Publications by authors named "Bruce K Tan"

116 Publications

Studies of the Role of Basophils in Aspirin Exacerbated Respiratory Disease Pathogenesis.

J Allergy Clin Immunol 2021 Apr 2. Epub 2021 Apr 2.

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

Background: Aspirin Exacerbated Respiratory Disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 (COX-1) enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type-2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear.

Objective: To characterize the systemic and local basophil responses in AERD compared to CRSwNP patients.

Methods: Sinonasal tissues including inferior turbinate (IT) and/or nasal polyps (NP) and peripheral blood were collected from controls, AERD, and CRSwNP patients. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63) and intracellular (2D7) markers associated with basophils were characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained.

Results: The mean number of basophils (CD45CD203cFcεRICD117) detected in AERD NP (147±28 cells/mg tissue) was significantly elevated compared to CRSwNP (69±20 cells/mg tissue; p=0.01). The number of circulating basophils was significantly elevated in AERD (p=0.04). Basophils in NP had significantly higher CD203c and CD63 MFI compared to blood in both conditions (p<0.01). Basophils from AERD NP had lower expression of the granule content marker 2D7 than matched blood (p<0.01) or NP of CRSwNP (p=0.06), suggesting ongoing degranulation. Basophil 2D7 MFI significantly correlated with pulmonary function (r=0.62, p=0.02) and inversely correlated with sinonasal inflammation (r=-0.56, p=0.004).

Conclusions: Increased basophil numbers and extent of ongoing degranulation in NP of patients with AERD compared to CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.
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http://dx.doi.org/10.1016/j.jaci.2021.02.045DOI Listing
April 2021

Responsiveness and convergent validity of the chronic rhinosinusitis patient-reported outcome (CRS-PRO) measure in CRS patients undergoing endoscopic sinus surgery.

Int Forum Allergy Rhinol 2021 Mar 16. Epub 2021 Mar 16.

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

Background: The chronic rhinosinusitis patient-reported outcome (CRS-PRO) measure is a 12-item measure with previously demonstrated validity in chronic rhinosinusitis (CRS) patients receiving medical therapy. This study establishes the factor structure, responsiveness, and convergent validity of the CRS-PRO following endoscopic sinus surgery (ESS).

Methods: Northwestern CRS Subject Registry patients had pre-ESS, 3-month (n = 111; CRS without nasal polyps [CRSsNP] = 60, CRS with nasal polyps [CRSwNP] = 51), and 6-month (n = 86; CRSsNP = 47, CRSwNP = 39) post-ESS assessments where patients completed the CRS-PRO, 22-item Sino-Nasal Outcome Test (SNOT-22), and four Patient-Reported Outcomes Measurement (PROM) Information System (PROMIS) short forms (general health measures). Patients had pre-ESS objective testing (endoscopic and radiographic assessment). Factor analysis was conducted using principal axis factoring with varimax rotation on the baseline CRS-PRO. The clinically important difference (CID) was estimated using both distribution-based and anchor-based methods.

Results: Factor analysis found the CRS-PRO comprised the "rhino-psychologic," "facial discomfort," and "cough" factors, which were responsive to ESS and correlated with the other PROMs. The changes observed in the CRS-PRO at 3 months had strong correlation with the corresponding changes in SNOT-22 (r = 0.792, p < 0.0001) and moderate correlations with changes in PROMIS fatigue and sleep domains. These changes had a very large effect size (Cohen's d 1.44) comparable to the longer SNOT-22 (Cohen's d 1.41) with slightly larger effect sizes observed in CRSwNP compared to CRSsNP patients. Similar convergent validity and responsiveness were observed in the 6-month data. The CRS-PRO CID was estimated to be between 5.0 and 7.5 (midpoint 6.0) using distribution-based and anchor-based methods.

Conclusion: This study demonstrates the validity and responsiveness of the CRS-PRO in subjects receiving ESS.
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http://dx.doi.org/10.1002/alr.22782DOI Listing
March 2021

Targetable pathogenic mechanisms in nasal polyposis.

