Discussion
This study demonstrates the feasibility and utility of supine spirometry
in children with NMD. To our knowledge this is the first study in
children where heathy contemporary controls performed supine spirometry
to generate comparative data. The majority of children with NMD (73%)
who agreed to participate in this study were able to perform supine
spirometry reliably. This study demonstrated a significantly greater
decline in spirometry in the supine position in 30 children with NMD
compared to 30 healthy controls (9% vs 4%, p=0.03). Supine spirometry
also showed greater decline in children NMD who required nocturnal
non-invasive ventilation compared to those breathing spontaneously (12%
vs 7%, p=0.02). The implications of the postural drop in FVC in
children with NMD therefore suggest that its’ sensitivity to the level
of respiratory muscle compromise occurring in the supine position
relates to disease severity.
The falls in supine spirometry for this cohort were relatively mild
compared to previous studies, and we speculate that this reflects
generalised weakness of respiratory muscles rather than being a measure
of early diaphragmatic weakness.(29)
Lechtzin et al. showed that in a heterogeneous group of NMD disorders
and using invasive measures of diaphragmatic function, a 25% drop in
spirometry in the supine position was suggestive of diaphragmatic
weakness(14). Certain NMDs, including
congenital muscular dystrophy and their subtypes LAMA2-RD and COL6-RD,
demonstrate progressive respiratory failure due to disproportionate
diaphragmatic involvement.(29) None of
the patients in the current cohort dropped their lung function [FVC]
by >25% [Maximum change was 20%], as described in
previous studies performed on adults with NMD to suggest significant
diaphragmatic weakness.(15) From limited
studies, performed predominantly in adult patients, an increasing
difference between seated and supine spirometry is thought to indicate
weakness in a combination of diaphragmatic and other inspiratory
muscles, especially the intercostal muscles, resulting in inability to
expand the chest wall against the abdominal contents in the supine
position. Therefore, we believe the larger postural drop in spirometry
demonstrated in the present study in NMD children established on
nocturnal NIV suggests more severe generalised respiratory muscle
weakness.
This is the first study in children to demonstrate a difference in the
postural changes in FVC with NMD breathing spontaneously compared to
those established on nocturnal NIV. Previously, Chen et al. compared the
relationship of the postural changes in FVC and FEF25-75and the need to initiate NIV in patients with neuromuscular disorders in
an adult cohort with a heterogeneous group of underlying disorders with
the largest subset having ALS.(33) There was a substantial difference in
postural FVC between patients who were spontaneously breathing and those
on nocturnal NIV. This led to the conclusion that a 14-fold difference
in postural change in FVC% is more significant than just the reduction
of supine FVC<75% as an indication to start nocturnal NIV.
Our paediatric study demonstrated an approximately 2-fold difference in
postural change in spirometry between those breathing spontaneously as
compared to those on NIV. The findings by Chen et al. were greater than
previous studies performed by Schmidt et al. who showed a change of 16%
and Varrato et al. who demonstrated a drop of
13%.(30,
31) In the study by Varrato et al. on
adults with ALS, patients who experienced breathlessness, orthopnoea and
daytime lethargy had a postural drop of 25% as compared to those who
did not demonstrate these symptoms. Their study did not compare ALS
subjects with other adults established on NIV.
Polysomnography results confirmed that 93% of children in this cohort
had SDB, which was predominantly obstructive in nature. The presence of
obstructive sleep apnoea may be explained by an abnormal increase in
upper airway resistance, muscle weakness, or a combination of the two.
The high prevalence of obstructive sleep apnoea is similar to other
published literature which shows that between 30% and 60% of children
with DMD had obstructive findings on polysomnography.(19, 20) Our cohort
was a heterogeneous group of patients with NMD which may have
contributed to the high prevalence of OSA. Other co-morbidities
including obesity [related to chronic oral corticosteroid treatment
and immobility] may also have played a role in the presence of sleep
disordered breathing.
Considering sleep hypoventilation, while we considered the greater rise
in the NIV group (9 compared to 6 mmHg) to reflect greater muscular
weakness, we found no correlation between this measure and the postural
changes in spirometry. REM hypoventilation may be due to loss of
intercostal muscle activity in this sleep
state.(32) However, it cannot be
distinguished from effects of SDB due to upper-airway weakness and
reduced pharyngeal tone in this sleep state, as previously reported in
studies performed on children with DMD as well as congenital myopathies.
(9, 32,
33)
Our
findings of a poor correlation of supine FVC% as a single measure with
the severity of SDB are in agreement with another study performed by
Khan et al., on 21 subjects with DMD aged 13 to 23
years.(33)