Cough-provocation tests with hypertonic aerosols

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.

Differential features of chronic cough according to etiology and the simple decision tree for predicting causes

“…Remarkably, voice hoarseness was an independent feature of UACS, supposed to be caused by post-nasal drip or inflammation on larynx located nearby. Female sex and hypersensitivity to irritants were predictors for asthma/CVA, consistent with previous description 18 , 19 . Less hoarseness was characteristics of EB and feeling fed-up and hoarseness were less common features of GERD; less severe cough may less likely induce secondary laryngitis.…”

Utility of Cough Provocation Tests in Chronic Cough and Respiratory Diseases: A Comprehensive Review and Introduction of New Reference Ranges for the Capsaicin Test

“… 25 At the moment, the mannitol test is the only CPT, which is standardized. 26 Unfortunately, there is no data to calculate reference ranges for the cough responsiveness to mannitol or any other cough provocation agents than capsaicin. Also, the reference ranges for the maximal cough response to capsaicin are lacking.…”

“…The possible reasons for this discrepancy have been discussed in detail elsewhere. 26 In a clinical setting, high cough sensitivity to hypertonic aerosols may suggest asthma as the most probable cough background disorder.…”

“…There are some obvious reasons for the unpopularity of the CPTs. 24 25 26 First, numerous provocative agents with different mechanisms of action have been utilized. While it may be advantageous to utilize a tussive agent specific for a mechanism of action, the optimal tussive agent is not known in many situations.…”

“…These agents provoke cough without stimulating the TRPV1. 26 In addition, water mist and adenosine have been utilized. Secondly, there are many methods to administer provocative agents, but they have not been standardized.…”