Int Forum Allergy Rhinol 2021 Mar 3. Epub 2021 Mar 3.

Department of Otolaryngology, Head and Neck Surgery, Chicago, Illinois, USA.

Chronic rhinosinusitis with nasal polyps (CRSwNP) represents a challenging disease entity with significant rates of recurrence following appropriate medical and surgical therapy. Recent approval of targeted biologics in CRSwNP compels deeper understanding of underlying disease pathophysiology. Both of the approved biologics for CRSwNP modulate the type 2 inflammatory pathway, and the majority of drugs in the clinical trials pathway are similarly targeted. However, there remain multiple other pathogenic mechanisms relevant to CRSwNP for which targeted therapeutics already exist in other inflammatory diseases that have not been studied directly. In this article we summarize pathogenic mechanisms of interest in CRSwNP and discuss the results of ongoing clinical studies of targeted therapeutics in CRSwNP and other related human inflammatory diseases.
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http://dx.doi.org/10.1002/alr.22787DOI Listing
March 2021

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

J Allergy Clin Immunol 2021 Apr 14;147(4):1306-1317. 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
April 2021

International consensus statement on allergy and rhinology: rhinosinusitis 2021.

Int Forum Allergy Rhinol 2021 Mar;11(3):213-739

Capital Medical University, Beijing, China.

I.

Executive Summary: 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.
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http://dx.doi.org/10.1002/alr.22741DOI Listing
March 2021

Patient satisfaction survey experience among American otolaryngologists.

Am J Otolaryngol 2020 Nov - Dec;41(6):102656. Epub 2020 Aug 5.

Division of Otolaryngology, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America. Electronic address:

Background: Patient Satisfaction (PS) is a commonly used metric in health care settings to assess the quality of care given by physicians. Monitoring physicians in this way may impact physician quality of life. Studies evaluating this impact are not available. This study sought to examine the physician experience of measuring PS among practicing otolaryngologists.

Methods: Using an online survey platform, a 34-item survey was given to practicing otolaryngologists through email distribution. The survey included questions about physician, practice and patient demographics, as well as inquiries regarding the way in which PS was measured and how it affected physician work and personal life. Data from these questions were reviewed and analyzed.

Results: 174 otolaryngologists responded to the survey. A majority of physicians' (55.3%) PS scores had been tracked with 89.9% reporting being tracked for a length of at least 1 year. PS scores for individual physicians were noted to be inconsistent and vary significantly between reports. Measuring patient satisfaction led to increased occupational stress, yet most physicians (63.8%) felt the monitoring did not lead to improvements in their practice. Some physicians (36.2%) reported that the collection of patient satisfaction scores had negatively influenced the way they practiced medicine, including the pressure to order superfluous tests or to prescribe unnecessary medications.

Conclusion: Overall, physicians are negatively affected by the tracking of patient satisfaction scores. Occupational stress caused by the collection of patient satisfaction scores may contribute to physician burnout.
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http://dx.doi.org/10.1016/j.amjoto.2020.102656DOI Listing
December 2020

A new approach to categorization of radiologic inflammation in chronic rhinosinusitis.

PLoS One 2020 29;15(6):e0235432. Epub 2020 Jun 29.

Department of Environmental Health and Engineering, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

Chronic rhinosinusitis (CRS) is a prevalent condition. Clinical diagnosis requires subjective evidence (i.e. symptoms) and objective evidence of inflammation (e.g. sinus computed tomography [CT]). Few studies have assessed differences in common CT scoring approaches for CRS, the Lund-Mackay (LM) system and its modified version (mLM); none in a general population sample. The aims of this study were to answer the following: (1) Is mLM superior to LM? (2) Should nasal cavity opacification be included in scoring? (3) How should location-specific scores be utilized? (4) If location-specific scores are summed, what should be the cutoff? (5) Are associations of opacification with symptoms observed when using different measurement approaches? We scored sinus CTs using LM and mLM from 526 subjects selected from a larger CRS study. Exploratory factor analysis (EFA) assessed similarity of mLM and LM. Latent class analysis (LCA) identified subgroups of sinus opacification patterns. Factors associated with group membership and relations with nasal and sinus symptoms (NSS) guided clinical relevance. EFA suggested no differences between LM and mLM, or after addition of nasal cavity opacification. LCA identified three opacification groups: no/mild, localized, and diffuse. Males were 2.7x more likely to have diffuse opacification than females, as were those with asthma or hay fever. A LM cutoff of 3 had similar performance to the currently used 4. Diffuse opacification was associated with nasal blockage and smell loss. Differing patterns of opacification may be clinically relevant, improving measurement of objective evidence in studies of CRS and sinus diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235432PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323942PMC
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

