Sputum Eosinophils and the Response of Exercise-Induced Bronchoconstriction to Corticosteroid in Asthma

Duong, MyLinh T.; Subbarao, Padmaja; Ädelroth, E; Obminski, George; Strinich, Tara X.; Inman, Mark D.; Pedersen, Søren; O'Byrne, Paul M.

doi:10.1378/chest.07-2048

Cited by 90 publications

(69 citation statements)

References 22 publications

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“…Phenotyping of asthma with inflammometry, especially with the use of sputum cytology (6), might offer advantages such as predicting treatment responses (7,8), highlighting mechanistic pathways involved in disease pathogenesis (9), and predicting future risk (10). Investigations of granulocyte infiltration in induced sputum suggested eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic phenotypes.…”

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confidence: 99%

Untangling asthma phenotypes and endotypes

Agache

Akdiş

Jutel

et al. 2012

Allergy

292

235

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Asthma phenotypes have been developed to address the complexities of the disease. However, owing to a lack of longitudinal studies, little is known about the onset as well as the stability of phenotypes. Distinguishing phenotypes with regard to the severity or duration of the disease is essential. A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term 'endotype'. Classification of asthma based on endotypes provides advantages for epidemiological, genetic, and drug-related studies. A successful definition of endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic mechanism underlying phenotypes or subgroups within a phenotype is important. Whether newly defined asthma endotypes predict the individual course of asthma has to be validated in longitudinal studies. The accurate endotyping reflects natural history of asthma and should help to predict treatment response. Thus, understanding asthma endotypes might be useful in clinical practice.

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confidence: 99%

Untangling asthma phenotypes and endotypes

Agache

Akdiş

Jutel

et al. 2012

Allergy

292

235

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“…30 In addition, the results of several studies suggest that the presence and severity of EIB is significantly associated with the number of eosinophils measured from the blood and sputum of subjects with asthma. [31][32][33][34] Therefore, we hypothesized that eosinophils contribute to the mechanisms underlying EIB and the therapeutic effects of LTRA therapy, and then we investigated the effects of polymorphism combinations on LTRA drug responsiveness and on TEC in children with asthma. Interestingly, we found that the presence of the PTGDR À441C and LTC4S À444C alleles appeared to be associated with increased TEC in children with asthma, especially children with atopic asthma.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma

et al. 2011

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Activation of the prostaglandin D2 receptor (PTGDR) may contribute to pulmonary vasodilation, bronchoconstriction, recruitment of eosinophils, basophils and T-lymphocytes, and enhanced synthesis of leukotriene C4. We investigated whether polymorphisms of the leukotriene C4 synthase (LTC4S) À444A/C and PTGDR À441T/C were associated with clinical phenotypes and responsiveness to leukotriene receptor antagonist (LTRA) in Korean asthmatic children. We enrolled 270 normal and 870 asthmatic children. We prescribed montelukast (5 mg per day) to 100 of asthmatic children, and analyzed the responsiveness to LTRA by exercise challenge tests. Polymorphisms were genotyped by PCR-restriction fragment length polymorphism. As the number of minor alleles of the PTGDR À441T/C and LTC4S À444A/C polymorphisms increased, the log total eosinophil counts increased in atopic asthmatic children (P-value¼0.03). We found a significant association between responsiveness to montelukast and the PTGDR polymorphism (P-value¼0.038). However, the LTC4S À444A/C and PTGDR À441T/C were not associated with the susceptibility for asthma (LTC4S, AA versus AC+CC, adjusted odds ratio of 0.98 (95% confidence interval, 0.73-1.31); PTGDR, TT versus TC+CC, adjusted odds ratio of 0.90 (95% confidence interval, 0.68-1.19)) or clinical phenotypes (P-value40.05). The effects of the PTGDR and LTC4S polymorphisms on the enhancement of eosinophil counts were additive in the Korean children with asthma. In addition, the PTGDR polymorphism seems to be associated with the responsiveness to LTRA. Therefore, therapies that target the PTGDR may be useful for modulating the responsiveness to LTRA.

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“…What is not known is how long the benefit of the ICS treatment lasts following cessation of ICS treatment. If the benefit of ICSs against EIB is a reduction in the number of inflammatory cells, for example eosinophils and mast cells, then the benefit should last until these cells return in significant numbers with adequate concentrations of mediators [17,18]. This timing will depend on the subject's exposure to relevant allergens, viruses and other exacerbating factors.…”

Section: Editorialmentioning

confidence: 99%

The prevention of exercise-induced bronchoconstriction: what are the options?

Anderson

2012

Expert Review of Respiratory Medicine

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Sputum Eosinophils and the Response of Exercise-Induced Bronchoconstriction to Corticosteroid in Asthma

Cited by 90 publications

References 22 publications

Untangling asthma phenotypes and endotypes

Untangling asthma phenotypes and endotypes

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma

The prevention of exercise-induced bronchoconstriction: what are the options?

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