Inspiratory muscle training prior to peripheral muscle training in patients adolescents with Cystic Fibrosis.

Cystic fibrosis (CF) primarily affects the respiratory and digestive systems in
patients with CF. Due to the continual bronchial airway obstruction a chronic
hyperinflation of the thorax develops, thereby decreasing the efficiency of
inspiratory muscle work and increasing work of breathing (WOB) in rest and
during exercise. The increased WOB and the corresponding fatigue of the
inspiratory muscles (diaphragm and supportive inspiratory muscles) are thought
to induce a so called respiratory muscle induced metaboreflex causing a reflex
vasoconstriction of the locomotor muscle blood vessels. It is feasible that
this decreased blood supply to the locomotor muscles will limit maximal
exercise capacity.
The hypothesis of this study is therefore: A home-based peripheral muscle
training program (Five Basic Exercises program (5BX)) is more effective in (a)
increasing peak work rate and (b) patients* preferred occupational performance
when it is preconditioned by inspiratory muscle training (IMT).

1. Is a home-based peripheral muscle training program (5BX) more effective in
(a) increasing peak work rate and (b) patients* preferred occupational
performance in patients with CF who are preconditioned by IMT?
2. Which variables are indicators of response to 5BX, preconditioned by IMT?

This study is a double blinded randomized clinical trial. After screening for
inclusion and exclusion criteria and after given approval, patients are
included and followed during a maximal 6 week baseline measurement. After the
baseline period and measurements at 6 weeks, participants are randomized in an
IMT Training group and an IMT Sham group. After undergoing 6 weeks IMT or sham
IMT and subsequent, after 6 weeks 5BX, measurements are repeated. A 6 weeks
wash-out period is entered after 5BX and measurements are repeated afterwards.
Additionally, we developed an alternative version of the research protocol for
the previous participants in the *Skeletal Muscle Metabolism in CF* study (METC
11-084). As these patients recently successfully performed a CPET in an MR
scanner (as described in METC 11-084), these patients are asked if they would
like to volunteer to perform the six weeks home based training protocol (5BX)
and afterwards perform the same two exercise tests, one in the MR scanner, as
they previously did in study 11-084. The IMT intervention and wash-out period
will not be part of this alternative protocol.

Included participants subsequently undergo:
- 6 weeks of standardised (sham) IMT with an inspiratory threshold-loading
device (Threshold IMT, PT Medical, Leek, The Netherlands). Progression of
intensity in the training group is based on rate of perceived exertion.
Trainingfrequency is 5 times a week, 11 minutes a day. Patients in the Training
Group start at a resistance of 30 % maximal inspiratory pressure, Sham IMT is
stabilisized at 10% maximal inspiratory pressure. Proper information about the
training protocol is given at the start of IMT in a Dutch users guide.
- 6 weeks of home-based peripheral muscle training program (The 5 Basic
eXercise Program; 5 BX). Frequency is 5 days a week, 11 minutes a day.
Patients are instructed at follow-up points and controlled by e-mail and
telephone by one of the physiotherapists from the WKZ (H.J. Hulzebos).

The alternative protocol for the former participants in METC 11-084 will only
consist of the six weeks home-based 5BX.

Up to date, exercise training and nutritional therapy are the cornerstone of CF
care, which increased the median survival of patients with CF dramatically over
the past decades.
As intervention all patients are asked to perform home-based IMT for 6 weeks, 5
times a week 11 minutes. Subsequent to IMT, patients undergo 6 weeks of 5BX, 11
minutes a day, 7 days a week. IMT* intensity is based on the patients* rate of
perceived exertion, progression of intensity of the 5BX protocol is based on
the ability of the participant to perform the exercises in 11 minutes.
No serious adverse effects are noted concerning IMT in children and young
adults. Only one case of earache is found in a study concerning IMT in
children. 5BX exercises are part of the physiotherapeutic care in children. For
evaluation of intervention, several tests are performed and patients are asked
to visit the hospital 5 times during the protocol. Tests are performed at
baseline (t=0), after 6 weeks baseline measurements (t=6), after both
interventions (t=12 and t=18) and after a six weeks wash-out period (t=24). At
the hospital visits, a maximal exercise test is performed, three questionnaires
are filled out, two functional physical performance tests (BOT2 and Timed up &
go) are performed and strength tests, lung function and anthropometric measures
are taken. At home, patients are asked to fill out a dairy concerning habitual
physical activity and a training diary concerning compliance. Participants are
also asked to wear an accelerometer at home to asses habitual physical
activity.
The alternative protocol for the former participants in METC 11-084 will only
consist of the six weeks home-based 5BX. Furthermore, beside spirometry and
anthropometry, the additional measurements for the alternative protocol are two
CPET*s (one in a 31P-MRS scanner) after the training period. The other
measurements of the original protocol will not be performed. Considering the
alternative protocol, no risks are reported in literature concerning exercise
in an MRS scanner. Progressive insight in the possible role of training induced
altered muscle oxygen consumption or oxygen delivery in patients with CF will
give a more fundamental explanation for possible results in the original study
protocol. This insight will help to aim and institute interventions as exercise
training.