Inhaled Corticosteroids, Combined with Long-acting β₂-Agonists, Improve the Perception of Bronchoconstriction in Asthma

Abstract

The relationship between asthma medication and the perception of asthma symptoms is of interest for daily practice. Poor perception of asthma symptoms might influence patients' health care behavior and subsequently might lead to undertreatment and deterioration of their disease. This study investigated the influence of the chronic use of short-acting and long-acting beta(2)-agonists, compared with the additional use of inhaled corticosteroids on the perception of histamine-induced bronchoconstriction. Patients with asthma (33 male and 31 female, mean age 35 +/- 11 yr, FEV(1) 87 +/- 14% of the reference value, PC(20) geometric mean 1.08 mg/ml (95% CI: 0.76-1.52) were selected and randomly allocated to the use of either a short-acting beta(2)-agonists (salbutamol, n = 22) or a long-acting beta(2)-agonists (formoterol, n = 22) or placebo (n = 20), which has been used for 12 wk. This medication treatment was repeated exactly 1 yr later, with patients receiving the same medication plus an inhaled corticosteroid. Perception of histamine-induced bronchoconstriction was measured at the start of each treatment period and every 4 wk thereafter. Subjects quantified their sensation of respiratory discomfort during the challenge tests on a modified Borg scale. The perceptive "sensitivity" for changes in FEV(1) was analyzed by the linear regression slope (alpha) "Borg versus percentage fall in FEV(1)." The "absolute perceptual magnitude" was determined by the perception score at the 20% fall in FEV(1) (PS(20)). The additional use of inhaled corticosteroids during the second year resulted in an improved perception of histamine-induced bronchoconstriction (slope alpha) compared with the first year for only the long-acting beta(2)-agonists group (p value 0.036). This improvement was not observed for the "absolute perceptual magnitude" (PS(20)). The additional use of inhaled corticosteroids during chronic use of long-acting beta(2)-agonists improves the perceptive "sensitivity" for changes in FEV(1) during histamine-induced bronchoconstriction, which was not observed for short-acting bronchodilators. This result might indicate that the positive effects on perception of airway obstruction might be another reason (besides the beneficial effects on the clinical condition) for prescribing a combination of long-acting beta(2)-agonists and inhaled steroids.

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

“…Recently, in a subgroup of the present study population [14], the authors showed that the additional use of inhaled corticosteroids resulted in an improvement in the perception of bronchoconstriction in patients using long-acting b 2 -agonists but not in patients using short-acting b 2 -agonists. This difference might be related to the increase in BHR in the group using short-acting b 2 -agonists, resulting in greater airflow inflammation and perhaps a reduction in perception.…”

“…Initially, patients (aged 16-60 yrs) were selected by their general practitioner (GP) if they had a history of bronchial symptoms or a clinical diagnosis of asthma [13,14]. Eligible patients then visited the lung function laboratory for an inclusion assessment.…”

“…Recently, the authors showed that in a small group of 64 asthmatic patients, additional use of inhaled corticosteroids resulted in an improved perception of bronchoconstriction in patients using long-acting b 2 -agonists [14]. In the study, patients used either a short-or long-acting b 2 -agonists or placebo over a period of 12 weeks, followed by another period of 12 weeks in which beclomethasone diproprionate was added.…”

Relation between inflammation and symptoms in asthma

“…These results confirm the findings of Roisman et al (95) that patients treated with inhaled corticosteroids had an increased perception of symptoms than cortocosteroid-naive patients for a given degree of eosinophil inflammation. Bijl-Hofland et al (117) showed that compared with long-acting b 2 -agonists used alone, a combination of long-acting b 2 -agonists and inhaled corticosteroids had a positive effect on the perception of bronchial obstruction. A longitudinal Australian study (118) with administration of high doses of inhaled corticosteroids (budesonide) failed to show any difference between naive or previously treated patients, in terms of variation in the Borg score during the reduction of FEV 1 induced by challenge tests.…”

Blunted sensation of dyspnoea and near fatal asthma

“…Inhaled corticosteroids have recently been demonstrated to heighten the sensation of dyspnoea in asthma [27,28]. Earlier research suggests theophylline (a higher centre and muscle stimulant) may increase perception of asthma [29].…”