Patients with neuromuscular diseases are uniquely susceptible to respiratory complications, not only because of increased prevalence of aspiration but also because of reduced effectiveness of airway clearing mechanisms.¹ Of these, cough—whether voluntary or reflex—is particularly important because it generates high expiratory laminar flow in the smaller airways that dislodge and eject foreign material from the pulmonary system.^2,3 Many studies have shown that ineffective cough production is associated with a higher prevalence of respiratory complications in neurological diseases.^4–,⁸ Despite the importance of cough in airway protection, few studies have been undertaken in human subjects to understand the neuromuscular mechanisms involved in the generation of different types of cough.

Much of our current knowledge of motor events during cough production has been inferred from animal experiments.^9–,¹⁶ However, voluntary cough cannot be studied in animals,¹⁷ and reflex cough generated by mechanical or chemical stimulation of airways does not simulate physiological conditions in humans.^11,13–,¹⁶ Many studies were undertaken in anaesthetised animals, which may alter cortical input or depress spinal reflexes and are unrepresentative of neuromuscular events in awake human subjects.¹⁷ Nevertheless, these studies showed that anterolateral abdominal muscles have a major role in cough generation,¹⁵ but pectoral muscles may also contribute to cough.^12,14

The importance of abdominal muscles in cough production was confirmed by electromyography (EMG) studies in humans, which showed activation of the rectus abdominis, internal oblique, external oblique, and transversus abdominis muscles during voluntary cough.^18,19 Abdominal muscle activation was proportional to cough flow rate, and a linear relationship has been demonstrated between increases in EMG activity and voluntary cough flow rates.^18–,²¹ In addition to abdominal muscles, EMG bursts over the latissimus dorsi and pectoralis major muscles have been demonstrated during voluntary cough efforts in healthy volunteers and tetraplegic subjects in whom corticospinal abdominal inputs were interrupted.^22,23

Despite studies mapping different muscles involved in cough production, motor programmes underlying voluntary or reflex cough have not been investigated. It is possible that muscle activation patterns for the brainstem mediated reflex cough, which is characterised by rapid generation of high intrathoracic pressures and forceful expulsion of air in response to noxious stimuli,²⁴ are different from those associated with voluntary cough in response to stimulation of receptors in the laryngeal mucosa, nervousness or spoken command, which can be initiated and modulated by cortical inputs.²⁵ Understanding motor mechanisms which underlie different types of cough may be clinically significant in developing techniques to enhance airway clearing mechanisms in patients with neurological diseases (such as chronic stroke, Parkinson’s disease, Alzheimer’s disease, and motor neurone disease) who are at increased risk of aspiration.^{5,6,8,20,26,27}

The objective of this study was to study motor activation of various muscle groups during voluntary cough in healthy subjects and to compare the patterns of motor activation between voluntary and reflex cough after matching for cough flow rates.

METHODS

RESULTS

The mean (SD) peak cough flow rate of voluntary cough was 568 (127) l/min and that of the two reflex coughs (R1 and R2) were 370 (156) l/min and 272 (121) l/min, respectively (p<0.0001 for both). The maximal cough flow rate achieved in any one effort was also higher for voluntary cough than for reflex cough (mean difference 146 (95% CI 70 to 222) l/min, p<0.01). The mean duration of the voluntary cough effort was longer than for the reflex cough for both R1 (mean difference 99 ms (95% CI 68 to 130), p<0.005) and R2 (mean difference 114 ms (95% CI 12 to 216), p<0.05). Although the mean peak cough flow rate of R1 was greater than R2 (difference 116 l/min (95% CI 68 to 164), p<0.001), there were no significant differences in cough duration between R1 and R2. Differences between voluntary, R1 and R2 cough flow rates and duration were consistent within individual subjects.

Motor activation in voluntary cough

All subjects showed similar patterns of EMG and cough flow rate recordings during voluntary cough, a typical example of which is shown in fig 1A⇓. Voluntary cough was associated with equal EMG activity in expiratory muscles which increased linearly in proportion with cough flow rate (r² = 0.62, p<0.001, table 1⇓). In contrast, accessory muscles showed little activity at low cough flow rates but this increased exponentially at high cough flow rates (fig 2A⇓). Mean EMG burst duration increased with cough flow rate for both expiratory and accessory muscles (p<0.001 for both, table 1⇓). Expiratory muscles had longer EMG burst duration than accessory muscles (mean difference 68 ms (95% CI 102 to 34), p<0.01) which did not change with increasing muscle activation or cough flow rate (fig 2B⇓). Although onset of EMG activity in all muscle groups preceded cough onset, it was consistently earlier in the expiratory muscles than in the accessory muscles for all flow rates of voluntary cough (mean difference 44 ms (95% CI 20 to 68), p<0.0001, table 1⇓). This difference in the timing of EMG burst onset between expiratory and accessory muscles remained constant across flow rates (fig 2C⇓).

