Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy

doi:10.1016/j.jaci.2012.01.079

Journal of Allergy and Clinical Immunology

Volume 129, Issue 6, June 2012, Pages 1522-1528.e5

https://doi.org/10.1016/j.jaci.2012.01.079 Get rights and content

Background

Nasal polyps (NPs) are characterized by eosinophilic inflammation, which is generally considered sensitive to corticosteroid treatment.

Objectives

We evaluated levels of neutrophilia in NPs and investigated whether increased neutrophilia in polyp tissue affected the response to corticosteroid treatment.

Methods

We studied 3 independent cross-sectional groups of patients with NPs. Levels of infiltration by different types of inflammatory cells were determined by using immunohistochemical analyses and compared with those seen in control nasal tissues from subjects without NPs. Levels of inflammatory mediators were measured by using real-time PCR, ELISA, and FlowCytomix analyses. Patients with NPs received oral corticosteroid therapy (30 mg of prednisone once daily for 7 days); clinical parameters of efficacy were associated with NP phenotypes.

Results

Among patients with NPs, 76.5% had an eosinophilic phenotype, 46.0% had a neutrophilic phenotype, and 35.8% had a mixed phenotype (indicated by double staining). Overall, patients' symptoms improved after corticosteroid treatment; numbers of eosinophils and levels of their mediators (IL-4 and IL-5), but not numbers of neutrophils or levels of their mediators (IL-8 and interferon-inducible protein 10), were reduced (P < .05). After corticosteroid treatment, patients with the nonneutrophilic phenotype (neutrophil negative) had significantly greater reductions in bilateral polyp size scores, nasal congestion scores, total nasal symptom scores, and nasal resistance than patients with the neutrophilic phenotype (neutrophil positive, P < .05).

Conclusions

There are different phenotypes of NPs based on the type of immune cell infiltrate and cytokines produced (eosinophilic or neutrophilic). Patients with the neutrophilic phenotype have less response to treatment with corticosteroids based on symptom scores.

Section snippets

Study design and subjects

Subjects with NPs were recruited from participating hospitals; they received their diagnoses based on the standard criteria for NPs issued in the European Position Paper on Rhinosinusitis and Nasal Polyps 2007 guidelines.¹ The control group comprised patients undergoing septoplasty for anatomic variations. Tissues were removed from the inferior turbinate during septal surgery. None of the subjects used oral or nasal corticosteroids or other medications (eg, antibiotics or antileukotrienes) for

Eosinophil and neutrophil infiltration of NP and control tissues

The clinical characteristics of group 1 are shown in Table I. The presence of eosinophils and neutrophils in nasal tissues was determined by means of immunohistochemical staining for MBP and HNE. Representative results for eosinophils, neutrophils, and IL-17⁺ cells are presented in Fig E1 in this article's Online Repository at www.jacionline.org.

Eosinophils and neutrophils were each frequently detected in polyp tissues. The lamina propria in polyp tissues had strong and extensive staining for

Discussion

In the present study we demonstrated that NPs have higher levels of neutrophil infiltration and neutrophil-related mediators than nasal tissues from control subjects. We can define different phenotypes of NPs based on cell composition and levels of neutrophil-associated mediators. NPs with these different phenotypes (neutrophil negative and neutrophil positive) have different levels of response to prednisone therapy. Polyp histology might therefore be used to predict the response to

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: Supported by National Natural Science grants of China (no. 30872845, 81070771, 81070772, and U0832007), a grant from the Ministry of Hygiene (no. 201202005), Guangdong Province Natural Science grants (no. 9151006001000014, S2011010004634, and S2011020002295), and the Program for New Century Excellent Talents in University (no. NCET-10-0851).

: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

^∗: These authors contributed equally to this study.

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Rhinitis, sinusitis, and upper airway diseaseIncreased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy

Background

Objectives

Methods

Results

Conclusions

Section snippets

Study design and subjects

Eosinophil and neutrophil infiltration of NP and control tissues

Discussion

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Immunol Allergy Clin North Am

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Otolaryngol Head Neck Surg

Chest

Rhinitis, sinusitis, and upper airway disease
Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy