Effect of formoterol with or without budesonide in repeated low-dose allergen challenge

Abstract

The use of combination therapy in mild asthma is debated. The current authors evaluated the effects of formoterol alone and a formoterol/budesonide combination inhaler on asthma deterioration induced by repeated low-dose allergen exposure.In total, 15 subjects with intermittent allergic asthma inhaled low doses of allergen on seven consecutive weekdays in a three-period, crossover, double-blind, double-dummy comparison between formoterol 4.5 mg Turbuhaler TM , budesonide 160 mg/formoterol 4.5 mg Turbuhaler TM and placebo, each taken as two puffs 30 min after allergen dosing. The outcome variables were: provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20), exhaled nitric oxide fraction (FeNO), sputum eosinophils and prostaglandin D 2 , and diary card recordings of symptoms (on a scale of 0-10), short-acting b 2 -agonist use and evening forced expiratory volume in one second (FEV1). With placebo treatment, allergen exposure caused significant increases in airway hyperresponsiveness (geometric mean (coefficient of variation) PD20: 397 (98) mg before versus 168 (82) mg after), FeNO (mean¡SD 46¡31 ppb before versus 73¡46 ppb after) and asthma symptom score (mean¡SD 0.39¡0.55 before versus 0.68¡0.67 after). Budesonide/formoterol abolished these changes and significantly improved baseline FEV1. Formoterol alone, while providing symptom relief, was no better than placebo in protecting against the allergen-induced increase in airway inflammation.Signs of deteriorating asthma, provoked by low-dose allergen, are prevented by short-term use of budesonide/formoterol but not by temporary use of formoterol alone.

High‐ and low‐dose allergen challenges in asthmatic patients using inhaled corticosteroids

“…In previous repeated low-dose allergen challenge studies, ICS-naïve asthmatics demonstrated small reductions in FEV1 immediately after allergen exposure (ranging from 6.50 to 9.2%) without any significant effect on FEV1 measured the next morning [16][17][18][25][26][27][28][29]; this is similar to our findings. However, these previous studies also demonstrated increased airway inflammation; FeNO, sputum measurements of eosinophils and sputum Th2 mediators increased after low-dose challenge [18,27,28].…”

“…However, these previous studies also demonstrated increased airway inflammation; FeNO, sputum measurements of eosinophils and sputum Th2 mediators increased after low-dose challenge [18,27,28]. We did not observe any upregulation of airway inflammation.…”

“…The low-dose allergen challenge model has been developed in order to administer a more physiologically relevant concentration of allergen repetitively over a period of days. Low-dose allergen challenge increases airway inflammation and bronchial hyper-reactivity [15][16][17] and is inhibited by ICS and antileukotriene drugs in ICS-naïve asthma patients [15,18]. The low-dose allergen challenge model has not been evaluated in patients taking ICS.…”

Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease

“…Plasma YKL-40 was not affected by either high-dose allergen challenge or repeated low-dose allergen challenge, although both challenges resulted in significant physiological responses (i.e., reductions in FEV 1 and increased responsiveness toward inhaled methacholine) (18,19). Sputum YKL-40 levels were significantly higher following high-dose allergen challenge (before challenge, 68 ng/g sputum; after challenge, 113…”

“…Plasma and sputum samples were collected from well-characterized patients with mild atopic asthma taking part in two separate allergen challenge studies (see online supplement for details). Patients underwent either (1) high-dose allergen challenge (n = 16) to produce a 20% acute fall in FEV 1 (18) or (2) repeated low-dose allergen challenge (n = 15) leading to minimal bronchoconstriction but eosinophilic airway inflammation and increased bronchial hyperresponsiveness to methacholine (19).…”