Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy Weiping Wen, PhD, Wenlong Liu, MD, Luo Zhang, PhD, Jing Bai,

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Presentation transcript:

Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy Weiping Wen, PhD, Wenlong Liu, MD, Luo Zhang, PhD, Jing Bai, MD, Yunping Fan, PhD, Wentong Xia, MD, Qing Luo, PhD, Jing Zheng, PhD, Hongtian Wang, MD, Zuwang Li, MD, Jiahong Xia, PhD, Hongyan Jiang, MD, Zheng Liu, PhD, Jianbo Shi, PhD, Huabin Li, PhD, Geng Xu, PhD Journal of Allergy and Clinical Immunology Volume 129, Issue 6, Pages 1522-1528.e5 (June 2012) DOI: 10.1016/j.jaci.2012.01.079 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Numbers of eosinophils (EOS), neutrophils (NEU), and IL-17+ cells in NP and control tissues. A-C, On the basis of immunohistochemical analysis, levels of eosinophils, neutrophils, and IL-17+ cells were significantly higher in NP than control tissues. D, The different proportions of eosinophils and neutrophils in NP tissues are also presented. Data are represented by box-and-whisker plots; the Mann-Whitney U test was used for statistical analysis. Journal of Allergy and Clinical Immunology 2012 129, 1522-1528.e5DOI: (10.1016/j.jaci.2012.01.079) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Protein levels of MPO, IL-8, and IP-10 in NP and control tissues. A-C, Levels of MPO (Fig 2, A), IL-8 (Fig 2, B), and IP-10 (Fig 2, C) in NP tissues were significantly higher than in control tissues. D-F, When subdivided into neutrophil-negative and neutrophil-positive phenotypes, levels of MPO (Fig 2, D), IL-8 (Fig 2, E), and IP-10 (Fig 2, F) were significantly higher in neutrophil-positive than in neutrophil-negative NPs. Data are represented by a box-and-whisker plot. Solid bars represent median values; the Mann-Whitney U test was used for statistical analysis. Journal of Allergy and Clinical Immunology 2012 129, 1522-1528.e5DOI: (10.1016/j.jaci.2012.01.079) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Changes from baseline in clinical parameters and cytokine levels in patients treated with oral prednisone. A and B, After 1 week of treatment with oral prednisone, levels of eosinophils (Fig 3, A), but not neutrophils (Fig 3, B), were significantly reduced in NP tissues. C-G, Levels of IFN-γ (Fig 3, C), IL-4 (Fig 3, D), and IL-5 (Fig 3, E), but not IL-8 (Fig 3, F) and IL-17 (Fig 3, G), were significantly decreased in nasal secretions after treatment. Solid bars represent mean values; the paired Student t test was used for statistical analysis. NS, Not significant. Journal of Allergy and Clinical Immunology 2012 129, 1522-1528.e5DOI: (10.1016/j.jaci.2012.01.079) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Changes from baseline in NP size, TNSS, nasal congestion score, and nasal resistance after oral prednisone treatment. A, Patients with neutrophil (NEU)–low and neutrophil-high NPs had significantly smaller decreases in bilateral polyp size scores than patients with neutrophil-negative NPs. B-D, Patients with neutrophil-low and neutrophil-high NPs also had significantly smaller decreases in nasal congestion scores (Fig 4, B), TNSSs (Fig 4, C), and nasal resistance (Fig 4, D). Baseline variables were analyzed with the ANOVA test, followed by a paired Student t test for differences before and after treatment, to determine efficacy. Comparisons between the 3 groups were performed with the ANCOVA model; the least-squares means were obtained from ANCOVA with the ages of the patients, duration of symptoms, numbers of eosinophils in polyp tissues, baseline values, atopy, and asthma status. ∗P < .05 compared with neutrophil negative. Journal of Allergy and Clinical Immunology 2012 129, 1522-1528.e5DOI: (10.1016/j.jaci.2012.01.079) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Immunohistochemical locations of eosinophils and neutrophils in NP and healthy control tissues. A-F, Representative staining of MBP+ cells (representing eosinophils), HNE+ cells (representing neutrophils), and IL-17+ cells is shown in healthy control (Fig E1, A, C, and E) and polyp tissues (Fig E1, B, D, and F) tissues. G and H, Representative double-staining of MBP+ cells (blue) and HNE+ cells (brown) is also shown in healthy control (Fig E1, G) and polyp (Fig E1, H) tissues. Journal of Allergy and Clinical Immunology 2012 129, 1522-1528.e5DOI: (10.1016/j.jaci.2012.01.079) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Numbers of eosinophils (EOS) and neutrophils (NEU) in patients with NPs with different polyp size, atopy, and comorbid asthma. A-C, Significantly higher levels of eosinophils were observed in patients with NPs with larger polyp size (Fig E2, A), atopy (Fig E2, B), and comorbid asthma (Fig E2, C). D-F, No significant increase in neutrophil numbers was observed in patients with larger polyp size (Fig E2, D), atopy (Fig E2, E), or comorbid asthma (Fig E2, F). Data are represented by a box-and-whisker plot, and Mann-Whitney U test was used for statistical analysis. NP with large size, NP size score is 3 on either 2 or 2 sides; NP with small size, NP size score is less than 3 on both sides; NS, not significant. Journal of Allergy and Clinical Immunology 2012 129, 1522-1528.e5DOI: (10.1016/j.jaci.2012.01.079) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 mRNA expression of chemokines (CCL2, CCL20, CXCL5, CXCL8, and CXCL10) in patients with NPs and healthy control subjects. mRNA levels of CCL2 (A), CCL20 (B), CXCL5 (C), CXCL8 (D), and CXCL10 (E) were significantly increased in polyp tissues compared with those seen in healthy control tissues. Data are represented by a scatter plot. Solid bars represent median values, and the Mann-Whitney U test was used for statistical analysis. Journal of Allergy and Clinical Immunology 2012 129, 1522-1528.e5DOI: (10.1016/j.jaci.2012.01.079) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions