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)