Outcomes and measures in studies of techniques to promote secretion clearance in individuals with neuromuscular conditions: a scoping review

Abstract

Background

Techniques to support secretion clearance for individuals with neuromuscular conditions and respiratory muscle weakness include mechanical insufflation–exsufflation and chest wall vibrations. Assessing the comparative efficacy of these techniques is challenging due to the absence of a core outcome set. We sought to describe outcomes and measurement instruments reported in studies of airway clearance techniques for individuals with neuromuscular conditions living in the community.

Methods

We conducted a scoping review of primary research studies. We searched six databases from inception to 22 February 2024. Two reviewers independently screened citations against the inclusion criteria and extracted data on outcomes and measurement characteristics. Outcomes were categorised according to the Core Outcome Measures in Effectiveness Trials (COMET) 38-domain taxonomy.

Results

We identified 75 eligible studies describing 55 outcomes. We grouped outcomes deemed overlapping and categorised them using the COMET 38-domain taxonomy, resulting in 34 distinct outcomes. Common physiological/clinical outcomes were cough strength (n=48 studies, 64%), lung volume (n=48, 64%) and insufflation capacity (n=22, 29%). The most common measurement tools for these outcomes were spirometer (n=38, 51%), peak flow meter (n=24, 32%) and pneumotachograph (n=20, 27%). The most common resource-use outcome was hospitalisation due to respiratory illness (n=13, 17%). Few studies reported on life impact outcomes, with the most common being comfort (n=6, 8%) and patient satisfaction (n=4, 5%).

Conclusion

We identified 34 outcomes from 75 studies, which were most commonly physiological/clinical, with resource-use and life impact outcomes being seldom reported. The number and range of outcomes and measures demonstrates the need for a core outcome set.

Shareable abstract

There is a wide range of outcomes and measures used in studies of interventions to promote secretion clearance in individuals with neuromuscular conditions, demonstrating the need to develop a core outcome set to allow better integration of trial results. https://bit.ly/40DrXCU

Introduction

Individuals with neuromuscular disorders often develop respiratory muscle weakness, involving both the inspiratory and expiratory muscles [1]. These neuromuscular disorders include congenital diseases such as the muscular dystrophies, and acquired diseases such as multiple sclerosis and amyotrophic lateral sclerosis. Cervical spinal cord injuries can also result in respiratory muscle weakness, due to interruption of the descending bulbospinal respiratory pathways [2]. In addition to respiratory muscle weakness, certain neuromuscular conditions can also lead to bulbar-innervated muscle dysfunction [3, 4]. The combination of respiratory and bulbar muscle weakness can lead to impaired secretion clearance [5] as these muscles are used to generate an effective cough [6]. Impaired secretion clearance can result in an increased risk of lower respiratory tract infections. This is significant because respiratory infection remains a common cause of death in individuals with neuromuscular disorders [7, 8].

To reduce the risk of respiratory infection, community-dwelling individuals with neuromuscular disorders are supported with interventions to augment secretion clearance. Methods used can be categorised into proximal (“cough augmentation”) or distal (“sputum mobilisation”) techniques [9]. Proximal techniques include assisted inspiration (e.g. air stacking, glossopharyngeal breathing, lung volume recruitment), assisted expiration (e.g. manually assisted cough) and assisted inspiration and expiration (e.g. mechanical insufflation–exsufflation) [9]. Distal techniques include high frequency chest wall oscillation or compression, and manual techniques (e.g. chest percussion and expiratory vibration) [9].

Secretion clearance used for individuals with a neuromuscular disorder varies in terms of type of technique, application of technique and equipment availability [10–12]. A frequently cited reason for this practice variation is the lack of evidence for the efficacy of these techniques [9, 13]. Furthermore, assessing the comparative efficacy of secretion clearance techniques is challenging due to the lack of consensus on which study outcomes to measure and which measurement instruments to use when designing a clinical trial. A key stakeholder-informed core outcome set (COS) would assist with homogeneity in the selection of trial outcomes in the future. A COS is an agreed set of outcomes which should be measured and reported in all trials undertaking an investigation into a particular area [14]. This set is agreed upon via item generation and consensus building activities using an expert panel including individuals living with the disease, caregivers and family members.

