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Background Patient-reported outcome measures (PROMs) measure health states in chronic rhinosinusitis (CRS) and have become the dominant metrics of treatment outcomes. Interpersonal traits (IPTs) are patient-specific factors that include personality type, perceived social support, and trust in physicians. The association of IPTs on treatment outcomes among patients with CRS has not been described previously, and IPTs may represent major clinical factors influencing treatment outcomes. Methods Adult patients electing medical or surgical treatment for recalcitrant CRS were prospectively enrolled into a multi-institutional, observational outcomes study. Validated measures of IPTs, including the Big Five Inventory-10 Short Version (BFI-10), Multidimensional Scale of Perceived Social Support (MSPSS), and the Trust in Physician Scale (TPS), were completed and compared with PROMs, which included the 22-item SinoNasal Outcome Test (SNOT-22), the Medical Outcomes Study Short Form-6D (SF-6D), and the Patient Health Questionnaire-2 (PHQ-2). Results Three hundred fifty-four participants were included and followed for an average (± standard deviation) of 16.3 (±4.8) months. Significant within-subject improvement in mean PROM scores was reported (all p <0.001). No association was detected between PROM score improvement and baseline BFI-10 or MSPSS scores ( p > 0.050). Significant, but weak, absolute correlations were reported between baseline TPS scores and improvement in SNOT-22, SF-6D, and PHQ-2 total scores ( p < 0.050; r ≤ 0.138). Conclusion Personality type and perceived social support do not associate with improvement after treatment for CRS. However, increased trust in physicians is weakly associated with greater posttreatment improvement. Further study is needed to examine the relationship between physician trust, patient satisfaction, and treatment outcomes among patients with CRS. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disease process that is driven, in part, by intrinsic mucosal inflammation. Surgery plus continued medical therapy is commonly elected by medically recalcitrant, symptomatic patients. The objective was to evaluate the prevalence of nasal polyp recurrence up to 18 months after endoscopic sinus surgery (ESS) with congruent continuing medical management.Study Design: Prospective, multicenter cohort of adult patients undergoing ESS for medically recalcitrant CRSwNP performed between August 2004 and February 2015.Methods: All patients received baseline nasal endoscopy quantified using Lund-Kennedy grading. All patients included for final analysis provided at least 6 months of postoperative endoscopy examinations. Multivariate analysis was used to identify risk factors for polyp recurrence.Results: Three hundred sixty-three CRSwNP patients having undergone ESS involving polypectomy were enrolled. A total of 244 (67%) participants had graded postoperative endoscopies with average of follow-up of 14.3 ± 7.0 months. Surgery plus postoperative medical management significantly improved endoscopy total scores at 6 months (P < .001). The recurrence of nasal polyposis 6 months after ESS was 35% (68/197), compared to 38% (48/125) after 12 months, and 40% (52/129) after 18 months. Multivariate analysis identified both prior ESS (odds ratio [OR]: 2.6, 95% confidence interval [CI]: 1.5-4.6; P = .001) and worse preoperative polyposis severity (OR: 1.4, 95% CI: 1.1-1.8; P = .016) as risk factors for recurrent polyposis.Conclusions: Polyp recurrence is common after ESS with control of polyps up to 18 months found in approximately 60% to 70% of patients. Investigation into both surgical and medical management strategies is warranted to improve upon the observed prevalence of recurrence.Level Of Evidence: 2c. Laryngoscope, 127:550-555, 2017. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Patients with chronic rhinosinusitis (CRS) who experience minimal reductions in quality of life (QoL) may present for treatment despite QoL scores comparable to controls without CRS. This study seeks to identify cofactors influencing patients with CRS and low 22-item Sinonasal Outcome Test (SNOT-22) scores to seek care.Study Design: Prospective, multicenter, observational cohort.Methods: Patients with CRS were enrolled between April 2011 and September 2015. Patients with sinonasal mucocele or unilateral sinus opacification were excluded. Control subjects without CRS were enrolled for comparison. Low-SNOT CRS was defined as a SNOT-22 score < 20.Results: A total of 774 subjects (low-SNOT CRS, n = 38; high-SNOT CRS, SNOT-22 ≥ 20, n = 641; controls without CRS, n = 95) were enrolled. Low SNOT scores were identified in 6% of subjects with CRS. After adjustment, low-SNOT CRS and control groups without CRS reported similar baseline average SNOT-22 total scores (P = .879). Unexpectedly, compared to controls, low-SNOT CRS patients had significantly better average psychological (2.1 ± 2.3 vs. 5.8 ± 6.0; P = .030) and sleep dysfunction (2.7 ± 3.4 vs. 6.0 ± 5.2; P = .016) scores. Fourteen of 38 (37%) low-SNOT patients elected to undergo endoscopic sinus surgery (ESS), with a significantly lower likelihood of reporting a minimal clinically important difference (MCID) when compared to high-SNOT patients (43% vs. 82%; P < .001) after a mean follow-up of ∼15 months.Conclusions: Low-SNOT CRS patients represent an outlier population for which measures of QoL fail to identify factors influencing the decision to seek treatment. Low-SNOT CRS patients electing ESS have a decreased likelihood of reporting MCIDs following ESS. Further study is required to identify novel factors associated with treatment-seeking behavior in this population.Level Of Evidence: 3B Laryngoscope, 127:22-28, 2017. [ABSTRACT FROM AUTHOR]

