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.
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 (FEV
), 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 FEV
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: %FEV
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 FEV
, - 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 FEV
values measured in either sitting or supine position.
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 FEV
or FVC in both sitting and supine position. These data may serve as a reference to assess longer-term outcomes in clinical trials.
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.
Respiratory complications are the most important cause of morbidity and mortality in spinal muscular atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract ...infections and eventually can cause respiratory failure. We assessed longitudinal patterns of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline throughout life.
We measured maximal expiratory and inspiratory pressure (PE
and PI
), Sniff Nasal inspiratory pressure (SNIP), peak expiratory flow (PEF), and peak cough flow (PCF) in treatment-naïve patients with SMA. We used mixed-models to analyze natural history patterns.
We included 2172 measurements of respiratory muscle function from 80 treatment-naïve patients with SMA types 1c-3b. All outcomes were lower in the more severe phenotypes. Significant differences in PEF were present between SMA types from early ages onwards. PEF decline was linear (1-2%/year). PEF reached values below 80% during early childhood in types 1c-2, and during adolescence in type 3a. PE
and PI
were severely lowered in most patients throughout life, with PE
values abnormally low (i.e. < 80 cmH
O) in virtually all patients. The PE
/PI
ratio was < 1 throughout life in all SMA types, indicating that expiratory muscles were most affected. All but SMA type 3b patients had a lowered PCF. Patients with types 2b and 3a had PCF levels between 160 and 270 L/min, those with type 2a around 160 L/min and patients with type 1c well below 160 L/min. Finally, SNIP was low in nearly all patients, most pronounced in more severely affected patients.
There are clear differences in respiratory muscle strength and its progressive decline between SMA types. We observed lower outcomes in more severe SMA types. Particularly PEF may be a suitable outcome measure for the follow-up of respiratory strength in patients with SMA. PEF declines in a rather linear pattern in all SMA types, with clear differences at baseline. These natural history data may serve as a reference for longer-term treatment efficacy assessments.
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.
Progressive lung function decline, resulting in respiratory failure, is an important complication of spinal muscular atrophy (SMA). The ability to predict the need for mechanical ventilation is ...important. We assessed longitudinal patterns of lung function prior to chronic respiratory failure in a national cohort of treatment-naïve children and adults with SMA, hypothesizing an accelerated decline prior to chronic respiratory failure.
We included treatment-naïve SMA patients participating in a prospective national cohort study if they required mechanical ventilation because of chronic respiratory failure and if lung function test results were available from the years prior to initiation of ventilation. We analyzed Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV
), Peak Expiratory Flow (PEF) and Maximum Expiratory Pressure (PE
). We studied the longitudinal course using linear mixed-effects models. We compared patients who electively started mechanical ventilation compared to patients who could not be weaned after acute respiratory failure.
We analyzed 385 lung function tests from 38 patients with SMA types 1c-3a. At initiation of ventilation median age was 18.8 years (IQR: 13.2-30.1) and median standardized FVC, FEV
and PEF were 28.8% (95% CI: 23.5; 34.2), 28.8% (95% CI: 24.0; 33.7) and 30.0% (95% CI: 23.4; 36.7), with an average annual decline of 1.75% (95% CI: 0.86; 2.66), 1.72% (95% CI: 1.04; 2.40) and 1.65% (95% CI: 0.71; 2.59), respectively. Our data did not support the hypothesis of an accelerated decline prior to initiation of mechanical ventilation. Median PE
was 35.3 cmH
O (95% CI: 29.4; 41.2) at initiation of mechanical ventilation and relatively stable in the years preceding ventilation. Median FVC, FEV
PEF and PE
were lower in patients who electively started mechanical ventilation (p < 0.001).
Patterns of lung function decline cannot predict impending respiratory failure: SMA is characterized by a gradual decline of lung function. We found no evidence for an accelerated deterioration. In addition, PE
remains low and stable in the years preceding initiation of ventilation. Patients who electively started mechanical ventilation had more restrictive lung function at initiation of ventilation, compared to patients who could not be weaned after surgery or a respiratory tract infection.
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.
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.
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.
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.
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,
< .001). Subject satisfaction was high, though possibly influenced by major bias.
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.
In neuromuscular disorders (NMDs), nocturnal non-invasive ventilation (NIV) via a nasal mask is offered when hypercapnic respiratory failure occurs. With disease progression, nocturnal NIV needs to ...be extended into the daytime. Mouthpiece ventilation (MPV) is an option for daytime NIV. MPV represents a difficult task for home ventilators due to rapidly changing load conditions resulting from intermittent connections and disconnections from MPV circuit. The 252nd ENMC International Expert Workshop, held March 6th to 8th 2020 in Amsterdam, reported general guidelines for management of daytime MPV in NMDs. This report could not present all the detail regarding the technical issues important for clinical success of MPV. Based on the expert workshop discussions and the evidence from existing studies, the current narrative review aims to identify the technical issues of MPV and offers guidance via a decisional algorithm and educational figures providing relevant information that is important for successful implementation of MPV.
•Mouthpiece ventilation (MPV) represents a difficult task for home ventilators due to rapidly changing load conditions.•Circuit leakage is a natural part of MPV.•Volume-cycled ventilation copes better with circuit leakage than pressure-cycled ventilation.•Volume-cycled ventilation is considered as the first line mode to initiate MPV since it allows intermittent lip sealing without leak compensation.•Ventilators equipped with a dedicated MPV mode provide 10 new technological properties which favors the use of MPV at home.
PDF
