Publications by authors named "Anju Peters"

126 Publications

Indirect Treatment Comparison of Biologics in Chronic Rhinosinusitis with Nasal Polyps.

J Allergy Clin Immunol Pract 2021 Feb 3. Epub 2021 Feb 3.

Regeneron Pharmaceuticals, Inc., Tarrytown, N.Y.

Background: Among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), randomized clinical trials (RCTs) of biologics, such as anti-IL-4/IL-13 (dupilumab) and anti-immunoglobulin E (omalizumab), have demonstrated efficacy versus intranasal corticosteroids (INCS). However, no head-to-head RCTs exist between biologics.

Objective: To perform an indirect treatment comparison (ITC) of the efficacy of biologics plus INCS versus placebo (INCS) as a common comparator.

Methods: Embase®, MEDLINE®, and Cochrane were searched for RCTs of biologics in CRSwNP. Bucher ITCs were performed for outcomes at Week 24: nasal polyp score (NPS; range 0-8), nasal congestion (NC; 0-3), loss of smell (LoS; 0-3), University of Pennsylvania Smell Identification Test (UPSIT; 0-40), total symptom score (TSS; 0-12), sino-nasal outcomes test (SNOT-22; 0-110), and responder analyses based on NPS/NC improvement ≥1.

Results: Assessment of trial design, baseline characteristics, and outcome measures suggested ITC was feasible with four phase 3 RCTs: dupilumab SINUS-24/-52 (NCT02912468/NCT02898454); omalizumab POLYP1/2 (NCT03280550/NCT03280537). In the intent-to-treat population, dupilumab had significantly greater improvements from baseline to Week 24 versus omalizumab across key outcomes: NPS (least squares mean difference [95% CI] -1.04 [-1.63, -0.44]), NC (-0.35 [-0.60, -0.11]), LoS (-0.66 [-0.90, -0.42]), UPSIT (6.70 [4.67, 8.73]), and TSS (-1.18 [-1.95, -0.41]). Improvement in SNOT-22 was greater in dupilumab versus omalizumab but was not statistically significant. Dupilumab patients were significantly more likely to achieve ≥1-point improvement in NPS (odds ratio [95% CI] 3.85 [1.82, 7.04]) and NC (2.13 [1.12, 4.04]) versus omalizumab.

Conclusion: Although ITCs have limitations, these results demonstrated dupilumab had consistently greater improvements in key CRSwNP outcomes versus omalizumab at Week 24.
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http://dx.doi.org/10.1016/j.jaip.2021.01.031DOI Listing
February 2021

Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps.

J Allergy Clin Immunol 2020 Dec 14. Epub 2020 Dec 14.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) is a common disease that is characterized by multiple inflammatory endotypes. However, the molecular mechanisms in CRSsNP are poorly understood compared with those of polypoid CRS.

Objective: Our aim was to identify mechanisms and biomarkers associated with inflammatory endotypes underpinning CRSsNP.

Methods: Ethmoid tissues and nasal lavage fluids (NLFs) were obtained from control patients and patients with CRS. The gene expression profiles were determined by microarray analysis and quantitative RT-PCR, and expression of proteins was measured by ELISA and Luminex analysis.

Results: Microarray found that compared with their levels of expression in control tissue, the levels of expression of 126, 241, and 545 genes were more than 3-fold and significantly elevated in CRSsNP with type 1 (T1) endotype, type 2 (T2) endotype, and type 3 (T3) endotype, respectively. Selected identified genes were confirmed by RT-PCR. Gene set enrichment analysis suggested that T1 CRSsNP was associated with IFN-γ signaling and antiviral immunity controlled by T cells (T1 and CD8), natural killer cells, and antigen-presenting cells; T2 CRSsNP was associated with STAT6 signaling and IgE-mediated activation controlled by eosinophils, mast cells, T2 cells, group 2 innate lymphoid cells, and antigen-presenting cells; and T3 CRSsNP was associated with IL-17 signaling, acute inflammatory response, complement-mediated inflammation, and infection controlled by neutrophils, T17 cells, B cells, and antigen-presenting cells. The results suggest that T1 (CXCL9 and CXCL10), T2 (eosinophilic proteins and CCL26), and T3 (CSF3) endotypic biomarkers in NLF may be able to distinguish tissue endotypes in CRSsNP.

