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Review
. 2020 Apr 19;6(2):00338-2019.
doi: 10.1183/23120541.00338-2019. eCollection 2020 Apr.

Cough-provocation tests with hypertonic aerosols

Heikki O Koskela  1   2 , Hanna M Nurmi  1   2 , Minna K Purokivi  1
Affiliations
Review

Cough-provocation tests with hypertonic aerosols

Heikki O Koskela et al. ERJ Open Res. .

Abstract

Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

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Conflict of interest statement

Conflict of interest: H.O. Koskela reports grants from Kuopion Seudun Hengityssäätiö Foundation and Hengityssairauksien Tutkimussäätiö during the current work; personal fees from Mundipharma Ltd, Orion Pharma Ltd, Oy, Eli Lilly Finland Ltd, Boehringer Ingelheim Finland Ltd and MSD Finland Ltd, as payments for giving scientific lectures in gatherings organised by medical companies; personal fees from Takeda Leiras Ltd, Boehringer Ingelheim Ltd, Mundipharma Ltd and AstraZeneca Ltd, to visit international scientific meetings; and owning shares of Orion Pharma Ltd. Conflict of interest: H.M. Nurmi reports personal fees from Boehringer-Ingelheim Finland Ltd and Roche Ltd, as lecturer fees/consulting fees in gatherings organised by medical companies; personal fees from Boehringer-Ingelheim Finland Ltd, Roche Ltd and Sanofi Genzyme Ltd as congress travel grants to visit international scientific meetings; and grants from the Kuopio region Respiratory Foundation and the North Savo Regional Fund of the Finnish Cultural Foundation for previous studies, outside the submitted work. Conflict of interest: M.K. Purokivi reports personal fees from Boehringer-Ingelheim Finland Ltd for lecturing and work preparing educational material for healthcare professionals, and travel and accommodation costs to attend the ERS International Congress (via employer, Kuopio University Hospital) from Roche, all outside the submitted work.

Figures

FIGURE 1
FIGURE 1
The cumulative number of coughs in relation to minute ventilation evoked by isocapnic hyperpnoea of dry air challenge in 10 healthy (a) and 30 asthmatic (b) subjects. The horizontal lines at or below zero indicate subjects who did not cough at all. Reproduced from [13] with permission.
FIGURE 2
FIGURE 2
The cumulative number of coughs evoked by hypertonic saline challenge in 19 healthy subjects (a), 21 patients with chronic cough but without asthma (b), and 26 asthmatic patients with chronic cough (c). The dashed line indicates 15 cumulative coughs. The horizontal lines at or below zero indicate subjects who did not cough at all. Reproduced from [20] with permission.
FIGURE 3
FIGURE 3
The correlation between the coughs-to-dose ratios (CDR) of mannitol and citric acid among 36 subjects with chronic cough. r=0.65, p<0.001. Reproduced from [48] with permission.
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