Evidence for Beneficial Effect of Daily Use of Mechanical Insufflation-Exsufflation in Patients With Neuromuscular Diseases.

BACKGROUND: Daily application of mechanical insufflation-exsufflation (MI-E) is used increasingly in patients with neuromuscular diseases (NMDs) to prevent pulmonary congestion and thereby respiratory tract infections, although its beneficial effect remains uncertain. We, therefore, conducted a systematic review, registered in PROSPERO (CRD42020158278), to compile available evidence for daily MI-E use in subjects with NMDs and stable respiratory condition. METHODS: We performed a systematic comprehensive search of MEDLINE, Embase, CINAHL, and Web of Science up to December 23, 2021. We excluded articles studying the effect of MI-E in case of acute respiratory failure or infections and studies comparing different MI-E devices and settings. Studied outcomes were prevalence and severity of respiratory infections, lung function, respiratory characteristics, and patient satisfaction. We performed a meta-analysis using DerSimonian-Laird random effects model and assessed methodological quality by using the Alberta Heritage Foundation for Medical Research tool. RESULTS: A total of 3,374 records were screened, of which 25 were included, studying 608 subjects. One randomized controlled trial (RCT) found a trend toward reduced duration of respiratory infections compared to air stacking (AS) that was not statistically significant. Long-term effects on pulmonary function tests (PFT) results were reported in one RCT and one retrospective study, with mixed results regarding vital capacity. Most studies compared PFT results before and immediately after MI-E use. Meta-analysis showed an overall beneficial effect of MI-E on cough peak flow (CPF) compared to unassisted CPF (mean difference 91.6 L/min [95% CI 28.3-155.0], P < .001). Subject satisfaction was high, though possibly influenced by major bias. CONCLUSIONS: There is limited evidence available to support beneficial effects of daily use of MI-E in clinically stable subjects with NMDs, with the possible exception of increased CPF immediately after MI-E application. Lack of longitudinal studies preclude conclusions regarding long-term effects. The very limited data comparing MI-E to AS preclude comparisons.

Oscillometry: A substitute of spirometry in children with neuromuscular diseases?

INTRODUCTION: Spirometry plays an important role in the assessment of possible respiratory failure in children with neuromuscular diseases (NMDs). However, obtaining reliable spirometry results is a major challenge. We studied the relation between oscillometry and spirometry results. Oscillometry is an easy, noninvasive method to measure respiratory resistance R and reactance X. We hypothesized an increased R and reduced X in patients with more reduced lung function. METHODS: In this prospective single-center study, we included all children with NMDs able to perform spirometry. We consecutively measured R and X at 5, 11, and 19 Hz and (forced) vital capacity, peak expiratory flow. Spearman correlation coefficients and positive and negative predictive values were calculated. Regression curves were estimated. RESULTS: We included 148 patients, median age 13 years (interquartile range: 8-16). A negative correlation was found between R and spirometry outcomes (Spearman correlation coefficient [ρ]: -0.5 to -0.6, p < 0.001). A positive correlation was found between X (i.e., less negative outcomes) and spirometry outcomes (ρ: 0.4-0.6, p < 0.001). Highest correlation was found at lower frequencies. Regression analysis showed a nonlinear relation. Measurement of inspiratory and expiratory R and X did not provide added value. Positive predictive values of 80%-85% were found for z-scores of R measured at 5 Hz versus (F)VC ≤ 60%. CONCLUSION: We found a nonlinear relation between oscillometry and spirometry results with increased R and reduced X in patients with more restrictive lung function decline. Given the difficulties with performing spirometry, oscillometry may be a promising substitute.

Short-term effect of air stacking and mechanical insufflation-exsufflation on lung function in patients with neuromuscular diseases.

Air stacking (AS) and mechanical insufflation-exsufflation (MI-E) aim to increase cough efficacy by augmenting inspiratory lung volumes in patients with neuromuscular diseases (NMDs). We studied the short-term effect of AS and MI-E on lung function. We prospectively included NMD patients familiar with daily AS or MI-E use. Studied outcomes were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) prior to, immediately after, and up to 2 h after treatment. Paired sample T-test and Wilcoxon signed-rank test was used. Sixty-seven patients participated. We observed increased FVC and FEV1 immediately after AS with a mean difference of respectively 0.090 L (95% CI 0.045; 0.135, p < .001) and 0.073 L (95% CI 0.017; 0.128, p = .012). Increased FVC immediately after MI-E (mean difference 0.059 L (95% CI 0.010; 0.109, p = .021) persisted 1 hour (mean difference 0.079 L (95% CI 0.034; 0.125, p = .003). The effect of treatment was more pronounced in patients diagnosed with Spinal Muscular Atrophy, compared to patients with Duchenne muscular dystrophy. AS and MI-E improved FVC immediately after treatment, which persisted 1 h after MI-E. There is insufficient evidence that short-lasting increases in FVC would explain the possible beneficial effect of AS and MI-E.

Natural history of lung function in spinal muscular atrophy.

