Allergy Asthma Immunol Res.  2010 Jul;2(3):188-194. 10.4168/aair.2010.2.3.188.

Eosinophilic Bronchitis, Eosinophilia Associated Genetic Variants, and Notch Signaling in Asthma

Affiliations
  • 1Genome Research Center for Allergy and Respiratory Disease, Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea. mdcspark@unitel.co.kr

Abstract

While much has indeed been learned about the biology and role of eosinophils, the paradigm of eosinophils has the pros and cons in development of asthma. To answer the questions in the black box, this review firstly discusses the biological and morphological differences between asthma and eosinophilic bronchitis (EB). EB is an interesting clinical manifestation of eosinophilic airway disease that does not involve airway hyperresponsiveness (AHR), demonstrating that airway eosinophilia alone is insufficient to merit a diagnosis of asthma. Secondly, I will describe and discuss the effect(s) of single-nucleotide polymorphisms (SNPs) in the genes CCR3, IL-5 RECEPTOR ALPHA (IL5RA), and IL1RL1, and finally the in vitro and in vivo effects of Notch inhibition on both eosinophil differentiation and experimental asthma. Eosinophilic airway inflammation is not as important in the pathogenesis and maintenance of asthma as had previously been thought. However, the role of eosinophils in other asthma subphenotypes, including refractory or severely remodeled asthma, needs to be evaluated further. High-throughput methodologies such as genomics will facilitate the discovery of new markers of inflammation; these, in turn, will aid in the evaluation of the role of eosinophils in asthma and its various subphenotypes.

Keyword

Eosinophils; bronchitis; polymorphism, single nucleotide; notch; asthma

MeSH Terms

Asthma
Biology
Bronchitis
Eosinophilia
Eosinophils
Genomics
Inflammation
Interleukin-5
Polymorphism, Single Nucleotide
Interleukin-5

Figure

  • Fig. 1 Comparison of the (A) percentage of wall area (WA%), (B) prominence of centrilobular structures, and (C) air trapping on HRCT scans between patients with eosinophilic bronchitis (EB), mild asthma, and normal controls. The WA% was comparable in patients with EB than in normal controls (A). The prominence of centrilobular structures (B) and airway trapping (C) were comparable in patients with EB and mild asthma.12

  • Fig. 2 IL-13 (A) and -5 (B) levels in the induced-sputum of asthmatic patients (BA), those with eosinophilic bronchitis (EB), and healthy control subjects (NC). Open and closed symbols represent atopic and non-atopic subjects, respectively. Horizontal bars represent the median values for each of the three groups. (C) Correlation between sputum IL-13 levels and the PC20 for methacholine in the asthmatic patients. There was a significant, inverse correlation between the IL-13 level and PC20 for methacholine (r=0.484; P=0.02).15

  • Fig. 3 Time-dependent changes in the FEV1 of patients with non-recurrent (solid line) and recurrent (dashed line) eosinophilic bronchitis (EB). FEV1 was significantly lower in the latter group compared with the former during months 9 and 12 of the study period. The data are presented as mean values + SEM. *P=0.01 compared to the group with nonrecurrent EB.16

  • Fig. 4 Therapeutic effects of γ-secretase inhibitor (GSI) administration on airway inflammation in ovalbumin (OVA)-induced mice.30 (A) Inhibition of inflammatory cell infiltration by GSI. Bronchoalveolar lavage fluid (BALF) was collected 48 hr after the final OVA challenge. Total and differential cell counts were performed by enumerating a minimum of 300 cells. The data represent the mean + SEM; n=18 per group. (B) Airway hyperresponsiveness (AHR) was assessed as airway resistance in mice (n=8-10 per group) treated with GSI (0.3, 0.03 or 0.003 mg/kg) after challenge with increasing concentrations of aerosolized methacholine; *P<0.05 and **P<0.01, compared with the OVA-challenged group. Dimethyl sulfoxide (DMSO; 2% v/v) was used in combination with OVA. (C) Effect of incubation time and GSI dose on cytokine production by BAL cells. BAL cells were collected from the airways of mice sensitized and challenged with OVA. Cells were stimulated with PMA (P) and ionomycin (I) in the presence of varying concentrations of GSI for the indicated time periods. The results are expressed as the mean values of triplicate determinations (selected as representative from a total of three to five independent experiments) + SEM.


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