Pulmonary Function Decline in Pediatric Duchenne Muscular Dystrophy

An urgent need exists — both in the clinical setting and in translational research — to identify disease-specific outcome measures for evaluating the progression pulmonary function in pediatric patients with Duchenne muscular dystrophy (DMD), according to an analysis published in Neurology.

It is known that the decline of respiratory function in individuals with DMD is associated with sleep-disordered breathing and the alteration of nocturnal gas exchange, which initially manifests as nocturnal hypoventilation.

Recognizing that the relationship between pulmonary function tests (PFTs), as measured by spirometry, and the onset of sleep-disordered breathing with or without nocturnal hypoventilation remains unclear, researchers sought to identify the prevalence and features of sleep-disordered breathing, along with exploring the link between lung function determined by forced vital capacity (FVC) and sleep abnormalities in a large pediatric DMD population.

The retrospective, single-center cohort study was conducted at Great Ormond Street Hospital, London, United Kingdom, between 2010 and 2020.

In the study, FVC% predicted (FVC%) was computed using predicted equations from the Global Lung Function Initiative. Nocturnal hypoventilation was defined as a transcutaneous (tc) CO₂ level of >50 mm Hg for >25% of total sleep time; borderline nocturnal hypoventilation was defined as a mean tcCO₂ between 45 and 50 mm Hg or a tcCO₂ of >50 mm HG for ≤25% of the time. Clinically meaningful obstructive sleep apnea (OSA) was defined by an Apnea-Hypopnea Index of >5. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the FVC% <50 threshold were calculated as well, to detect the presence of nocturnal hypoventilation, by using the first available sleep study for each patient.

A total of 134 patients with DMD who were <18 years were enrolled in the study. These individuals underwent 284 sleep studies and 1222 PFTs. The mean participant age at the initial and the final sleep study was 12.9±2.7 years and 14.3±2.6 years, respectively.

Overall, 31 patients (per 43 sleep studies) fulfilled the criteria for borderline nocturnal hypoventilation (B-NH), at a median age of 14.2 years (range, 12.4-15.8 years). Among nonambulant participants, B-NH was detected at a median age of 4.2 years (range, 2.0-5.4 years) following loss of ambulation; 7 individuals with B-NH were still ambulant. In 26 of the 43 sleep studies, B-NH was associated with significant respiratory events.

In all, 100% of the 14 participants with nocturnal hypoventilation were nonambulant. Despite an FVC of >50%, nocturnal hypoventilation was detected in 4 of the 14 patients. Further, 17 of 26 participants with OSA presented with concomitant nocturnal hypoventilation or B-NH. FVC of <50% was associated with nocturnal hypoventilation, which was indicative of a sensitivity of 73% and a specificity of 86%. The PPV and NPV were 32% and 97%, respectively. In 18% of patients, PFTs demonstrated a nonlinear, sudden FVC% decline.

A key limitation of the study is the fact that although the results of both the sleep study and the PFTs were recorded prospectively, additional data were retrospectively obtained from a review of case notes. Additionally, since nocturnal hypoventilation was detected in only a small proportion of the sleep studies, this became a major shortcoming in creating a strong prognostic model.

The researchers concluded that “Large, prospective studies are needed to identify those parameters who mandates a closer follow-up also in a less-advanced stage of the disease.”

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.