As the first step to informing a COS for interventional studies of airway clearance techniques for individuals with neuromuscular disease living in the community, our primary objective was to conduct a scoping review to identify outcomes reported in studies recruiting these individuals. Our secondary objective was to characterise the instruments used to measure the outcomes identified.

Methods

We conducted a preliminary search of PROSPERO, MEDLINE, the Cochrane Database of Systematic Reviews, and Joanna Briggs Institute Evidence Synthesis and did not find published or in-progress scoping reviews or systematic reviews on this topic. We searched the Core Outcome Measures in Effectiveness Trials (COMET) database and did not identify any ongoing COS relevant to this work.

We followed the scoping review methods published by Levac et al. [15], which built upon the original framework proposed by Arksey and O’Malley [16], alongside the amendments made by the Joanna Briggs Institute by Peters et al. [17]. This review was registered a priori on the Open Science Framework platform (https://doi.org/10.17605/OSF.IO/JKMG2). The COS was registered on the COMET database, (www.comet-initiative.org/Studies/Details/1987). Findings were reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) extension for Scoping Reviews (PRISMA-ScR) [18].

Inclusion criteria

We included primary research studies recruiting community-dwelling participants with a neuromuscular condition resulting in respiratory muscle weakness requiring an airway clearance technique. We included studies recruiting participants (both adult and paediatric) who were either using long-term tracheostomy ventilation, noninvasive ventilation, or self-ventilating (i.e. not using supplementary ventilation, noninvasive ventilation or long-term tracheostomy ventilation). Studies that recruited mixed populations with individuals without neuromuscular conditions were included if more than 50% of the population had neuromuscular conditions. We included studies that recruited individuals living at home or in long-term care facilities, but not those who were inpatient in hospital receiving acute medical care. Grey literature was included where appropriate.

Exclusion criteria

We excluded reviews, editorials and commentaries, as well as case reports, qualitative, and animal studies. For pragmatic reasons related to resourcing, we included only studies published in English.

Search strategy

Our search strategy (supplementary material) was informed by search strategies used in two previous Cochrane reviews on cough augmentation techniques in patients with respiratory failure [13, 19], and an initial search of MEDLINE (PubMed) and CINAHL (EBSCO). The finalised search strategy was conducted from database inception to 14 November 2024 in MEDLINE (PubMed), EMBASE, Web of Science and CINAHL (EBSCO). Each search strategy was validated by ensuring that a publication that we knew to be eligible for inclusion was identified by the search. We searched the World Health Organization International Clinical Trials Registry Platform (https://apps.who.int/trialsearch/) for ongoing or completed trials, and the Cochrane Library for systematic reviews. We screened reference lists of relevant reviews for additional studies. We searched OpenGrey for potential studies that are ongoing or had not been published via a traditional route.

Screening, data extraction and critical appraisal

Two independent reviewers (NS and CA) screened titles and abstracts against the inclusion criteria using EndNote X9 (Clarivate Analytics, PA, USA). All full texts of potentially eligible citations were retrieved and assessed by two independent reviewers (NS and CA) with a third author (LR) available for further discussion. We used a PRISMA flow diagram to present our search results [20].

