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 microM) 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 microM capsaicin. At higher concentrations (>50 microM) 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.

Fig. 1

The average increase in the number of expulsive events at each capsaicin concentration as determined by EMG tracings (closed circles). Data are shown for expulsive events associated with CR’s (open triangles) and ER’s (open squares). C2 and C5, indicating threshold and suprathreshold responses, occurred at 50 and 150 μM of capsaicin, respectively.

Fig. 2

Representative airflow tracing from one subject illustrating a CR3 and a CR3 following inhalation of 150 μM of capsaicin. A CR is defined as an inspiration followed by one or more expulsive events.

Fig. 3

Number of airway defensive behaviours (expressed as a percentage of total CR and ER) for each type (CRn and ERn) increased with increasing capsaicin concentration. CR’s and ER’s with a greater number of expulsive events appeared at higher concentrations. CR2 was the most common response at all concentrations.

Fig. 4

Representative tracing of raw and integrated EMG signals for the IC8, RA and EO from the same subject illustrated in Fig. 2. Tracings show EMG activation for a CR3 and a CR2.

Fig. 5

Total sum of the integrated IC8 EMG signal. CR’s greater than 4 and ER’s greater than 2 were not included since not all subjects exhibited these responses. While total muscle activation was greater for airway defense behaviours with more expulsive events, there was no effect of capsaicin concentration on the muscle activation.

Fig. 6

Percent increase in integrated EMG for IC8, RA and EO for expulsive events from each type of airway defensive behaviour. Muscle activation was greatest with the initial expulsive event, and subsequently declined with successive expulsive events. Bars indicate SEMs.

Fig. 7

Illustration of the parameters measured from the airflow tracing. IPD: inspiratory phase duration; CPD: compressive phase duration; PEFRS: peak expiratory flow rate slope (i.e. airflow acceleration); PEFR: peak expiratory flow rate; RT: rise time; PPD: plateau phase duration.

Fig. 8

Duration of the compressive phase (CPD), rise time (RT) and plateau phase (PPD) for expulsive events from each type of airway defensive behaviour. Rise time and plateau duration were greatest with the initial expulsive event, and subsequently declined with successive expulsive events. Bars indicate SEM.

Fig. 9

Percent increase in mean airflow slope (i.e. airflow acceleration) and mean airflow (i.e. plateau velocity) for expulsive events from each type of airway defensive behaviour. Similar to muscle EMG, airflow acceleration and velocity were significantly greater in the initial expulsive event and subsequently decline with successive expulsive events.