neither any physical activity nor an exercise task can be considered as solely aerobic or anaerobic. The nature of a child’s activity requires an interplay of both aerobic and anaerobic metabolism. An update on aerobic and anaerobic performance in children with CF is outlined below. 2.1.1. Aerobic Responses to Exercise. Aerobic exercises include any kind of activities using large muscle groups that can be maintained continuously in a rhythmic manner (e.g., swim- ming, cycling, or running). Activities with moderate eﬀort can be performed over hours without signiﬁcant decline in International Journal of Pediatrics exercise performance (although there is some variation on individuals’ physical ﬁtness, energy intake during exercise, etc.). Aerobic capacity of children with CF over a long period of time is less researched, indicating the dearth of data regarding longitudinal assessment of peak V˙O2. Klijn et al. investigated the longitudinal relationship between peak V˙ O2, pulmonary function, and body composition in 65 children with mild CF lung disease (10.5 ± 2.9 years of age; forced expiratory volume in 1 s (FEV1) 92.6 ± 20.5% predicted) over two years. The authors found that longitudinal changes in lung function were associated with functional changes in peak V˙O2 and to a lesser extent with fat free mass (FFM). While FFM is a critical determinant of maximal exercise capacity, FFM may be important for maintaining overall functional capacity and to improve long- term outcome in CF [26, 27]. Peak V˙O2 during maximal exercise is an established prognostic marker in CF [21–23]. In particular, longitudinal data of peak V˙O2 in children with CF indicate a decline in peak V˙O2 over time; however, those with higher peak V˙O2 values have a prolonged survival [23]. In comparison to healthy subjects, children with CF show reduced maximal exercise performance, decreased respiratory function, malnutrition, and physical inactivity as well as intrinsic abnormalities of the skeletal muscle, all likely to be contributing factors [28, 29]. Diminished eﬃciency of mitochondrial oxidative Adenosine Triphosphate (ATP) synthesis or abnormalities in myoﬁbril mechanics may also aﬀect maximal exercise capacity in CF [26, 30]. It has also been reported that peak V˙O2 and early oxygen consumption ( V˙O2) recovery are signiﬁcantly related in children with chronic lung disease, implying that the greater the aerobic ﬁtness, the faster the rate of recovery following exercise [31]. Hebestreit et al. reported slower V˙ O2 kinetics at the onset of exercise in children with CF compared to healthy children, probably due to an impairment in oxygen delivery [32]. CF lung disease is often associated with physical inactiv- ity and deconditioning. Improvements in CPF require indi- vidual dosages of training stimuli and vary among individ- uals. However, the optimal training modes for patients with CF have not yet been identiﬁed. It has been demonstrated that the time spent on physical activity in children with CF is similar to that of healthy children, but healthy children spend more time exercising at vigorous intensities [33]. In contrast, Selvadurai et al. observed diﬀerences in activity behaviours between prepubertal and pubertal children with CF of diﬀerent stages of disease severity and their healthy peers using accelerometry and activity diaries. Prepubertal and pubertal children with mild CF lung disease were more active compared to their healthy controls. Interestingly, between prepubertal children with moderate-to-severe CF lung disease and a control group no diﬀerences were found. Gender diﬀerences occurred between pubertal girls and boys with CF, as girls’ habitual physical activity levels were signiﬁcantly lower. However, compared to healthy controls, pubertal children with moderate to severe CF disease were signiﬁcantly less active [34]. Gender diﬀerences in habitual physical activity levels between healthy girls and boys are well known, not only when comparing to chronically diseased children [35, 36].