Nocturnal Oxygenation and Prognosis in Duchenne Muscular Dystrophy

Abstract

REM-related oxygen desaturation occurs in advanced Duchenne muscular dystrophy (DMD) and might be an independent predictor of disease progression. We have followed 18 patients for 10 yr after an initial respiratory sleep study or until death or onset of nasal ventilation. We measured baseline spirometry, blood gas tensions, maximal respiratory pressures, and body mass index. In 11 cases, VC was recorded serially. Median survival was 50 (range, 13 to 89) mo from initial study and unrelated to age at time of study, BMI, or mouth pressures but correlated with PaCO2 (r = -0.72, p < 0.005, n = 17), minimal nocturnal SaO2 (r = 0.62, p < 0.007, n = 18) and VC (r = 0. 65, p < 0.005, n = 17). Cox regression analysis showed a VC of less than 1 L at the time of study to be the best single predictor of subsequent survival. The only measure associated with age of death was the age at which the VC fell below 1 L (r = 0.79, p < 0.004). These data suggest measurement of PaCO2 or serial assessment of VC should be studied further as valid methods of assessing prognosis in DMD.

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

“…In addition, loss of ambulation is a crucial disease milestone that carries significant emotional as well as physical and practical implications for patients and families, marking a transition to progressively decreasing independence and increasing need for assistance with activities of daily living 36, 37, 38, 39…”

“…Although preservation of ambulation is strongly desired, respiratory failure is a leading cause of death for patients with DMD 36, 38. The importance of respiratory abnormalities is well understood in later stages of DMD, but early subclinical deterioration of respiratory muscles with a mean annual decline in %pMIP and %pMEP of approximately 4% and %pFVC of approximately 5% has only recently been recognized 3, 31.…”

Sleep and breathing in neuromuscular disease

“…Less consistent and weaker relationships have been shown between nocturnal oxygen saturation and VC [10,39,40], fall in VC supine [38,39], forced expiratory volume in one second (FEV1) [10], maximal expiratory pressure (PE,max) [9] and functional residual capacity [43] (table 1). However, it is important to note that indices of daytime lung function (VC and maximal inspiratory pressure (PI,max)) are better predictors of survival than overnight oxygen saturation [4,44] and orthopnoea in the presence of substantial impairment of daytime respiratory muscle function may be a better predictor of benefit from NIV than nocturnal desaturation [45].…”

“…In common with other neuromuscular conditions, the relation between daytime function and nocturnal oxygen desaturation or respiratory events is poor [7,9,10], but daytime function, specifically VC v1 L, is a more powerful prognostic predictor than any nocturnal index [44]. Evidence on the relationships between sleep-disordered breathing and symptoms is contradictory [7][8][9], which may reflect how carefully symptoms were sought.…”

Novel Methods of Ambulatory Physiologic Monitoring in Patients With Neuromuscular Disease

“…Our current measures consist of spirometry (forced vital capacity, forced expiratory volume at 1 second, oxygen saturation awake and asleep, and peak inspiratory and peak expiratory pressure) and rates of pneumonia, hospitalization, and respiratory failure. [6][7][8] The routine evaluation of sleep has been hindered by the expense associated with technician-monitored studies geared at screening for the justification of expensive home therapies for adults with obstructive sleep apnea syndrome, lack of pediatric sleep laboratories (with the insufficiency made more difficult by the increased recommendations for evaluation of primary snoring with inadequate infrastructure in place), variability in interpretation, and inadequately developed standards of "normal." 9 Home sleep monitoring has been hindered by the frequent need for restudy, which has resulted in the denial of development of a payment structure to foster a business case for innovation.…”