*2.2.6. Physical activity*

In ventilatory endurance tasks, inspiratory muscle endurance has been measured through the sustained maximum inspiratory pressure (SMIP). This sustained pressure is determined using an electronic manometer, with a fixed leak via a 2 mm diameter during the inspiratory manoeuver, and a specific computer software. The leak sets a maximum flow during the inspiratory effort and allows continuous measurement of pressure over a full range of lung volumes, until no further pressure can be generated. During this technique, patients are asked to take a maximal and sustained inspiratory effort from residual volume to total lung capacity. SMIP is measured as the area under the pressure–time curve and is generally expressed in

The coefficient of reliability for measurements of SMIP in CF was previously established as 90% [131]. Albinni et al. (2004) reported that inspiratory muscle endurance, measured by the SMIP, improved significantly in patients with CF (n=16) after 12 weeks of inspiratory muscle training (p=0.0002) [135]. Enright et al. (2004) investigated the effect of an 8-week inspiratory muscle training with a training intensity of either 80% of maximal inspiratory effort (n=9) or 20% of maximal inspiratory effort (n=10) [43]. The SMIP improved significantly in the two

In endurance to external loads, inspiratory muscle endurance has been determined with incremental loading tests using threshold devices. During these tests, patients have to generate sufficient inspiratory pressure to open the valve and allow inspiratory flow. The test starts with an inspiratory load of 20–30% of Pimax for 2 min. The load is then increased every 2 min in increments of 10% of Pimax. The maximal load is defined by the maximal inspiratory pressure sustained for 1 or 2 min (Plim), which can be expressed in absolute values and as a

The reliability of the Plim in CF has not yet been explored. In patients with COPD and in healthy people, however, it has been demonstrated that the reproducibility of the inspiratory pressure of the threshold was excellent, with small coefficients of variation in both groups (<1%) [136]. Future studies should assess the reliability and test–retest reliability of the Plim

Only one small study was found using Plim as an outcome measure in CF population. In this study, patients with CF (n=7) were submitted to a 6-week inspiratory muscle training. Plim, expressed as a percentage of the Pimax, increased significantly from 49% to 66% (Cohen's dz 1.29) [132]. Using Plim, inspiratory muscle training was also found to have large effect sizes in patients with COPD (n=16; Cohen's dz 0.83) [137] and with chronic heart failure (n=16; Cohen's dz 1.09) [138]. Further research is needed to assess the sensitivity and responsiveness

Both SMIP and Plim appear to be adequate outcome measures to assess the effectiveness of inspiratory muscle training in the inspiratory endurance of patients with CF. Nevertheless, this evidence emerges from few studies with small sample sizes. More research is needed to determine the responsiveness of these two outcome measures to inspiratory muscle training,

as well as to other respiratory interventions, such as respiratory retraining.

groups (from 654–782 to 808–923 pressure–time units; Cohen's dz 0.46 and 0.51) [43].

absolute values (pressure–time units) [43, 112, 131].

54 Cystic Fibrosis in the Light of New Research

percentage of the Pimax [132, 134].

of Plim to inspiratory muscle training in patients with CF.

in the CF population.

Given the clinical implications of regular physical activity in patients' pulmonary function [139], exercise tolerance [140] and airway clearance [141], its assessment and monitoring in patients with CF has also become a topic of great interest in research and clinical practice. An assessment of physical activity (and inactivity) in the free living environment can be performed using subjective and objective methods [142, 143], although no gold standard is still available.

Subjective methods rely on the individuals' self-report through physical activity question‐ naires. These instruments are simple, inexpensive and easy to employ for routine assessment of patients' physical activity levels [142]. Examples of questionnaires used in CF include the Habitual Activity Estimation Scale [144] and the Seven Day Physical Activity Recall [145]. Although the Habitual Activity Estimation Scale has presented good test–retest reliability results (intraclass correlation coefficients of 0.72) in patients with CF [146], a previous system‐ atic review concluded that these two instruments were not able to generate valid activity data or provide a valid assessment of aerobic fitness at the individual level [147]. Thus, the use of these questionnaires for individual assessment and counselling may provide imprecise data. For these purposes, objective measures are recommended.

Objective measures to assess daily physical activity include heart rate monitoring devices and motion sensors, such as pedometers, accelerometers and multisensor devices [143, 148]. These measures have been used in studies involving patients with CF [149-151] and show promising results in evaluating the impact of respiratory physiotherapy interventions [56, 123]. Given the small size of the devices, low participant burden and relatively low cost, objective measures are appropriate for use in research and clinical practice [148]. Heart rate monitoring devices enable the assessment of patients' level of exertion since heart rate increases in a linear fashion with oxygen consumption, especially in moderate to strenuous intensity activities [152]. As such, these devices have been mostly used as a feedback tool to ensure patients' compliance with the intensity recommendations when exercising at home [56, 153]. Regarding motion sensors, there are a large number of options available that makes the choice of the best device challenging. Pedometers are designed to measure the number of steps taken by an individual by detecting vertical movement at the hip or waist. They may be desirable in simpler studies due to their lower cost and limited data [143]. Furthermore, since pedometers provide immediate feedback to the user [143], they may be valuable in self-monitoring interventions delivered to patients with CF. Despite their potential applications, no data is still available regarding the validity and reliability of pedometers in CF [154]. Still, pedometers have provided good reliability results in healthy and chronic respiratory diseases except when walking at slower speeds [155].

