Cough challenge

Diepinigaitis PV (2003) Short- and long-term reproducibility of capsaicin cough challenge testing. Pulm Pharmacol Ther 16 61-65... 

Diepinigaitis PV, Alva RV (2005) Safety of capsaicin cough challenge testing. Chest 128 196-202 Fontana GA, Widdicombe JG (2007) What is cough and what should be measured Pulm Pharmacol Ther 20 307-312... 

Laude FA, Higgins KS, Morice AH (1993) A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man. Pulm Pharmacol 6 171-175... 

Davenport PW, Chan PY, Zhang W, Chou YL (2007b) Detection threshold for inspiratory resistive loads and respiratory-related evoked potentials, J Appl Physiol 102(l) 276-285 Dicpinigaitis PV (2003) Short- and long-term reproducibility of capsaicin cough challenge testing, Pulm Pharmacol Ther 16(l) 61-65... 

Fig. 5 Citric acid cough challenge in a patient with cough-variant asthma the effect of inhaled corticosteroids...

Tussive Agents used in Inhalation Cough Challenge. 298... 

Published Data on Reproducibility of Inhalation Cough Challenge.303... 

As opposed to the delivery of capsaicin and citric acid during experimental cough challenge, which will be discussed in detail later, water aerosols must be provided by an ultrasonic nebulizer, which typically produces a much larger output per unit volume of air than a conventional nebulizer (Mercer 1981). As experience with fog... 

The two main methods of aerosol delivery in capsaicin (and cinic acid) cough challenge testing are the single-dose and dose-response methods (Morice et al. 2001). In the single-dose method, one specific concentration of capsaicin is utilized. Typically, the number of coughs induced by a fixed time period of tidal breathing would be determined. 

A high degree of reproducibility is essential for the performance of quality research, especially when serial cough challenges are required. Several aspects of inhalation cough challenge methods must be recognized and controlled to yield maximally reproducible results. 

The rate of inspiratory flow will affect the deposition of aerosol within the respiratory tract, as well as its concentration at the site of action, depending on the method of delivery. Indeed, variations in inspiratory flow rate have been demonstrated to affect the results of capsaicin (Barros et al. 1991) and citric acid (Barros et al. 1990) cough challenge, with higher rates of inspiratory flow in those studies being inversely correlated with the number of coughs induced. Unless the inspiratory flow... 

To ensure a consistent inspiratory flow rate during cough challenge studies, the author employs a compressed-air-driven nebulizer (model 646 De Vilbiss Health Care, Somerset, PA, USA) controlled by a dosimeter (KoKo DigiDoser nSpire Health, Louisville, CO, USA) that is modified by the addition of an inspiratory flow regulator valve (RIFR nSpire Health). The valve limits inspiratory flow rate to... 

Once these modifications have been performed, the exact output (milliliters per minute) of the nebulizer is measured (characterized nebulizer nSpire Health). With the exact nebulizer output known, modulation of the duration of aerosol delivery by the dosimeter allows the determination of aerosol output per inhalation. For example, the author currently uses a characterized nebulizer with an output of 1.007ml min with a dosimeter programmed to deliver pressurized air for 1.2 s, thus allowing the nebulizer to deliver exactly 0.02 ml aerosol per inhalation. Since investigators worldwide will likely continue to use different equipment for the performance of cough challenge studies, one way to achieve a measure of standardization would be to control nebulizer output per breath, with the aforementioned... 

Another potential issue relevant to cough challenge end points primarily affects measurement of C5. In a small minority of subjects, mainly those with high cough... 

Fig. 1 Dose-response curve of capsaicin cough challenge. In this study, C2, the concentration of capsaicin inducing two or more coughs, is 7.8 pM and C5, the concentration of capsaicin inducing five or more coughs, is 31.25 pM...

The safety of citric acid cough challenge was reported during the initial development of the method over a half century ago (Bickerman et al. 1954, 1957), but more recent data have not been published. Citric acid inhalation can induce a small decrease in the forced expiratory volume in 1 s (less than 5%) that is unlikely to be of clinical significance (Laude et al. 1993). 

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