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Table 1

 Mean (SD) EMG activity (normalised to the mean value of the top quartile), EMG burst duration (ms), and time between EMG burst onset and cough onset (ms) during voluntary cough at each quintile of cough flow in 10 subjects

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Figure 1

 (A) Average flow curve and EMG signals during voluntary cough in a single subject. EMG signals were collected relative to the time of flow onset (time zero) and 10 trials were rectified, averaged, and smoothed. (B) Average flow curve and EMG signals during reflex cough in the same subject as in (A). EMG signals were collected relative to the time of flow onset (time zero) and 10 trials were rectified, averaged, and smoothed. Note the EMG signals show a rise after 0.2 seconds because, in this subject, pairs of coughs were induced.

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Figure 2

 (A) Mean EMG activity, (B) burst duration, and (C) time of onset associated with voluntary cough effort in 10 patients.

Motor activation in reflex cough

Motor activation patterns during reflex cough are shown in fig 1B⇑ and were compared with motor activation patterns of voluntary cough producing the same quintile of cough flow rates in each subject (table 2⇓). There were no significant differences in the EMG activation patterns between R1 and R2. Reflex cough was associated with significantly greater mean EMG activity (mean 110.2% v 56.1%, p<0.001) but shorter mean EMG burst duration (206 v 280 ms, p = 0.013) in all muscle groups compared with voluntary cough of comparable flow rate. In contrast to voluntary cough, EMG activity was significantly greater in accessory than in expiratory muscles (table 2⇓). EMG burst duration of accessory muscles was comparable to the EMG burst duration of expiratory muscles during reflex cough (difference 27 ms (95% CI −4 to 58), fig 3A⇓). There were also no differences in the mean duration of EMG burst onset before cough onset between expiratory and accessory muscles during reflex cough (difference 8 ms (95% CI −9 to 25), fig 3B⇓). These observations varied significantly from the consistent differences in EMG burst onset and duration between expiratory and accessory muscles seen during voluntary cough (p<0.0001 and p<0.005, respectively).

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Table 2

 Comparison of mean (SD) EMG activity, burst duration (ms), and burst onset pre-cough (ms) between reflex cough and the comparable quintile of voluntary cough flow rate

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Figure 3

 Paired comparisons of (A) the delay in onset of EMG activity and (B) EMG burst duration between expiratory and accessory muscles during reflex cough and voluntary cough matched for cough flow rate.

DISCUSSION

This study is the first to our knowledge to demonstrate motor sequences involved in the production of voluntary and reflex cough in healthy human subjects. Voluntary cough production was associated with coordinated activation of expiratory and accessory muscles, which showed a graded increase in mean EMG activity and burst duration proportional to cough flow rates produced. Low cough flow rates were produced largely by the activation of expiratory muscles, but accessory muscles became involved sequentially and increasingly for the production of higher flow rates. Reflex cough, on the other hand, was associated with simultaneous onset of EMG activity in expiratory and accessory muscles, increased EMG activity of all muscle groups and shorter EMG burst duration, consistent with rapid and widespread activation of expiratory and accessory muscles in unison. These patterns reflect differences in the functional organisation of muscle activation between voluntary and reflex cough. Sensory inputs from airway afferents in the brainstem mediated reflex cough result in simultaneous efferent outputs to all expiatory and accessory muscles in order to generate maximum airflow for the lung volume at the beginning of the cough. In contrast, cortical inputs to medullary centres (or even bypassing these centres) in voluntary cough can modulate the level and sequence of activation of different muscles and produce more controlled airflows depending upon perceived need.²⁸

