Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness

Subjects

The study was approved by the local ethics committee and all subjects and/or their parents gave informed consent. All patients (adults and children) had a history of recurrent chest infections and/or ineffective cough. The aim was to study subjects during a period of clinical stability; therefore, those who had required antibiotic therapy within the preceding month and those with a resting arterial oxygen saturation measured by pulse oximetry (S_p,O2) of <90% and/or end-tidal carbon dioxide tension (P_ET,CO2) of >7 kPa were excluded. Additional exclusion criteria were the presence of severe bulbar dysfunction and a previous history of pneumothorax. Age-matched controls were recruited from staff and their families.

Measurements

Sniff nasal inspiratory pressure (SNIP) 7, maximal static inspiratory (P_I,max) and expiratory (P_E,max) mouth pressure 9, and maximal whistle mouth pressure (P_mo,W) 10 were used as noninvasive indices of inspiratory and expiratory muscle strength. During recording of respiratory muscle strength, subjects were seated comfortably in front of a computer monitor, allowing visual feedback during each manoeuvre. Maximal sniff manoeuvres were performed from functional residual capacity with the subject seated comfortably without a noseclip 7. Pressures were measured at the nose via a pressure line inserted into a bung. Repeated sniffs were performed until no further increase in pressure was seen, with the highest value being recorded as the SNIP 11. P_I,max was measured during a maximal inspiratory manoeuvre from residual volume via a mouthpiece with a noseclip in situ, performed against a closed shutter 12. P_E,max was recorded using the same equipment during a maximal expiratory manoeuvre from total lung capacity (TLC). P_mo,W was measured during a maximal expiration of <500 ms from TLC through a reversed paediatric inhaler whistle (Turbohaler trainer; Astra Pharmaceuticals Ltd, Kings Langley, UK) connected to a flange mouthpiece, without a noseclip 10. Manoeuvres were repeated at least six times until three readings were within 10% of each other. The highest of these readings was recorded. All signals were measured using a differential pressure transducer (Validyne, CA, USA) and amplified. The signals passed via an analogue/digital board to a computer running Labview software (National Instruments, Austin, TX, USA). During testing, subjects received strong verbal encouragement 13. Forced expiratory volume in one second and forced vital capacity were measured using a hand-held spirometer (2120; Vitalograph Ltd, Maids Moreton, UK) 14. Resting S_p,O2 was recorded using a fingertip probe and portable pulse oximeter (NPB-40; Nellcor, Pleasanton, CA, USA). S_p,O2 was taken as the highest recorded value measured during a 3–5-min period with the subjects seated in the upright position. P_ET,CO2 was recorded while subjects breathed through a full face mask connected via a rigid catheter to a capnograph (PK Morgan, Gillingham, UK), with the baseline reading taken as the P_ET,CO2 at the end of 5 min of resting breathing.

The primary outcome measures of PCF and patient comfort were evaluated during each test procedure. PCF was measured by coughing into a tight-fitting full face mask (Mirage Full-face mask; Resmed, Abingdon, UK) connected via plastic tubing to a metal tube (41 cm long; 3.5 cm internal diameter). The tube was connected to a Fleisch No. 4 pneumotachograph head (Fleisch, Lausanne, Switzerland) and an electrospirometer (GM Instruments, Kilwinning, UK). The pneumotachograph head was connected via ventilator tubing to a mechanical insufflator/exsufflator (“Cough-Assist”; JH Emerson Co., Cambridge, MA, USA). Mask pressure was measured from a side port. A technician secured the mask on to the subject's face to minimise air leak.

The comfort of and distress caused by the intervention together with perceived strength of cough were evaluated using a Visual Analogue Scale (VAS) 15. Following each intervention, the subjects rated comfort of intervention, distress and strength of cough produced (0: least; 10: most).

Cough interventions

All subjects were studied in their preferred position, usually seated. Initial assessment consisted of at least six maximal unaided coughs followed in random order by the cough intervention techniques; at least six maximal efforts were made during each intervention, with rest periods between them. The cough intervention techniques were: standard physiotherapy-assisted cough 4; cough after inspiration supported by a noninvasive positive pressure ventilator (BiPAP (bilevel positive airway pressure) from Respironics, Inc., Murrysville, PA, USA, or PV401 from Breas Medical, Moinlycke, Sweden) 17; exsufflation-assisted cough with delivery of negative pressure initiated manually at the end of inspiration; insufflation (given manually during inspiratory phase); and exsufflation-assisted cough with delivery of the negative pressure immediately preceding the cough effort. Use of pressure-limited or preset ventilators meant that patients were unable to “breath stack”, with multiple inspirations prior to coughing, as would be possible with volume preset ventilators. Both insufflatory and exsufflatory pressures were titrated to patient comfort.

