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. Author manuscript; available in PMC: 2020 Jun 10.
Published in final edited form as: Int Forum Allergy Rhinol. 2018 Feb;8(2):108–352. doi: 10.1002/alr.22073

TABLE VIII.I-2.

Studies investigating allergic rhinitis pathophysiology by nasal histology from biopsies

Study Year LOE Study design Study groups Clinical endpoint Conclusion
Sivam et al.1103 2010 1b DBRPCT SAR (n = 17):
  1. Mometasone (n = 10);

  2. Placebo (n = 7)

Measurement of olfactory function and histological analysis of the olfactory region. Mometasone use associated with reduced olfactory eosinophilic inflammation and improved AR symptoms.
Uller et al.1104 2010 1b DBRPCT SAR to grass or birch (n = 21)
  1. Budesonide (n = 10);

  2. Placebo (n = 11)

Mucosal eosinophilia, apoptotic eosinophils, and expression of CCL5 and CCL11 (eotaxin). Inhibition of CCL5-dependent recruitment of cells to diseased tissue, reduced cell proliferation, and general cell apoptosis, but not increased eosinophil apoptosis, are involved in early phase steroid-induced resolution of AR.
Yang et al.1105 2010 1b DBRPCT PAR to dust mite or animal epithelia (n = 100):
  1. Chinese herbal Xin-yi-san (n = 62);

  2. Placebo (n = 38)

To determine the effectiveness of Xin-yi-san in the treatment of AR and investigation of its molecular mechanism of anti-allergic activity. Xin-yi-san exerts diverse immunomodulatory effects, including suppression of serum IgE levels and increased production of IL-10, sICAM-1, and IL-8 compared to placebo group.
Asai et al.1106 2008 1b RPCT SAR to ragweed (n = 19):
  1. AIT (n = 12);

  2. Placebo (n = 7)

To determine the in vivo effect of short-course AIT on CD4+CD25+ regulatory T-cells in the nasal mucosa of ragweed-sensitive subjects. AIT increases CD4+ CD25+ regulatory T-cell infiltration in the nasal mucosa following allergen challenge after seasonal ragweed-pollen.
Rak et al.1107 2005 1b DBRPCT (double dummy) SAR to birch (n = 41):
  1. AIT;

  2. Budesonide

Measurement of the number of CD1a+, IgE+, and FcεRI+ cells during birch pollen season. Treatment with budesonide, but not AIT, decreased the number of CD1a+, IgE+, and FcεRI+ cells.
Plewako et al.1108 2002 1b SBRPCT SAR to grass (n = 30):
  1. Omalizumab (n = 19);

  2. Placebo (n = 11)

Comparison of anti-CD4, CD8, anti-eosinophil peroxidase, anti-human neutrophil lipocalin, and antibodies against IgE and FcεRI. The number of eosinophil peroxidase-positive staining cells significantly increased in the placebo-treated patients but not in the actively treated patients.
Pullerits et al.1109 2001 1b RPCT SAR to grass pollen (n = 21):
  1. Beclomethasone (n = 16);

  2. Placebo (n = 5)

Comparison of IL-16 expression during the pollen season in actively vs placebo-treated patients. Local upregulation of IL-16 expression contributes to the inflammation observed in seasonal AR.
Wilson et al.1110 2001 1b RPCT SAR to grass pollen (n = 37):
  1. AIT (n = 20);

  2. Placebo (n = 17)

Relationship between symptomatic improvement after AIT and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season. Improvement in symptoms after grass pollen AIT may result from inhibition of IL-5-dependent tissue eosinophilia during the pollen season.
Kujundzić et al.1111 2013 3b Case-control AR (n = 90):
  1. Mometasone (n = 30);

  2. Control (n = 30);

  3. Untreated (n = 30)

Compare by histochemical staining with anti-CD31 and VEGF-C the vascularization of the nasal mucosa of non-allergic, non-treated allergic, and allergic patients treated with mometasone. Significantly lower values of CD31 and VEGF-C expression were observed in non-allergic compared with non-treated allergic and patients treated with mometasone.
Radulovic et al.1112 2008 3b Case-control SAR to grass pollen (n = 22):
  1. AIT (n = 13);

  2. Control (n = 9)

Effect of AIT on the numbers of Foxp3(+) CD4(+) and Foxp3(+) CD25(+) T-cells in and out of season and expression of IL-10 in nasal mucosa. The presence of local Foxp3(+)CD25(+) cells in the nasal mucosa, their increase after AIT, and their association with suppression of seasonal allergic inflammation support a role for T-reg cells in the induction of allergen-specific tolerance.
Till et al.1113 2001 3b Case-control SAR to grass pollen (n = 46):
  1. Fluticasone (n = 23);

  2. Control (n = 23)

Effect of allergen exposure on nasal antigen-presenting cell and epithelial CD1a+ Langerhans cells, CD68+ macrophages, and CD20+ B-cells. Recruitment of CD1a+ Langerhans cells to the nasal mucosa during seasonal allergen exposure may contribute to local T-cell responses.

AIT = allergen immunotherapy; AR = allergic rhinitis; DBRPCT = double-blind randomized placebo-controlled trial; ICAM = intercellular adhesion molecule; IgE = immunoglobulin E; IL = interleukin; LOE = level of evidence; PAR = perennial allergic rhinitis; RPCT = randomized placebo-controlled trial; SAR = seasonal allergic rhinitis; SBRPCT = single-blind randomized placebo-controlled trial; T-reg = T-regulatory cell; VEGF = vascular endothelial growth factor.

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