Minna Purokivi

Cough response to isocapnic hyperpnoea of dry air and hypertonic saline are interrelated

BackgroundMechanisms behind asthmatic cough are largely unknown. It is known that hyperosmolar challenges provoke cough in asthmatic but not in the healthy subjects. It has been postulated that isocapnic hyperpnea of dry air (IHDA) and hypertonic aerosols act via similar mechanisms in asthma to cause bronchoconstriction. We investigated whether there is an association between cough response induced by IHDA and hypertonic saline (HS) challenges.MethodsThirty-six asthmatic and 14 healthy subjects inhaled HS solutions with increasing osmolalities administered via ultrasonic nebuliser until 15 cumulative coughs were recorded. The IHDA consisted of three three-minute ventilation steps: 30%, 60% and 100% of maximal voluntary ventilation with an end-point of 30 cumulative coughs. The challenges were performed on separate days at least 48 hours between them and within one week. Inhaled salbutamol (400 mcg) was administered before the challenges to prevent bronchoconstriction. The cough response was expressed as the cough-to-dose ratio (CDR) which is the total number of coughs divided by the maximal osmolality inhaled or the maximal ventilation achieved.ResultsCough response to IHDA correlated with the HS challenge (Rs = 0.59, p < 0.001). Cough response to IHDA was at its strongest during the first minute after the challenge. IHDA induced more cough among asthmatic than healthy subjects CDR being (mean ± SD) 0.464 ± 0.514 and 0.011 ± 0.024 coughs/MVV%, p < 0.001, respectively. Salbutamol effectively prevented bronchoconstriction to both challenges.ConclusionsAsthmatic patients are hypersensitive to the cough-provoking effect of hyperpnoea, as they are to hypertonicity. Cough response induced by IHDA and HS correlated well suggesting similar mechanisms behind the responses.

Utility of cough response during hypertonic histamine challenge in diagnosing asthma.

Airway responses to bronchial provocation tests are traditionally assessed with spirometry which necessitates considerable patient co-operation. It has been shown that coughing during bronchial provocation tests is related to the degree of bronchoconstriction which, in turn, is independent of patient co-operation. The aim of the present study was to evaluate the utility of coughing induced by the hypertonic histamine challenge in the differential diagnosis of asthma in a clinically relevant patient population. The study population consisted of 25 healthy volunteers, 30 asthmatics, and 82 non-asthmatic subjects with respiratory symptoms due to other diseases. Hypertonic histamine solution was administered with ultrasonic nebuliser with the challenges being videotaped. The cough response was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). The geometric mean (95% CI) of CCR for asthmatics was 302 (166-562) coughs per mg/ml, for the symptomatic controls 29.5 (20.0-43.7) coughs per mg/ml (p<0.001) and for the healthy controls 6.61 (3.02-14.5) (p<0.001) coughs per mg/ml. According to the ROC curve, the optimal cut-off point for logCCR was 2.22, with the specificity and sensitivity to detect asthma among symptomatic subjects being 86% and 70%. Cough response to hyperosmolar challenge may be useful in the differential diagnosis of airway diseases.

Neurotrophins in chronic cough: association with asthma but not with cough severity

Background and Aims:u2002 Chronic cough is associated with an enhanced excitability of airway cough receptors, possibly due to action of neurotrophins. The present study aimed to compare the neurotrophin levels between healthy subjects and patients with chronic cough and to analyze the factors associated with these levels.

The Cough Receptor TRPV1 Agonists 15(S)-HETE and LTB4 in the Cough Response to Hypertonicity

Asthmatic patients are hypersensitive to the cough-provoking effect of hypertonic aerosols. 15- hydroxyeicosatetraenoic acid (15(S)-HETE) and leukotriene (LT) B4 are asthma-related mediators which can be released upon hypertonic stimuli, and both are potent agonists of the transient receptor potential vanilloid subfamily member 1 (TRPV1), a major cough receptor. Therefore, they are potential mediators for hypertonicity-provoked cough. Twenty-six asthmatic and ten healthy subjects underwent a hypertonic saline cough provocation test. Exhaled breath condensate was collected before and after the test, and the concentrations of 15(S)-HETE and LTB4 were analysed. Neither the baseline concentrations of these mediators nor the saline test-induced changes in them were associated with cough responsiveness to hypertonicity. High baseline 15(S)-HETE was associated with aspirin hypersensitivity and high LTB4 with male sex and large variability in ambulatory peak flow measurements. The TRPV1 agonists 15(S)-HETE and LTB4 seem not to be involved in the cough response to hypertonicity in asthmatic patients.

Simultaneous versus video counting of coughs in hypertonic cough challenges

BackgroundThe coughs occurring during cough provocation tests are usually counted at the same time when the test is being conducted, i.e., simultaneously. It is unknown whether cough counting from video recording might increase the accuracy of the cough counting. During recent years, cough challenges with hypertonic aerosols have been introduced. They often provoke very frequent coughing which may complicate the simultaneous cough counting.ObjectiveTo assess whether cough counting from video recording is superior to simultaneous cough counting in two different hypertonic cough challenges.MethodsThe analysis includes 82 hypertonic saline challenges performed on 66 subjects, providing 1984 observation minutes with both simultaneous and video cough counting. The cough sensitivity was expressed as the osmolality to provoke 15 cumulative coughs (CUM15). The analysis also includes 136 hypertonic histamine challenges performed on 114 subjects providing 5373 observation minutes with both simultaneous and video counting. The cough sensitivity was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). This challenge involved several additional measurements to cough counting.ResultsFor the saline challenge, the mean difference between the counting types was 0.0 coughs per minute with 95% limits of agreement of -1.2 to 1.2 coughs per minute. For the hypertonic histamine challenge the respective figures were 0.3 (-1.9 to 2.5) coughs per minute. At high coughing frequency the video counts tended to outnumber the simultaneous counts. The counting type had no effect on the hypertonic saline CUM15 and only a marginal effect on its repeatability. On the contrary, video counting resulted to significantly higher hypertonic histamine CCR values than simultaneous counting (p < 0.001).ConclusionThe agreement between simultaneous and video counting of coughs is generally good. However, as the coughing frequency increases, simultaneous counting may miss coughs, especially if the nurse has to share his/her attention to several activities simultaneously. Video recording is advisable for the hypertonic histamine challenge but unnecessary for the hypertonic saline challenge. To ensure reliable simultaneous cough counting, cough provocation tests should be performed in a quiet environment, applying as little unnecessary equipment and measurements as possible.

Assessment of inhaled corticosteroid treatment response in asthma using hypertonic histamine challenge-induced cough

Background and Aims:u2002 Bronchial provocation tests may be utilised to monitor the efficacy of the corticosteroid treatment. Unfortunately, these measurements necessitate good patient cooperation during the spirometry. Coughing during such tests is related to the degree of the bronchoconstriction and occurs involuntarily, i.e. independent of patient cooperation. This study aimed to evaluate the utility of a hypertonic histamine challenge‐induced cough in assessing the efficacy of inhaled corticosteroid treatment.

Utility of hypertonic histamine challenge in distinguishing difficult-to-diagnose asthma

Introduction:u2002 Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC).