US EPA

2262751 

Journal Article 

Abstract 

Airway inflammation, as detected by exhaled nitric oxide, predicts loss of bronchoprotection against exercise-induced bronchospasm (EIB) from long-acting 2-2 beta-2 agonists (LABAs) 

Bonini, M; Permaul, P; Kazani, S; Sorkness, C; Israel, E 

2010 

Yes 

American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 

181 

A3722 

English 

10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A3722 

WOS:000208771003079 

is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans

Introduction: LABAs produce bronchodilation and initially protect against airway narrowing in response to bronchoprovocative stimuli. However, with regular use, the degree of bronchoprotection is diminished. It is unclear who is at greatest risk for the loss of bronchoprotection (LOB).

Aim: To evaluate whether phenotypic characteristics and markers of inflammation can identify subjects at risk of LOB from LABA use.

Methods: We examined associations between LOB against EIB from salmeterol and phenotypic characteristics in an ongoing study on homozygosity at Arg16Gly in ADRB2. Subjects with asthma, not on controller drugs, with >20% fall in FEV1 after at least one of two standardized exercise challenges, took salmeterol 50 mcg b.i.d for 2 weeks. The max. % fall in FEV1 in response to exercise, 9h after salmeterol, was measured on day 1 and after 2 weeks of treatment and compared to the baseline average fall. eNO was measured at baseline on day 1. LOB was expressed as: max. % fall in FEV1 (after last salmeterol dose - after first salmeterol dose) / max. % fall in FEV1 (at baseline - after first salmeterol dose).

Results: 18 subjects were enrolled. Results were expressed as mean+sem. Seventeen (5M/12F) of 18 experienced bronchoprotection (mean inhibition of FEV fall of 65.1% 4.9%) after the first dose of salmeterol and were analyzed (Fig. 1). FEV fell 26.3% 1.3% at baseline, 1+1+9.1%+1.4% after the first dose of salmeterol and 25.9%+4.0% after 2 weeks. The mean LOB was 97.9%. Three patients, all females, were still protected (<10% LOB) against EIB after 2 weeks of salmeterol. Compared to the rest of the cohort these patients had significantly lower baseline levels of eNO (13.0+3.2ppb vs 64.8+8.6ppb p=0.0009). They didn’t differ from the remainder of the population (subjects with a LOB >10) in: baseline FEV (86.0%+5.5% vs. 81.1%+2.6% p>0.05); ACQ score (1.1+0.4 vs. 1.1+0.2 p>0.05); use of rescue medication (0.1+0.1+1 vs. 0.7+0.4 p>0.05); bronchodilator response (10.5%+5.3% vs. 12.0%+2.3% p>0.05). The remaining 9F didn’t differ from the 5M in any examined characteristics.

Conclusions: Low exhaled eNO in asthmatics with EIB identifies a group that does not lose bronchoprotection in response to regular use of LABAs. Since eNO is associated with airway inflammation, it is interesting to speculate whether airway inflammation potentiates down-regulation of bronchoprotection in response to β-2 agonists and whether such effects may be corrected by inhaled corticosteroids. 

American Thoracic Society 2010 International Conference 

New Orleans, LA 

May 14-19, 2010