Two independent reviewers (NS and CA) extracted data using a bespoke data extraction tool which was initially piloted with five studies and revised as needed. Data extracted comprised study characteristics (including country of study, clinical conditions, year of publication, types of participants and study design), a description of the intervention and comparator group (if applicable), outcomes verbatim as described and measurement instruments. We categorised outcomes using the COMET 38-domain taxonomy [21]. We summarised study characteristics, interventions, outcomes and measures reported in studies using descriptive statistics. Two authors (NS and CA) independently applied the Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT) criteria [22] to assess the quality of outcome reporting. This tool assesses how well primary and secondary outcomes have been identified and explained. Although it is not a validated assessment tool for outcome reporting, it has been used previously to assess the quality of describing and reporting outcomes in systematic and scoping reviews of the literature [23–30], and in the development of COS [31, 32]. The six questions (each scored as one point) include: 1) Was the primary outcome stated?; 2) Was the primary outcome clearly defined so that another researcher would be able to reproduce its measurement?; 3) Were the secondary outcomes clearly stated?; 4) Were the secondary outcomes clearly defined?; 5) Do the authors explain the choice of outcomes they have selected?; and 6) Were methods used to enhance quality of outcome measurement, if appropriate? This scoring system ranges from 0–6, with a score of ≥4 representing high-quality outcome reporting [22]. This assessment will facilitate an exploration of the relationship between reporting quality and the nature of the outcomes reported. Reporting on the quality of outcome identified will provide support behind which of these outcomes should be taken forward into COS development.

Results

We screened 8514 citations and included 75 studies meeting our inclusion criteria (figure 1). Of these, 42 (56%) recruited only adult participants, 5 (7%) only paediatric participants and 28 (37%) a mixed population. The age range included in the studies that included paediatric participants was 11 months to 15 years. Congenital muscular dystrophy was the most commonly included clinical condition (n=48, 64%). Most studies were conducted in Europe (n=31, 41%) or North America (n=25, 33%) between the years of 2010 to 2019 (n=33, 44%) (table 1). The most common study designs were cohort studies (n=44, 59%) with 13 (17%) randomised controlled trials.

FIGURE 1.

Flow diagram displaying literature search process and identification of studies included in this review.

TABLE 1.

Characteristics of included studies

Country	Europe	31 (41)
	North America	25 (33)
	Asia	11 (15)
	Australasia	5 (7)
	South America	3 (4)
Clinical condition	Congenital muscular dystrophy	48 (64)
	Spinal muscular atrophy	29 (39)
	Motor neurone disease	27 (36)
	Spinal cord injury	16 (21)
	Myotonic dystrophy	12 (16)
	Polio/poliomyelitis	11 (15)
	Glycogen storage disease/metabolic disease	11 (15)
	Peripheral system disorder	10 (13)
	Cerebral palsy	7 (9)
	Myasthenia gravis	6 (8)
	Multiple sclerosis	5 (7)
	Inflammatory myopathy	2 (3)
	Other#	12 (16)
Publication	Before 1980	1 (1)
	1980–1989	1 (1)
	1990–1999	3 (4)
	2000–2009	27 (36)
	2010–2019	33 (44)
	2020–present	10 (13)
Participants	Adults	42 (56)
	Paediatrics	5 (7)
	Mixed	28 (37)
Study design	Cohort	44 (59)
	Randomised controlled trial	13 (17)
	Randomised crossover trial	11 (15)
	Before/after	4 (5)
	Case–control	2 (3)
	Nonrandomised controlled trial	1 (1)

Data are presented as n (%) out of a total of 75 studies. Proportions do not always sum to 100% as individuals with multiple conditions were included in some studies. ^#: including Friedreich's ataxia, lissencephaly, Parkinson's disease, spinocerebellar degeneration, traumatic brain injury, static encephalopathy, cerebrovascular accident, spina bifida, familial dysautonomia, Lafora disease, osteogenesis imperfecta and chromosome 1 deletion.

The most commonly evaluated airway clearance techniques were breath stacking (including use of a lung volume recruitment bag) (n=34, 45%), manually assisted cough (n=30, 40%) and mechanical insufflation–exsufflation (n=25, 33%) (table 2). The treatment intervention was most frequently administered by clinicians, which included physiotherapists, respiratory therapists, physicians, nurses and technicians (n=25, 33%) followed by family members/carers (n=15, 20%).

TABLE 2.

