Description of the condition

There are many types of neuromuscular disorder (NMD), both acute and chronic, hereditary and acquired (Gozal 2000). The five major groups into which hereditary NMD can be classified are: muscular dystrophies, congenital and metabolic myopathies, neuromuscular junction disorders, peripheral neuropathies and anterior horn cell diseases (Gozal 2000).

People with NMD run the risk of significant morbidity and mortality from acute respiratory tract infections and chronic respiratory insufficiency as a consequence of diaphragmatic and or intercostal muscle weakness (Boitano 2006; Gozal 2000; Finder 2010; Panitch 2009). Weak cough is an important factor contributing to respiratory morbidity in patients with NMD (Boitano 2006).

Despite the heterogeneity in respiratory pathophysiology amongst the different NMDs, it is accepted that two main factors influence the progression of respiratory insufficiency ‐ respiratory muscle strength and thoracic cage abnormalities. These factors are also affected developmentally by advancing age. Infants with NMD have more cartilage in their rib cages than other infants, which results in increased chest wall compliance, more than twice that of controls (Papastamelos 1996). In addition, intercostal muscle weakness contributes to ribcage deformity, which further impacts on respiratory efficiency (Panitch 2009). Progessive pulmonary impairment, in terms of reduction in total lung capacity and forced vital capacity (FVC), occurs with progressive respiratory muscle weakness. Postural deformities, such as kyphosis, scoliosis and spinal rigidity, as well as shortening and fibrosis of the chest wall muscles due to an inability to fully expand the chest, result in a progressive decrease in chest wall compliance leading to a restrictive pattern of disease (Fauroux 2008; Gozal 2000; Panitch 2009). Microatelectasis from breathing at low lung volumes, secretion retention (Fauroux 2008), and the loss of sigh capacity (Bach 2000) cause further loss of lung compliance (Panitch 2009; Sharma 2009). Although total lung volumes are decreased in NMD, residual volume may be preserved or even increased as a result of preferential expiratory muscle weakness (Gozal 2000).

An effective cough is essential for the clearance of pulmonary secretions, during both respiratory infections and stable periods. Components of the cough which may be missing in people with NMD include an inability to take a deep inspiration to up to 80% of the vital capacity, failure to close the glottis in certain conditions (Bach 2003), and insufficient expiratory flow rates (Finder 2010). In addition to an impaired cough, other causes of impaired secretion clearance include the presence of infection with altered sputum viscosity, difficulty swallowing (dysphagia) (Bannister 1985; Finder 2010) and gastro‐oesophageal reflux (Iannaccone 2007). 

Retention of pulmonary secretions leads to airway obstruction, increased work of breathing, hypoxia and ultimately respiratory failure. Long‐term retention of secretions may predispose to lower respiratory tract infections, atelectasis and chronic lung disease (Homnick 2007). The vast majority of episodes of respiratory failure in patients with muscular dystrophy are reported to be a result of ineffective coughing during intercurrent chest infections (Bach 2003). Identification of effective, safe measures to optimise cough efficacy is therefore key to improving the quality of life and preventing morbidity in people with NMD.

Description of the intervention

A number of physiotherapy techniques aimed at mobilising secretions and increasing lung volumes are used to assist airway clearance in people with NMD: manual techniques including postural drainage, percussion and vibrations; respiratory muscle training with inspiratory and/or expiratory resistance in early disease; techniques using different breathing patterns including active cycle of breathing technique, forced expiratory technique, and autogenic drainage; and positive pressure therapy including the use of flutter valves, positive expiratory pressure (PEP) therapy, intermittent positive pressure breathing (IPPB), and continuous positive airways pressure (CPAP) (Anderson 2005; Bott 2009; Finder 2010). Most PEP devices are effort‐dependent and therefore not useful in people with severe respiratory muscle weakness (Finder 2010).

For successful secretion clearance, one needs both secretion mobilisation and effective cough (Finder 2010). Cough augmentation may be achieved by several manual or mechanical methods (Finder 2010). When voluntary deep breathing becomes impossible, breath stacking or glossopharyngeal breathing and mechanical or manual (bagging) hyperinflation provide sufficient inspiratory lung volumes (Bott 2009). Manual chest compressions or abdominal thrusts and mechanical exsufflation achieve cough augmentation by improving expiratory flow rates (Anderson 2005; Finder 2010). Suctioning may be needed in patients unable to clear secretions, but this intervention is generally uncomfortable and poorly tolerated (Bott 2009). If an artifical airway is present, suctioning is associated with significant complications, including hypoxia, changes in blood pressure and cerebral blood flow, cardiac arrhythmia, increased intracranial pressure, mucosal trauma and atelectasis (Anderson 2005; Morrow 2008).

