Airway responsiveness to hypertonic saline: dose-response slope or PD15?

Abstract

The result of airway challenge test with hypertonic saline (HS) is expressed as the dose causing a 15% fall in forced expiratory volume in one second (FEV1; PD15). A noncensored measure, such as the dose-response slope (DRS), allows the evaluation of the risk of asthma for subjects with a fall in FEV1 ,15%. The aim of this study was to assess the relationship between airway responsiveness to HS by PD15 or DRS, asthma symptoms and markers of eosinophilic inflammation.Data on current wheeze and airway responsiveness were obtained for 1,107 children (aged 8-13 yrs). Blood eosinophils and serum eosinophil cationic protein (ECP) were assessed in subsets (n5683 and 485). PD15 was assessed if FEV1 fell o15%, and the DRS was calculated for all tests. Graphs were constructed to visualise relationships with current wheeze, blood eosinophils and serum ECP. Odds ratios and Spearman's correlation coefficients were calculated to quantify these relationships.Children with features of asthma had lower PD15 and higher DRS, and separation was most pronounced for DRS. Prevalence of current wheeze increased continuously over the entire range of DRS values. Blood eosinophils were significantly higher only for the highest values of DRS.In conclusion, the continuous relationship between airway responsiveness and asthma symptoms is in favour of a noncensored measure of airway responsiveness, such as the doseresponse slope.KEYWORDS: Airway hyperresponsiveness, childhood asthma, dose-response slope, epidemiology, hypertonic saline, provocative dose causing a 15% fall in forced expiratory volume in one second W orldwide, airway challenge with hypertonic saline (HS) is performed in childhood population studies that adhere to the International Study on Allergy and Asthma in Childhood (ISAAC) [1]. HS is an indirect stimulus that causes bronchoconstriction, presumably by the release of inflammatory mediators from intermediary cells. There is evidence to suggest that, in children with asthma, airway hyperresponsiveness (AHR) to HS is more closely related to the underlying airway inflammation than AHR to direct stimuli, such as methacholine or histamine [2,3].Conventionally, AHR to HS is considered to be present if the forced expiratory volume in one second (FEV1) falls by o15% fall after inhalation of a provocative dose of f23 g HS (PD15 f23 g), which is the cumulative dose after 15.5 min inhalation at a minimal nebuliser output of 1.5 mL?min -1 [1]. According to this definition, the presence of AHR to HS has a specificity of up to 92% for asthma symptoms in the past 12 months and a doctor's diagnosis of asthma [4]. In children with AHR, the PD15 provides a measure of severity of airway hyperresponsiveness. However, PD15 can only be assessed in individuals with AHR and will be of limited value in general population studies in which the prevalence of AHR is modest. It is not clear whether subjects who have a sub-threshold (i.e. ,15%) fall in FEV1 have an increased probability of asthma symptoms and pathology compared to nonresponsive ...

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“…A positive response to histamine in childhood was defined as a 20% fall in forced expiratory volume in 1 s (FEV1) ( provocative concentration of histamine causing a 20% fall in FEV1). DRS was used rather than PC40 , as epidemiological studies have demonstrated that the DRS is a better measure when examining the continuous relationship between increased airway responsiveness and asthma symptoms [16,17]. The DRS for each airway responsiveness assessment was calculated by dividing the percentage reduction in V′maxFRC in infancy or FEV1 in childhood by the concentration of histamine last administered [18].…”