Summary of interventions investigated in the studies included in this review

Secretion clearance techniques	Breath stacking/air stacking, lung volume recruitment	34 (45)
	Manual assisted cough	30 (40)
	Mechanical insufflation–exsufflation	25 (33)
	High-frequency chest wall compression/high-frequency chest wall oscillation	8 (11)
	Glossopharyngeal breathing	5 (7)
	Manual insufflation	5 (7)
	Positioning/postural drainage	5 (7)
	Intermittent positive pressure breathing	4 (5)
	External glottic device	3 (4)
	Intrapulmonary percussive ventilation	3 (4)
	Exsufflation only	2 (3)
	Functional electrical stimulation	2 (3)
	Inspiratory muscle training	1 (1)
	Positive expiratory pressure/bubble positive expiratory pressure	1 (1)
	Other#	7 (9)
Individual administering intervention	Clinician (physician, physiotherapist, respiratory therapist, nurse, technician)	25 (33)
	Family member/carer	15 (20)
	Patient	11 (15)
	Not reported	33 (44)

Data are presented as n (%) out of a total of 75 studies. Proportions do not always sum to 100% as multiple interventions were used in some studies and multiple individuals administered the intervention. ^#: includes incentive spirometry, proprioceptive neuromuscular facilitation, continuous positive airways pressure, noninvasive ventilation, expiratory flow accelerator, forced expiration technique and breathing exercises.

Outcomes

Data extraction identified 55 outcomes. Following iterative discussion, three authors (NMS, CA and LR) deemed 21 to be overlapping or similar (e.g. vital capacity and forced vital capacity). This resulted in 34 distinct outcomes in seven domains of the 38-domain COMET taxonomy (table 3). At least one physiological/clinical outcome was included in 69 (92%) studies. Outcomes in the life impact core domain were reported in 15 (20%) studies; outcomes in the resource-use domain were reported in 16 (21%) studies.

TABLE 3.

Outcomes reported in studies included in this scoping review. Outcomes are classified according to the 38-domain COMET taxonomy

Core area	Outcome domain	Outcome	n (%)
Death	Mortality/survival	Survival	4 (5)
Physiological/clinical	Physiological/clinical	Cough strength (e.g. peak cough flow)	48 (64)
		Lung volume (e.g. vital capacity, forced vital capacity, forced expiratory volume, expiratory reserve volume)	48 (64)
		Insufflation capacity (e.g. maximum insufflation capacity, lung insufflation capacity)	22 (29)
		Respiratory muscle strength (e.g. maximal inspiratory pressure, maximal expiratory pressure, sniff nasal inspiratory pressure)	16 (21)
		Oxygen levels (e.g. saturation of peripheral oxygen)	15 (20)
		Air flow (e.g. peak expiratory flow, forced expiratory flow)	13 (17)
		Respiratory rate	8 (11)
		Carbon dioxide levels	6 (8)
		Lung expansion/compliance	5 (7)
		Heart rate	5 (7)
		Airway pressure (e.g. peak inspiratory pressure, peak expiratory pressure, transpulmonary pressure)	3 (4)
		Cough volume	2 (3)
		Mean arterial pressure	2 (3)
		Airway resistance	2 (3)
		Other#	14 (19)
Life impact	Global quality of life	Quality of life	3 (4)
	Functioning	Breathlessness	3 (4)
		Impact on functional ability	3 (4)
		Job/school absence	2 (3)
		Fatigue	1 (1)
	Delivery of care	Comfort	6 (8)
		Patient satisfaction	4 (5)
		Adherence to secretion clearance techniques	3 (4)
		Patient-reported cough strength	2 (3)
		Impact of delivering secretion clearance technique on caregiver	2 (3)
		Patient-reported effectiveness of secretion clearance	1 (1)
		Side effects of treatment	1 (1)
Resource use	Resource use	Admissions to hospital due to respiratory illness	13 (17)
		Respiratory illnesses	8 (11)
		Supplementary secretion clearance treatments	4 (5)
		Use/duration of antibiotics	4 (5)
		Amount of medication for secretion clearance in a treatment session	1 (1)
		Doctor visits	1 (1)
Adverse events	Adverse events/effects	Adverse events	3 (4)

Data are presented as n (%) out of a total of 75 studies. COMET: Core Outcome Measures in Effectiveness Trials [21]. Proportions do not always sum to 100% as multiple outcomes were used in some studies. ^#: including airway collapsibility, sputum weight, effective cough time, effective suctioning, rapid shallow breathing index, inspiratory/expiratory time, lung aeration, need for tracheostomy, invasive ventilation/noninvasive ventilation time, deposition of inhaled particles, ventilator-free breathing ability, pulmonary perfusion, seizures and sleep efficiency/sleep disordered breathing.