BACKGROUND: Respiratory muscle weakness is an important feature of spinal muscular atrophy (SMA). Progressive lung function decline is the most important cause of mortality and morbidity in patients. The natural history of lung function in SMA has, however, not been studied in much detail. RESULTS: We analysed 2098 measurements of lung function from 170 treatment-naïve patients with SMA types 1c-4, aged 4-74 years. All patients are participating in an ongoing population-based prevalence cohort study. We measured Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), and Vital Capacity (VC). Longitudinal patterns of lung function were analysed using linear mixed-effects and non-linear models. Additionally, we also assessed postural effects on results of FEV1 and FVC tests. In early-onset SMA types (1c-3a), we observed a progressive decline of lung function at younger ages with relative stabilisation during adulthood. Estimated baseline values were significantly lower in more severely affected patients: %FEV1 ranged from 42% in SMA type 1c to 100% in type 3b, %FVC 50 to 109%, and %VC 44 to 96%. Average annual decline rates also differed significantly between SMA types, ranging from - 0.1% to - 1.4% for FEV1, - 0.2% to - 1.4% for FVC, and + 0.2% to - 1.7% for VC. In contrast to SMA types 1c-3a, we found normal values for all outcomes in later-onset SMA types 3b and 4 throughout life, although with some exceptions and based on limited available data. Finally, we found no important differences in FVC or FEV1 values measured in either sitting or supine position. CONCLUSIONS: Our data illustrate the longitudinal course of lung function in patients with SMA, which is characterised by a progressive decline in childhood and stabilisation in early adulthood. The data do not support an additional benefit of measuring FEV1 or FVC in both sitting and supine position. These data may serve as a reference to assess longer-term outcomes in clinical trials.

Effect of mechanical insufflation-exsufflation in children with neuromuscular weakness.

INTRODUCTION: Children with neuromuscular diseases develop cough impairment. Airway clearance techniques (ACTs) may help to prevent recurrent respiratory tract infections (RTIs). A commonly used ACT is mechanical insufflation-exsufflation (MI-E), but evidence for efficacy is limited. We hypothesize that MI-E has beneficial effect on RTI related hospital admission rate. METHODS: In this single-center retrospective study, we reviewed all children who used daily MI-E between 2005 till June 2019. Primary outcome studied was the number of RTIs requiring hospital admission. Patient satisfaction and burden experienced by MI-E use were explored by questionnaires using a Likert scale. The relative number of RTIs requiring admission and the number of admission days per eligible period before and after the introduction of MI-E were compared using the Friedman test and the Wilcoxon signed-rank test. RESULTS: Thirty-seven children were included. The median number of RTI related hospital admissions per 1000 eligible days after the introduction of MI-E was 0.9 (interquartile range [IQR] 0.0-3.1) compared to the 3 preceding years (median 3.7; IQR 1.4-5.9; P = .006). The median number of RTI related admission days per 1000 eligible days after the introduction of MI-E was significantly lower with a median of 2.7 (IQR 0.0-17.4) compared to the 3 preceding years (median 33.6; IQR 15.0-51.1; P = .001). Patient satisfaction was high with low burden, even in patients who discontinued treatment. CONCLUSION: A significantly lower number of RTIs requiring hospital admission and shorter admission duration after the introduction of MI-E was found, with high patient satisfaction and low burden.

Thirty years of home mechanical ventilation in children: escalating need for pediatric intensive care beds.

PURPOSE: To describe trends in pediatric home mechanical ventilation (HMV) and their impact on the use of pediatric intensive care unit (PICU) beds. METHODS: Review of all children who had started HMV in a single center for HMV. RESULTS: Between 1979 and 2009, HMV was started in 197 patients [100 (51%) with invasive and 97 with noninvasive ventilation], with a median age of 14.7 (range 0.5-17.9) years. Most patients (77%) were males with a neuromuscular disorder (66%). The number of children receiving HMV increased from 8 in the 1979-1988 period to 122 in the 1999-2008 period. This increase occurred foremost in patients aged 0-5 years and was accompanied by a sharp rise in the use of PICU beds. In 150 patients (76%), HMV was initiated on an ICU with a total of 12,440 admission days, of which 10,385 days (83%) could be attributed to 67 patients who started non-electively with invasive HMV. Of the latter, 52 patients had been admitted to a PICU with a total of 9,335 admission days. At the end of the study, 134 patients (68%) were still being ventilated, 43 patients (22%) had died, 11 patients (6%) were weaned from HMV, 4 patients (2%) did not want to continue HMV and 5 patients (3%) were lost to follow-up. CONCLUSIONS: Over time, there was an impressive increase in the application of HMV in children. This increase was most obvious in the youngest age group with invasive HMV, and these children had very long stays in the PICU.

[Lung volume recruitment in impending respiratory failure]. / Longvolumerekrutering bij dreigend respiratoir falen.

Lung volume recruitment can improve peak cough flows and respiratory compliance in patients who either do or do not require mechanical ventilation. There are several lung volume recruitment techniques: air stacking, glossopharyngeal breathing and mechanical insufflation-exsufflation with cough assist devices. The principle of lung volume recruitment is based on the insufflation of air in the lungs after maximal inspiration. In air stacking, a manual resuscitation bag is used for insufflation. Glossopharyngeal breathing requires the use of oropharyngeal and laryngeal muscles by the patient. The mechanical cough assist device exsufflates the air after insufflation. These techniques may prevent pulmonary complications, hospital admission and tracheotomy in patients with a reduced ability to cough, a proclivity towards atelectasis and recurrent airway infections. The combination of long-term mechanical ventilation with lung volume recruitment has led to further improvement in the prognosis of chronic respiratory failure. More patients may potentially benefit from lung volume recruitment than only those being converted from short-term to long-term mechanical ventilation.