Cough Assistance Techniques in Adolescents and Young Adults with Neuromuscular Diseases Using Home Noninvasive Ventilatory Support: A Preliminary Cross-Sectional Physiological Study

Abstract

Background

Progressive respiratory muscle weakness in neuromuscular diseases (NMD) impairs cough effectiveness and increases respiratory morbidity. We compared peak cough flow (PCF) and vital capacity (VC) across airway clearance/cough augmentation techniques in adolescents and young adults using home noninvasive ventilation (NIV).

Methods

In this cross-sectional physiological study, adolescents and young adults with NMD receiving home NIV were evaluated at home. PCF and VC were measured at baseline and immediately after manual assisted cough (MAC), NIV at usual settings, NIV at inspiratory positive airway pressure of 30 cmH2O, air stacking (AS), glossopharyngeal breathing (GPB), and mechanical insufflation-exsufflation (MI-E). Techniques were tested alone and in combination with MAC; the sequence was randomized within participants.

Results

Twenty-four participants (70.8% male; age 17.5 ± 2.4 years) were included. Baseline PCF was 211.2 ± 89.4 L/min. Compared with baseline, PCF increased with MAC, AS, NIV at usual settings, NIV at 30 cmH2O, and MI-E (all p < 0.05), whereas GPB showed no significant change. When combined with MAC, all techniques further increased PCF (e.g., AS + MAC, 306.7 ± 98.4; NIV-30 + MAC, 297.1 ± 94.0 L/min; all p < 0.001), with no between-technique differences. VC increased after AS, MI-E, and NIV (all p < 0.005), but not after GPB.

Conclusions

In adolescents and young adults with NMD using home NIV, AS, NIV, and MI-E improved cough effectiveness and lung volume, and adding MAC produced additional PCF gains.

Keywords

neuromuscular diseases peak cough flow noninvasive ventilation air stacking mechanical insufflation–exsufflation

Introduction

One of the most prevalent neuromuscular diseases (NMD) that benefits from noninvasive ventilation (NIV) is Duchenne muscular dystrophy (DMD) (Bach & Martinez, 2011; Güell et al., 2007). In this condition, progressive weakness of the respiratory muscles leads to a significant reduction in forced vital capacity (FVC), which becomes evident at an early age, around 12 years (Bach, 2017a; Lisboa et al., 2003; Panitch, 2017). As respiratory impairment progresses, daytime carbon dioxide (CO₂) retention often develops, usually between the ages of 18 and 20, and its presence is associated with a higher risk of death from respiratory failure in the absence of ventilatory support strategies (Bach, 2017a; Lisboa et al., 2003; Panitch, 2017).

The second most prevalent NMD that results in progressive respiratory decline is spinal muscular atrophy (SMA) (Castiglioni et al., 2011; Fauroux, Griffon et al., 2020a; Finkel et al., 2018). The severity of involvement varies, and the disease is typically classified into subtypes based on age of onset and the clinical progression of muscle weakness (Hull et al., 2012; Kolb & Kissel, 2015). From a respiratory standpoint, children with SMA may develop progressive ventilatory restriction and respiratory complications that frequently require structured respiratory management and, in selected cases, NIV support (Fauroux, Griffon et al., 2020a; Finkel et al., 2018; Hull et al., 2012; Kolb & Kissel, 2015; Torres-Castro, Monge et al., 2014a). Although both DMD and SMA lead to restrictive respiratory impairment, their respiratory muscle involvement may differ, with DMD typically showing progressive inspiratory and expiratory muscle weakness, whereas SMA may show relatively greater expiratory than diaphragmatic involvement. Ullrich muscular dystrophy is also associated with progressive respiratory muscle weakness and restrictive ventilatory impairment (Fauroux, Griffon et al., 2020a; Finkel et al., 2018; Hull et al., 2012; Kolb & Kissel, 2015; Torres-Castro, Monge et al., 2014a; Voulgaris et al., 2019)

Respiratory impairment in NMD is characterized by alveolar hypoventilation (hypoxemia and hypercapnia) due to progressive weakness of the ventilatory muscles and consequent reduction in ventilatory pump activity in morphologically healthy lungs (Fauroux, Griffon et al., 2020a; Hull et al., 2012; Kolb & Kissel, 2015; Levine et al., 2023; Torres-Castro, Monge et al., 2014a; Voulgaris et al., 2019). As respiratory muscle dysfunction progresses, patients typically generate lower tidal volumes and reduced lung volumes, which contribute to ventilatory limitation and impaired airway clearance (Chatwin et al., 2018; Levine et al., 2023; Voulgaris et al., 2019).

