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What Is New In Small Airways Research

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By Ves Dimov, MD
Assistant Professor of Medicine and Pediatrics
University of Chicago

Small airway involvement is present in all stages of asthmatic disease despite being referred to as silent zone

This review provides an update on the importance of the peripheral, small airways in asthma. As the small airways account for less than 10% of total airway resistance, thus having little impact on standard lung function measures such as forced expiratory volume and peak flow, they have been referred to as the silent zone.

Small airway involvement is present in all stages of asthmatic disease, and is related to important clinical phenotypes such:

  • nocturnal asthma
  • exercise-induced asthma
  • difficult-to-control asthma
  • patients with the risk of repeated asthma exacerbations

Uncontrolled small airway inflammation is related to airway remodeling and progression of the disease, with a more rapid decline in the lung function.

In order to control the disease, we need to target small airway inflammation, which is difficult to reach by standard inhaled medications. A better understanding of the role small airways are playing in asthma shows that the silent zone is not silent at all.

Source: Bejermer L. The role of small airway disease in asthma. Current Opinion in Pulmonary Medicine 2014; 20(1):23-30. (doi:10.1097/MCP.0000000000000018)

Image Source: Wikipedia Commons, public domain

ICS/LABA study questions recommendation of prescribing albuterol as only treatment for exercise-induced bronchoconstriction (EIB) in mild asthma

In mild asthma, exercise-induced bronchoconstriction (EIB) is usually treated with inhaled short-acting beta 2 agonists (SABAs) on demand.

This 6-week, double-blind, parallel-group study from Sweden included 66 patients with asthma (older than 12 years of age) with EIB who were randomized to:

- SABA (terbutaline) on demand
- budesonide (400 µg) daily and terbutaline on demand
- combination budesonide (200 µg) and?formoterol (6 µg) on demand

After 6 weeks of treatment with budesonide daily or combination budesonide and formoterol on demand, the post-exercise FEV1 decrease was smaller than in the group on terbutaline on demand. The total budesonide dose was 2.5 times lower in the combination budesonide and formoterol group than in the budesonide daily group.

The combination of budesonide and formoterol on demand improves asthma control by reducing EIB in the same order of magnitude as daily budesonide treatment despite a lower total steroid dose. Both these treatments were superior to terbutaline on demand, which did not alter the bronchial response to exercise. The results question the recommendation of prescribing SABAs as the only treatment for EIB in mild asthma.

Source: Lazarinis N, Jørgensen L, Ekström T, Bjermer L, Dahlén B et al. Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction. Thorax 2014;69:130-136 (doi:10.1136/thoraxjnl-2013-203557)
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“Frequent exacerbator” is a distinct phenotype of severe asthma, risk factors determined

This multinational trial aimed to characterize the “frequent exacerbator” asthma phenotype and to identify risk factors associated with exacerbations.

93 severe asthmatics and 76 mild-to-moderate patients were prospectively followed for 1 year. During the study, 104 exacerbations were recorded in the severe asthmatics group and 18 in the mild-to-moderate group.

Frequent exacerbators were characterized by:

  • use of higher doses of inhaled (1700 vs. 800 µg) and oral (6.7 vs. 1.7 mg) glucocorticosteroids
  • worse asthma control (ACQ score 2.3 vs. 1.4)
  • lower quality of life
  • higher sputum eosinophils (25.7% vs. 8.2%)
  • more rapid decline in FEV1 /FVC ratio
  • exhaled NO greater than 45 p.p.b. and a history of smoking were associated with an increased risk of frequent exacerbations (odds ratios: 4.32 and 2.90 respectively)

The researchers attempted to characterize a subphenotype of asthma subjects – frequent exacerbators who are significantly more prone to exacerbations. Patients with FeNO > 45 p.p.b. and a history of smoking are at increased risk of frequent exacerbations and require close monitoring in clinical practice.

Source: : Kupczyk M, Ten Brinke A, Sterk PJ, Bel EH, Papi A et al. Frequent exacerbators – a distinct phenotype of severe asthma. BIOAIR investigators. Clinical and Experimental Allergy 2014;44(2): 212-21. (doi: 10.1111/cea.12179)

Last updated: Thursday, May 14th, 2015