An important finding of this study was that voluntary cough was associated consistently with EMG activation of shoulder girdle and thoracic (accessory) muscles which increased with increasing cough flow rate. Previous reports support abdominal muscles working as a coordinated unit to generate the high intra-abdominal pressure required for cough,^15,18,19 but there are no reports that extend this functional unit to include accessory muscles. EMG activity of pectoral and intercostal muscles during voluntary cough has been observed inconsistently in previous studies and interpreted as evidence for variability in motor programmes for voluntary cough.^22,29 Evidence from this study supports a common neural drive to functionally related expiratory and accessory muscles which is involved in both reflex and voluntary cough. It also appears that activation of expiratory and accessory muscles during voluntary cough can be modulated and integrated, at least in part, by cortical inputs in response to volitional commands or other stimuli and results in graded recruitment of expiratory and accessory muscles to produce cough with high flow rates. This observation has clinical implications for the training of respiratory muscles in patients with chronic neurological or respiratory diseases who may have reduced airway clearance.

One strength of this study is that EMG activity of muscles involved in cough and cough flow rates were measured simultaneously and voluntary and reflex cough were studied in the same subjects. Motor activation was studied for matched flow rates of voluntary and reflex cough and the lowest concentration of tartaric acid required to produce a consistent reflex cough in individual subjects was used to avoid confounding effects of other protective responses at higher concentrations.³⁰ Potential sources of bias due to subject variability or methodology were minimised by careful selection of healthy subjects within a relatively narrow age range, predefined protocols for respiratory and EMG measurements, and calibration of equipment before each experimental session.

A limitation of the study was that surface electrodes were used to measure EMG activity. The accuracy of surface EMG may vary because of differences in subcutaneous fat interfering with a good surface EMG signal. However, all subjects were of normal weight for their height and this is an unlikely source of bias. There is a possibility that volume conducted activity in the surface recording of muscles may have prevented selective recordings. More selective recordings could have been undertaken using needle or fine wire electrodes, but the activity, although selective, would not have been representative of the total activity emanating from the muscle, the measurement of which was one of the primary aims of the study. It can be argued that, although EMG recordings may not have been selective for a given muscle, the predominant contribution would be from the muscle closest to the electrodes. As the study compares voluntary with reflex coughs and if the same muscles are assumed to be active in both, then differences in the EMG burst area, duration, and onset can be reasonably attributed to differences in activation pattern rather than volume conducted contamination from other muscles.

The second reflex cough was an unexpected but consistent finding of this study and this pairing of reflex cough efforts has not been described previously. However, there were no significant differences in the EMG activation patterns of R1 and R2. It was not possible to measure lung volumes immediately before reflex cough; differences in lung volumes at cough onset may be partially responsible for lower flow rates seen with reflex cough, especially R2. Low lung volumes also affect muscle length and may affect EMG activation. As the volume of air inspired before acid induced coughs is likely to have been much smaller than for voluntary cough, this may have affected the level of activation of expiratory muscles and the recruitment of accessory muscles. There is no pragmatic method for controlling the volume of air inspired before reflex cough induced by acid inhalation. However, bias due to this is likely to be small because of the similarity of EMG activation patterns for R1 and R2 despite the possibility that lung volumes for R2 would have been smaller than for R1.

It is probable that reflex cough produced by chemical stimulation under experimental conditions does not simulate clinical conditions in which aspiration occurs.³¹ Inhaled tartaric acid may also stimulate other reflex inputs that interact with cough, and it is possible that this complexity of afferent inputs may have modulated EMG activation. There is an additional afferent component due to accumulated secretions in many lung diseases and muscle activation patterns in supine patients may be very different from healthy subjects sitting upright. However, life threatening situations associated with aspirates of fluid or food which simulate clinical settings cannot be replicated in experimental situations because of safety and ethical considerations. In addition, the study does not investigate neural mechanisms that may underlie differences in muscle activation and there is a possibility that these too may differ between health and disease states.

In conclusion, this study has demonstrated different motor mechanisms underlying voluntary and reflex cough. Although the cough reflex remains the major defence against the risk of aspiration,³² sequential activation of expiratory and accessory muscles during voluntary cough is capable of generating high airflows and may offer additional protection in patients with neurological disease who have impaired pharyngeal and laryngeal function.^6,33,34 This implies that assessment of voluntary cough should become an integral part of the overall assessment of neurological patients. It may also be possible to develop simple interventions such as voluntary cough exercises in these patients which will help to reduce morbidity and mortality associated with chronic neurological disease. Further research is needed to determine how cough mechanisms are affected in disease and to assess the effectiveness of interventions to improve voluntary cough in clinical settings.