Discussion:
In this quality improvement project, we successfully introduced a PT
evaluation of gross motor skills in school-aged children with CF
utilizing the BOT-2. Within a year we completed evaluations in over
two-thirds of eligible children. This study is one of the few published
gross motor assessments using a standardized tool in school-age children
with CF. Prior studies have been very small, although the results were
similar to our findings. In an observational study of 14 infants with
CF, 27% had motor delays using The Bayley Scales of Infant and Toddler
Development® - III Edition(1). In another cross-sectional study
examining 12 school aged children with CF, 33% had motor delays using
the Movement Assessment Battery for Children 2ndedition (MABC-2)(12).
The most common area of impaired gross motor function was strength.
There is CFTR expression in the skeletal muscle of humans(5, 13).
Decreased CFTR function in skeletal muscle affects sodium transport and
calcium release, which is crucial for a robust muscle contraction(5,
13). In addition, impaired CFTR function impacts ATPase and
mitochondria, which is essential for energy production(5). While this
quality improvement project was not designed to determine the cause of
gross motor delays in this CF cohort, there may be intrinsic CF-related
factors leading to skeletal muscle weakness and peripheral muscle
atrophy in pwCF(5). We did not identify a difference in gross motor
assessments in those receiving CFTR modulators compared to those not
eligible. However, relatively few of these children were receiving
highly effective modulator therapy (HEMT). Further evaluation of the
impact of CFTR modulators on gross motor assessment is indicated now
that elexacaftor-tezacaftor-ivacaftor is approved for those down to 2
years of age. A better understanding of how CFTR modulators impact
strength and gross motor skills in CF may also help to explain the
potentially clinically significant differences seen between genotypes in
this cohort given the higher rate of gross motor delays found in those
with the F508del/Other mutations (27%) compared to those with F508
homozygous (6%) and Other/Other (9%) genotypes. This is clinically
important as skeletal muscle strength impacts exercise capacity, which
is a known predictor of survival in CF(14).
The relationship between lung function and gross motors skills is not
fully understood. Our data suggests that lower FEV1 and
FVC measurements were associated with lower TMC and TMC% scores. It is
unknown whether this association is independent or if other factors,
such as hospitalizations or presence of comorbidities could be
contributing. A study by Wilkes and coworkers highlighted the
longitudinal relationship between physical activity and lung health in
CF, determining that a greater increase in habitual physical activity
was associated with a slower rate of decline in FEV1(2).
This, along with the evidence by Nixon and colleagues that children with
CF participate in less physical activity than their healthy non-CF
peers(4), emphasizes the need for targeted evaluation and interventions
in young children with CF to facilitate successful participation in
exercise and recreation. If exercise improves lung function, it is
possible that optimizing gross motor skills may be one way to improve
pulmonary outcomes for children with CF. This would be important for
those who are ineligible for or cannot tolerate CFTR modulator therapy.
In our cohort, hospitalizations were also associated with lower TMC
scores. We elected to report hospitalizations that lasted 3 days or
longer, expecting that brief hospitalizations would have less of an
impact on gross motor skills. Gruet and coworkers found that
hospitalizations in adults with CF intensified peripheral muscle
dysfunction, specifically quadricep strength, which is likely due to
disuse and systemic inflammation(15). Decrease in quadricep strength
after hospitalization may contribute to decreased gross motor skills.
However, a prospective assessment of gross motor delays would better
clarify the relationship between physical function, FEV1decline and hospitalizations.
Forty-seven percent of the children in this sample were found to have
one or more comorbidities, and those with comorbidities had
statistically lower TMC scores compared to those without comorbidities.
In this evaluation we compared individuals with any comorbidities to
those without. Therefore, it remains unclear the role each separate
comorbidity has on gross motor evaluations, due to the infrequency of
many of them within this cohort. Understanding the role of individual
comorbidities could be helpful in determining the need for specific PT
interventions in this population.
Surprisingly, in our sample, we did not observe an association between
BMI and gross motor skills given the close association between
FEV1 and BMI and prior studies demonstrating this
relationship (2, 16-18). Lack of an association may be attributed to fat
free mass depletion that can be seen in pwCF with a normal BMI(19, 20).
Despite advancements in the nutritional status of many pwCF, a recent
study demonstrated high rates of fat-free mass depletion in a cohort of
children with CF.
There was also no significant difference in BOT-2 scores between males
and females in our sample. This may be related to the age range
evaluated (4 to 12 years) as previous studies have demonstrated no
gender differences in activity level in prepubescent children with CF
but increased activity levels in post-pubescent males compared to
females(21). Evaluation with the BOT-2 in the adolescent population may
help to better define the relationship between gross motor skills and
gender.
Implementation of a 6-week exercise program has been shown to
significantly improve pulmonary function, walking distance on 6 minute
walk test (6MWT), and scores on the modified Munich fitness test, which
assesses flexibility, balance, strength and coordination(22). Similarly,
significant improvements in 6MWT, quadricep strength and fat free mass
has been demonstrated after an 8-week program(23). A longer-term
exercise program has also been shown to be beneficial for children and
adolescents with CF by improving motor performance fitness(24). This is
very reassuring data to support the implementation of a home program in
children with CF, when impairments are identified using a gross motor
assessment and exercise testing. As a next step we will be
longitudinally evaluating BOT-2 scores in school-aged children in our
clinic to determine the impact of a home program on gross motor skill
acquisition.
Limitations of these results include that it is a convenience sample and
observational with the primary purpose being a quality improvement
project to implement gross motor assessments in children with CF. In
terms of the BOT-2 assessment tool, it is important to note the TMC is
an average of all subsections. For a child that scored high in the body
coordination section and low in the strength agility section, they may
appear to have average gross motor abilities in evaluating TMC alone.
Data from individual sections must therefore be considered when
determining the plan of care, PT interventions, and how a child may be
functioning in relation to same-age peers. Although associations between
gross motor findings and clinical outcomes and demographic
characteristics were noted, a causal relationship cannot be established.
The strengths of this project include the number of children evaluated,
which is the largest published assessment of gross motor skills in
children with CF. Additionally, we report novel information on the
prevalence of gross motor delays in children with CF including outcomes
using the BOT-2 and components of the TMC that were abnormal in this
cohort.
The results of this intervention support the need for a PT in the care
of children with CF to assess for gross motor delays. This assessment
could ultimately lead to earlier detection of delays, improved quality
of care, and allows PT to provide individualized recommendations to
facilitate participation and success in physical activity from an early
age. If, based on clinic workflow, PT is not embedded within CF clinic
or cannot be involved in assessing all children with CF, priority should
be given or an outpatient referral to PT should be considered, in those
with a history of repeat hospitalizations and co-morbidities, due to the
increased rate of gross motor delays in children with these risk
factors. More data are needed to understand how motor delays impact
health outcomes, and how PT interventions impact clinically meaningful
outcomes in children. Longitudinal data are needed to trend changes in
gross motor abilities in the CF population and determine risk factors
for gross motor delays. Finally, as we enter the era of highly effective
CFTR modulator therapies for younger children, it will be important to
understand the impact of these therapies on gross motor abilities.
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Table 1: Summary of baseline clinical characteristics (N=72)