Mechanical insufflation‐exsufflation (MI‐E) was first described in 1952 (Barach 1952) for patients with poliomyelitis. Initially, commercially available in‐exsufflators used high negative pressures (tank devices) for insufflation followed by rapid assisted exsufflation to atmospheric pressures (Barach 1952). Following the advent of invasive positive pressure ventilation, this form of negative pressure MI‐E was discontinued but the technique regained popularity as an adjunct to non‐invasive ventilation (NIV) in the late 1980s (Bach 1996). Modern MI‐E devices such as the CoughAssist In‐Exsufflator (Respironics Corporation, PA), the Pegaso (Dimla Italia, Bologna, Italy), and the Nippy Clearway (B & D Electromedical, Warwickshire, UK), deliver a preset positive pressure for a set duration into the airways during inspiration (insufflation), immediately followed by an abrupt change to a preset negative exsufflation pressure, thus simulating a cough with high expiratory flow rates (Anderson 2005; Boitano 2009; Fauroux 2008). MI‐E can be delivered noninvasively via the nose (mask) or mouth (mouthpiece), or via tracheostomy (Boitano 2009). MI‐E has been shown to enhance peak cough flow in patients with advanced NMD, and may assist in maintaining lung volume, both of which are necessary for effective secretion clearance (Anderson 2005; Bach 1993; Chatwin 2003). A study of 11 consecutive older children and adults (age range 11 to 72 years) with NMD and acute respiratory tract infections treated with chest physiotherapy and MI‐E, compared with 16 historically matched controls who had received chest physiotherapy alone, found that treatment failure (the need for mini‐tracheostomy or intubation) was significantly less in the MI‐E group and there were no serious complications of MI‐E. Other measured outcomes, of days requiring mechanical ventilation, duration of hospital stay and number of patients requiring bronchoscopy‐assisted aspiration, were not significantly different between the groups (Vianello 2005). Significant short‐term improvements in oxygenation and dyspnoea have been reported in adults treated with 40 cmH₂O MI‐E settings, but differences were not significant when using lower pressures (Winck 2004). A small cross‐over study of eight NMD patients aged four to 44 years demonstrated that airway clearance treatment time was significantly shortened with the addition of MI‐E. Both standard intervention and MI‐E resulted in improved auscultation scores and secretion clearance but there were significantly higher levels of fatigue after MI‐E (Chatwin 2009).

MI‐E has been shown to be well tolerated and physiologically beneficial in the short term in 17 stable children (age five to 18 years) with NMD in an observational study with no control group (Fauroux 2008). Benefits of a single treatment session included improved end‐tidal expired carbon dioxide pressure, and improved peak cough flow and self‐assessed respiratory comfort (Fauroux 2008). A retrospective descriptive study of 62 children with NMD concluded that MI‐E was “mostly safe” and effective in preventing and treating pulmonary complications (Miske 2004). Four individuals demonstrated resolution of chronic atelectasis following the implementation of MI‐E and five children (eight per cent) experienced a reduction in the frequency of lower respiratory tract infections (Miske 2004). In a recent case series, 13 infants and young children with spinal muscular atrophy type 1 were followed from the time of diagnosis. Seven subjects used MI‐E at home in combination with goal‐directed NIV (Chatwin 2011).The median age at initiation of MI‐E was 13 months (range 10 to 43 months) and the typical MI‐E pressures used were +25 to ‐30 cm H₂O, increasing to +35 to ‐45 cm H₂O as clinically indicated. In these subjects, MI‐E was reported to be well tolerated and may have prevented the need for intubation and invasive ventilation (Chatwin 2011).

It has been suggested that MI‐E may be used to prevent and treat intercurrent infections in both the hospital and home settings (Hanayama 1997; Whitney 2002), in combination with NIV where indicated (Anderson 2005; Tzeng 2000). In a retrospective cohort study of children (over 10 years old) and adults, the trial authors found that participants managed with a respiratory protocol including prevention or reversal of oxyhaemoglobin desaturation by the use of noninvasive intermittent positive pressure ventilation (IPPV) and assisted coughing (manual and mechanical, including MI‐E) as needed experienced reduced rates of hospitalisation and hospital days compared to non‐protocol participants on IPPV via tracheostomy (Bach 1997). A similar retrospective cohort study of 94 adults and children demonstrated a reduction in the number of hospitalisations per year and hospital days per year in individuals using a respiratory muscle aid protocol, which included MI‐E as needed (Tzeng 2000).