Physiological/clinical outcomes

Of the 16 physiological/clinical outcomes, cough strength (e.g. peak cough flow) (n=48 studies, 64%) [33–80] and lung volume (e.g. forced vital capacity, forced expiratory volume and expiratory reserve volume) (n=48, 64%) [33–37, 40, 42, 43, 46–48, 51, 52, 54–60, 66–73, 75, 77–95] were the most frequently reported outcomes. Other commonly reported outcomes were insufflation capacity (e.g. maximum insufflation capacity, lung inflation capacity) (n=22, 29%) [34, 35, 42, 45, 46, 52, 54–59, 63, 66, 67, 71, 73, 76, 77, 79, 87], respiratory muscle strength testing (n=16, 21%) [33, 43, 47, 51, 57–59, 68, 71, 72, 77–79, 90, 93, 96], oxygen levels (n=15, 20%) [47, 51, 64, 80, 82, 84–86, 88–90, 97–100] and air flow (e.g. peak expiratory flow (n=13, 17%)) [37, 47, 60, 66, 67, 80, 81, 83, 84, 88, 89, 95, 99].

Life impact outcomes

Six studies (8%) reported on the outcome of patient comfort [41, 45, 47, 63, 74, 101]; four (5%) reported on patient satisfaction [51, 52, 70, 89] and three (4%) reported on health-related quality of life [52, 69, 77, 89]. Breathlessness [80, 89, 90] and impact on functional ability [51, 77, 89] were each reported by three studies (4%).

Resource-use outcomes

13 studies (17%) reported on the number of hospital admissions due to respiratory illness [51, 69, 71, 77, 82, 84, 93, 100, 102–106] and eight studies (11%) reported on frequency of respiratory illnesses [51, 71, 77, 82, 84, 102, 105, 106].

Other resource-use outcomes included number of supplementary secretion clearance techniques (n=4, 5%) [71, 93, 101, 106] and use/duration of antibiotics (n=4, 5%) [77, 84, 93, 100].

Quality assessment

Of the 75 studies, we scored 51 (68%) as ≥4 on the MOMENT criteria indicating high-quality outcome reporting (table 4).

TABLE 4.

The quality of outcome reporting in each study included in this scoping review, assessed according to the MOMENT criteria

Is the primary outcome clearly stated?	46 (61)
Is the primary outcome clearly defined so that another researcher would be able to reproduce the measurement?	46 (61)
Are the secondary outcomes clearly stated?	64 (85)
Are the secondary outcomes clearly defined?	64 (85)
Do the authors explain the use of the outcomes they have selected?	36 (48)
Are methods used to enhance the quality of outcome measurement (e.g. repeated measurements, training) used if appropriate?	46 (61)

Data are presented as n (%) out of a total of 75 studies. MOMENT: Management of Otitis Media with Effusion in Children with Cleft Palate [22]. If the outcomes were stated and defined as a whole, but we were unable to determine the primary outcome, we included these data as part of secondary outcomes.