What is the Optimal Timing of Computed Tomography Imaging to Objectively Confirm Chronic Rhinosinusitis?

Laryngoscope 2021 02 23;131(2):248-249. Epub 2020 Apr 23.

Division of Otolaryngology-Head and Neck Surgery, University of Utah Health, Salt Lake City, Utah, U.S.A.

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http://dx.doi.org/10.1002/lary.28684DOI Listing
February 2021

Clinical Research Needs for the Management of Chronic Rhinosinusitis with Nasal Polyps in the New Era of Biologics: A National Institute of Allergy and Infectious Diseases Workshop.

J Allergy Clin Immunol Pract 2020 05 4;8(5):1532-1549.e1. Epub 2020 Mar 4.

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address:

The development of biologics targeting various aspects of type 2 inflammation for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) will provide clinicians with powerful tools to help treat these patients. However, other therapies are also available, and positioning of biologics in a management algorithm will require comparative trials. In November 2019, the National Institute of Allergy and Infectious Diseases convened a workshop to consider potential future trial designs. Workshop participants represented a wide spectrum of clinical specialties, including otolaryngology, allergy, and pulmonary medicine, as well as expertise in CRSwNP pathophysiology and in trial methodology and statistics. The workshop discussed the current state of knowledge in CRSwNP and considered the advantages and disadvantages of various clinical trial or observational study designs and various clinical outcomes. The output from this workshop, which is presented in this report, will hopefully provide investigators with adequate information and ideas to design future studies and answer critical clinical questions. It will also help clinicians understand the current state of the management of CRSwNP and its gaps and be more able to interpret the new information to come.
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http://dx.doi.org/10.1016/j.jaip.2020.02.023DOI Listing
May 2020

Predicting Obstructive Sleep Apnea Status With the Reflux Symptom Index in a Sleep Study Population.

Laryngoscope 2020 12 2;130(12):E952-E957. Epub 2020 Mar 2.

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

Objectives/hypothesis: Otolaryngologic symptoms of obstructive sleep apnea (OSA) and their diagnostic utility are not well studied. We aimed to elucidate the prevalence of otolaryngologic symptoms among patients being evaluated for OSA. Given findings that the Reflux Symptom Index (RSI) was strongly associated with OSA status, we evaluated the diagnostic utility of the RSI for predicting OSA status.

Study Design: Cross-sectional.

Methods: We recruited 101 adults presenting for ambulatory polysomnograms to the Northwestern Sleep Disorders Center from July 2017 to July 2018. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Leicester Cough Questionnaire (LCQ), RSI, Gastroesophageal Reflux Disease Questionnaire, Sino-Nasal Outcome Test-22, Nasal Obstruction Symptom Evaluation, Eustachian Tube Dysfunction Questionnaire 7, and Headache Impact Test were administered. Polysomnogram results were subsequently obtained. Patients with OSA (apnea-hypopnea index ≥ 5) and without OSA were compared.

Results: Of the 101 participants, 98 had valid sleep study results. Of those, 72 were diagnosed with OSA and 26 were not. The two groups differed significantly in age and body mass index (BMI). Of the questionnaires, only the RSI and LCQ means differed significantly, with worse symptoms in the OSA group (P = .003 and .014, respectively). Upon univariate regression, age, BMI, and RSI were associated with OSA status. Using regression coefficients, a clinical score of 2 (RSI) + 1.5 (BMI) + age yielded a diagnostic model (C-statistic = 0.807, P < .001). A threshold score of 104.21 was 76.4% sensitive and 73.1% specific.