Statistical analysis

All values are expressed as mean±sd unless stated otherwise. A p‐value of ≤0.05 was considered significant. Differences in PCF from baseline using different cough-enhancing techniques were analysed using analysis of variance with analysis of significant differences using Tukey's multiple comparison test. Differences in respiratory muscle strength between patient and control groups were compared using a Mann-Whitney U‐test as the data were not normally distributed. Spearman's rank correlation coefficient was used to examine the relationship between PCF and inspiratory and expiratory respiratory muscle strength.

Limitations of the study

The patient group was highly selected in that it showed evidence of extreme muscle weakness, to the extent that the majority (77%) of the group used domiciliary NIPPV. Thus, the present data cannot be used to support the use of mechanical insufflation/exsufflation in patients with less advanced disease. However, the observation that mechanical insufflation/exsufflation confers an advantage over NIPPV-assisted or physiotherapy-assisted cough is particularly impressive given that the majority of the present patients were experienced ventilator users. In addition, patients with severe bulbar dysfunction were excluded, primarily because of the difficulty in interpreting reduced PCF in this group.

The patients were clinically stable and different results might be obtained in patients who are acutely unwell. Previous work suggests that respiratory tract infections can cause a reduction in expiratory muscle strength 18, in which case mechanical insufflation/exsufflation and/or the other techniques applied might confer even greater benefit. In addition, NIPPV-assisted physiotherapy may be helpful in patients with respiratory failure as a consequence of chest infection.

When mechanical insufflation/exsufflation is used in clinical practice, it has been stated that pressures of −40–40 cmH₂O are necessary for clinical efficacy 19. The pressures delivered via the insufflator/exsufflator in the present study, measured at the facemask, were lower than this. “Cough assist” was used in line with the manufacturer's recommendations in a study group who were unfamiliar with this device. However, in spite of the relatively modest pressures applied in the present study, it was still possible to demonstrate a significant increase in peak cough flow. This study was designed to achieve a physiologically significant result, rather than to study the clinical effects of varying forms of cough augmentation. Identification of the optimal clinical pressures required to enhance cough is a subject for future prospective clinical study.

Barometric (pressure preset) ventilators were used in preference to volume preset ventilators, which may increase augmentation of tidal volume 21, because it was felt preferable to use a ventilator that the individual was familiar with, and pressure preset models are the machines most widely available in the UK.

The position in which physiotherapy was performed was not standardised. It was ensured that patients were studied in the most comfortable position; this meant only two were supine. The authors simulated their own clinical practice in that airway clearance techniques were performed in the patient's preferred body position, which encouraged maximal patient cooperation. However, it is acknowledged both that posture influences expiratory flow mechanics directly 22 and some techniques, for example manually assisted cough, may be more effectively applied in the supine position.

Significance of the findings

It is of interest that P_mo,W correlated more closely with PCF than P_E,max. This observation is consistent with a previous study in adults with amyotrophic lateral sclerosis in which P_E,max was a poor predictor of the ability to generate transient supramaximal flow 2. It has been hypothesised previously that P_E,max may be a poor screening tool as patients find it hard to generate an airtight seal around the mouthpiece. Observations from the current study suggest that subjects found P_mo,W manoeuvres easier to perform. No correlation was found between SNIP and P_ET,CO2 but this may be due to the fact that most of the present patients were receiving long-term nocturnal NIPPV, which might influence daytime arterial carbon dioxide tension.

A cough gastric pressure threshold (50 cmH₂O), which it is necessary to exceed to generate transient supramaximal flow, has previously been identified 22. Although cough gastric pressure was not directly measured in the present study, a relationship between cough gastric pressure and P_mo,W has been recently demonstrated 10, and, on this basis, it would be expected that all but two of the present patients would have been unable to produce transient supramaximal flow during an unassisted cough. It is acknowledged that the best cough assist technique for the individual may be dependent on the degree and distribution of respiratory muscle weakness, as well as other factors, including the presence of irreversible expiratory airflow obstruction.