Measurement

Of the most common physiological/clinical outcomes, cough strength was measured using a peak flow meter in 22 (46%) studies [33–39, 43, 44, 46, 49, 50, 53–58, 60, 65, 69, 80], pneumotachograph in 15 (31%) studies [41, 45, 47, 63, 64, 66, 68, 70–72, 74–77, 79] and spirometer in 14 (29%) studies [40, 41, 48, 52, 59, 60, 62, 66–68, 70–72, 78]. Lung volume was measured using a spirometer in 32 (67%) studies [33–37, 40, 43, 46, 48, 52, 54–57, 59, 60, 66, 69, 71, 72, 78, 81, 83, 84, 87, 88, 90, 91, 93–95, 107] or a pneumotachograph in 10 (21%) studies [47, 66, 68, 70, 75, 77, 79, 86, 90, 91]. In the other outcome domains, patient comfort was measured by a visual analogue scale in five (83%) studies [41, 45, 47, 63, 74]; and the Visual Numeric Scale in one (17%) study [101]. Health-related quality of life was measured by the 36-item Short Form Survey (SF-36) [108] in two (67%) studies [52, 69] (table 5).

TABLE 5.

Reporting the instruments used to measure the outcomes reported in this scoping review

Outcome domain	Outcome	Measurement instruments per outcome	n (%)
Mortality/survival	Survival	_
Physiological/clinical	Cough strength (e.g. peak cough flow)	Peak flow meter	22 (46)
		Pneumotachograph	15 (31)
		Spirometer	14 (29)
		Flow analyser	2 (4)
		Plethysmography	1 (2)
		Not reported	1 (2)
	Lung volume (e.g. vital capacity, forced vital capacity, forced expiratory volume, expiratory reserve volume)	Spirometer	32 (67)
		Pneumotachograph	10 (21)
		Plethysmography	3 (6)
		Electrical impedance tomography	3 (6)
		Flow analyser	1 (2)
		Helium dilation	1 (2)
		Not reported	3 (6)
	Insufflation capacity (e.g. maximum insufflation capacity, lung insufflation capacity)	Spirometer	14 (64)
		Pneumotachograph	5 (23)
		Plethysmography	2 (9)
		Flow analyser	1 (5)
		Helium dilation	1 (5)
		Calculation from ventilator	1 (5)
	Oxygen levels (e.g. saturation of peripheral oxygen)	Transcutaneous monitor	13 (87)
		Plethysmography	1 (7)
		Polysomnography	1 (7)
	Air flow (e.g. peak expiratory flow, forced expiratory flow)	Spirometer	8 (62)
		Pneumotachograph	3 (23)
		Peak flow meter	2 (15)
		Plethysmography	1 (8)
	Respiratory muscle strength (e.g. maximal inspiratory pressure, maximal expiratory pressure, sniff nasal inspiratory pressure)	Manometer	10 (63)
		Electrometer	2 (13)
		Not described	4 (25)
	Respiratory rate	Pneumotachograph	4 (50)
		Plethysmography	2 (25)
		Electrical impedance tomography	1 (13)
		Spirometer	1 (13)
		Transcutaneous monitor	1 (13)
	Airway pressure (e.g. peak inspiratory pressure, peak expiratory pressure, transpulmonary pressure)	Manometer	3 (100)
	Carbon dioxide levels	Transcutaneous monitor	3 (50)
		Capnography monitor	3 (50)
	Lung expansion/compliance	Pneumotachograph	2 (40)
		Manometer	2 (40)
		Spirometer	1 (20)
		Pulse method	1 (20)
		From a previous study – unable to obtain details	1 (20)
	Heart rate	Transcutaneous monitor	2 (40)
		Photoplethysmography	1 (20)
		Electrocardiogram	1 (20)
		Not reported	1 (20)
	Cough volume	Spirometer	2 (100)
		Pneumotachograph	1 (50)
	Mean arterial pressure	Photoplethysmography	2 (100)
	Airway resistance	Oscilloresistometry	1 (50)
		Plethysmography	1 (50)
	Airway collapsibility	Spirometer	1 (100)
	Sputum weight	Balance	1 (100)
Global quality of life	Quality of life	36-Item Short Form Survey	2 (67)
		Sickness impact profile	1 (33)
		Assessment of quality of life 8-dimension	1 (33)
		Severe respiratory insufficiency questionnaire	1 (33)
		Sleep apnoea quality of life index	1 (33)
Functioning	Breathlessness	Borg scale	2 (67)
		Baseline dyspnoea Index/transitional dyspnoea index	1 (33)
	Impact on functional ability	Amyotrophic lateral sclerosis functional rating scale - revised	2 (67)
		Amyotrophic lateral sclerosis assessment questionnaire 5	1 (33)
	Fatigue	Fatigue severity scale	1 (100)
Delivery of care	Comfort	Visual analogue scale	5 (83)
		Visual numeric scale	1 (17)
	Patient satisfaction	Questionnaire/survey	3 (75)
		Visual analogue scale	1 (25)
	Patient-reported cough strength	Visual analogue scale	2 (100)
	Patient-reported effectiveness of secretion clearance	Visual analogue scale	1 (100)
	Impact of delivering secretion clearance technique on caregiver	Caregiver strain index	1 (50)
		Purposely designed survey	1 (50)
	Adherence to secretion clearance techniques	Diary	2 (67)
		Caregivers therapy adherence questionnaire	1 (33)
		Lung volume recruitment counter	1 (33)

Data are presented as n (%). Proportions do not always sum to 100% as multiple instruments were used in some studies to measure the same outcome and some studies do not report which measurement instruments were utilised. The denominators for the calculation are the number of studies who reported using the outcome.

Discussion

From this scoping review we identified 75 studies recruiting community-dwelling participants with a neuromuscular condition who received an airway clearance technique, with 34 distinct outcomes. When grouped according to the COMET 38-domain taxonomy, most studies included at least one physiological/clinical outcome. Few studies included life impact outcomes such as health-related quality of life, or outcomes concerning resource use such as hospital admission. There were no differences in outcomes selected in studies that recruited adult only, mixed adult and paediatric populations, and paediatric-only populations. However, no studies with a paediatric-only population included life impact outcomes.

The heterogeneous use of outcomes and their measurement included by studies identified in our scoping review indicates a lack of consensus on outcomes to include in research studies in this patient group. To help patients and clinicians make robust evidence-based decisions about secretion clearance management, clinical trial data must be collected in a manner to facilitate synthesis between multiple studies. This is of particular importance for neuromuscular diseases, because they tend to be rare, with patients living across vast geographical locations, so large high-powered randomised studies can be difficult to deliver [109].

Life impact outcomes can be considered synonymous with patient-reported outcomes (PROs). The importance of PROs is growing within health research and has become more widely recognised in recent years [110, 111]. PROs provide valuable insight into the impact of a medical condition and associated treatment on an individual and are a way of ensuring patient-centred care [112–114]. The inclusion of PROs in health research helps to ensure a more holistic view of a condition or treatment is achieved [111]. Secretion clearance interventions can be invasive and/or uncomfortable [9]. Moreover, there is insufficient evidence demonstrating the superiority of one technique over another [115, 116]. Therefore, including PROs is particularly important in this area of research. The data presented here demonstrate that life impact outcomes were only included in a small number of studies, none of which were solely in the paediatric population. The low inclusion of PROs is consistent with the wider literature. A review of all clinical trials registered on ClinicalTrials.gov between 2007 and 2013 revealed that only 27% included PROs. Of respiratory trials, 12% included PROs [117]. Another review of phase IV trials registered on ClinicalTrials.gov between 1999 and 2021 reported that 21% of studies included PROs [118]. Reasons provided for the poor uptake of PROs in study design included a lack of relevant PROs or PRO measures for specific disease groups, lack of consensus about the optimal PROs and how they should be measured, and the additional resources required to collect them. In addition, specifically in phase IV trials, it was also suggested that collecting PROs in the real-world context may be particularly difficult [118]. Most of the studies included in this scoping review were cohort studies. There may have been similar challenges incorporating PROs into these studies. The lack of PROs in paediatric studies may be in part due to the age of some participants who were too young to engage with these outcomes [119]. It is worth noting that we did not identify any studies focusing on caregivers’ perspectives on secretion clearance. In the community setting, individuals who require secretion clearance interventions often need support from a parent or caregiver. It would therefore be important to include their perspective on the efficacy of secretion clearance in future studies.

