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What Is New In Small Airways Research

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Author: Ves Dimov, M.D.
Allergist/Immunologist at Cleveland Clinic
Clinical Associate Professor
FAU Charles E. Schmidt College of Medicine
Small Airways Working Group

Biomarker-based asthma phenotypes of corticosteroid response: high Feno and urinary BrTyr predict ICS response

Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma, but the clinical response to ICSs is variable. In this study authors hypothesized that a panel of inflammatory biomarkers (ie, fraction of exhaled nitric oxide [Feno], sputum eosinophil count, and urinary bromotyrosine [BrTyr] level) might predict steroid responsiveness.

In the study, after 28-day trial of ICSs, Feno values decreased in 82% of asthmatic patients, sputum eosinophil counts decreased in 60%, and urinary BrTyr levels decreased in 58%. Each of the biomarkers at the steroid-naive phase had utility for predicting steroid responsiveness, but the combination of high Feno values and high urinary BrTyr levels had the best power to predict a favorable response to ICS therapy. However, the magnitude of the decrease in biomarker levels was unrelated to the magnitude of clinical response to ICS therapy.

In conclusion, a noninvasive panel of biomarkers in steroid-naive asthmatic patients can predict clinical responsiveness to ICS therapy.

Source: Cowan DC, Taylor DR, Peterson LE, Cowan JO, Palmay R, Williamson A, Hammel J et al. Biomarker-based asthma phenotypes of corticosteroid response. The Journal of Allergy and Clinical Immunology 2015;135(4):896-902. (doi:

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Image Source: Wikipedia, Dibromotyrosine; public domain

Elevated exhaled leukotriene B₄ may be used as a noninvasive marker of small airways disease

Inflammatory processes in the asthmatic lung involve the large and small airway and alveolar sites. Leukotriene B4 (LTB) is an important disease marker, but its role in inflammation of the small airways in asthma has not been established yet.

In this study used the new technique of fractionated exhaled breath condensate sampling to distinguish between large and small airway or alveolar LTB₄ concentrations in children with asthma.

Sixty-eight children (9-17 years old, 33 children with asthma, and 35 controls) underwent fractional exhaled nitric oxide (FeNO) measurements, lung function testing, and collection of fractionated exhaled breath condensate using a capnograph-based approach.

Children with asthma had higher LTB₄ concentrations in the small airway or alveolar fraction than controls (5.58 pg/mL vs 2.0 pg/mL).

LTB₄ is detectable and elevated in the small airway or alveolar fraction of exhaled breath condensate in pediatric asthma. Because of the possibility of detecting elevated levels in patients without lung function impairment in controlled disease, it may be used as a noninvasive marker of small airways disease; however, future long-term studies are needed.

Source: Trischler J, Muller CM, Konitzer S, Prell E, Korten I, Unverzagt S, and Lex C. Elevated exhaled leukotriene B₄ in the small airway compartment in children with asthma.

Annals of Allergy Asthma & Immunology 2015;114(2):111-116. (doi:10.1016/j.anai.2014.11.022).



3.6% of asthmatic adults have severe refractory asthma (10.4 patients per 10,000 inhabitants), lower than previous estimates

Severe asthma is characterized by difficulty to achieve disease control despite high-intensity treatment. However, prevalence figures of severe asthma are lacking, whereas longstanding estimates vary between 5% and 10% of all asthmatic patients. Knowing the exact prevalence of severe refractory asthma as opposed to difficult-to-control asthma is important for clinical decision making, drug development, and reimbursement policies by health authorities.

Severe refractory asthma was defined by the Innovative Medicine Initiative consensus. Adult patients with a prescription for high-intensity treatment (high-dose inhaled corticosteroids and long-acting beta2-agonists or medium- to high-dose inhaled corticosteroids combined with oral corticosteroids and long-acting beta2-agonists) were extracted from 65 Dutch pharmacy databases, representing 3% of the population (500,500 inhabitants). Questionnaires were sent to 5,002 patients, of which 2,312 were analyzed. Inhalation technique was assessed in a random sample of 60 adherent patients (prescription filling 80% or higher). Patients with difficult-to-control asthma, adherence to treatment, and a correct inhalation technique were qualified as having severe refractory asthma.

Of asthmatic adults, 3.6% (95% CI, 3.0% to 4.1%) qualified for a diagnosis of severe refractory asthma, representing 10.4 patients per 10,000 inhabitants.

The prevalence of severe refractory asthma might be lower than estimated by expert opinion. This implies that currently recognized severe asthma subphenotypes could meet the criteria of rare diseases.

Source: Hekking PPW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, and Bel EH. The prevalence of severe refractory asthma. Journal of Allergy and Clinical Immunology 2015;135(4):896–902. (doi:


Last updated: Monday, April 20th, 2015