With mechanical insufflation/exsufflation, a large increase in mean PCF was noted in the NMD group (76%). A smaller but still significant increase of 9% was observed in the control group. Given that the control subjects were not flow-limited, the observed increase in PCF is in keeping with the expected increase in transpulmonary pressure caused by mechanical insufflation/exsufflation. However, it should be stated that this increase was small in magnitude, in contrast to that in patients with NMD, and does not suggest a clinical role for mechanical insufflation/exsufflation in patients with normal expiratory muscle strength. The value of insufflation/exsufflation in obstructive lung disease was not assessed in the present study. Previous work has assessed the changes induced by cough augmentation in adults 19; however, few previous studies have carried out detailed physiological assessment of the effect of cough augmentation in both adults and children with the degree of respiratory muscle weakness observed in the present patient group.

Cough is crucially important for adequate airway clearance. The present study examined the effect on PCF of a variety of interventions and showed that a combination of insufflation and exsufflation causes the greatest increase in PCF. An increase in inspiratory tidal volume is also desirable in mobilisation of secretions, as this enables the generation of higher peak expiratory flows. Patients with respiratory muscle weakness are often unable to generate the increased tidal volume required and repeated attempts to do so may fatigue the individual. To prevent exhaustion, the use of noninvasive ventilation, particularly during acute hypercapnic exacerbations, can provide an increase in tidal volume and therefore aid mobilisation of secretions. However, in the current study, this approach was less effective than mechanical insufflation/exsufflation in increasing PCF.

Sivasothy et al. 25 studied the effects of cough augmentation, including mechanical insufflation, in subjects with respiratory muscle weakness. The present work differs from their study in several respects. In their study, mechanical insufflation/exsufflation pressures were set at 20 and −20 cmH₂O, two insufflator/exsufflator cycles were used to aid inflation and deflation of the thorax and, after a third inspiration, the subject was asked to make a maximal voluntary cough without the aid of negative pressure. The coughs were, therefore, performed without the aid of exsufflation. The present authors found greater improvement in PCF with the combined insufflation/exsufflation-assisted cough than with insufflation alone. Sivasothy et al. 25 found that patients with scoliosis showed no increase in PCF and hypothesised that higher insufflation pressures may be required in this subgroup. In the present study, it was ensured that the pressure was titrated to patient comfort and, with this approach, it was possible to show significant benefit in patients with scoliosis. Like Sivasothy et al. 25, the present authors believe a pneumotachograph gives a more accurate measure of PCF than a standard peak flow meter.

A further notable observation in the present study was that, during titration of mechanical insufflation/exsufflation pressures to patient comfort, the highest insufflation and exsufflation pressures did not necessarily produce the greatest PCF. One reason for this discrepancy could be vocal cord dysfunction, either due to the disease (despite exclusion of patients with moderate or severe bulbar involvement) or as a result of upper airway collapse, secondary to the application of positive or negative pressure during insufflation or exsufflation, respectively 26.

Bach and coworkers 1 have previously suggested that a minimum assisted PCF of 160 L·min⁻¹ is required to clear airway debris, where assistance consists of air stacking to maximal insufflation and an abdominal thrust at the time of coughing. Previous retrospective case series 1 from the same group suggest that it may be possible to improve survival and reduce pulmonary morbidity and hospitalisation rate in patients with a PCF below this level, using noninvasive ventilation and mechanical insufflation/exsufflation, without resorting to tracheostomy. These retrospective data require confirmation in a controlled prospective study.

In conclusion, the present data confirm that a combination of insufflation and exsufflation increases peak cough flow in both children and adults with severe respiratory muscle weakness secondary to childhood-onset neuromuscular disease, in the absence of severe bulbar dysfunction. The use of mechanical insufflation/exsufflation is widespread in North America in subjects with neuromuscular disease. Several case series 1 suggest an important role for mechanical insufflation/exsufflation in the prevention of respiratory morbidity in patients with neuromuscular disease. In the absence of prospective evidence, based upon well-designed randomised studies, there may remain considerable obstacles to the widespread adoption of this device within the UK and Europe. Therefore, randomised trials are now warranted, not only to assess whether regular use of an insufflator/exsufflator can reduce the long-term impact of chest infections in these patients but also to investigate whether the combination of insufflation and exsufflation during acute respiratory tract infections can improve clinical outcome more effectively than existing cough augmentation techniques.