Although more expensive than pedometers, accelerometers provide a more detailed analysis of daily physical activity by capturing the frequency, duration and intensity of physical activity through the collection of body accelerations during movements [143]. They have also the advantage of storing the data for several weeks [143]. Multisensor devices combine acceler‐ ometry data with physiologic information collected from other sensors, such as heart rate and skin temperature, and also have a memory function. The use of accelerometers and multisensor devices in CF has increased dramatically in recent years [140, 146, 156–158] and this will likely continue with the technology advances. The clinimetric properties of these devices in CF are described in a recent systematic review [154]. The authors found that only one accelerometer (ActiGraph model 7164) and one multisensor device (BodyMedia SenseWear armband) were tested. The ActiGraph presented good convergent validity [157, 159], test–retest reliability (intraclass correlation coefficient of 0.63) and feasibility [146, 157] in adolescent and adult patients with CF. Discriminate validity [160] and responsiveness [123] were only evaluated in children with CF. Selvadurai et al (2002), exploring the effects of exercise training in children with CF admitted to hospital (n=66), found a significant improvement in activity levels after five sessions of endurance training (8.64%, p<0.001, Cohen's dz 0.82) or resistance training (3.81%, p<0.001, Cohen's dz 0.85) measured by accelerometry [123]. Therefore, accelerometers may be a useful tool to assess changes in physical activity levels of patients with CF in response of respiratory physiotherapy interventions. Regarding the SenseWear armband device, its validity (discriminate, convergent and concurrent) [140, 161] was only determined for adult patients with CF and no data on reliability and responsiveness exist. Further research is needed to determine which motion sensors provide the best clinimetric properties in CF in order to improve physiotherapy assessment. Moreover, as children have typically higher physical activity levels than adults [162], validation studies should be conducted in children and adults with CF. Finally, it would be useful to develop specific guidelines for the use (e.g., number of monitoring days, duration) of these motion sensors in CF, in order to standardise the collection of activity data and optimise their interpretation.

### *2.2.7. Burden of treatment*

The concept of burden of treatment has been receiving increasing attention in patients with CF. Burden of treatment is described as the increased demand experienced from performing self-care activities required to undertake treatment regimens and monitor health outcomes [163]. Recent evidence demonstrated, however, that from a patient's perspective, treatment burden is beyond the workload arising from treatment regimens, being experienced in three disruption domains: biological (physical side effects), biographical (sense of self) and relational (impact on valued relationships) [164].

A large observational cohort study explored treatment complexity in patients with CF (n=7252) over a 3-year period [165]. It may be hypothesised that treatment regimens would be more complex only among patients with more severe disease. Indeed, in this cohort, the highest treatment complexity was presented by patients with more severe disease. Nevertheless, over the 3-year period, the complexity of treatment regimens increased in all age and disease severity groups. This study showed that the recommended management of CF resulted in high burden of treatment for patients.

In the specific case of respiratory physiotherapy, vigorous airway clearance and exercise regimens are recommended for patients with CF [166], which may result in increased burden of treatment. Burden of treatment, in turn, is associated with non-adherence and poor health outcomes [158, 163, 167–169]. This is particularly important for physiotherapists since the level of adherence to exercise and physiotherapy is generally reported to be poor (40–55%) [170, 171], in contrast with moderate to high adherence to nebulised medications, pancreatic enzymes and antibiotics (65–95%) [170, 172].

These levels of adherence suggest that patients with CF make decisions based on the com‐ plexity of recommended therapies they can complete, while fulfilling their responsibilities and commitments to family and work. As the number of adjunct therapies increase in CF, there may be a point at which perceived treatment burden outweighs the benefits of new or adjunct therapies, adversely affecting patient's adherence. Physiotherapists therefore, need to be sensitive recognising, understanding and supporting the reduction of burden of treatment, in order to balance the potential benefits and burdens of physiotherapy interventions and maximise adherence [158, 173].

The recognition of this concept led to the development of specific instruments for assessing burden of treatment. Burden of treatment has been incorporated into the CFQ [89]. Specifically, the burden of treatment domain is comprised of three questions: 'to what extent do your treatments make your daily life more difficult?', 'how much time do you currently spend each day on your treatments?' and 'how difficult is it for you to do your treatments each day?'. The score ranges from 0 to 100, with lower scores representing higher burden of treatment.

The burden of treatment domain of the CFQ has been used in recent studies evaluating the effectiveness of novel interventions [91, 174]. In a trial with patients with CF (n=12), assessing the effect of a nebulised hypertonic saline therapy, a significant improvement was found in respiratory symptoms together with an increased in perceived burden of treatment (Cohen's dz 3.05) [174]. Schmidt et al. (2011) evaluated a 12-week individually tailored unsupervised aerobic exercise programme in patients with CF (n=14) [91]. Patients were instructed to exercise at least 30 minutes, three times a week with a heart rate target above 70% of their maximum. This study showed that an exercise programme could significantly increase VO2max and, at same time, significantly decrease the perceived burden of treatment (Cohen's dz 1.03) [91]. These two studies, despite being distinct, show that the burden of treatment domain of the CFQ is sensitive to change over time and demonstrate large effect sizes. Physiotherapists can, therefore, confidently rely on the burden of treatment domain of the CFQ to assess their interventions.

One of the disadvantages of the burden of treatment domain is the fact that it mainly addresses the complexity and time consuming routine of self-care. However, recent research has demonstrated that burden of treatment goes beyond these aspects and is experienced as biological, biographical and relational disruptions [164]. Therefore, when designing future instruments and methods for assessing burden of treatment, these three disruption domains should also be taken into account. This highlights the relevance of assessing burden of treatment as an outcome measure of respiratory physiotherapy in CF. The evaluation of burden of treatment will also inform the development of new and minimally disruptive interventions.
