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
Posting date: 8 May 2012
Sleep-disordered breathing is a modifiable risk factor for severe asthma
A study of 108 children examined the relationships among obesity, sleep-disordered breathing (SDB, defined as intermittent nocturnal hypoxia and habitual snoring), and asthma severity. Children aged 4-18 years (mean age 9 years) were recruited sequentially from a specialty asthma clinic. Asthma severity was determined after 1 year of follow-up and guideline-based treatment, 45% of patients were African-American; 68% male.
Obesity and sleep-disordered breathing (SDB) were common, affecting 43% and 30% of subjects, respectively.
Children with sleep-disordered breathing (SDB) had a 3.62-fold increased odds of having severe asthma at follow-up. Obesity was not associated with asthma severity.
Obesity, asthma, and sleep-disordered breathing are triangular protagonists. The coexistence of 2 or more of these disorders is common and carries a greater risk for worse outcomes. We need to determine if treating SDB improves asthma morbidity.
Ross KR, Storfer-Isser A, Hart MA, Kibler AMV, Rueschman M et al. Sleep-disordered breathing is associated with asthma severity in children. The Journal of Pediatrics 2012; 160(5): 736-742 (doi: 10.1016/j.peds.2011.10.008)
Kheirandish-Gozal L and Gozal D. Obesity, asthma, and sleep-disordered breathing. The Journal of Pediatrics 2012; 160(5): 713-714 (doi: 10.1016/j.peds.2011.11.036)
HDAC1 and HDAC2 expression is not downregulated in severe asthma - contradicting previous studies
Upregulation of glucocorticoid receptor beta (GR beta) has been implicated in steroid resistance in severe asthma in previous studies with some conflicting results. GR beta has been proposed as a dominant negative isoform of glucocorticoid receptor alpha (GR alpha). It has been suggested that GR beta can cause steroid resistance via reduced expression of histone deacetylase 2 (HDAC2).
This bronchoscopic study from two UK centers found that protein and RNA expression for GR alpha, GR beta, and HDAC2 did not differ between patients with different asthma severity and controls. HDAC1 expression was increased in patients with severe asthma compared with healthy volunteers.
The authors concluded that HDAC1 and HDAC2 expression was not downregulated in severe asthma. These data do not support upregulated GR beta and reduced HDAC expression as the mechanism of steroid resistance in severe asthma. Conflicting literature findings may be explained by cross-reactivity of commercially-available antibody tests.
Source: Butler CA, McQuaid S, Taggart CC, Weldon S, Carter R et al. Glucocorticoid receptor β and histone deacetylase 1 and 2 expression in the airways of severe asthma. Thorax 2012; 67(5): 392-398 (doi: 10.1136/thoraxjnl-2011-200760)
Histone deacetylase. Image source: Hdac4 Catalytic Domain. PDB 2vqj, Wikipedia, Creative Commons 3.0 license
Elevated exhaled inflammatory markers (IL-2, IL-4, IL-8, IL-10, sICAM) at age 3 predict wheezing at age 5
Wheezing is a heterogeneous symptom in preschool children. “Not all that wheezes is asthma” is a common expression and it reflects the difficulty of predicting whether symptoms will pass or persist and develop into asthma.
This prospective study evaluated if inflammatory markers in exhaled breath condensate (EBC) at preschool age are associated with wheezing later in life, at school age. Inflammatory markers IL-2, IL-4, IL-8, IL-10, sICAM were measured in 230 children.
Persistent wheezers had elevated levels of all interleukins at preschool age compared to children who never wheezed. However, the markers did not differ between the persistent and transient wheezers.
The study demonstrated that 5-year-old children with persistent wheezing already had elevated exhaled inflammatory markers at preschool age compared to never wheezers. However, the fact that there was no statistical difference between persistent and intermittent users limits the practical implications of this study.
Source: van de Kant KDG, Jansen MA, Klaassen EMM, van der Grinten CP, Rijkers GT et al. Elevated inflammatory markers at preschool age precede persistent wheezing at school age. Pediatric Allergy and Immunology 2012; 23(3): 259-264. (doi: 10.1111/j.1399-3038.2011.01244.x)
Posting date: 8 May 2012