Respiratory weakness compromises cough effectiveness and contributes to respiratory failure, which is among the leading causes of morbidity and mortality in patients with NMD, such as DMD and SMA (Chatwin et al., 2018; Panitch, 2017; Senent et al., 2011). Ineffective cough leads to impaired airway clearance, recurrent lower respiratory tract infections, and frequent hospitalizations, further deteriorating pulmonary function in a vicious cycle of impairment (Chatwin et al., 2018; Ishikawa et al., 2008; Senent et al., 2011; Voulgaris et al., 2019). Despite the widespread clinical use of cough augmentation, high-certainty evidence for clinically meaningful outcomes (e.g., hospitalizations, gas exchange, quality of life) remains limited in both adults and children with NMD, and between-technique comparisons often rely on small crossover trials with incomplete reporting (Morrow et al., 2021).

An effective cough is a crucial defense mechanism against respiratory infections, which remain the most common cause of hospitalization in this population (Chatwin et al., 2018; Hull et al., 2012). Impaired cough in NMD is commonly reflected by reduced peak expiratory flow (PEF) or peak cough flow (PCF), resulting from inspiratory and expiratory muscle weakness that limits the pressure required to generate adequate expiratory airflow (Kang & Bach, 2000; Suárez et al., 2002).

Additionally, bulbar dysfunction may further reduce PCF by compromising the rapid glottic opening and upper airway patency required (Bach, 1993; Suárez et al., 2002). International guidelines recommend initiating cough-assistance techniques when PCF falls below 270 L/min, or FVC is less than 50% of the predicted value (Chatwin et al., 2018; Hull et al., 2012). This PCF threshold (<270 L/min) remains widely cited as a pragmatic trigger for implementing assisted coughing in NMD (Willis, 2023).

Assisted cough techniques are therapeutic interventions designed to enhance or simulate the natural cough mechanism in individuals with impaired cough generation. These techniques aim to increase expiratory flow and promote airway clearance by applying external manual, mechanical, or combined assistance to support respiratory muscle function and facilitate the expulsion of secretions (Torres-Castro, Monge et al., 2014a).

In people with NMD, Glossopharyngeal Breathing (GPB) increased VC and PCF. Air stacking (AS) increases inspiratory lung volumes through multiple insufflations, thereby improving expiratory flow via a combination of static recoil and expiratory muscle recruitment (Chatwin & Simonds, 2020; Nygren-Bonnier et al., 2009; Toussaint et al., 2016). Mechanical insufflation–exsufflation (MI-E) may be preferred within a stepwise cough-augmentation strategy when lung volume recruitment (e.g., AS) is not feasible or when a higher level of cough assistance is required, based on the patient's clinical context (Torres-Castro, Monge et al., 2014a). Unlike AS, MI-E also assists expiration by rapidly shifting from positive to negative airway pressure, simulating the dynamic changes during a natural cough (Auger et al., 2017; Camela et al., 2019). A comparative study including adults and children with NMD found that MI-E produced the most significant increase in PCF compared with other standard cough augmentation techniques, with similar acceptability across techniques (Chatwin et al., 2003). In pediatric NMD, MI-E has also demonstrated good tolerance and short-term physiologic benefits, with improvements in inspiratory/expiratory flows and cough-related measures in stable children (Fauroux et al., 2008). Likewise, lung volume recruitment via breath stacking has been evaluated in children with NMD, showing that stacking can substantially increase lung volumes above tidal breathing and may be particularly useful in younger or less cooperative patients (Jenkins et al., 2014).

However, comparative data directly contrasting multiple cough augmentation strategies within the same protocol in adolescents and young adults receiving home NIV remain scarce, and contemporary syntheses highlight uncertainty regarding differential effects across techniques (Morrow et al., 2021). This study aimed to compare the PCF and VC achieved during spontaneous cough with those achieved with different assisted cough techniques, including manual-assisted cough (MAC), GPB, AS, MI-E, and NIV, in adolescents and young adults with NMD using home NIV. Additionally, we aimed to determine the incremental effect of adding MAC to each ACT.

Materials and Methods

This was a cross-sectional, single-visit assessment study conducted at the Home Mechanical Ventilation Service of the Chilean Ministry of Health (https://respiratorio.minsal.cl/) Recruitment was based on the service registry, and all patients who met eligibility criteria were invited to participate. The study design followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational research (Von Elm et al., 2007). All evaluations were conducted at the participants’ homes by a trained research team, ensuring standardized data collection in a familiar environment. Inclusion criteria were age between 12 and 20 years; confirmed diagnosis of NMD; documented use of NIV for at least 6 months with a minimum daily use of 4 h; and previous tolerance to the oronasal mask. Exclusion criteria were the presence of an acute respiratory infection at the time of evaluation or refusal to provide informed consent.

