Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response

Gurrola, José; Borish, Larry

doi:10.1016/j.jaci.2017.10.006

Cited by 91 publications

(101 citation statements)

References 89 publications

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“…It is increasingly recognized that CRS comprises a spectrum of conditions with distinct clinical presentations and pathogenic mechanisms. 19 Although CRSsNP is recognized as being predominantly neutrophilic Th1 driven and CR-SwNP as eosinophilic Th2 (high-cytokine IL-4, IL-5, IL-13) driven, there is some overlap between the different phenotypes and endotypes. CRSwNP in Asian populations is driven by Th17 (raised cytokines IL-6, IL-17, and IL-22, tumor necrosis factor-α).…”

Section: Discussionmentioning

confidence: 99%

The role of biologics in chronic rhinosinusitis: a systematic review

Iqbal

Kao²,

Ooi

2019

Int Forum Allergy Rhinol

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Background Chronic rhinosinusitis (CRS) refractory to medical and surgical treatment is challenging. It impacts patients’ quality of life significantly. The pathophysiology of CRS has some similarities to allergic asthma and allergic rhinitis (AR) and includes eosinophilia, T‐helper cell 2 cytokines, and local immunoglobilin E formation. Monoclonal antibody therapy has been used successfully in asthma and AR and more recently in CRS. Our was aim to systematically review the literature and identify the role of monoclonal antibodies (MAbs) in the treatment of CRS with polyps (CRSwNP) and without polyps (CRSsNP), especially with regard to comparability with current medical treatment, efficacy, and risk of complications. In addition, the role of surgery and biologics was evaluated. Methods We identified at total of 5341 relevant studies after a comprehensive database search. Six studies met the inclusion criteria, all 6 randomized, controlled trials. Results Treatment with omalizumab and mepolizumab demonstrated improvements in endoscopic nasal polyp score (EPS) and symptoms score in patients with CRSwNP when compared with placebo. Reslizumab reduced nasal polyp size in patients with raised intranasal interleukin‐5 levels. Dupilumab treatment resulted in a 70% reduction in EPS compared with 20% in the placebo group (p < 0.001). These MAbs target different inflammatory markers involved in the pathophysiology of CRSwNP. None of the studies reported on CRSsNP or combined surgery with biologics. No severe adverse events were reported. Conclusion Evidence demonstrates that use of MAbs leads to clinical improvement in CRSwNP. However, further research is required to determine their long‐term effects, comparability to other medical treatments, and potential side effects.

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Section: Discussionmentioning

confidence: 99%

The role of biologics in chronic rhinosinusitis: a systematic review

Iqbal

Kao²,

Ooi

2019

Int Forum Allergy Rhinol

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“…In addition to antimicrobial properties, some antibiotics have also been found to inhibit different inflammatory pathways as well. For example, doxycycline negatively effects Th2 inflammation, while low‐dose macrolides have been more successful in patients with non‐eosinophilic, neutrophilic inflammation or low IgE CRS . In contrast, topical antibiotics, surfactants and homeopathic treatments such as Manuka honey have not been shown to exert a specific effect on a particular endotype and use of these medications continues to be empiric …”

Section: Discussionmentioning

confidence: 99%

“…In Europe and North America, many studies have shown that the Th2 inflammatory response is predominantly seen in CRSwNP whereas non‐Th2 mediated processes are found more prominently in CRSsNP. However, recent findings have demonstrated that there is in fact a mix of inflammatory processes regardless of polyp status . Non‐Th2 inflammation may be present and have a dominant role in the pathophysiology of both CRSwNP and CRSsNP.…”

Section: Discussionmentioning

confidence: 99%

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Understanding and clinical relevance of chronic rhinosinusitis endotypes

