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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

Routinely used lung function tests can underestimate dysfunctions occurring in the small airways

Asthma is a disease characterized by inflammation which affects both proximal and distal airways. This French study evaluated the prevalence of small airway obstruction (SAO) in 441 stable asthmatics with both normal FEV1 and normal FEV1/FVC and treated with inhaled corticosteroids (ICSs) and long acting β2-agonists (LABAs).

The prevalence of SAO was estimated by spirometry and plethysmography.

Small airway obstruction (SAO) was defined by the presence of one or more of the following criteria:

  • functional residual capacity (FRC) higher than 120% predicted
  • residual volume (RV) higher than predicted + 1.64 residual standard deviation (RSD)
  • RV/total lung capacity (TLC) higher than predicted + 1.64 RSD
  • forced expiratory flow (FEF)25–75% lower than predicted − 1.64 RSD
  • FEF50% lower than predicted − 1.64 RSD
  • slow vital capacity (SVC) − FVC higher than 10%

At least one criteria of SAO was found in 52% of patients, mainly lung hyperinflation (39%). In asthmatics with normal FEV1 and FEV1/FVC, treated with ICS/LABA, SAO is found in more than half of the patients indicating that the routinely used lung function tests can underestimate dysfunctions occurring in the small airways.

Source: Perez T, Chanez P, Dusser D, Devillier P. Small airway impairment in moderate to severe asthmatics without significant proximal airway obstruction. Respiratory Medicine 2013; 107(11): 1667-1674. (November) 

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Wheezing preschoolers presenting to Emergency Department (ED) are a unique population: high rate of positive asthma-predictive-index and eosinophilic inflammation

Most preschoolers with viral wheezing exacerbations are not atopic. However, wheezing preschoolers presenting to the ED may be a unique population.

This prospective trial from Israel included 41 wheezing preschoolers presenting to the ED; 30 of them had bronchial challenge tests; 22 had induced sputum.

Significantly more wheezing preschoolers (48.7%) had a positive stringent asthma predictive index (S-API) compared with the community control group (13.7%). In addition, 85.2% had a positive adenosine-bronchial challenge test (BCT) versus 17.5% in the control group. Among wheezing preschoolers presenting to ED, 50% showed eosinophilia in the induced sputum.

Wheezing preschoolers presenting to the ED are a unique population with significantly higher rate of positive stringent asthma predictive index (S-API) and adenosine-BCT compared with controls and frequently (50%) express eosinophilic airway inflammation.

Source: Ater D, Bar BE, Fireman N, Fireman E, Shai H, Tasher D, Dalal I, Mandelberg A. Asthma-predictive-index, bronchial-challenge, sputum eosinophils in acutely wheezing preschoolers. Pediatric Pulmonology 2013; published online before print, 25 October. (doi:10.1002/ppul.22926)

Inhaled dual PDE3/PDE4 inhibitor appears effective bronchodilator and anti-inflammatory drug in asthma and COPD

Many patients with asthma or chronic obstructive pulmonary disease (COPD) routinely receive a combination of an inhaled bronchodilator and anti-inflammatory glucocorticosteroid; but those with severe disease often respond poorly to these classes of drug. This company-sponsored study assessed the efficacy and safety of a new inhaled dual phosphodiesterase 3 (PDE3) and PDE4 inhibitor, RPL554.

Four trials in The Netherlands, Italy, and the United Kingdom suggested that nebulized RPL554 is an effective and well tolerated bronchodilator, bronchoprotector, and anti-inflammatory drug. Further studies will establish the full potential of this new drug for the treatment of patients with COPD or asthma.

Source: Franciosi LG, Diamant Z, Banner KH, Zuiker R, Morelli N, Kamerling IMC, de Kam ML et al. The efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials. The Lancet Respiratory Medicine 2013; 1(9): 714-727. [doi:10.1016/S2213-2600(13)70187-5]

Last updated: Thursday, May 14th, 2015