Conclusions: Inflammatory endotypes in CRSsNP were controlled by different molecular mechanisms. NLF biomarker assays may allow for more precise and personalized medical treatments in CRS.
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http://dx.doi.org/10.1016/j.jaci.2020.11.037DOI Listing
December 2020

Efficacy of type 2-targeted biologics in patients with asthma and bronchiectasis.

Ann Allergy Asthma Immunol 2021 Mar 1;126(3):302-304. Epub 2020 Dec 1.

Division of Allergy and Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2020.11.014DOI Listing
March 2021

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis.

Int Forum Allergy Rhinol 2020 Nov 24. Epub 2020 Nov 24.

Capital Medical University.

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document.

Methods: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.

Results: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided.

Conclusion: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/alr.22741DOI Listing
November 2020

Targeted Molecular Therapies in Allergy and Rhinology.

Otolaryngol Head Neck Surg 2021 Jan 3;164(1_suppl):S1-S21. Epub 2020 Nov 3.

Scripps Clinic, La Jolla, California, USA.

Biologic agents, monoclonal antibodies that target highly-specific molecular pathways of inflammation, are becoming integrated into care pathways for multiple disorders that are relevant in otolaryngology and allergy. These conditions share common inflammatory mechanisms of so-called Type 2 inflammation with dysregulation of immunoglobulin E production and eosinophil and mast cell degranulation leading to tissue damage. Biologic agents are now available for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, eosinophilic granulomatosis with polyangiitis (EGPA), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). This paper summarizes the diagnosis and management of these conditions and critically reviews the clinical trial data that has led to regulatory approval of biologic agents for these conditions.
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http://dx.doi.org/10.1177/0194599820965233DOI Listing
January 2021

The Role of Biologics in Chronic Rhinosinusitis With Nasal Polyps.

Ear Nose Throat J 2021 Jan 9;100(1):44-47. Epub 2020 Oct 9.

Division of Allergy and Immunology, Department of Medicine, Feinberg School of Medicine, 12244Northwestern University, Chicago, IL, USA.

Biologic therapy is a new treatment option for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Currently, the only biologic with Food and Drug Administration-approval status for CRSwNP is dupilumab. Several other biologics are likely to be approved for CRSwNP, including mepolizumab and omalizumab, based on their promising phase 3 trial results. The role of biologics in the treatment paradigm requires consideration of multiple factors that have yet to be clearly established. This includes identifying patients most appropriate for biologic therapy while considering long-term safety and cost-effectiveness in the context of patient preferences and goals.
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http://dx.doi.org/10.1177/0145561320964653DOI Listing
January 2021

Reply to "Nasal cromolyn in the treatment of rhinitis".

J Allergy Clin Immunol Pract 2020 Sep;8(8):2842

Division of Allergy and Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Ill. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.06.014DOI Listing
September 2020

Decreased nasal polyp eosinophils but increased mast cells in a patient with aspirin-exacerbated respiratory disease treated with reslizumab.

Ann Allergy Asthma Immunol 2020 10 4;125(4):490-493.e2. Epub 2020 Jul 4.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2020.06.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529928PMC
October 2020

Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19.

J Allergy Clin Immunol 2020 08 15;146(2):307-314.e4. Epub 2020 Jun 15.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: The Centers for Disease Control and Prevention advises that patients with moderate to severe asthma belong to a high-risk group that is susceptible to severe coronavirus disease 2019 (COVID-19). However, the association between asthma and COVID-19 has not been well-established.

Objective: The primary objective was to determine the prevalence of asthma among patients with COVID-19 in a major US health system. We assessed the clinical characteristics and comorbidities in asthmatic and nonasthmatic patients with COVID-19. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use.

Methods: Medical records of patients with COVID-19 were searched by a computer algorithm (March 1 to April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients had PCR-confirmed COVID-19. Demographic and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization.

Results: Of 1526 patients identified with COVID-19, 220 (14%) were classified as having asthma. Asthma was not associated with an increased risk of hospitalization (relative risk, 0.96; 95% CI, 0.77-1.19) after adjusting for age, sex, and comorbidities. The ongoing use of inhaled corticosteroids did not increase the risk of hospitalization in a similar adjusted model (relative risk, 1.39; 95% CI, 0.90-2.15).

