Ultrasound imaging as a new tool for assessment of respiratory muscle structure and function in patients with Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease, which
also includes respiratory muscle weakness, resulting in respiratory failure and
life-threatening pulmonary infections. Therefore, respiratory outcome measures
are of vital importance to guide respiratory management and evaluate novel
therapies in clinical trials. Currently, spirometry is frequently used to
assess pulmonary function. However, this is not a direct measurement of
respiratory muscle function, and is difficult to perform for young children.
Recently, the applicant evaluated advanced ultrasound techniques and
demonstrated that these techniques provide reliable outcome measures on
respiratory muscle structure and function. Quantitative muscle ultrasound
(echogenicity) detects structural changes due to fat infiltration or fibrous
tissue, whilst conventional muscle ultrasound (thickening, excursion) detects
respiratory muscle dysfunction.

Primary objective: To quantify the degree of respiratory muscle degeneration
and dysfunction using ultrasound in patients with DMD over a wide age range;
from early childhood to adults.
Secondary objective: To determine the association between respiratory muscle
ultrasound measures and pulmonary function in DMD patients and healthy subjects
over a wide age range

The proposed study is an cross-sectional study in patients with Duchenne
Muscular Dystrophy (DMD) and healthy age-matched subjects. The measurements
will be performed at the Amalia Children*s Hospital at Radboudumc in Nijmegen,
the Netherlands. The measurements will take 30 minutes for patients and 1 hour
for healthy participants. The visitations for patients will be scheduled
following other visitations at Radboudumc. DMD patients come to Radboudumc one
time per year, to minimize the burden of travelling to Nijmegen multiple times.
Therefore the schedule is very full. The measurements for this study will be
performed directly after logopedics, who also use the ultrasound device. This
minimizes the duration before starting of the measurements. Four muscle groups
will be measured:
1. Diaphragm (both subcostal and intercostal approach)
2. Abdominal wall muscles (internal oblique, external oblique, transverse
abdominis)
3. Parasternal muscles
4. Sternocleidomastoid.

The risk of this study for the participants is negligible, according to the NFU
risk classification. Subjects will not directly benefit from participating in
this study. The scientific benefit of this study is find outcome measures for
degeneration and function of respiratory muscles in DMD patients, which can
possibly be used as outcome measures in future clinical trials.
Patients will continue their medication as usual. This prevents patients from
experiencing worsening of symptoms caused by participation of the study.

The pulmonary function test may be experienced as mildly unpleasant. However,
the patients need to perform pulmonary function testing as regular care.
Therefore, the relatively small burden of the PFT will only be applicable for
healthy participants.

The burden of the ultrasound is relatively small. The participants are asked to
perform tidal breathing and maximal inspiratory breathing. The duration of the
ultrasound will probably not be experienced as unpleasant. There are no
invasive procedures in this study.