Characterization of pulmonary function in 10–18 year old patients with Duchenne muscular dystrophy

Abstract

Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10-18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.gov, number NCT01027884). Baseline PEF percent predicted (PEF%p) was <80% and patients had stopped taking glucocorticoids at least 12 months prior to study start. At baseline PEF%p, FVC%p and FEV1%p correlated well with each other (Spearman's rho: PEF%p-FVC%p: 0.54; PEF%p-FEV1%p: 0.72; FVC%p-FEV1%p: 0.91). MIP%p and MEP%p correlated well with one another (MIP%p-MEP%p: 0.71) but less well with PEF%p (MIP%p-PEF%p: 0.40; MEP%p-PEF%p: 0.41) and slightly better with FVC%p (MIP%p-FVC%p: 0.59; MEP%p-FVC%p: 0.74). The within-subject coefficients of variation (CV) for successive measures were 6.97% for PEF%p, 6.69% for FVC%p and 11.11% for FEV1%p, indicating that these parameters could be more reliably assessed compared to maximum static airway pressures (CV for MIP%p: 18.00%; MEP%p: 15.73%). Yearly rates of PFT decline (placebo group) were larger in dynamic parameters (PEF%p: -8.9% [SD 2.0]; FVC%p: -8.7% [SD 1.1]; FEV1%p: -10.2% [SD 2.0]) than static airway pressures (MIP%p: -4.5 [SD 1.3]; MEP%p: -2.8 [SD 1.1]). A considerable drop in dynamic pulmonary function parameters was associated with loss of upper limb function (transition from Brooke score category 4 to category 5). In conclusion, these findings expand the understanding of the reliability, correlation and evolution of different pulmonary function measures in DMD patients who are in the pulmonary function decline phase.

Breathe Duchenne: what natural history studies tell us about the progression of pulmonary morbidity in Duchenne muscular dystrophy

“…For example 80% of patients with a Brooke score of 5, indicating inability to move the hand to the mouth, presented with FVC%p below 50%. Similar findings were independently reported for a smaller data set [9] .…”

Association between pulmonary function and left ventricular volume and function in duchenne muscular dystrophy

“…Twenty-seven boys and adolescent and young adult males (median age 15 years; range, [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] were included in the study. Most of the participants had 3 or 4 clinic visits (median, 3; range, 1-10).…”

“…Peak expiratory flow rate (PEFR) and measures of static airway pressure including maximal inspiratory and expiratory pressure (MIP and MEP) are also expected to steadily decline . Because deteriorating ventilation is the result of loss of strength in respiratory muscles, the degree of ventilatory insufficiency and the strength of the respiratory pump are expected to have an inverse correlation …”

“…7,8 Because deteriorating ventilation is the result of loss of strength in respiratory muscles, the degree of ventilatory insufficiency and the strength of the respiratory pump are expected to have an inverse correlation. 9 In addition to respiratory failure, dilated cardiomyopathy is common in advanced DMD, 10 and progressive deterioration of the left ventricular end-diastolic volume (LVDV) measured by an echocardiogram (ECHO) can be used as an indicator of advanced cardiomyopathy. 11,12 A reduction in left ventricular ejection fraction (LVEF) is an indicator of left ventricular (LV) systolic dysfunction that can be measured serially by ECHO in DMD.…”

Measurement of respiratory function decline in patients with Duchenne muscular dystrophy: a conjoint analysis

“…To this end, a number of measures are used, including lung volume recruitment, cough-assisted devices, ventilation techniques and pharmacological therapy [11][12][13]. This latter was based, until some years ago, on glucocorticoids [5,6]; however, not all patients respond to these medications, which are also associated with relevant side effects [14].…”