Husain

Sedaghat

2019

Clinical Otolaryngology

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Background Chronic rhinosinusitis (CRS) is the downstream manifestation of heterogeneous pathophysiologic mechanisms leading to chronic sinonasal inflammation. Traditional grouping of patients by symptoms or clinical findings/phenotypes is being replaced by classification of CRS patients based on the underlying pathophysiologic mechanisms: endotypes. Objective of Review To provide an up‐to‐date review on the current knowledge of CRS endotypes with a focus on how the pathophysiologic mechanisms defined by each endotype may be targeted therapeutically. Special emphasis is placed on the clinical relevance of the material and how it may inform the current practice of otolaryngologists. Type of Review A systematic review of contemporary literature review focusing on the latest studies examining the role of endotypes in the management and treatment of CRS. Search Strategy A MEDLINE and PubMed Central search were undertaken to perform this review using the keywords “Endotype” and “Sinusitis.” Evaluation Method Articles containing the keywords, as well as the references of those articles, were then examined for relevance. Results The endotypes for CRS are often defined based on the balance of T‐helper cell patterns of inflammation and can be grouped into Th2 and non‐Th2 inflammation. These groups have shown a variable response to medical and surgical therapy, demonstrating that existing mainstream treatments can be tailored to patients with specific endotypes. The inflammatory mediators of Th2 inflammation, IL‐4, IL‐5 and IL‐13 as well as IgE, are targeted by available biologic drugs that can be used for treatment of refractory disease. Conclusions Increased understanding of CRS endotypes has led to the identification of biomarkers that define these endotypes and act as targets for potential therapeutics. Increasing knowledge about characteristics associated with these endotypes and their responses to treatments, including both established mainstream CRS treatments and novel biologic medications, has allowed incorporation of CRS endotypes into the current clinical decision‐making. Treatment of CRS patients based on consideration of their endotypes is therefore not only presently possible but may improve clinical outcomes of those patients as well.

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“…Although the immunopathology and endotypes present in nasal polyposis are diverse, in North America and Europe it is frequently characterized by T2 inflammation. This includes tissue infiltration with eosinophils, mast cells, T and B cells, among other immunocytes, and expansion of tissue-resident populations such as ILC2s 38,39 (Fig 1). Additionally, EpCs produce chemokines and innate type 2 cytokines (TSLP, IL-25, and IL-33), which are variably demonstrated in these patients, [40][41][42][43] highlighting a potential role for EpCs in initiating or perpetuating inflammatory circuits.…”

Section: Diversity Matters: Airway Epithelial Subsets In Health and Pmentioning

confidence: 99%

Epithelial cell function and remodeling in nasal polyposis

Bankova

Barrett

2020

Annals of Allergy, Asthma & Immunology

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Key MessagesThe respiratory epithelium serves important barrier, innate immune, and repair functions.Differentiated airway epithelial cells are highly specialized and include ciliated, goblet, solitary chemosensory, neuroendocrine, and ionocyte subsets, all of which derive from basal progenitor cells.Basal cell dysplasia is a prominent feature of airway remodeling in chronic rhinosinusitis (CRS) with nasal polyposis, with some molecular signatures that recapitulate developmental programs and promote the persistence of chronic inflammation.Alterations in epithelial composition segregate with CRS phenotype, reflecting the plasticity of basal programs under the influence of type 2 cytokines.Further studies are needed to understand the molecular mechanisms driving airway remodeling and the contribution of rare epithelial cell types to airway health and disease. A B S T R A C TObjective: To review the latest discoveries on airway epithelial cell diversity and remodeling in type 2 inflammation, including nasal polyposis. Data Sources: Reviews and primary research manuscripts were identified from PubMed, Google, and Bioarchives, using the search words airway epithelium, nasal polyposis, or chronic rhinosinusitis with nasal polyposis AND basal cell, ciliated cell, secretory cell, goblet cell, neuroendocrine cell, pulmonary neuroendocrine cell, ionocyte, brush cell, solitary chemosensory cell, microvillus cell, or tuft cell. Study Selections: Studies were selected based on novelty and likely relevance to airway epithelial innate immune functions or the pathobiology of type 2 inflammation. Results: Airway epithelial cells are more diverse than previously appreciated, with specialized subsets, including ionocytes, solitary chemosensory cells, and neuroendocrine cells that contribute to important innate immune functions. In chronic rhinosinusitis with nasal polyposis, the composition of the epithelium is significantly altered. Loss of ciliated cells and submucosal glands and an increase in basal airway epithelial progenitors leads to loss of innate immune functions and an expansion of proinflammatory potential. Type 2 cytokines play a major role in driving this process. Conclusion: Airway epithelial remodeling in chronic rhinosinusitis is extensive, leading to loss of innate immune function and enhanced proinflammatory potential. The mechanisms driving airway remodeling and its sequelae deserve further attention before restitution of epithelial differentiation can be considered a reasonable therapeutic target.

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Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response

Cited by 91 publications

References 89 publications

The role of biologics in chronic rhinosinusitis: a systematic review

The role of biologics in chronic rhinosinusitis: a systematic review

Understanding and clinical relevance of chronic rhinosinusitis endotypes

Epithelial cell function and remodeling in nasal polyposis

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