What Is New In Small Airways Research
By Ves Dimov, MD
Allergist/Immunologist, Assistant Professor of Medicine and Pediatrics
University of Chicago
Web Content Editor, WAO Small Airways Working Group
Posted: 12 April 2012
There is inconclusive evidence that macrolide antibiotics may have an effect on asthma exacerbations through their antibacterial and/or anti-inflammatory properties. This open-label, randomized, prospective study from Greece included 40 school-aged children with intermittent or mild persistent asthma, presenting with an acute exacerbation. Clarithromycin was given as an add-on therapy, at a dose of 15 mg/kg for 3 weeks.
Children in the clarithromycin group had more symptom-free days (78 vs. 69 days) and less periods with loss of control (9 vs. 19) compared to controls. They had a reduced duration of the index episode (5.0 vs. 7.5 days). However, lung function did not differ between groups.
The authors concluded that when added to regular treatment, a 3-week course of clarithromycin was associated with an increase in the number of symptom-free days, reductions in the number and severity of days with loss of control following index episode, and a decrease in the duration of the initial asthma exacerbation. It would be interesting to see if these findings can be replicated in a larger population and in children with higher severity of asthma.
Source: Kotsoubari I, Papevangelou V, Konstantinou GN, Makrinioti H, Paraskevi X et al. Effect of clarithromycin οn acute asthma exacerbations in children: an open pilot randomized study. Pediatric Allergy and Immunology, 2012 (doi: 10.1111/j.1399-3038.2012.01280.x.) Published online ahead of print 21 March 2012
Image source: Clarithromycin structure. Wikipedia, public domain
Half of patients with mild-to-moderate asthma have noneosinophilic disease, suggesting why FeNO and inhaled steroids may not be helpful.
Airway eosinophilia is often found in asthma, and many controller treatments such as inhaled steroids target eosinophilic disease. However, asthma is a heterogeneous disease and a subgroup of patients do not have airway eosinophilia. This study included almost 1,000 patients with asthma and assessed the prevalence and clinical characteristics of the noneosinophilic asthma phenotype.
Sputum eosinophilia (≥2% eosinophils) was found in only 36% of patients with asthma not taking an inhaled corticosteroid (ICS) and 17% of ICS-treated subjects with asthma. Absence of eosinophilia was noted frequently.
In repeated analyses of people with asthma not taking an ICS, only 22% had sputum eosinophilia on every occasion (persistent eosinophilia), while 47% had no eosinophilia on every occasion (persistently noneosinophilic).
Two weeks of combined anti-inflammatory therapy caused improvements in airflow obstruction in eosinophilic asthma, but not in persistently noneosinophilic asthma. In contrast, bronchodilator responses to albuterol were similar in eosinophilic and noneosinophilic asthma.
Approximately half of patients with mild-to-moderate asthma have persistently noneosinophilic disease, a disease phenotype that responds poorly to currently available anti-inflammatory therapy such as ICS. Measurements of FeNO are recommended in the current ATS guidelines (American Journal of Respiratory and Critical Care Medicine 2011;184(5):602-615, abstract) However, FeNO may not be helpful in patients with noneosinophilic asthma.
Source: McGrath KW, Icitovic N, Boushey HA, Lazarus SC, Sutherland ER et al. A large subgroup of mild-to-moderate asthma is persistently noneosinophilic. American Journal of Respiratory and Critical Care Medicine, 2012; 185(6): 612-619. (doi: 10.1164/rccm.201109-1640OC) Published online ahead of print, 20 January 2012
Sensitivity of methacholine challenge test for diagnosis of asthma is lower than previously reported: 69% in Caucasian and 52% in nonatopic patients.
This cohort study included 126 patients with asthma receiving controller medications and 93 nonasthmatic control participants.
The sensitivity of the methacholine challenge test was 77% and the specificity was 96% with a threshold PC(20) (the provocative concentration of methacholine that results in a 20% drop in FEV(1)) of 8 mg/mL.
The sensitivity was lower in white than in African American participants (69% vs 95%). It was higher in atopic compared with nonatopic (82% vs 52%).
Increasing the PC(20) threshold from 8 to 16 mg/mL did not improve the performance of the test. African American race, atopy, and lower FEV(1) were associated with a positive test result.
Clinicians should take into account the reduced sensitivity of the methacholine challenge test in white and nonatopic asthmatic patients when using this test for the diagnosis of asthma.
Source: Sugar EA, Irvin CG, Kaminsky DA, Shade D, Wei CY et al. Methacholine challenge test: Diagnostic characteristics in asthmatic patients receiving controller medications. American Lung Association Asthma Clinical Research Centers. The Journal of Allergy and Clinical Immunology. 2012 (doi: 10.1016/j.jaci.2012.02.025) Article in press, published online before print 2 April 2012.
Updated: 12 April 2012