Because the study invited all eligible patients from the registry during the inclusion period, the final sample reflects the available population and feasibility of home assessments rather than selective sampling. A flowchart summarizing the study design and procedures is shown in Figure 1.

Procedures

All participants underwent the same standardized protocol under the supervision of trained physiotherapists. Clinical diagnoses were confirmed from medical records and classified as DMD, SMA, Ullrich muscular dystrophy, or other myopathies.

All respiratory assessments were conducted at the participants’ homes using portable devices. Spirometry was performed with a SpiroLab II spirometer (MIR Medical, Rome, Italy) to obtain FVC, forced expiratory volume in the first second (FEV₁), and the FEV₁/FVC ratio. Respiratory muscle strength was evaluated by maximal inspiratory and expiratory pressures (MIP and MEP) measured with a PCE-005^® digital manometer (PCE Holding GmbH, Hamburg, Germany). Spirometry and respiratory pressure maneuvers adhered to American Thoracic Society/European Respiratory Society (ATS/ERS) acceptability and reproducibility standards, and predicted values were derived from population-specific reference equations (Barral-Fernández et al., 2025; Graham et al., 2019; Laveneziana et al., 2019; Lista-Paz et al., 2023; Quanjer et al., 2012).

Ventilatory support characteristics were recorded, including NIV use pattern (night-only vs day-and-night), ventilatory mode: spontaneous/timed (ST), spontaneous (S), average volume-assured pressure support (AVAPS), or intelligent volume-assured pressure support (iVAPS), and device settings: inspiratory positive airway pressure (IPAP, cmH₂O), expiratory positive airway pressure (EPAP, cmH₂O), backup respiratory rate (breaths/min), inspiratory time (s), rise time (s), pressure support (PS, cmH₂O), and target tidal volume/volume-assured parameters (VC/AVAPS, mL). The number of respiratory exacerbations and hospitalizations in the previous year was also documented. Respiratory exacerbation was operationally defined as an acute respiratory illness (typically a respiratory tract infection) reported in the clinical chart that required escalation of care, including initiation of antibiotic therapy and/or an unscheduled outpatient or emergency visit and/or hospitalization (Birnkrant et al., 2018; Khan et al., 2023).

Peak Cough Flow (PCF)

Baseline PCF was measured in the seated position using a MiniWright^® peak flow meter (Clement Clarke International Ltd., Harlow, UK). For each condition, three maximal cough efforts were performed, and the highest value was retained (Torres-Castro, Vilaró et al., 2014b). Given the clinical-scale resolution of this portable device, PCF values were interpreted as bedside estimates, consistently applied across within-subject comparisons, rather than as laboratory-grade flow measurements. To evaluate the influence of the interface on baseline PCF, measurements were obtained using both a mouthpiece with a nasal clip and a well-fitted oronasal mask (without a nasal clip). Interface comparison was performed exclusively at baseline to quantify potential interface-related variability under standardized conditions. Given that several cough augmentation strategies in this protocol are delivered through an oronasal mask and to ensure methodological consistency across conditions, mask-derived PCF values were pre-specified for the primary analyses. Mouthpiece-derived values were retained for descriptive purposes and to document potential interface-related differences (Hull et al., 2012). All PCF maneuvers were performed under direct physiotherapist supervision, and trials were repeated when visible air leakage was detected or when the effort was judged submaximal by the assessor.

Vital Capacity (VC)

Baseline VC was assessed in the seated position using a portable ventilometer (Ferraris Wright^® MK 8, Louisville, CO, USA) with a disposable mouthpiece and nasal clip. Participants performed a maximal inspiration followed by a slow, complete expiration; three trials were recorded, and the highest value was retained. VC was reassessed after each maneuver to quantify immediate post-maneuver changes.

Measurement consistency was supported by standardized procedures, trained physiotherapists, use of the same equipment across conditions, three recorded maneuvers for PCF and VC, and repetition of trials when air leakage or submaximal effort was detected. The use of a portable peak flow meter for PCF assessment is also supported by recent evidence in patients with NMD, which shows strong agreement with spirometry, supporting its feasibility as an accessible bedside tool for cough-flow assessment in clinical and home-based settings (Balañá Corberó & Martínez Llorens, 2025).

Randomization and the Sequence

After baseline PCF and VC assessments, the order in which cough augmentation maneuvers were evaluated was randomized for each participant to minimize potential order-related effects, including fatigue and carryover related to prior lung volume recruitment. NIV pressure conditions (baseline setting and 30 cmH₂O) were also applied in randomized order within the NIV block. All participants were already familiar with the evaluated cough-assistance techniques. Outcomes (PCF and VC) were measured systematically after each maneuver using the same procedures and equipment.

Manual Assisted Cough (MAC)

MAC was delivered by applying synchronized external thoracic and abdominal compression at the onset of the expiratory phase to augment expiratory flow (Torres-Castro, Monge et al., 2014a). MAC was evaluated as a stand-alone condition and in combination with each assisted technique (e.g., NIV-30 + MAC, AS + MAC, GPB + MAC, MI-E + MAC).

NIV-Assisted Cough Assessment

Participants were connected to NIV using their usual home ventilator settings and habitual oronasal mask interface and maintained for 5 min. At the end of each NIV condition, NIV was briefly paused and the interface removed to measure PCF (MiniWright^®) and VC (ventilometer) immediately thereafter. Subsequently, an IPAP level of 30 cmH₂O was applied, maintained for 5 min, followed by temporary NIV disconnection and immediate PCF and VC measurements (with a standardized interval of 10 s from disconnection to testing).

Air Stacking (AS)

AS was performed using a self-inflating bag (SIB; Hudson Lifesaver^®, Teleflex Medical, Morrisville, NC, USA) fitted with a one-way valve to prevent passive exhalation between insufflations (Bach et al., 2007; Toussaint et al., 2016). Participants were instructed to inhale maximally, and additional volumes were delivered via bag compressions to reach the maximum tolerated inspiratory capacity. Immediately after the maneuver, participants performed a maximal cough to measure PCF. A brief familiarization trial was provided before recording.

Glossopharyngeal Breathing (GPB)

GPB was performed under a physiotherapist's supervision using standardized instructions. Participants were coached to take sequential “gulps” of air using oropharyngeal musculature to increase inspiratory volume, followed by a maximal cough for PCF measurement (Nygren-Bonnier et al., 2009). A brief practice period was provided before data collection, and the maneuver was discontinued if discomfort occurred.

Mechanical Insufflation–Exsufflation (MI-E)

MI-E was delivered using a CoughAssist E70 device (Philips Respironics^®, Murrysville, PA, USA) via an oronasal mask. The device delivered an insufflation phase followed by an exsufflation phase by applying sequential positive and negative airway pressures (Bach, 1993; Chatwin et al., 2003). Insufflation and exsufflation pressures were set at +40 and −40 cmH₂O, respectively (Auger et al., 2017). Additional MI-E settings were: insufflation time 2.0 s, exsufflation time 2.0 s, pause 1.0 s, 5 cycles per trial, and 3 trials.

Across conditions, measurements were separated by a minimum 5-min interval, and additional rest was provided when needed until the participant returned to baseline Borg score before the next maneuver. Participants were continuously monitored throughout testing, and the protocol was interrupted if discomfort or adverse events occurred.

Outcomes

The primary outcome was the absolute difference (Δ) in PCF after each maneuver compared to baseline spontaneous cough (ΔPCF = PCF condition − PCF baseline). Secondary outcomes included: (i) the ΔPCF achieved by MAC alone and the incremental effect of adding MAC to each technique (e.g., AS + MAC, GPB + MAC, NIV + MAC, MI-E + MAC); (ii) the tolerability of NIV at the participant's baseline settings and at IPAP 30 cmH₂O; (iii) between-condition comparisons among AS, GPB, MI-E, and NIV with and without MAC; and (iv) the absolute difference (Δ) in VC after lung volume recruitment techniques compared to baseline VC (ΔVC = VC condition − VC baseline).

Statistical Analysis

The sample size was calculated to detect a minimum 30% increase in maximum PCF relative to baseline. Assuming a baseline PCF at 50% of predicted values, with a type I error of 0.05 (95% confidence), type II error of 0.1 (90% power), and accounting for 20% possible dropouts, the estimated sample size was 24 participants.

Data were analyzed using GraphPad Prism 8.0 (GraphPad Software Inc., San Diego, California, USA), which was also used to generate the figures. Continuous variables were expressed as mean and standard deviation. Normality was assessed using the Shapiro–Wilk test. Comparisons between baseline PCF and post-technique measures were performed using paired t-tests when data followed a normal distribution or Wilcoxon signed-rank tests otherwise.

To compare multiple techniques, a one-way repeated-measures ANOVA was conducted. When significant differences were detected, Dunnett's multiple-comparisons post hoc test was used to compare each maneuver with the baseline. A significance level of p < 0.05 and 95% confidence intervals were considered.

