What Is New In Small Airways Research
By Ves Dimov, MD
Assistant Professor of Medicine and Pediatrics
University of Chicago
Distances within 300-500 meters of roadways affect human health. In large North American cities, 30-45% of people live near a major roadway. Patients with asthma should ideally live at least 300 meters from major roadways, especially those with heavy truck traffic. In-vehicle exposure during commuting with open windows can also be very high. Air pollutants cause oxidative injury to airways, leading to inflammation, remodeling, and increased sensitization.
14% of incident asthma and 15% of all exacerbations of childhood asthma are attributed to road traffic pollutants. Air pollution can cause exacerbations of pre-existing asthma but it also might cause new-onset asthma. Cities with rapid economic and population growth (China and India) have some of the worst air quality in the world. Short-term exposures to ozone, nitrogen dioxide, sulphur dioxide, PM2·5, and TRAP are thought to increase the risk of exacerbations of asthma symptoms.
This comprehensive review from The Lancet presents a snapshot of our current understanding of the relationship between outdoor air pollution and asthma (free full text after registration).
Source: Guarnieri M and Balmes JR. Outdoor air pollution and asthma. The Lancet 2014; 383(9928): 1581-1592. [doi:10.1016/S0140-6736(14)60617-6]
Classification and treatment of preschool wheezing: 2014 update
Wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but they may also be considered in patients with episodic viral wheeze with frequent or severe episodes or when the clinician suspects that interval symptoms are being under reported.
Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect.
Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalized patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.
Source: Paul LP, Caudri D, Eber E, Gaillard EA, Garcia-Marcos L, Hedlin G, Henderson J et al. Classification and pharmacological treatment of preschool wheezing: changes since 2008. European Respiratory Journal 2014; 43(4): 1172-1177. [doi:10.1183/09031936.00199913]
Refractory asthma: mechanisms, targets, and therapy – 2014 review
This free, full-text review in the EAACI journal Allergy examines our current understanding of refractory asthma. Why do inhaled corticosteroids seem to be ineffective in some patients with severe asthma? Some of the reasons are discussed below.
Inhaled corticosteroids (ICS) target gene transcription through their interactions with the glucocorticoid (GC) receptor (GR) at the glucocorticoid response element (GRE). The GC/GR complex enhances anti-inflammatory but inhibits pro-inflammatory mediator production. Classically, asthma has been described as a Th2-associated eosinophil-predominant disease, but recently alternative models have been described including a Th17-mediated neutrophil-predominant phenotype resulting in patients with more severe disease who may be less responsive to steroids.
Additional mechanisms of steroid resistance include increased activity of GR phosphorylating kinases which modify the interactions of GR with transcription factors to inhibit the ability of GR to bind with GRE, leading to an increase in pro-inflammatory gene transcription. Oxidative stress also affects the balance between pro-inflammatory and anti-inflammatory gene transcription through the modification of transcription factors and cofactors (such as PI3K) leading to the inhibition of histone deacetylase 2.
Continued investigations into the mechanisms behind glucocorticoid resistance will lead to novel treatments that improve control of severe refractory asthma.
Source: Trevor JL and Deshane JS. Refractory asthma: mechanisms, targets, and therapy. Allergy 2014; Published online before print 29 April. (doi:10.1111/all.12412)