Capsaicin exposure elicits complex airway defensive motor patterns in normal humans in a concentration-dependent manner

Abstract

The airway defensive response to tussive agents, such as capsaicin, is frequently assessed by counting the number of cough sounds, or expulsive events. This method does not identify or differentiate important respiratory events that occur in the respiratory muscles and lungs, which are critical in assessing airway defensive responses. The purpose of this study was to characterize the airway defensive behaviours (cough and expiration reflex) to capsaicin exposure in humans. We observed complex motor behaviours in response to capsaicin exposure. These behaviours were defined as cough reacceleration (CRn) and expiration reflex (ERn), where n is the number of expulsive events with and without a preceding inspiratory phase, respectively. Airway defensive responses were defined in terms of frequency (number of expulsive events), strength (activation of abdominal muscles) and behaviour type (CRn vs. ERn). Thirty-six subjects (15 females, 24±4 yr) were instrumented with EMG electrodes placed over the rectus abdominis (RA), external abdominal oblique (EO) and the 8th intercostal space (IC8). A custom-designed mouth pneumotachograph was used to assess the airflow acceleration, plateau velocity and phase duration of the expulsive phase. Subjects inhaled seven concentrations of capsaicin (5-200 μM) in a randomized block order. The total number of expulsive events (frequency) and the sum of integrated EMG for the IC8, RA and EO (strength) increased in a curvilinear fashion. Differentiating the airway defense responses into type demonstrated predominately CR1 and CR2 (i.e. inspiration followed by one and two expulsive events, respectively) with very few ER's at <50 μM capsaicin. At higher concentrations (>50 μM) ER's with one or more expulsive events (≥ER1) appeared, and the number of CR's with three or more expulsive events (≥CR3) increased. The decrease in EMG activation and airflow measurements with each successive expulsive event suggests a decline in power and shear force as the number of expulsive events increased. Therefore, the airway defensive response to capsaicin is a complex motor pattern that functions to coordinate ER's and CR's with differing numbers of expulsive events possibly to prevent aspirations and keep air moving to promote clearance.

What is cough and what should be measured?

“…distilled water aerosol), tartaric acid, acetic acid and hypertonic solutions have also been administered. Cough number or frequency is usually measured, and a few papers show patterns of response [5,8,[10][11][12].…”

“…Spontaneous and induced coughs are associated with the sensation 'urge-to-cough', which may have a lower threshold than cough itself, and usually precedes it [8,10,12,14] The neural connections for cough between the cortex and the brainstem have not been worked out. Decerebrate animals can cough vigorously with an irritant stimulus [18], so at most the cortex can induce or facilitate cough (or inhibit it).…”

“…The expiratory muscles of the ventrolateral aspect of the abdominal wall are intensely activated during both the compressive and expulsive phases of cough [28] and the ER [8,12]. The chief expiratory muscles are the internal intercostals, the oblique (external and internal) muscle, the tranversus abdominis, and the rectus abdominis [see 29].…”

“…The chief expiratory muscles are the internal intercostals, the oblique (external and internal) muscle, the tranversus abdominis, and the rectus abdominis [see 29]. EMGs of the expiratory muscles have been used not only to study the neural mechanisms of cough but also to assess its intensity [8,[10][11][12].…”

Measuring voluntary and reflexive cough strength in healthy individuals

“…Conversely, the inclusion of the inspiratory phase in a CR enables a greater strength for the expulsive phase of the cough to enable more effective clearance of the airway and lungs (Tatar et al, 2008). Vovk et al (2007) reported that LERs are typically weaker and of shorter duration than CRs, which they postulated is due to a lack of an inspiratory phase.…”