Longitudinal pulmonary function testing outcome measures in Duchenne muscular dystrophy: Long-term natural history with and without glucocorticoids

Abstract

We describe changes in pulmonary function measures across time in Duchenne muscular dystrophy patients treated with glucocorticoids (GCs) > 1 year compared to GC naïve patients in the Cooperative International Research Group Duchenne Natural History Study, a multicenter prospective cohort study. 397 participants underwent 2799 pulmonary function assessments over a period up to 10 years. Fifty-three GC naïve participants (< 1 month exposure) were compared to 322 subjects with > 1 year cumulative GC treatment. Forced vital capacity (FVC), peak expiratory flow rate (PEFr), maximal inspiratory and expiratory pressures were performed and calculated as a percent predicted (%p). GC treatment slowed the rate of pulmonary decline as measured by FVC%p, in patients aged 7-9.9 years. GC treatment slowed 12 and 24-month progression of percent predicted spirometry to a greater degree in those with baseline FVC%p from < 80-34%. GC treatment resulted in higher peak absolute FVC and PEFr values with later onset of decline. Progression to an absolute FVC < 1 liter was delayed by GC treatment. Patients who reached a FVC below 1 L were 4.1 times more likely to die (p = 0.017). Long-term glucocorticoid treatment slows pulmonary disease progression in Duchenne dystrophy throughout the lifespan.

Pediatric Pulmonology Year in Review 2018: Rare lung disease, neuromuscular disease, and diagnostic testing

“…Finally, in the group A patients, percent predicted FVC declined progressively and smoothly over time, at a mean rate of 2.7% per year before reaching a very low plateau. This pattern of pulmonary function is consistent with a pulmonary phenotype, and argues against an environmental cause for the poor pulmonary function seen in the group A subjects. To help exclude nonphenotypic causes of the poor heart function in group B, the authors reviewed the patients’ records for use of cardiac medications and for illnesses that might have selectively affected heart function.…”

Therapies that are available and under development for Duchenne muscular dystrophy: What about lung function?

“…The principal clinical effect of steroids administration is deceleration (rather than reversal) of pulmonary disease progression, as reflected by spirometry. According to the study by McDonald et al this benefit seems to be greater in younger age groups. On the contrary, FVC does ultimately decline in the older age groups and falls to clinically hazardous levels.…”

“…We have identified 19 studies fulfilling our selection criteria (Figure ): nine studies exploring the effect of steroids on pulmonary function, six studies exploring the effect of idebenone (one study explored the effect of both steroids and idebenone), three studies about eteplirsen, one study about ataluren, and one study about stem‐cell therapy (Tables ).…”

“…With regard to study design, 5 of 19 original research papers were retrospective studies and 13 were prospective studies, including six randomized controlled trials, four prospective studies with no control group, three randomized controlled trials followed by an open‐label phase, and one prospective cohort study including a treatment and a nontreatment group . It is noteworthy that in three studies the control group was a natural history cohort or a historical control group .…”

“…Dosing schemas varied even within the same study (daily administration, alternating days, 10 days on/10 days off). From the standpoints of sample size and quality of methodology, the study by McDonald et al appears to be the “key study” in this field.…”