Conclusions: Patients with OSA have worse symptoms of laryngopharyngeal reflux as measured by the RSI. The addition of the RSI to the recognized factors of age and BMI improves diagnostic utility for OSA.

Level Of Evidence: 2 Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.28592DOI Listing
December 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

Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population-based sample.

Allergy 2020 04 2;75(4):911-920. Epub 2019 Dec 2.

Department of Population Health Sciences, Geisinger, Danville, Pennsylvania.

Background: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings.

Objective: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample.

Methods: We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRS ) was based on guideline criteria, and objective radiologic inflammation (CRS ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRS . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRS . Using weighted analysis, we calculated estimates for the source population.

Results: The proportion of women with L-M scores ≥ 3, 4, or 6 (CRS ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRS was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRS compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses.

Conclusion: In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRS .
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http://dx.doi.org/10.1111/all.14106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176524PMC
April 2020

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

Workplace Indirect Cost Impacts of Nasal and Sinus Symptoms and Related Conditions.

J Occup Environ Med 2019 08;61(8):e333-e339

Department of Environmental Health and Engineering (Mr Kuiper, Dr Hirsch, Dr Schwartz); Department of Epidemiology and Health Services Research, Geisinger, Danville, Pennsylvania (Dr Hirsch, Dr Sundaresan, Dr Schwartz); Department of Biostatistics (Dr Bandeen-Roche), Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Department of Otolaryngology Head and Neck Surgery (Dr Tan, Dr Kern, Dr Schleimer); and Division of Allergy and Immunology, Department of Medicine (Dr Tan, Dr Kern, Dr Schleimer), Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Objective: Evaluate associations of nasal and sinus and related symptoms, as well as selected health conditions which produce those symptoms, with total lost productive time (LPT) at work in the past 2 weeks.

Methods: We used a cross-sectional analysis of 2402 currently working subjects. Self-reported physician diagnoses, condition statuses measured with standardized instruments, and symptom-based factor scores from an exploratory factor analysis were used in survey weighted log-binomial regression.

Results: Pain and pressure, nasal blockage and discharge, and asthma and constitutional symptom factor scores as well as self-reported allergic rhinitis were associated with higher total LPT. Individuals who met operationalized criteria for multiple health conditions, especially chronic rhinosinusitis, had the greatest total LPT.

Conclusions: Better management of these symptoms, and awareness of how they impact an individual's ability to perform job-functions in the workplace, could improve overall productivity.
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http://dx.doi.org/10.1097/JOM.0000000000001636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766754PMC
August 2019

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

Do NERDy eosinophils accelerate nasal polyp growth?

Allergy 2019 12;74(12):2291-2292

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

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http://dx.doi.org/10.1111/all.13855DOI Listing
December 2019

Measuring the health utility of chronic eustachian tube dysfunction.

Laryngoscope 2020 02 22;130(2):E39-E44. Epub 2019 Mar 22.

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

Objective: To assess the health utility of chronic Eustachian tube dysfunction (ETD).

Methods: This is a prospective study of 53 patients with chronic ETD recruited from a tertiary clinic from April 2017 to July 2018. The 7-Item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) was administered, and health utility was evaluated using the EuroQol-5 Dimensions-3 Level Instrument (EQ-5D-3L), the visual analogue scale (VAS), time tradeoff (TTO), and standard gamble (SG). Participants were grouped into medical or procedural management groups. One-week follow-up included repeated health utility measures and ETDQ-7.

Results: Fifty-three patients were included in the final analysis. Of those, 34 were managed medically, and 19 received myringotomies ± PE tubes. The mean baseline ETDQ-7 was 4.26 ± 1.31; whereas health utility measures were different depending on the method utilized: EQ-5D-3L 0.90 ± 0.11; VAS 0.76 ± 0.21; TTO 0.85 ± 0.23; and SG 0.94 ± 0.11 (P < .001). There was a significant change in ETDQ-7 (P = .001) and TTO (P = .011) scores posttreatment. On the ETDQ-7, question 2 (pain in the ears) was significantly associated with VAS (P = .032), and question 4 (ear symptoms during a cold or sinusitis) was significantly associated with TTO (P = .006).

Conclusion: Chronic ETD has a significant burden on quality of life, with a health utility similar to gastroesophageal reflux disease and moderate asthma. Although treatment-related changes are measurable using disease-specific quality-of-life measures, only TTO was significantly changed after treatment. Health utility seemed to depend on the method of measurement but provided a benchmark for evaluating cost-effectiveness of innovations to manage ETD.

Level Of Evidence: 2 Laryngoscope, 130:E39-E44, 2020.
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http://dx.doi.org/10.1002/lary.27934DOI Listing
February 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

Utilization of a novel interactive mobile health platform to evaluate functional outcomes and pain following septoplasty and functional endoscopic sinus surgery.

Int Forum Allergy Rhinol 2019 04 26;9(4):345-351. Epub 2018 Dec 26.

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

Background: Whether for research or quality improvement, assessment of postoperative quality of life outcomes faces a challenge in reliable data collection. Typical coordinator-led studies cite response rates from 35% to 70%. This study evaluates the utility of a digital patient engagement platform to track patient-reported outcome measures (PROMs) following septoplasty and functional endoscopic sinus surgery (FESS).

Methods: A prospective cohort was recruited at a tertiary care center from January 2017 to March 2018. A mobile phone application relayed PROMs, including pain (assessed on a 0 to 10 visual analogue scale [VAS] every other day for 2 weeks, as well as the patient-reported outcome measure information system [PROMIS] pain interference short form 4a at baseline, 2 weeks, and 3 months) and timing of return to work.

Results: Of 288 patients enrolled, 249 (86.5%) provided clinical data, including 208 who underwent septoplasty or FESS. Granular VAS scores, submitted by 195 patients, demonstrated 80% of these patients achieved minimal pain by postoperative day 8. A nonsignificant trend of increased days to pain relief by procedure emerged: septoplasty (mean ± standard deviation [SD], 3.60 ± 2.44), FESS (3.96 ± 3.25), FESS with septoplasty (4.40 ± 3.04), and FESS with drilling (4.86 ± 3.68). Across procedures, PROMIS pain interference increased at 2 weeks (9.17 ± 4.15) and decreased at 3 months (5.32 ± 2.61) compared with baseline (7.09 ± 4.63), with greater improvement noted in the FESS subgroup at 3 months. Patients returned to work at mean 7.1 days regardless of procedure.

Conclusions: With its high response rate, mobile digital patient engagement platforms may effectively track postoperative outcomes with the potential for reduced sample bias.
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http://dx.doi.org/10.1002/alr.22273DOI Listing
April 2019

Are chronic cough and laryngopharyngeal reflux more common in obstructive sleep apnea patients?

Laryngoscope 2019 05 15;129(5):1244-1249. Epub 2018 Nov 15.

Department of Otolaryngology-Head and Neck Surgery, Kaiser Permanente Santa Clara, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Objectives/hypothesis: To assess if there is a significant difference in the prevalence and severity of chronic cough symptoms in obstructive sleep apnea (OSA) patients versus non-OSA patients and examine this relationship in regard to laryngopharyngeal reflux (LPR) symptoms.

Study Design: Prospective cohort study.

Methods: Patients referred to Northwestern Medicine Sleep Lab for home sleep testing were enrolled. Patients filled out the Leicester Cough Questionnaire (LCQ) and Reflux Symptom Index (RSI) before completing sleep testing. Home sleep testing results were reviewed, and patients were separated into non-OSA and OSA groups by standard Apnea-Hypopnea Index (AHI) criteria. Demographic characteristics and questionnaire scores of the two groups were compared. The relationship between OSA severity, as determined by AHI, and LCQ and RSI scores was assessed.