Conclusions: Despite a substantial prevalence of asthma in our COVID-19 cohort, asthma was not associated with an increased risk of hospitalization. Similarly, the use of inhaled corticosteroids with or without systemic corticosteroids was not associated with COVID-19-related hospitalization.
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http://dx.doi.org/10.1016/j.jaci.2020.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295471PMC
August 2020

Guidance for contemporary use of biologics in management of chronic rhinosinusitis with nasal polyps: discussion from a National Institutes of Health-sponsored workshop.

Int Forum Allergy Rhinol 2020 Sep 3;10(9):1037-1042. Epub 2020 Jul 3.

Department of Otolaryngology, Head and Neck Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX.

Background: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness.

Methods: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients.

Results: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice.

Conclusion: We suggest that physicians evaluate patients on an individual basis and closely monitor for improvement due to the high cost and unknown long-term effects of biologics.
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http://dx.doi.org/10.1002/alr.22633DOI Listing
September 2020

Development and Preliminary Validation of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2341-2350.e1. Epub 2020 May 4.

Department of Otolaryngology-Head and Neck Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Ill; Division of Allergy and Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: Patient-reported outcome (PRO) measures developed and validated on patients with the currently defined phenotypes of chronic rhinosinusitis (CRS) are needed to support clinical trials in CRS.

Objective: This study developed and examined the initial reliability and validity of the CRS-PRO, a new PRO measure of CRS.

Methods: Instrument development was performed through structured interviews and focus groups with clinical experts and 45 patients with CRS meeting current definitions of disease, 21 patients with CRS without nasal polyps (CRSsNP), and 24 patients with CRS with nasal polyps (CRSwNP) to identify items important to patients. Then another 50 patients (32 with CRSsNP and 18 with CRSwNP) with stable CRS symptoms were enrolled to evaluate the reliability of the instrument. Each patient completed the CRS-PRO, Sinonasal Outcome Test-22 (SNOT-22), and 4 Patient-Reported Outcome Measurement Information System short forms at the baseline visit and then at least 7 days later.

Results: After the development process, 21 items were identified from the conceptual domains of physical symptoms, sensory impairment, psychosocial effects, and life impact. Using the responses of the 50 patients with CRS, 21 draft items were further refined to 12 items by eliminating conceptually similar or highly correlated items or those with low mean symptom severity. The 12-item questionnaire was shown to have excellent internal consistency (Cronbach α, 0.86) and test-retest reliability with a high intraclass correlation coefficient (0.89) and Pearson's correlation (r = 0.82, P < .0001). The 12-item CRS-PRO correlated highly with the longer SNOT-22 (r = 0.83, P < .0001) demonstrating its concurrent validity. We also demonstrated validity and reliability in a separate analysis for patients with CRSsNP and CRSwNP.

Conclusion: The CRS-PRO is a concise, valid, and reliable measure that was developed with extensive input from patients with CRS with current disease definitions.
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http://dx.doi.org/10.1016/j.jaip.2020.04.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448958PMC
May 2020

Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.

J Allergy Clin Immunol 2021 Feb 1;147(2):600-612. Epub 2020 May 1.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD.

Objective: Our aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD.

Methods: Single-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence.

Results: The gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO epithelium in NPs from patients with AERD.

Conclusions: Epithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.
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http://dx.doi.org/10.1016/j.jaci.2020.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606335PMC
February 2021

Responsiveness and Convergent Validity of a New Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO).

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2351-2359.e2. Epub 2020 Apr 30.

Department of Otolaryngology - Head and Neck Surgery, Northwestern University, Feinberg School of Medicine, Chicago, Ill; Division of Allergy-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: The CRS-PRO is a new patient-reported outcome measure (PROM) for chronic rhinosinusitis (CRS) that was developed using extensive patient input per Food and Drug Administration guidance on PROMs acceptable for use as end points in clinical trials.

Objective: To assess the responsiveness and convergent validity of the CRS-PRO following standard-of-care medical therapy.

Methods: This was a prospective study of 51 patients (21 with nasal polyps and 30 without) with newly diagnosed CRS or having an acute CRS exacerbation who were initiated on appropriate medical therapy. At the baseline visit each patient completed the CRS-PRO questionnaire, the 22-item Sino-Nasal Outcome Test, the EuroQol 5-dimensional questionnaire, and 4 Patient-Reported Outcome Measure Information System short forms along with objective testing including endoscopic and radiographic scores, smell discrimination, and nasal inspiratory flow testing. This same battery of questionnaires and testing was administered at a follow-up visit 4 to 8 weeks later.

Results: We verified that shortening the 21-item CRS-PRO to 12 items as previously described maintains its psychometric properties. The 12-item CRS-PRO was responsive with a large effect size (Cohen's d, 0.94) comparable to the longer 22-item Sino-Nasal Outcome Test (Cohen's d, 0.93). The instrument was slightly more responsive to medically treated patients with CRS without nasal polyps compared with patients with CRS with nasal polyps (Cohen's d, 1.1 vs 0.89, respectively). The change in 12-item CRS-PRO total score has moderate correlation with change in Lund-Mackay computed tomography scores.

Conclusions: The CRS-PRO is a 12-item rigorously developed, responsive, and valid PROM that was developed using extensive input from patients with current definitions of CRS, including its 2 major phenotypes.
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http://dx.doi.org/10.1016/j.jaip.2020.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448959PMC
April 2020

The Rationale for Multidisciplinary Management of Chronic Rhinosinusitis with Nasal Polyposis.

J Allergy Clin Immunol Pract 2020 05 12;8(5):1565-1566. Epub 2020 Mar 12.

Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, AZ. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.03.001DOI Listing
May 2020

Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis.

Ann Allergy Asthma Immunol 2020 04 30;124(4):318-325. Epub 2020 Jan 30.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Objective: With the advent of new treatment options for Chronic Rhinosinusitis (CRS) comes the ability for physicians to provide more individualized patient care. Physicians are now tasked with identifying who may be the best candidate for a particular therapy. In this review, existing biomarkers and potentially new methods that could guide treatment choices in CRS patients will be discussed.

Data Sources: Published literature obtained through PubMed searches.

Study Selection: Studies relevant to inflammatory endotypes, phenotypes, and biomarkers in CRS were included.

Results: Currently, there are no clinically validated tools that determine the best therapeutic modality for CRS patients with or without nasal polyps (CRSwNP or CRSsNP). Patients with CRS can be classified into three endotypes based on the presence of type 1, type 2, or type 3 inflammation. CRS endotypes can be influenced by age and geographic location. Clinical application however may be limited since endotyping current requires basic research laboratory support. Clinical symptoms may also predict inflammatory endotypes with smell loss being indicative of type 2 inflammation. Numbers of tissue and/or peripheral eosinophils as well as levels of IgE may predict disease severity in CRSwNP but not necessarily treatment responses. Unique clinical phenotypes or biomarkers are especially lacking that predict type 1 or type 3 inflammation in CRSwNP or type 1, type 2, or type 3 inflammation in CRSsNP.

Conclusion: While significant progress has been made in characterizing endotypes, phenotypes, and biomarkers in CRS, additional studies are needed to determine if and how these factors could assist physicians in providing more individualized clinical care.
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http://dx.doi.org/10.1016/j.anai.2020.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192133PMC
April 2020

Current and Future Treatments of Rhinitis and Sinusitis.

J Allergy Clin Immunol Pract 2020 05 28;8(5):1522-1531. Epub 2020 Jan 28.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Advances in understanding the pathogenic mechanisms of both rhinitis and chronic rhinosinusitis have resulted in new treatment options, especially for chronic rhinosinusitis. A review of relevant medical and surgical clinical studies shows that intranasal corticosteroids, antihistamines, and allergen immunotherapy continue to be the best treatments for chronic rhinitis. Dupilumab is the first biologic approved for chronic rhinosinusitis with polyps. Omalizumab, mepolizumab, and benralizumab may have a future role in the treatment of chronic rhinosinusitis. Novel corticosteroid delivery devices such as an exhalation delivery system for fluticasone and bioabsorbable sinus implants provide enhanced and localized distribution of corticosteroids. Surgical management tailored to the underlying disease process improves clinical outcomes in chronic rhinosinusitis with or without nasal polyposis. Advances in the understanding of the heterogeneous nature of rhinitis and rhinosinusitis have resulted in more precise treatments. Improving the understanding of different endotypes should provide better knowledge to determine appropriate current and new therapies to treat these diseases.
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http://dx.doi.org/10.1016/j.jaip.2020.01.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416524PMC
May 2020

Clinical factors associated with acute exacerbations of chronic rhinosinusitis.

J Allergy Clin Immunol 2020 06 29;145(6):1598-1605. Epub 2020 Jan 29.

Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill; Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill. Electronic address:

Background: Chronic rhinosinusitis (CRS) is complicated by frequent acute exacerbations leading to significant health care burden and impaired quality of life.

Objective: The objective of this study was to identify clinical factors associated with frequent acute exacerbation of CRS (AECRS).

Methods: This is a retrospective cohort study of patients with CRS from January 1, 2014, to May 31, 2016. Frequent AECRS was defined as at least 4 episodes over a 12-month period in which an antibiotic was prescribed for worsening sinus symptoms, and infrequent AECRS was defined as 0 to 3 episodes. Clinical factors, including asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease, were evaluated for associations between the 2 groups.

Results: Of the 3109 patients with CRS who were identified, 600 (19.3%) were classified as having frequent exacerbation. Asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease were associated with frequent AECRS with statistically significant adjusted odds ratios (aORs) after controlling for age, race, and sex in multivariate analysis (asthma aOR = 2.61 [95% CI = 2.14-3.18]; allergic rhinitis aOR = 1.96 [95% CI = 1.58-2.42]; eosinophil count of at least 150 cells per microliter aOR = 1.54 [95% CI = 1.21-1.97]; and autoimmune disease aOR = 1.68 [95% CI = 1.36-2.07]). Antibody deficiency, antibiotic allergy, lower FEV, radiographic sinus disease severity, nasal polyposis, and systemic corticosteroid use were also associated with frequent AECRS.

Conclusion: Patients with frequent episodes of AECRS were characterized by a higher prevalence of asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, autoimmune disease, and other allergic and immunologic diseases. These findings identify a high-risk phenotype of patients with CRS for preventive interventions to reduce exacerbation frequency.
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http://dx.doi.org/10.1016/j.jaci.2020.01.023DOI Listing
June 2020

Comorbidities associated with severe asthma.

J Precis Respir Med 2019 Dec;2(1):5-9

Division of Allergy and Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Background: Severe asthma can be a challenging disease to manage by the provider and by the patient, supported by evidence of increased health-care utilization by this population. Patients with severe asthma should be screened for comorbidities because these often contribute to poorly controlled asthma. The impact of comorbidities, however, are not completely understood.

Objective: To review common comorbidities and their impact on severe asthma.

Methods: A review of relevant clinical research studies that examined comorbidities in severe or difficult-to-treat asthma.

Results: A number of comorbid diseases, including rhinitis, rhinosinusitis, gastroesophageal reflux, and obstructive sleep apnea, are associated with severe or difficult-to-treat asthma. If present and untreated, these conditions may adversely affect asthma control, quality of life, and/or lung function, despite adequate treatment with step-up asthma controller therapy.

Conclusion: Treatable comorbidities are associated with severe and difficult-to-control asthma. Failure to recognize these comorbidities may divert appropriate care and increase disease burden. Assessment and management of these risk factors may contribute to improved asthma outcome; however, more investigation is needed to understand the relationship of comorbidities and asthma due to inconsistency in the findings.
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http://dx.doi.org/10.2500/jprm.2019.190006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894622PMC
December 2019

Atopic dermatitis.

Allergy Asthma Proc 2019 11;40(6):433-436

Atopic dermatitis (AD), also known as atopic eczema, is a chronic relapsing inflammatory dermatosis characterized by pruritus, xerosis, and a close association with IgE mediated sensitization to aeroallergens and foods. More than 60% of children with AD are at risk to develop allergic rhinitis or asthma (the atopic march). The distribution of lesions varies by age. Infants tend to have lesions on the cheeks and scalp, and very young children typically have involvement over the extremities, cheeks, forehead, and neck. A rash in the diaper area of infants is rarely AD. Lesions in older children and adults are usually located in flexural areas, such as the antecubital and popliteal fossae, along with the head and neck. Acute lesions of AD begin as erythematous papules and serous exudates. Secondary lesions include excoriations and crusted erosions due to scratching. Subacute lesions appear as erythematous scaling papules and plaques. If the itch and rash progress uncontrolled, then chronic lichenified AD develops, which features accentuated skin markings with hyperpigmentation. Trigger avoidance, skin hydration, and topical steroids are the first steps for improvement. In acute lesions of AD, the T-helper type 2 cells produce interleukin (IL) 4, IL-13, and IL-31, which may potentiate barrier dysfunction and contribute to pruritus. In chronic lesions, the T-helper type 1 cells predominate and secrete interferon γ and IL-12. Barrier dysfunction from filaggrin predisposes patients to AD. Skin superinfection, particularly with Staphylococcus aureus, is common, and cultures of affected lesions help guide therapy. Eczema herpeticum from herpes simplex virus can be life threatening in patients with AD.
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http://dx.doi.org/10.2500/aap.2019.40.4265DOI Listing
November 2019