Ethical Considerations

This study was submitted for review and approved by the Ethics Committee of the Faculty of Medicine, University of Chile, under Project No. 235-2016 (N°171 - June 13, 2017). All procedures were conducted in accordance with the ethical principles outlined in the CIOMS International Ethical Guidelines for Health-related Research Involving Humans and the Declaration of Helsinki. Participants and their legal guardians received detailed information about the research's objectives, methods, potential risks, and benefits. After signing the informed consent and assent forms when applicable, participants were considered eligible for inclusion. Participation was entirely voluntary, and subjects were informed that they could withdraw from the study at any stage without any negative consequences.

Results

A total of 26 patients meeting all eligibility criteria were recruited for the study. Two participants developed an acute respiratory exacerbation before the evaluations and were therefore excluded from analysis. Consequently, 24 individuals completed all study procedures and were included in the final analysis (Figure 1). Table 1 presents the descriptive analysis of the sample studied, including both sexes and routine home cough-assistance use prior to the study.

Table 1.

Anthropometric Data, Diagnosis, and Pulmonary Function of the Participants.

Variables
Gender (Female / Male)	7 / 17
Age (years)	17.5 ± 2.4
Weight (kg)	49.5 ± 16.6
Height (cm)	155.4 ± 9.2
BMI (kg/m²)	20.3 ± 6.2
Diagnosis
Duchenne Muscular Dystrophy (DMD)	15 (62.5%)
Spinal Muscular Atrophy (SMA)	3 (12.5%)
Ullrich Muscular Dystrophy	2 (8.3%)
Other Myopathies	4 (16.7%)
Pulmonary function
FVC (L)	1.51 [1.11–2.50]
FVC % predicted	38 [26.25–64.00]
FEV₁ (L)	1.41 [1.03–2.35]
FEV₁ % predicted	39.5 [26.35–64.75]
FEV₁/FVC	91.2 [88.5–92.9]
MIP (cmH₂O)	46.9 ± 17.8
MIP % predicted	40.0 ± 16.0
MEP (cmH₂O)	37.8 ± 11.3
MEP % predicted	25.2 ± 9.4

Data are expressed as mean ± standard deviation for normally distributed variables, and median (interquartile range) for non-normally distributed variables.

A total of 24 patients were evaluated, of whom 70.8% were male (n = 17), with a mean age of 17.5 ± 2.4 years. Diagnoses included DMD (62.5%, n = 15), SMA (12.5%, n = 3), Ullrich muscular dystrophy (8.3%, n = 2), and other myopathies (16.7%, n = 4). Baseline pulmonary function showed a predominantly restrictive pattern, with a median FVC of 1.51 L [1.11–2.50], corresponding to 38% [26–64] of predicted values. Respiratory muscle strength was reduced, with a mean MIP of 46.9 ± 17.8 cmH₂O (40.0 ± 16.0% predicted) and a mean MEP of 37.8 ± 11.3 cmH₂O (25.2 ± 9.4% predicted).

Most participants used ventilatory support exclusively at night (83.3%, n = 20), while the remaining participants used NIV both during the day and at night (16.7%, n = 4). The most frequently used ventilatory mode was ST (87.5%, n = 21), while S, AVAPS, and iVAPS modes were each used in 4.2% (n = 1) of participants (Table 2).

Table 2.

Ventilatory Parameters of the Participants.

Variables
Use of NIV (Night / Day and night)	20 / 4 (83.3% / 16.7%)
Modality
ST	21 (87.5%)
S	1 (4.2%)
AVAPS	1 (4.2%)
iVAPS	1 (4.2%)
Parameters
IPAP (cmH₂O)	14 [12.4–16.0]
EPAP (cmH₂O)	6 [6–7]
Respiratory rate (bpm)	12 [11.0–14.5]
Inspiratory time (s)	1.0 [1.0–1.1]
Rise Time (s)	2 [1–3]
PS (cmH₂O)	7.5 ± 1.5 (n = 17)
VC/AVAPS (mL)	460.3 ± 84.6 (n = 6)
Exacerbations
Hospitalization last year	2 [1–2]
Exacerbations last year	2 [1–2]

Data are expressed as mean ± standard deviation for normally distributed variables, and median (interquartile range) for non-normally distributed variables.

Data are presented as mean ± SD. Comparisons versus baseline were performed using one-way repeated-measures ANOVA with Dunnett's post hoc test.

VC was measured at baseline and after AS, GPB, NIVb, NIV-30, and MI-E. Data are presented as mean ± SD. Comparisons versus baseline were performed using one-way repeated-measures ANOVA with Dunnett's post hoc test.

