Respiratory Function and Sleep Disordered Breathing in Pediatric Duchenne Muscular Dystrophy

Abstract

Background:The decline of respiratory function in Duchenne muscular dystrophy (DMD) is associated with sleep disordered breathing (SDB) and alteration of nocturnal gas exchange, first manifesting as nocturnal hypoventilation (NH). However, the correlation between pulmonary function measured by spirometry (PFT) and the onset of SDB with or without NH is unclear.Aim:To identify the prevalence and features of SDB and to investigate the relationship between lung function determined by forced vital capacity (FVC) and sleep abnormalities in a large paediatric DMD population.Methods:Retrospective, single-center cohort study. FVC% predicted (FVC%) was calculated using predicted equations from the Global Lung Function Initiative. NH was defined by transcutaneous (tc) CO2 >50 mmHg for >25% of total sleep time (TST); borderline NH by a mean tcCO2 between 45-50mmHg or tcCO2>50mmHg for ≤25% of TST; Clinically meaningful obstructive sleep apnea (OSA) by obstructive Apnea–Hypopnea Index >5. The sensitivity, specificity, positive and negative predictive value of FVC<50% to indicate presence of nocturnal hypoventilation were calculated.Results:134 patients underwent 284 sleep studies and 1222 PFT. Mean (SD) age at first and last sleep study was 12.9 (2.7) and 14.3 (2.6) years. Borderline NH (n=31) was detected in both ambulant and early-non ambulant subjects, while 100% of NH cases (n=14) were non-ambulant. NH was detected in 4/14 patients despite an FVC>50%. Seventeen/26 patients with OSA presented with concomitant NH or borderline NH. FVC<50% was associated with NH indicating a sensitivity and specificity of 73% and 86%, respectively. Positive and negative predictive value were 32% and 97% respectively. PFT showed a non-linear, sudden FVC% decline in 18% of cases.Conclusions:FVC% <50 was associated with NH in close to a third of patients. CO2 elevation can be associated with obstructive/pseudo-obstructive events and was also observed in early non-ambulant cases or in the presence of FVC>50%. These results are relevant for the clinical management of SDB.

Sleep apnoea and hypoventilation in patients with five major types of muscular dystrophy

“…Patients with CMD had the highest prevalence of hypoventilation, but it was also common in patients with DMD and DM; patients with LGMD had the lowest prevalence though differences in hypoventilation prevalence among types were not statistically significant. In a recent study of patients with DMD in their early teens,34 ~34% had hypoventilation; this proportion is somewhat lower than in our patients with DMD. Hypoventilation in patients with muscular dystrophy is usually most severe in rapid eye movement sleep 18…”

Pediatric pulmonology year in review 2022: Sleep medicine

“…They advocated for the necessity of early screening, particularly within the first 3 years after the loss of ambulation (LOA), even in individuals with FVC > 50%. 42 There has been increasing interest in SDB in children with spinal muscular atrophy (SMA) due to the high prevalence of respiratory complications in this population. With the development of disease-modifying therapies like nusinersen and onasemnogene-abeparvovec, there has been a shift in the management of SMA type 1 from palliative to proactive.…”

“…It is worth mentioning that in this cohort only 38% were patients with DMD. The retrospective study by Zambon et al 42 evaluated 134 patients with DMD and found that borderline NHH was detected in 31 patients. Only nonambulant patients in this cohort had frank NHH ( N = 14).…”

Evaluation and diagnosis of pediatric obstructive sleep apnea—An update

“…These include children with Trisomy 21, craniofacial anomalies, craniosynostoses, achondroplasia, and with neuromuscular disorders (ElMallah et al, 2017). Though AT is still considered the first line of treatment, these children have higher rates of residual OSA (Rosen, 2011;Zandieh et al, 2013;Cielo and Marcus, 2015;Moraleda-Cibrián et al, 2015;Thottam et al, 2015;Simpson et al, 2018;Zambon et al, 2022), often requiring additional therapy. Positive pressure may be added to treat residual disease or primarily used in those unsuitable for AT (Muntz, 2012;Nehme et al, 2019).…”