Studies of the role of basophils in aspirin-exacerbated respiratory disease pathogenesis.
BACKGROUND
Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type 2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear.


OBJECTIVE
We sought to characterize the systemic and local basophil responses in patients with AERD compared with patients with CRSwNP.


METHODS
Sinonasal tissues including inferior turbinate and/or nasal polyps (NPs) and peripheral blood were collected from controls, patients with AERD, and patients with CRSwNP. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63), and intracellular (2D7) markers associated with basophils was characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained.


RESULTS
The mean number of basophils (CD45+CD203c+FcεRI+CD117-) detected in AERD NPs (147 ± 28 cells/mg tissue) was significantly elevated compared with that detected in CRSwNP NPs (69 ± 20 cells/mg tissue; P = .01). The number of circulating basophils was significantly elevated in patients with AERD (P = .04). Basophils in NPs had significantly higher CD203c and CD63 mean fluorescence intensity compared with blood in both conditions (P < .01). Basophils from AERD NPs had lower expression of the granule content marker 2D7 compared with those from matched blood (P < .01) or NPs of patients with CRSwNP (P = .06), suggesting ongoing degranulation. Basophil 2D7 mean fluorescence intensity significantly correlated with pulmonary function (r = 0.62; P = .02) and inversely correlated with sinonasal inflammation (r = -0.56; P = .004).


CONCLUSIONS
Increased basophil numbers and extent of ongoing degranulation in NPs of patients with AERD compared with patients with CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.
['Stevens|Whitney W|WW|', 'Staudacher|Anna G|AG|', 'Hulse|Kathryn E|KE|', 'Poposki|Julie A|JA|', 'Kato|Atsushi|A|', 'Carter|Roderick G|RG|', 'Suh|Lydia A|LA|', 'Norton|James E|JE|', 'Huang|Julia H|JH|', 'Peters|Anju T|AT|', 'Grammer|Leslie C|LC|', 'Conley|David B|DB|', 'Shintani-Smith|Stephanie|S|', 'Tan|Bruce K|BK|', 'Welch|Kevin C|KC|', 'Kern|Robert C|RC|', 'Schleimer|Robert P|RP|']
D000328:Adult D001249:Asthma D001491:Basophils D002908:Chronic Disease D016861:Cyclooxygenase Inhibitors D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D009298:Nasal Polyps D012220:Rhinitis D012852:Sinusitis
basophil Aspirin-exacerbated respiratory disease AERD nasal polyp CRSwNP 2D7 chronic sinusitis