Further comparisons showed that, compared with baseline (211.2 ± 89.4 L/min), PCF increased significantly with MAC alone (256.5 ± 103.3 L/min), AS (257.1 ± 87.4 L/min), NIV at baseline settings (NIVb; 235.6 ± 89.2 L/min), NIV with IPAP 30 cmH₂O (NIV-30; 255.0 ± 89.2 L/min), and MI-E (249.2 ± 80.8 L/min), whereas GPB (228.3 ± 86.8 L/min) did not result in a significant increase. No significant differences were observed among the techniques performed without compression.

When MAC was added, all assisted techniques produced significantly higher PCF values than baseline, including AS + MAC (306.7 ± 98.4 L/min), NIV-30 + MAC (297.1 ± 94.0 L/min), MI-E + MAC (289.4 ± 105.2 L/min), NIVb + MAC (282.9 ± 104.3 L/min), and GPB + MAC (266.2 ± 94.2 L/min), with no significant differences between the combined conditions (Figure 2). In NIV conditions, PCF values increased numerically from NIVb to NIV-30, both with and without compression; however, these differences were not statistically significant.

When comparing baseline VC (1421 ± 714 mL) to values obtained with AS (2097 ± 809 mL, ΔVC +676 mL), NIVb (1749 ± 707 mL, ΔVC +328 mL), NIV-30 (2004 ± 753 mL, ΔVC +583 mL), MI-E (2045 ± 776 mL, ΔVC +624 mL), all techniques produced a significant increase versus baseline (p < 0.005), except for GPB (1582 ± 777 mL, ΔVC +161 mL, p = 0.26). Consistently, the largest mean increases were observed with AS (+676 mL), MI-E (+624 mL), NIV-30 (+583 mL). In contrast, NIVb showed a smaller but significant effect (+328 mL) and GPB only a modest, non-significant change (+161 mL), in line with its lack of statistical significance (Figure 3).

To complement statistical significance, mean differences versus baseline (ΔPCF) and standardized effect sizes (Cohen's d) were also estimated for each maneuver. Among techniques performed without manual compression, the most considerable improvements were observed for AS (ΔPCF +45.9 L/min; d = 2.23; p < 0.001), NIV-30 (ΔPCF +43.8 L/min; d = 2.05; p < 0.001), and MI-E (ΔPCF +38.0 L/min; d = 1.52; p < 0.001). MAC alone also increased PCF (ΔPCF +45.3 L/min; d = 1.10; p = 0.015), whereas NIV at baseline settings showed a smaller but significant effect (ΔPCF +24.4 L/min; d = 0.95; p = 0.047). In contrast, GPB alone did not significantly improve PCF (ΔPCF +17.1 L/min; d = 0.64; p = 0.97). When combined with MAC, all modalities demonstrated markedly larger effects (p < 0.001), with the most significant increases observed for AS + MAC (ΔPCF +95.5 L/min; d = 3.16), NIV-30 + MAC (ΔPCF +85.9 L/min; d = 2.70) and MI-E + MAC (ΔPCF +78.2 L/min; d = 2.53), followed by NIVb + MAC (ΔPCF +71.7 L/min; d = 2.41) and GPB + MAC (ΔPCF +55.0 L/min; d = 1.54), confirming substantial standardized improvements across assisted conditions.

Discussion

The present study aimed to evaluate and compare PCF achieved during spontaneous cough and after the application of various assisted cough maneuvers in adolescents and young adults with NMD. The results suggest that assisted cough techniques, including AS, NIV at different inspiratory pressures, and MI-E, significantly increased both PCF and VC compared with baseline values. Conversely, GPB alone did not result in a statistically significant increase in PCF or VC compared to baseline. These findings are broadly consistent with previous observational and crossover studies of cough augmentation in NMD. Accordingly, the main contribution of our study is not to claim entirely novel physiologic effects, but to provide a standardized within-subject comparison across commonly used techniques in adolescents and young adults receiving home NIV, a population that remains underrepresented in comparative studies (Morrow et al., 2021).

The absence of a significant response to GPB alone may be related to the learning-dependent nature of this technique. Haruyama et al. showed that boys with DMD required a structured, stepwise learning protocol of up to 60 min to master GPB, with no immediate mastery observed in the DMD group. GPB also requires coordinated glossopharyngeal movements, including soft palate elevation, tongue positioning, laryngeal movement, and glottic closure. Therefore, the brief familiarization period used in our single-visit protocol may have been insufficient to achieve effective lung volume recruitment, particularly in participants with reduced VC and long-term NIV use (Haruyama et al., 2020).

