Respiratory comorbidities and treatments in Duchenne muscular dystrophy: impact on life expectancy and causes of death

Abstract

Background: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder with progressive decline of pulmonary function increasing the risk of early mortality. The aim of this study was to explore the respiratory-related comorbidities, and the effect of these comorbidities and treatments on life expectancy and causes of death.

Methods: All male patients living in Sweden with DMD, born and deceased 1970-2019, were included. Data regarding causes of death were collected from the Cause of Death Registry and cross-checked with the medical records along with diagnostics and relevant clinical features.

Results: Hundred and twenty nine patients were included with a median lifespan of 24.3 years. Acute respiratory failure accounted for 63.3% of respiratory-related causes of death. 70.1% suffered at least one pneumonia, with first episode at a median age of 17.8 years. Hypoventilation was found in 73.0% with onset at 18.1 years. 60.5% had their first pneumonia before established hypoventilation. Age at onset of hypoventilation showed a strong correlation with age at first pneumonia. First pneumonia and scoliosis non-treated with scoliosis surgery increased the risk of dying of respiratory-related causes. In 10% of the patients, first pneumonia resulted in acute tracheostomy or early death. Patients treated with assisted ventilation had higher life expectancy compared to untreated patients.

Conclusions: Our results highlight the importance of identifying subclinical hypoventilation in a timely manner and the importance of an active treatment regime upon clinical signs of pneumonia.

Keywords: Cause of death; Duchenne muscular dystrophy; Pulmonary; Risk factors; Survival.

Fig. 1

Kaplan–Meier survival curve for respiratory and other causes of death (n = 129)

Fig. 2

Spearman’s correlation analysis for clinical events: a age at loss of ambulation (LoA) and age at scoliosis (n = 85); b age at LoA and age at start of hypoventilation (n = 90); c age at LoA and age at first pneumonia (n = 75); d age at scoliosis and age at start hypoventilation (n = 65); e age at scoliosis and age at first pneumonia (n = 56); and f age at start of hypoventilation and age at first pneumonia (n = 63)

Fig. 3

Age at start of treatment with Mechanical insufflation–exsufflation (MI-E) (n = 53), assisted ventilation (n = 87), assisted ventilation more than 16 h per day (n = 54) and tracheostomy (n = 23)

Fig. 4

Risk factors for death by respiratory-related causes and by other causes, devided by a) clinical events and b) treatments. Number of patients in parentheses. Analyses with cause-specific Cox proportional hazards regression with censoring for death by other cause as competing risk for death by respiratory causes. The Cox regression analyses were adjusted for potential confounding from year of birth (1970–1979, 1980–1989, and 1990 or later). CI confidence intervals, number of patients in parentheses