Results: Of the 52 patients enrolled, 33 patients met criteria for OSA and 19 patients did not. Comparing patients without OSA versus those with OSA, there was a significant difference in mean LCQ score (129.9 vs. 120.0, respectively; P = .02), implying worse cough symptoms among OSA patients, and mean RSI score (3.2 vs. 11.2, respectively; P = .0013), implying worse upper-airway reflux symptoms among OSA patients. There was a significant correlation between LCQ score and AHI (r = -0.39, P = .0061) and between RSI score and AHI (r = 0.37, P = .0078).

Conclusions: OSA patients demonstrate worse chronic cough and LPR-related quality of life versus non-OSA patients. Furthermore, the severity of these quality-of-life measures was correlated with the severity of the AHI. Chronic cough and particularly the pharyngeal LPR symptoms may be associated with the presence and severity of OSA.

Level Of Evidence: 2 . Laryngoscope, 129:1244-1249, 2019.
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http://dx.doi.org/10.1002/lary.27557DOI Listing
May 2019

Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting.

J Allergy Clin Immunol Pract 2019 03 25;7(3):1010-1016. Epub 2018 Oct 25.

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: Although patients with chronic rhinosinusitis without nasal polyps (CRSsNP) represent a majority of the chronic rhinosinusitis (CRS) population, they have not been completely characterized phenotypically.

Objective: To perform a comprehensive phenotypic characterization of subjects with CRSsNP, using CRS with nasal polyps (CRSwNP) as a comparator.

Methods: Patients with a history of CRS with positive sinus computed tomography (>18 years old) evaluated in the allergy/immunology or otolaryngology clinics of an academic center between 2002 and 2012 were identified via International Classification of Diseases, Ninth Revision codes. A retrospective chart review was performed on a subset of 507 patients with CRSsNP and 874 with CRSwNP. Characteristics analyzed included demographics, comorbid conditions, and radiologic sinus severity.

Results: Of the total CRS population, approximately 82% had CRSsNP and 18% had CRSwNP. Of the 507 patients in the CRSsNP group, 319 (63%) were female compared with 393 of 847 (45%) in the CRSwNP group. The prevalence of atopy was 52% in CRSsNP versus 76% in CRSwNP (P < .0001). In CRSsNP, atopic patients had more severe radiographic disease compared with nonatopic patients (P < .005). The prevalence of asthma was 36% in CRSsNP versus 56% in CRSwNP (P < .0001). Comorbid asthma was not associated with radiographic sinus disease severity in CRSsNP but was associated with severity in CRSwNP (P < .0001).

Conclusions: The relative prevalence of CRS phenotypes in the western population is approximately 80% CRSsNP and 20% CRSwNP. Patients with CRSsNP were predominantly female, whereas patients with CRSwNP were predominantly male. The prevalence of asthma was higher in our cohort of patients with CRSsNP than previously described. Atopy was associated with more severe radiographic sinonasal disease in CRSsNP, whereas asthma was not associated with radiographic sinonasal disease severity.
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http://dx.doi.org/10.1016/j.jaip.2018.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862765PMC
March 2019

Pathogenic and protective roles of B cells and antibodies in patients with chronic rhinosinusitis.

J Allergy Clin Immunol 2018 05;141(5):1553-1560

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

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nose and sinuses that affects up to 12% of the population in Europe and the United States. This complex disease is likely driven by multiple environmental, genetic, and inflammatory mechanisms, and recent studies suggest that B cells might play a critical role in disease pathogenesis. B cells and their antibodies have undisputed roles in health and disease within the airway mucosae. Deficient or inadequate B-cell responses can lead to susceptibility to infectious disease in the nose, whereas excess antibody production, including autoantibodies, can promote damaging inflammation. Thus, patients with B-cell defects often have either chronic or recurrent acute infections, and this can be associated with nonpolypoid CRS. In contrast, many patients with CRS with nasal polyps, which is less likely to be driven by pathogens, have excess production of local immunoglobulins, including autoreactive antibodies. These B-cell responses activate complement in many patients and likely contribute to immunopathogenic responses. A better understanding of the B cell-associated mechanisms that drive disease in patients with CRS should be a high priority in the quest to understand the pathogenesis of this disease.
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http://dx.doi.org/10.1016/j.jaci.2018.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942230PMC
May 2018