Among the patients evaluated, DMD was the most frequent etiology, affecting more than half of the sample (62.5%), in line with the literature, which recognizes DMD as the most prevalent NMD in childhood and adolescence (Camela et al., 2019; Fauroux, Khirani et al., 2020b). Previous studies (Camela et al., 2019; Chatwin et al., 2003) have emphasized that progressive respiratory muscle weakness in these individuals leads to reduced VC and impaired PCF, particularly after the second decade of life. In the present study, 78.9% of patients showed a restrictive ventilatory pattern on spirometry, with mean FVC substantially reduced compared to predicted values, corroborating previous reports of progressive and predictable pulmonary function decline in NMD (Bach, 2017b; Brito et al., 2009). Furthermore, the mean MIP and MEP indicate significant respiratory muscle weakness, which directly impairs the ability to generate adequate intrathoracic pressures during cough (Bach et al., 2007). The clinical relevance of these PCF changes should also be interpreted in the context of established cough-flow thresholds. In our sample, the mean baseline PCF was below 270 L/min, a commonly used threshold for identifying individuals with neuromuscular weakness who may be vulnerable to secretion retention and respiratory deterioration during infections (Bach et al., 1997; Brennan et al., 2022; Hull et al., 2012). Although several techniques significantly increased mean PCF, our study was not designed to determine how many participants crossed this threshold after each intervention. Future studies should therefore include threshold-crossing analyses, reporting the proportion of patients who move from an at-risk PCF range to values ≥270 L/min, as this may provide a more clinically interpretable estimate of cough augmentation effectiveness (Brennan et al., 2022; Hull et al., 2012).

The main finding of the study was the significant increase in PCF following the application of assisted techniques, including MAC, AS, NIV-30, and MI-E. Chatwin et al. reported that MI-E produced the greatest increase in PCF among standard techniques in cohorts including children with NMD, with similar acceptability. In our sample, the comparable performance between NIV-30 and MI-E may relate to the ability of higher IPAP to achieve effective lung volume recruitment and expiratory flow when maneuvers are supervised and titrated, underscoring that technique performance is sensitive to settings, interface, and patient-specific mechanics (Chatwin et al., 2003, p. 2). These results corroborate previous studies demonstrating the benefit of AS and MAC in increasing lung volume and cough effectiveness in patients with muscular dystrophies (Bach et al., 2007; Brito et al., 2009; Toussaint et al., 2016).

The absence of statistically significant differences between NIV-30 and MI-E suggests that optimized NIV may represent a pragmatic alternative for short-term cough augmentation when MI-E is unavailable, rather than evidence of superiority or cost-effectiveness (Graustein et al., 2023; Khan et al., 2023). Additionally, AS combined with compression was as effective as MI-E combined with compression, highlighting the importance of recruiting maximal lung volumes to generate adequate cough flows. These findings support the physiological rationale for using assisted cough techniques to improve cough flows and lung volume recruitment, which are clinically relevant mechanisms for airway clearance in patients with NMD (Cesareo et al., 2018; Fauroux, Khirani et al., 2020b). Importantly, pediatric physiologic data indicate that MI-E is generally well tolerated in stable children with NMD and can improve cough-related flows and comfort while maintaining stable oxygenation (Fauroux et al., 2008). The substantial VC gains observed after AS, NIV-30, and MI-E further emphasize the potential of lung volume recruitment strategies to improve inspiratory capacity for cough generation. However, because MAC was delivered by trained physiotherapists under controlled conditions, these gains may not be fully replicated when MAC is performed by caregivers in routine home care. Effective caregiver-delivered MAC requires adequate training and coordination with the patient's inspiratory and expiratory efforts.

The use of an oronasal mask may better reflect real-world NIV- and MI-E-assisted cough delivery in patients receiving home ventilatory support and may facilitate testing in individuals with limited lip sealing. However, mask-based measurements can be affected by interface fit and leaks, and may limit comparability with previous studies that mainly used mouthpieces. Thus, our findings should be interpreted as mask-based physiological responses rather than as directly interchangeable with mouthpiece-derived PCF values (Brennan et al., 2022).

Beyond the significant increase in PCF, assisted techniques also demonstrated a positive impact on VC, improving pulmonary function in patients with NMD. Clinically, the most relevant finding is that lung-volume recruitment strategies produced substantial VC gains relative to baseline, consistent with improved inspiratory capacity for cough generation. These VC improvements were accompanied by large standardized effects, supporting that the observed changes are likely meaningful for airway clearance. These results are consistent with previous findings indicating that maximal lung volume recruitment may contribute to improved pulmonary mechanics and airway clearance capacity (Bach et al., 2007; Brito et al., 2009; Toussaint et al., 2016).

