Potential masking effect on dyspnoea perception by short- and long-acting β₂-agonists in asthma

Abstract

Asthma patients evaluate the effect of medication treatment through the degree of their asthma symptoms, which might be affected by their ability to perceive these symptoms. It has been suggested that b 2 -agonists may mask the effects of an increase in airway inflammation. This study compared the perception of histamineinduced bronchoconstriction during monotherapy with short-or long-acting b 2 -agonists.Asthmatic patients (68 male and 60 female, mean age 35¡11 yrs, forced expiratory volume in one second (FEV1) 86¡15% of the reference value, provocative concentration causing a 20% fall in FEV1 (PC20) geometric mean 0.97 mg?mL -1 (95% confidence interval (CI): 0.73-1.30)) were selected and randomly allocated to use either a shortacting (salbutamol, n=41) or long-acting b 2 -agonist (formoterol, n=46) or placebo (n=41) for 12 weeks. Perception of dyspnoea provoked by histamine-induced bronchoconstriction was measured at the start and every 4 weeks thereafter. Subjects quantified their sensation of breathlessness during the challenge tests on a modified Borg scale at the start of the study and every 4 weeks thereafter. The sensitivity to changes in FEV1 was analysed by the linear regression slope (a) Borg versus % fall in FEV1. The absolute perceptual magnitude (PS20) was determined by the perception score at the 20% fall in FEV1.Although the geometric mean PC20 decreased significantly within the group using short-acting b 2 -agonists (in the group with initial PC20 o2 mg?mL -1 there was a drop from 5.26-1.94 mg?mL -1 ; p=0.013), repeated measurement analysis showed no difference in the course of time of perception (both slope a and PS20) between the three medication groups.This study showed that chronic use of short-or long-acting b 2 -agonists in asthmatics for a period of 12 weeks, did not significantly change the perception of histamineinduced bronchoconstriction compared with placebo. Further investigation is required to establish whether this suggests that these drugs do not mask a deterioration of asthma.

Differentiation between the sensory and affective aspects of histamine-induced bronchoconstriction in asthma

“…There was no relation at baseline between subjective symptoms and lung function, probably due to temporal adaptation to pre-existing obstruction 32,33 : at the end of the histamine provocation there was a correlation between changes in subjective symptoms and lung function. In contrast to previous findings, 3,4,34 we found no relation between the participants' perceptual sensitivity for dyspnea and physiological measures of disease severity such as FEV 1 and histamine dose level at 20% decrease of FEV 1 .…”

Impact of Race on Asthma Treatment Failures in the Asthma Clinical Research Network

“…This difference supports prior reports suggesting that African Americans may have differential perception of their asthma symptoms and perhaps their asthma severity, compared with whites, similar to other ethnicities (18). Because LABA use has been reported to attenuate asthma symptom perception (24), it is possible that in this population of individuals who already report fewer symptoms and use less asthma rescue medication, this class of therapy may be potentially detrimental and Table 4 and survival analysis is used for the figures. The subset of subjects used for each treatment in each analysis is the same.…”

ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions

“…Excessive use of short-acting β 2 -agonists (SABAs) in the absence of ICS use has long been linked to hospitalisations and asthma deaths, best exemplified by asthma death epidemics related to high doses of fenoterol reported in New Zealand and other countries [136]. Also, regular use of long-acting β 2 -agonists (LABAs) in the absence of ICS has been shown to increase significantly the risk of asthma exacerbations and asthma deaths potentially through a "masking" effect [137][138][139]. Not only overuse, but also regular use, of SABA (without ICS [140]) has also been associated with paradoxical asthma worsening [52,141].…”