How the intervention might work

The peak expiratory cough flow needed for an effective cough in adults is 2.7 L/s, with adults having normal peak cough flows of 6 to 12 L/s (Bach 1993; Bach 1995; Bach 1997; Gómez‐Merino 2002; Tzeng 2000). The value for infants and children is not known. An initial inspiration to up to 90% of maximum insufflation capacity (vital capacity >1.5 L), and sufficient thoraco‐abdominal pressure (>100 cmH₂O) is needed to achieve an effective peak cough flow (Anderson 2005). MI‐E has been shown to improve cough expiratory flow rates in adults and children with NMD (Bach 1993; Chatwin 2003; Winck 2004). Bach 1993 reported an increase in the mean peak cough flow rate from 1.81 ± 1.03 L/s unassisted to 7.47 ± 1.02 L/s in adults when using the exsufflator, whilst Winck 2004 reported an increase in mean peak cough flow from 180 L/min at baseline to 220 L/min following MI‐E of 40 cmH₂O. Change in cough flow rates using lower MI‐E pressures were not measured (Winck 2004). In a controlled study of adults and older children (over 10 years old) with NMD, MI‐E resulted in a significant increase in mean peak cough flow from 169 L/min unassisted to 235 L/min (Chatwin 2003).

It has been suggested that MI‐E may obviate the need for suctioning in people with NMD, as peak cough flow rates generated are sufficient to clear secretions (Bach 1993; Hanayama 1997).

Why it is important to do this review

MI‐E is recommended in a number of international guidelines for the management of people with NMDs (American Thoracic Society 2004; Finder 2004; Rosiere 2009; Wang 2007). Of particular concern, is that the pressures that have been recommended for all age groups reach or exceed ‐40 cmH₂O (exsufflation) to +40 cmH₂O (insufflation), with four to five sets of breaths being performed as often as needed to clear secretions (Boitano 2006; Gómez‐Merino 2002; Miske 2004; Respironics 2009; Tzeng 2000). Whilst some studies have used these pressures in adults and children for both insufflation and exsufflation (Bach 1993; Fauroux 2008; Sivasothy 2001), another study of MI‐E in older children and adults used lower, "comfortable" pressures of 15 cmH₂O (Chatwin 2003). The optimum pressures, frequency of use and insufflation‐exsufflation times are not currently known (Anderson 2005).

With any mechanical positive‐pressure device, there is a risk of complications such as abdominal distention, discomfort, gastro‐oesophageal reflux, cardiovascular effects, such as changes in blood pressure and cardiac arrhythmia, and pneumothorax (Homnick 2007). Cases of pneumothorax have been described in adult patients following use of MI‐E (Suri 2008) and long‐term non‐invasive positive pressure ventilation (Vianello 2004). Considering the differences between the paediatric and adult respiratory systems (particularly relating to high chest wall compliance in the infant), there may be a greater risk of baro‐ or volutrauma in young children with the use of such high pressures, and more so in infants with NMD where chest wall compliance is further increased relative to lung compliance. It is notable that applied volume is not measured during mechanical insufflation, and high tidal volume has been implicated in ventilator‐induced lung injury (Albuali 2007), along with repeated alveolar collapse and re‐expansion (atelectrauma) (Saharan 2010). Current lung‐protective ventilation strategies include limiting inspired tidal volumes and preventing derecruitment by loss of PEEP and/or wide swings in pressure (Saharan 2010). Use of MI‐E appears to contradict all these strategies.

Whilst MI‐E is gaining popularity amongst professionals and consumers alike, this therapy requires expensive equipment which may not be readily available, whilst other, inexpensive, readily available techniques have also been shown to be effective in improving cough flow (Anderson 2005; Finder 2010). Although assisted airway clearance is necessary in people with advanced NMD, the optimal respiratory management to clear secretions is not clear.

Specific respiratory anatomical and physiological considerations must be made according to different age groups and specific neuromuscular conditions when assessing the effects of MI‐E. Application of positive pressure will affect the lungs differently according to the prevailing pathology and physiology, including the presence of heterogenous lung disease, baseline lung volumes, and respiratory system compliance and resistance (Gattinoni 2003; Gattinoni 2010).