AS produced a greater VC increase than NIV at baseline pressures, suggesting that simpler, less costly techniques may be effective in maintaining or improving pulmonary function over time. Pediatric studies of breath stacking/lung volume recruitment demonstrate that stacking can increase breath volumes substantially above tidal breathing and may be feasible even in children with limited cooperation, supporting its role as a lower-cost strategy to recruit lung volume (Jenkins et al., 2014). This supports the potential clinical value of early cough-augmentation strategies, although their impact on disease progression or long-term respiratory outcomes requires longitudinal evaluation (Graustein et al., 2023; Khan et al., 2023).

This study has some limitations. The relatively small sample size reflects the challenges of recruiting participants with rare NMD and the strict inclusion criteria required to exclude patients during clinical exacerbations. Despite achieving the planned sample size (n = 24), this remains a modest cohort for subgroup analyses by disease type, such as DMD, SMA, Ullrich muscular dystrophy, or other myopathies, and the findings should be interpreted as preliminary and hypothesis-generating. In addition, the study population was restricted to clinically stable adolescents and young adults receiving long-term home NIV, which may limit the generalizability of these findings to younger children, adults, or patients with more advanced respiratory instability. In contrast, GPB showed a small effect on VC and non-significant changes in PCF, and these estimates should be interpreted cautiously due to limited precision and the potential influence of individual technique execution; therefore, the effectiveness of GPB as a stand-alone strategy warrants confirmation in larger cohorts. All participants were familiar with the evaluated techniques, and rest periods were allowed until the Borg score returned to baseline; however, residual carryover effects cannot be completely excluded. Moreover, MAC was delivered by trained physiotherapists under controlled conditions, and its effectiveness may differ when performed by caregivers in routine home practice. Because this was a single-visit physiological study, the observed immediate increases in PCF and VC cannot be interpreted as evidence of reduced long-term clinical outcomes, such as pneumonia, respiratory exacerbations, or hospitalizations. Further longitudinal studies are warranted to determine whether these short-term physiological improvements translate into clinically meaningful benefits. In addition, PCF was measured with a portable peak flow meter, which—although feasible and widely used in home assessments—may present greater measurement variability than laboratory pneumotachography; therefore, PCF estimates and between-condition differences should be interpreted with this limitation in mind. Finally, PCF was primarily analyzed using an oronasal mask interface to minimize leaks and reflect real-world assisted cough delivery; however, this choice may limit comparability with studies using a mouthpiece-based approach.

Conclusion

This study shows that assisted cough strategies such as AS, NIV at higher inspiratory pressure (NIV-30), and MI-E meaningfully improve cough effectiveness and lung volumes in adolescents and young adults with NMD, whereas GPB alone provides limited benefit. Importantly, adding MAC consistently amplifies the response across techniques, including GPB, supporting its role as a key adjunct to achieve clinically adequate cough flows in this population. These findings indicate that simpler and more widely available approaches—particularly AS and NIV-30—can deliver comparable functional gains to MI-E when appropriately implemented. Overall, combining lung volume recruitment with MAC may be considered an important component of individualized cough augmentation strategies. At the same time, individualized selection based on patient tolerance, feasibility, and local resources remains essential for optimal respiratory care.

Footnotes

Acknowledgments

The authors thank all participants and their families for their collaboration in this study.

Ethical Considerations

The study was approved by the Ethics Committee of the Faculty of Medicine, Universidad de Chile (Project No. 235-2016, Acta No. 171).

Consent to Participate

Written informed consent to participate was obtained from all participants or their legal guardians before enrollment.

Author Contributions

Roberto Vera Uribe: Conceptualization, methodology, investigation, project administration, writing – review and editing.

Edna Karla Ferreira Laurentino: Formal analysis, writing – original draft, writing – review and editing.

Rodrigo Torres-Castro: Conceptualization, methodology, investigation, project administration, writing – review and editing.

Luis Vasconcello-Castillo: Methodology, investigation, data curation, writing – review and editing.

Marisol Barros-Poblete: Methodology, investigation, writing – review and editing.

Matías Otto-Yáñez: Conceptualization, methodology, investigation, project administration, writing – review and editing.

Javiera Rosales-Fuentes: Methodology, investigation, writing – review and editing.

Jaime Ahumada: Methodology, investigation, writing – review and editing.

Rebeca Paiva Reinero: Methodology, investigation, writing – review and editing.

Guilherme Augusto de Freitas Fregonezi: Formal analysis, writing – original draft, writing – review and editing.

Jordi Vilaró: Conceptualization, writing – original draft, writing – review and editing.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to ethical and confidentiality restrictions.

ORCID iDs

Roberto Vera-Uribe

Rodrigo Torres-Castro

Luis Vasconcello-Castillo

Marisol Barros-Poblete

Matías Otto-Yáñez

Guilherme Augusto De Freitas Fregonezi

Jordi Vilaró

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