Effects of Mechanical Insufflation-Exsufflation on the Breathing Pattern in Stable Subjects With Duchenne Muscular Dystrophy: "A Step Into New Knowledge".

Duchenne muscular dystrophy (DMD) is characterized by progressive degeneration, wasting and weakness of skeletal musculature including respiratory muscles. With disease progression also cough, is compromised. Among cough-augmentation techniques, Mechanical insufflation-exsufflation (MI-E) demonstrated several clinical benefits in patients with chronic airway secretion obstruction and muscular weakness. In clinical practice, the use of MI-E in DMD patients is suggested also when they are in stable state, with no airway infections. However, there is a paucity of studies that consider the effect of MI-E specifically on DMD patients in stable state, and adapted to the use of the MI-E. To verify the effect on respiratory system of a single treatment with MI-E in DMD patients in stable state, 20 DMD patients with no active upper airways or lung infections, using MI-E device regularly at home, were enrolled. They received a single in-exsufflation treatment, consisting of 5 cycles of 5 insufflations-exsufflations with habitual-adapted setting. Volume variations during quiet breathing, vital capacity and cough before and after treatment were measured by using Opto-Electronic Plethysmography. Results show that a single treatment of MI-E in DMD patients in stable state and already adapted to the device, although not increasing lung volume recruitment nor unassisted peak cough flow, can foster a beneficial change in ventilatory pattern through a significant decrease of breathing frequency and a reduced rapid and shallow breathing index (RSBi), suggesting an improvement in terms of reduced shortness of breath and better gas exchange.

a.Clinical data

For all the subjects, clinical information including mutations in the DMD gene, use of noninvasive mechanical ventilation, years of use of cough assistive devices, episodes of upper or lower airways infection in the last year, corticosteroids, cardiac function, severity of scoliosis, presence of spinal fusion, nutritional status and use of percutaneous endoscopic gastrostomy (PEG) were recorded.

b.Pulmonary Function Tests

Data of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25–75% of FVC (FEF25–75%), forced expiratory flow at 50% of FVC (FEF50%), and peak expiratory flow (PEF) were acquired. Moreover, subdivisions of lung volumes (functional residual capacity (FRC), residual volume (RV) and total lung capacity (TLC)), were obtained by using the nitrogen washout technique.

c.Effects of MI-E treatment

Quiet breathing (QB) analysis with Opto-Electronic Plethysmography (OEP)

Total and compartmental chest wall volumes were measured by Opto-Electronic Plethysmography.

Breathing and thoraco-abdominal pattern during QB immediately before the first (QB T0) and after the last (QB T1) MI-E applications were analyzed, considering a normalized breath obtained by at least four breaths for both QB periods. The following breathing pattern parameters were computed on chest wall tracing: tidal volume (VT), calculated as the average of total VCW variations (ΔVCW), total time of the respiratory cycle (TTOT), inspiratory and expiratory times (TI and TE), breathing frequency (f), minute ventilation (V’E=VT*f), and Rapid Shallow Breathing index (RSBi=f/ VT). To characterize thoraco-abdominal pattern, percentage contribution of the different compartments to VT (%ΔVRC, and %ΔVAB) were computed. End-expiratory and end-inspiratory volumes of the chest wall and its compartments were also measured and reported as variations from the baseline volumes at end expiration before treatment.

SVC Maneuver

SVC maneuvers were measured synchronously by OEP and the portable spirometer. Starting from data collected with OEP, ribcage, abdominal and total chest-wall volume changes during inspiratory capacity (IC) and Vital capacity (VC) were computed and compared with VC and IC measured by the portable spirometer.

Cough Maneuver

Cough maneuvers were measured synchronously by OEP and the portable spirometer. Starting from data collected with OEP, both a volume analysis and a peak cough flow (PCF) analysis were performed. For what concern volume analysis, the instants of the start of cough inspiration (IS), end of cough inspiration (IE), and end of cough (CE) were identified. Ribcage, abdominal and total chest-wall volume changes during Inspiratory Cough Phase (ICP) and Expiratory Cough Phase (ECP) were respectively computed as the volume variation between IS and IE, and between IE and CE for each cough maneuver. The mean over the three cough maneuvers was then computed at T0 and T1, for each parameter. To compute PCF, flow was obtained as the time derivative of the total chest wall volume (V’=dVCW /dt) measured with OEP and filtered with a moving-average filter where each value was computed as the mean over 5 samples. At T0 and T1, expiratory peaks during the three cough maneuvers were selected and the PCF was computed as their mean. PCF values obtained with OEP were then compared with PCF obtained with the spirometer.

d.Statistical analysis

For clinical, anthropometric, pulmonary function parameters, mean values ± SD were calculated.

Median values and interquartile ranges (IQR=75th percentile – 25th percentile) were computed for parameters related to QB, SVC and cough.

To evaluate differences in QB, SVC and cough parameters between pre-treatment (T0) and post-treatment (T1), the parametric paired Student t-test was used. When data were not normally distributed, non-parametric Wilcoxon signed-rank test was used. We applied Bonferroni correction for multiple dependent variables for QB analysis (breathing pattern: N=6, thoraco-abdominal pattern: N=2, end-inspiratory and end-expiratory volumes: N=10), for SVC analysis (N=6) and cough (N=6). The significance level was set at p < 0.05/N.

Spearman's rank-order correlation was run to determine the relationship between measurements obtained with the portable spirometer and with OEP for VC and IC, during SVC maneuvers. All the data recorded during the SVC maneuvers at T0 and T1 were used to compute the correlations. To assess the agreement between OEP and portable spirometer measures during SVC maneuvers Bland-Altman analysis was performed, considering VC and IC at T0 and T1. The mean percentage error was also computed for both the maneuvers, and expressed as mean ± SD.  All computations were performed with SPSS version 23.0 for Windows; SPSS, Chicago, IL.