Asthma in adults: Principles of treatment.

Allergy Asthma Proc 2019 11;40(6):396-402

The goals of treatment are prevention of fatalities, hospitalizations, and emergency department visits, along with achieving good long-term control of asthma, with reduction of symptoms, maintenance of normal activity level, prevention of exacerbations and accelerated loss of pulmonary function (forced expiratory volume in the first second of expiration [FEV]), and avoidance of harm from therapies. Treatment is often initiated based on the severity of symptoms, physical examination findings, and, for some patients, the FEV or peak expiratory flow rates. Comorbidities such as gastroesophageal reflux disease and laryngopharyngeal reflux, rhinitis or rhinosinusitis, sleep apnea, recurrent infections, smoking, and substance abuse should be addressed. Two treatment modalities are indicated only for individuals with allergic asthma: allergen-specific immunotherapy (commonly known as allergy shots), and biologic therapies that target type-2 (T2) inflammation. Allergen immunotherapy is effective in decreasing symptoms and medication use in select patients with mild-to-moderate allergic asthma. In addition, patients who receive allergen immunotherapy for allergic rhinitis may have a decreased risk of developing asthma. Omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab are monoclonal antibodies that target T2 inflammation and are indicated for either moderate-to-severe or severe asthma. These have been well studied to improve asthma symptoms and have specific characteristics unique to each individual medication. A focus on adherence can be considered in choosing therapy because it is not clear which biologic to choose in T2 high asthma at this time.
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http://dx.doi.org/10.2500/aap.2019.40.4256DOI Listing
November 2019

Nasal polyps and rhinosinusitis.

Allergy Asthma Proc 2019 11;40(6):380-384

Rhinosinusitis is defined as inflammation of one or more of the paranasal sinuses and affects approximately 12% of the population. Acute rhinosinusitis is defined as symptoms that last < 12 weeks, and chronic rhinosinusitis (CRS) is defined as symptoms that last > 12 weeks. CRS is divided into three groups: CRS with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and allergic fungal rhinosinusitis. Nasal polyps are inflammatory outgrowths of paranasal sinus mucosa caused by chronic mucosal inflammation and are present in 20% of patients with CRS. Nasal polyps typically present with nasal congestion, nasal obstruction, and anosmia or hyposmia, and occur more frequently in patients with persistent asthma, aspirin-exacerbated respiratory disease (AERD), CRS, and cystic fibrosis. The sinus cavities are lined with pseudostratified ciliated columnar epithelial cells interspersed with mucous goblet cells. Cilia continuously sweep the mucous toward the ostial openings and are important in maintaining the proper environment of the sinus cavities. The frontal, maxillary, and anterior ethmoid sinuses drain into the ostiomeatal unit of the middle meatus. The posterior ethmoid sinuses and superior sphenoid sinuses drain into the sphenoethmoid recess of the superior meatus. Most acute sinus infections are caused by viruses, and, therefore, it is not surprising that the majority of patients improve within 2 weeks without antibiotic treatment. A bacterial infection should be considered if symptoms worsen or fail to improve within 7-10 days. Combining an intranasal corticosteroid with an antibiotic reduces symptoms more effectively than antibiotics alone. Topical nasal steroids are the treatment of choice for nasal polyps. They significantly decrease polyp size, nasal congestion, and rhinorrhea, and increase nasal airflow. Short courses of oral steroids may be needed to reduce polyp size, followed by maintenance therapy with topical steroids. Surgery is reserved for patients in which polyps cause severe obstruction or recurrent sinusitis and for patients for whom medical therapy has failed. Aspirin desensitization may decrease the requirement for polypectomies and sinus surgery in patients with AERD.
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http://dx.doi.org/10.2500/aap.2019.40.4252DOI Listing
November 2019

Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Mucosal Immunol 2020 01 22;13(1):86-95. Epub 2019 Oct 22.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, 60611, IL, USA.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including T2 cells in NPs. The co-culture of NP-derived ILC2s and T2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.
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http://dx.doi.org/10.1038/s41385-019-0215-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917894PMC
January 2020

Prevalence and characterization of chronic rhinosinusitis in patients with non-cystic fibrosis bronchiectasis at a tertiary care center in the United States.

