Allergic rhinitis and asthma: inflammation in a one-airway condition

Abstract

Background: Allergic rhinitis and asthma are conditions of airway inflammation that often coexist.

Discussion: In susceptible individuals, exposure of the nose and lungs to allergen elicits early phase and late phase responses. Contact with antigen by mast cells results in their degranulation, the release of selected mediators, and the subsequent recruitment of other inflammatory cell phenotypes. Additional proinflammatory mediators are released, including histamine, prostaglandins, cysteinyl leukotrienes, proteases, and a variety of cytokines, chemokines, and growth factors. Nasal biopsies in allergic rhinitis demonstrate accumulations of mast cells, eosinophils, and basophils in the epithelium and accumulations of eosinophils in the deeper subepithelium (that is, lamina propria). Examination of bronchial tissue, even in mild asthma, shows lymphocytic inflammation enriched by eosinophils. In severe asthma, the predominant pattern of inflammation changes, with increases in the numbers of neutrophils and, in many, an extension of the changes to involve smaller airways (that is, bronchioli). Structural alterations (that is, remodeling) of bronchi in mild asthma include epithelial fragility and thickening of its reticular basement membrane. With increasing severity of asthma there may be increases in airway smooth muscle mass, vascularity, interstitial collagen, and mucus-secreting glands. Remodeling in the nose is less extensive than that of the lower airways, but the epithelial reticular basement membrane may be slightly but significantly thickened.

Conclusion: Inflammation is a key feature of both allergic rhinitis and asthma. There are therefore potential benefits for application of anti-inflammatory strategies that target both these anatomic sites.

Figure 1

Thickening of the bronchial wall in asthma. Schematic illustrating the thickening of the bronchial wall in asthmatic conditions (right) as compared with normal conditions (left). Reprinted with permission from Jeffery [65].

Figure 2

Plugging of the airways in fatal asthma. Gross view of a sliced lung specimen to show plugging of the airways in fatal asthma. Reprinted with permission from Jeffery [65].

Figure 3

Plug of eosinophil-rich inflammatory exudate and mucus in the airway of a patient with asthma. Concentric lamellae of eosinophils appear blue (alkaline phosphatase antialkaline phosphatase). Reprinted with permission from Jeffery [65].

Figure 4

Eosinophils in the airway wall in fatal asthma. Fatal asthma with eosinophils (blue) in the airway wall showing the origin of the eosinophils that migrate across the mucosa, enter the lumen, and contribute to the inflammatory exudate shown in the previous figure. Reprinted with permission from Jeffery [65].

Figure 5

Eosinophil emerging from a bronchial vessel to enter the bronchial mucosa. Eosinophil emerging from a bronchial vessel to enter bronchial mucosa, as seen by transmission electron microscopy. Reprinted with permission from Jeffery [65].

Figure 6

Colocalization of the cysteinyl leukotriene type 1 receptor with eosinophils in asthma exacerbation. Double immunofluorescence staining for identification of colocalization of the cysteinyl leukotriene type1 (cysLT₁) receptor with eosinophils in a bronchial biopsy from a patient with asthma with severe exacerbation. (a) cysLT₁-receptor protein immunopositivity is illustrated with Texas red fluorescence. (b) Eosinophils stained with anti-human EG₂ coupled to fluorescein isothiocyanate conjugate. (c) EG₂⁺ eosinophils (internal scale bar = 10 μm). Nuclei are counterstained blue with 4',6-diamidino-2-phenylindole. EG₂ is a monoclonal antibody to the cleaved (activated) form of eosinophil cationic protein. Reprinted with permission from Zhu and colleagues [35].

Figure 7

Cysteinyl leukotriene type 1 receptor mRNA and protein-positive cells in bronchial biopsies. Graphs of counts for cysteinyl leukotriene type 1 (cysLT₁) receptor mRNA and protein-positive cells in bronchial biopsies of nonsmoker control (normal), stable asthma, and exacerbated asthma (exac) groups. Data expressed as the number of positive cells per mm² of subepithelium. Dots show individual counts and horizontal bars show median values (Mann-Whitney U test). Reprinted with permission from Zhu and colleagues [35].

Figure 8

Bronchial biopsies in asthma and chronic obstructive pulmonary disease. (a) Bronchial biopsy in a nonsmoker with mild asthma. Note thickening of the epithelial reticular basement membrane in comparison with (b). (b) Bronchial biopsy in a smoker with chronic obstructive pulmonary disease (alkaline phosphatase antialkaline phosphatase, original ×240). Reprinted with permission from Jeffery [66].