In the few studies that did identify PROs, patient comfort and satisfaction were reported the most frequently. None of the outcome measures used to assess these outcomes was validated, highlighting a need to develop validated tools to be able to assess PROs in the field of neuromuscular respiratory failure. This may facilitate an increase in the inclusion of PROs in future studies in this field. Health-related quality of life, breathlessness, impact on functional ability and patient-reported effectiveness were seldom reported. Perception of treatment techniques can in turn influence adherence, and subsequent treatment effectiveness [120]. Adherence rates to some airway clearance techniques have been found to be poor in the literature [59, 121–123]; thus, patient preference is an important factor to consider [115]. It should be noted that all the studies that included PROs were undertaken between 2003 and 2023. This may potentially indicate the changing landscape of outcome reporting and the move toward involvement of patients in health and research [111]. PROs are becoming increasingly more common in COS, with 73% of COS published to 2021, including life impact outcomes [124]. However, patient participation in the COS was a key factor in the inclusion of PROs. Only 62% of COS included a PRO when patients were not stakeholders in the COS process, compared with 86% when patients were participants [124]. The literature demonstrates that patients’ perspectives on outcomes often differ to that of clinicians’ [124, 125]. Patients focus on outcomes pertaining to the impact of a condition or treatment on their life, including functional ability and treatment burden, whereas clinicians focus on physiological outcomes or mortality [124, 126]. Patient involvement in COS is imperative to ensure outcomes of importance to patients remain central to the research process [124].

We also identified few studies including outcomes pertaining to healthcare utilisation and resource use. Studies designed to investigate these outcomes tend to be longitudinal, requiring more resources over a longer period of time than laboratory-based studies. As neuromuscular conditions tend to be rare, there may have been difficulties designing longitudinal studies with sufficient statistical power, within the resources available to researchers. Healthcare utilisation, such as hospital admission, can have significant consequences. These consequences include important cost implications and profound effects on health-related quality of life and patient satisfaction [127]. With healthcare needs often surpassing available resources [128] and competition for funding a feature in several healthcare systems [129–131], incorporating healthcare utilisation outcomes may be an important consideration for future research.

This scoping review adds to our understanding about the broad range of outcomes and outcome measures employed in this patient group and emphasises the need to harmonise objectives and data collection techniques among clinical studies. It will therefore be a useful contribution to the item generation phase of a future COS focused on studies investigating secretion clearance interventions being used in the community.

Strengths and limitations

Our review has several strengths. These include a rigorous search design based on previous Cochrane reviews, searching multiple databases, not limiting publication dates and having two independent authors screen citations. Additionally, we utilised the PRISMA-ScR reporting format. Outcomes were classified according to the 38-domain COMET taxonomy and study quality was assessed using the MOMENT criteria. A limitation of our review is the exclusion of studies published in languages other than English; this may have resulted in missed outcomes. In addition, this review has included studies that reported on individuals with a broad range of neuromuscular conditions. As different secretion clearance interventions have different degrees of effectiveness in different neuromuscular conditions, the outcomes identified in the study may not be universally applicable to all secretion clearance interventions, and all neuromuscular conditions. The COS should aim to be applicable to as wide a range of interventions and conditions as possible. It is important to note that 40% of the studies identified were published prior to 2010. The pattern of use of specific secretion clearance interventions may have changed over time, making the outcomes identified potentially less applicable to current practice. Nevertheless, it was important to identify all potential outcomes for inclusion in the COS, so that the COS development methodology can consider all of the available evidence and include the most appropriate outcomes [14].

Conclusions

In this scoping review we confirmed the heterogeneity of outcome selection and measurement in research on interventions to promote airway clearance in individuals with neuromuscular disease living in the community. Use of physiological and clinical outcomes in studies was more common, with few studies including outcomes relating to life impact and resource use. This outcome heterogeneity confirms the need for a COS to be developed with patients, relatives and healthcare professionals to ensure outcomes are clinically relevant and meaningful to all stakeholder groups.