Int Forum Allergy Rhinol 2019 12 7;9(12):1424-1429. Epub 2019 Oct 7.

Division of Allergy and Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Background: Chronic rhinosinusitis (CRS) is associated with bronchiectasis; however, this relationship has not been well studied in the United States (US) population. In this work we aimed to determine the prevalence of CRS among patients with bronchiectasis affiliated with a US tertiary medical center and identify which comorbid diseases are associated with the presence of CRS in patients with bronchiectasis.

Methods: This was a retrospective cohort study in which data were obtained from a large database warehouse at a tertiary care center. Patients with bronchiectasis were identified from 2007 to 2017 using diagnosis codes from the the ninth and tenth revisions of the International Classification of Diseases (ICD-9/10) and confirmed by radiographic evidence of bronchiectasis on chest computed tomography (CT) scans. Patients were divided into cohorts based on presence or absence of concomitant CRS. Characteristics analyzed included demographics, comorbidities, peripheral eosinophil counts, and pulmonary function testing.

Results: CRS was present in 45% (408 of 900) of patients with bronchiectasis. Females represented a majority of bronchiectasis patients, both with and without CRS (69% and 64%, respectively, p = 0.09). After controlling for demographic factors, asthma (p < 0.01), allergic rhinitis (p < 0.01), gastroesophageal reflux disease (p < 0.01), and antibody deficiency (p < 0.01) were associated with the presence of CRS in patients with bronchiectasis.

Conclusion: CRS had a high prevalence and was associated with numerous comorbid conditions in patients with bronchiectasis. These findings have clinical implications for the treatment of patients with bronchiectasis and future research.
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http://dx.doi.org/10.1002/alr.22436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913921PMC
December 2019

Increased thrombin-activatable fibrinolysis inhibitor levels in patients with chronic rhinosinusitis with nasal polyps.

J Allergy Clin Immunol 2019 12 25;144(6):1566-1574.e6. Epub 2019 Sep 25.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease subdivided based on the presence or absence of nasal polyps (NPs). Histologic features of chronic rhinosinusitis with nasal polyps (CRSwNP) include inflammatory cell infiltration and excessive fibrin deposition in NPs. Thrombin-activatable fibrinolysis inhibitor (TAFI) is an enzyme that plays an antifibrinolytic role in the body. The significance of TAFI has been documented in patients with chronic inflammatory diseases, including chronic lung disease; however, it has not been evaluated in the pathogenesis of NPs.

Objective: The objective of this study was to evaluate the potential role of TAFI in the pathogenesis of NPs.

Methods: Nasal lavage fluid was collected from control subjects and patients with CRS. We measured levels of thrombin/anti-thrombin complex (TATc) and TAFI protein using an ELISA.

Results: TATc levels in nasal lavage fluid were significantly increased in patients with CRSwNP and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with control subjects, and TAFI levels in nasal lavage fluid were also significantly increased in patients with CRSwNP compared with those in control subjects and patients with CRSsNP. There was a significant correlation between TATc and TAFI levels in nasal lavage fluid. Interestingly, patients with CRS and asthma showed increased TATc and TAFI levels in nasal lavage fluid compared with those in patients with CRS without asthma, especially patients with CRSwNP.

Conclusions: Increased TATc and TAFI levels in nasal passages of patients with CRSwNP might participate in fibrin deposition in NPs and might play a role in the pathogenesis of CRSwNP and asthma.
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http://dx.doi.org/10.1016/j.jaci.2019.08.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900453PMC
December 2019

TNF induces production of type 2 cytokines in human group 2 innate lymphoid cells.

