Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge

Abstract

Rationale: Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments.

Objective: To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study.

Methods: We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n = 14) compared with immunotherapy-treated allergics (n = 14), plus a nonatopic control group (n = 14). Volunteers underwent a standardized NAC with 2000 biological units of timothy grass allergen (equivalent to 1.3 μg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed.

Results: Immunotherapy-treated patients had lower symptom scores (P = 0.04) and higher PNIF (P = 0.02) after challenge than untreated allergics. They had reduced early (P = 0.0007) and late (P < 0.0001) skin responses, and lower retrospective seasonal symptom scores (P < 0.0001). Compared to untreated allergics, immunotherapy-treated patients had reduced nasal fluid concentrations of IL-4, IL-9 and eotaxin (all P < 0.05, 8 h level and/or area under the curve comparison), and trends for reduced IL-13 (P = 0.07, area under the curve) and early-phase tryptase levels (P = 0.06).

Conclusions: Nasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies.

Keywords: Th2; allergic rhinitis; chemokine; cytokine; tryptase.

Figure 1

Response to nasal allergen challenge. A, total nasal symptom score (TNSS); B, change from baseline peak nasal inspiratory flow (∆PNIF); both mean ± SE. C, TNSS per hour combined early (EPR, 0–1 h)‐ and late (LPR, 1–8 h)‐phase responses with equal weighting; D, ∆PNIF per hour combined EPR and LPR; both median and interquartile range, between‐group comparisons by Mann–Whitney U‐test.

Figure 2

A, nasal fluid tryptase; B, nasal fluid eotaxin; both pg/ml, median and interquartile range. †P < 0.1, untreated allergics vs immunotherapy at 8 h, Mann–Whitney U‐test.

Figure 3

A, nasal fluid IL‐9; B, IL‐4; C, IL‐5; D, IL‐13; median and interquartile range. *P < 0.05, untreated allergics vs immunotherapy, 8 h, Mann–Whitney U‐test.

Figure 4

Response to intradermal injection of 1 BU purified timothy grass pollen allergen at 15 min (A, early‐phase response, EPR) and 8 h (B, late‐phase response, LPR). Mean of longest diameter and perpendicular diameter at midpoint of longest diameter, in millimetres. Median and interquartile range shown; between‐group comparisons by Mann–Whitney U‐test. Squares represent individuals receiving sublingual immunotherapy; and triangles, subcutaneous immunotherapy.