ASTHMA

Bronchial mucosal inflammation and upregulation of CXC chemoattractants and receptors in severe exacerbations of asthma

Yusheng Qiu¹, Jie Zhu¹, Venkata Bandi², Kay K Guntupalli², Peter K Jeffery¹

¹ Lung Pathology, Department of Gene Therapy, Imperial College, Royal Brompton Hospital, London, UK
² Department of Medicine, Baylor College of Medicine, Ben Taub General Hospital, Houston, Texas, USA

Correspondence to:
Professor Peter K Jeffery
Lung Pathology, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK; p.jeffery{at}ic.ac.uk

Background: A study was undertaken to test the hypothesis that severe exacerbations of asthma are characterised by increased bronchial mucosal neutrophilia associated with upregulation of neutrophil chemoattractant ligands and their specific cell surface receptors.

Methods: Immunohistology and in situ hybridisation were applied to endobronchial biopsy specimens from three groups: (1) 15 patients admitted to hospital with a severe exacerbation of asthma (E-asthma), (2) 15 with stable asthma (S-asthma) and (3) 15 non-atopic and non-smoker surgical controls (NSC).

Results: There were significantly more neutrophils and eosinophils in the epithelium and subepithelium of patients in the E-asthma group (median (range) neutrophils 7 (0–380) and 78 (10–898)/mm², eosinophils 31 (0–167) and 60 (6–351)/mm², p0.01 compared with NSC: 0 (0–10, 0–7, 0–18 and 0–3)/mm², respectively), resulting in similar final densities of eosinophils and neutrophils. With respect to neutrophil chemoattractants and receptors, counts of CXCL5, CXCL8, CXCR1 and CXCR2 mRNA-positive cells in the subepithelium of the E-asthma group were, respectively, 5, 4, 4 and 18 times greater (p0.01) than those of the NSC group. In the E-asthma group, cells expressing CXCL5 or CXCR2 were eightfold and threefold more frequent than those expressing CXCL8 or CXCR1 mRNA, respectively (p<0.01). CXCL5 and CXCR2 in E-asthma were associated with the number of eosinophils (r = 0.59 and 0.66, p<0.02 for both) rather than the number of neutrophils.

Conclusion: In severe exacerbations of asthma there is a bronchial mucosal neutrophilia, eosinophilia and upregulation of CXC chemoattractants and their receptors. CXCL5 and CXCR2 have an association with eosinophila only, and these represent potentially new targets for treatment in exacerbations of asthma.

Abbreviations: COPD, chronic obstructive pulmonary disease; EG2, anti-eosinophil cationic protein; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; NE, neutrophil elastase; RBM, reticular basement membrane

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