J Allergy Clin Immunol 2020 01 14;145(1):437-440.e8. Epub 2019 Sep 14.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2019.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949387PMC
January 2020

Dupilumab Efficacy in Uncontrolled, Moderate-to-Severe Asthma with Self-Reported Chronic Rhinosinusitis.

J Allergy Clin Immunol Pract 2020 02 24;8(2):527-539.e9. Epub 2019 Jul 24.

Sanofi, Bridgewater, NJ.

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV) and quality-of-life measures in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in those with a high baseline type 2 phenotype.

Objective: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS).

Methods: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV, patient-reported outcomes, type 2 biomarkers, and safety were assessed.

Results: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P < .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup.

Conclusion: Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS.
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http://dx.doi.org/10.1016/j.jaip.2019.07.016DOI Listing
February 2020

Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis.

J Allergy Clin Immunol Pract 2019 Nov - Dec;7(8):2812-2820.e3. Epub 2019 May 22.

Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address:

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation in the nose and paranasal sinuses. Inflammation in CRS is also heterogeneous and is mainly characterized by type 2 (T2) inflammation, but subsets of patients show type 1 (T1) and type 3 (T3) inflammation. Whether inflammatory endotypes are associated with clinical phenotypes has yet to be explored in detail.

Objective: To identify associations between inflammatory endotypes and clinical presentations in CRS.

Methods: We compared 121 patients with nonpolypoid CRS (CRSsNP) and 134 patients with polypoid CRS (CRSwNP) and identified inflammatory endotypes using markers including IFN-γ (T1), eosinophil cationic protein (T2), Charcot-Leyden crystal galectin (T2), and IL-17A (T3). We collected clinical parameters from medical and surgical records and examined whether there were any associations between endotype and clinical features.

Results: The presence of nasal polyps, asthma comorbidity, smell loss, and allergic mucin was significantly associated with the presence of T2 endotype in all patients with CRS. The T1 endotype was significantly more common in females, and the presence of pus was significantly associated with T3 endotype in all patients with CRS. We further analyzed these associations in CRSsNP and CRSwNP separately and found that smell loss was still associated with T2 endotype and pus with the T3 endotype in both CRSsNP and CRSwNP. Importantly, patients with CRS with T2 and T3 mixed endotype tended to have clinical presentations shared by both T2 and T3 endotypes.

Conclusions: Clinical presentations are directly associated with inflammatory endotypes in CRS. Identification of inflammatory endotypes may allow for more precise and personalized medical treatments in CRS.
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http://dx.doi.org/10.1016/j.jaip.2019.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842686PMC
October 2020

Procalcitonin as a Biomarker in Rhinosinusitis: A Systematic Review.

Am J Rhinol Allergy 2019 Mar 3;33(2):103-112. Epub 2018 Dec 3.

1 Department of Otolaryngology - Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Objectives: (1) To describe the existing literature on procalcitonin (PCT) as a biomarker in patients with acute rhinosinusitis (ARS), (2) to analyze outcomes in ARS patients who were treated with PCT-guided therapy versus traditional management, and (3) to compare PCT to other biomarkers used in diagnosis of bacterial ARS. Data Sources: PubMed and Embase. Review Methods: A systematic search in the PubMed and Embase databases was performed to identify studies related to PCT as a biomarker in ARS. After critical appraisal of validity by 2 authors, 6 studies with a total of 313 patients were selected for data extraction and analysis. We identified 2 randomized control trials (RCTs) of PCT-based guidelines for antibiotic management of ARS in outpatient settings and 4 observational studies that compared PCT to other biomarkers in patients with ARS.

Results: The 2 RCTs demonstrated a reduction (41.6% in 1 study and 71% in the other) in antibiotic prescription rate in the PCT-guided group versus the control group with no change in the number of days with impaired activity due to illness (9.0 vs 9.0 days [ P = .96]; 8.1 vs 8.2 days [95% confidence interval -0.7 to 0.7]), number of days of work missed, and percentage of patients with persistent symptoms at 28 days. In the observational cohort studies, PCT did not consistently correlate with C-reactive protein, body temperature, and/or white blood cell counts.

Conclusions: The limited existing literature on the role of PCT in diagnosis, management, and prediction of clinical outcomes in ARS suggests that PCT-based guidelines for antibiotic prescription are a safe and effective method of minimizing unnecessary antibiotic use.
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http://dx.doi.org/10.1177/1945892418810293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421617PMC
March 2019