Relationship Between Serum Vitamin D, Disease Severity and Airway Remodeling in Children with Asthma.

Am J Respir Crit Care Med. 2011 Sep 15;

Authors: Gupta A, Sjoukes A, Richards D, Banya W, Hawrylowicz C, Bush A, Saglani S

Abstract
Rationale Little is known about vitamin D status and its effect on asthma pathophysiology in children with severe, therapy resistant asthma (STRA). Relationships between serum vitamin D, lung function, and pathology were investigated in pediatric STRA. Methods Serum 25-hydroxyvitamin D (25[OH]D3) was measured in 86 children (mean age 11.7 years), 36 STRA, 26 moderate asthmatics (MA) and 24 non-asthmatic controls. Relationships between 25[OH]D3, the asthma control test (ACT), spirometry, corticosteroid usage, and exacerbations were assessed. 22/36 children with STRA underwent fibreoptic bronchoscopy, bronchoalveolar lavage and endobronchial biopsy with assessment of airway inflammation and remodeling. Results 25[OH]D3 levels (median [IQR]) were significantly lower in STRA (28[22-38])nmol/L than MA (42.5[29-63])nmol/L and controls (56.5[45-67])nmol/L (p<0.001). There was a positive relationship between 25[OH]D3 levels and %predicted forced expired volume (FEV1) (r=0.4, p<0.001) and forced vital capacity (FVC) (r=0.3, p=0.002) in all subjects. 25[OH]D3 levels were positively associated with ACT (r=0.6, p<0.001), and inversely associated with exacerbations (r=-0.6, p<0.001) and inhaled steroid dose (r=-0.39, p=0.001) in MA & STRA. Airway smooth muscle (ASM) mass, but not epithelial shedding or reticular basement membrane thickness, was inversely related to 25[OH]D3 levels (r=-0.6, p=0.008). There was a positive correlation between ASM mass and bronchodilator reversibility (r=0.6, p=0.009) and an inverse correlation between ASM mass and ACT (r=-0.7, p<0.001) Conclusions Lower vitamin D levels in children with STRA were associated with increased ASM mass, worse asthma control and lung function. The link between vitamin D, airway structure and function suggests vitamin D supplementation may be useful in pediatric STRA.

PMID: 21908411 [PubMed - as supplied by publisher]

Profiling of Sputum Inflammatory Mediators in Asthma and Chronic Obstructive Pulmonary Disease.

Respiration. 2011 Sep 7;

Authors: Bafadhel M, McCormick M, Saha S, McKenna S, Shelley M, Hargadon B, Mistry V, Reid C, Parker D, Dodson P, Jenkins M, Lloyd A, Rugman P, Newbold P, Brightling CE

Abstract
Background: Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation. Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown. Objectives: To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD. Methods: Subjects with asthma and COPD (n = 54 and n = 49) were studied. Clinical characteristics and sputum were collected at entry into the study. A 2-step sputum processing method was performed for supernatant and cytospin preparation. Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels. Results: Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17. There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02]. In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes. However, these phenotypes were unrelated to the diagnosis of asthma or COPD. Conclusion: Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique. Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease. Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated.

PMID: 21912093 [PubMed - as supplied by publisher]

Optimal management of severe/refractory asthma.

Clin Med Insights Circ Respir Pulm Med. 2011;5:37-47

Authors: Pakhale S, Mulpuru S, Boyd M

Abstract
Asthma is a chronic inflammatory disease of the airways, affecting approximately 300 million people worldwide. Asthma results in airway hyperresponsiveness, leading to paroxysmal symptoms of wheeze, cough, shortness of breath, and chest tightness. When these symptoms remain uncontrolled, despite treatment with high doses of inhaled and ingested corticosteroids, asthmatic patients are predisposed to greater morbidity and require more health care support. Treating patients with severe asthma can be difficult and often poses a challenge to physicians when providing ongoing management. This clinical review aims to discuss the definition, prevalence and evaluation of severe asthmatics, and provides a review of the existing pharmacologic and non-pharmacologic treatment options.

PMID: 21912491 [PubMed - in process]

Pediatric asthma: natural history, assessment, and treatment.

Mt Sinai J Med. 2011 Sep;78(5):645-60

Authors: Herzog R, Cunningham-Rundles S

Abstract
Wheezing and childhood asthma are not synonymous but rather comprise a heterogeneous group of conditions that have different outcomes over the course of childhood. Most infants who wheeze have a transient condition associated with diminished airway function at birth and have no increased risk of asthma later in life. However, children with persistent wheezing throughout childhood and frequent exacerbations represent the main challenge today. Studying the natural history of asthma is important for the understanding and accurate prediction of the clinical course of different phenotypes. To date, a great improvement has been achieved in reducing the frequency of asthma symptoms. However, neither decreased environmental exposure nor controller treatment, as recommended by the recent National Asthma Education And Prevention Program, can halt the progression of asthma in childhood or the development of persistent wheezing phenotype. This review focuses on the recent studies that led to the current understanding of asthma phenotypes in childhood and the recommended treatments. Mt Sinai J Med 78:645-660, 2011. © 2011 Mount Sinai School of Medicine.

PMID: 21913196 [PubMed - in process]