Understanding the exploration patterns of foragers in the wild provides fundamental insight into animal behavior. Recent experimental evidence has demonstrated that path lengths (distances between consecutive turns) taken by foragers are well fitted by a power law distribution. Numerous theoretical contributions have posited that "Lévy random walks"--which can produce power law path length distributions--are optimal for memoryless agents searching a sparse reward landscape. It is unclear, however, whether such a strategy is efficient for cognitively complex agents, from wild animals to humans. Here, we developed a model to explain the emergence of apparent power law path length distributions in animals that can learn about their environments. In our model, the agent's goal during search is to build an internal model of the distribution of rewards in space that takes into account the cost of time to reach distant locations (i.e., temporally discounting rewards). For an agent with such a goal, we find that an optimal model of exploration in fact produces hyperbolic path lengths, which are well approximated by power laws. We then provide support for our model by showing that humans in a laboratory spatial exploration task search space systematically and modify their search patterns under a cost of time. In addition, we find that path length distributions in a large dataset obtained from free-ranging marine vertebrates are well described by our hyperbolic model. Thus, we provide a general theoretical framework for understanding spatial exploration patterns of cognitively complex foragers.s [ABSTRACT FROM AUTHOR]

Objective: Paranasal sinus balloon catheter dilation (BCD) represents a commonly used tool in the management of chronic rhinosinusitis (CRS) for which the indications, utilization, and outcomes have not been well established. A systematic review and meta-analysis were undertaken to evaluate change in quality of life and sinus opacification following paranasal sinus BCD in the treatment of CRS.Data Sources: MEDLINE and EMBASE databases.Review Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were utilized to identify English-language studies reporting patient outcomes following BCD for CRS. Primary outcomes included the impact of BCD on validated measures of quality of life and sinonasal opacification.Results: Systematic review identified 17 studies for qualitative analysis. Studies generally included cases with limited disease based on radiographic opacification. Five studies contained extractable data for change in 20-Item Sinonasal Outcome Test (SNOT-20) 1 year following BCD, with significant improvement in self-reported quality of life (P = .04). Five studies reported a significant change in paranasal sinus opacification following BCD (P < .001). Two studies directly compared change in SNOT-20 between BCD and endoscopic sinus surgery, without demonstration of significant difference in outcome (P = .07). Subgroup analysis found that change in SNOT-20 score was greater after BCD in the operating room than in the office (P = .004).Conclusion: Current evidence supporting the role of BCD in CRS remains incomplete. Long-term within-group improvements in quality-of-life and sinus opacification scores are demonstrated among a restricted adult population with CRS. Additional study is needed to further evaluate the role for BCD in specific settings and patient subgroups. [ABSTRACT FROM AUTHOR]

In addition, the reported efficacy of type 2 biologic therapy varies significantly by molecular target and is not universal to all patients with uncontrolled nasal polyps. It is only through a multidisciplinary approach with close collaboration between allergy and otolaryngology disciplines that we will be able to maximize the effect of these treatments and advance patient care. We read with great interest Dr Bosso's recent correspondence.1 In that communication he nicely describes the emergence of aspirin therapy after desensitization (ATAD), as type 2 biologics represent highly promising therapies in the treatment of our most recalcitrant patients. [Extracted from the article]

Tight junctions regulate epithelial barrier function and have been shown to be influenced by multiple classes of proteins. Apical integrins have been identified as potential regulators of epithelial barrier function; however, only indirect approaches have been used to measure integrin regulation of the epithelial barrier. Here, we used polymeric nanowires conjugated with anti-integrin β1 antibodies to specifically target apically localized integrins in either their closed or open conformation. Barrier regulation by apical integrins was found to be conformation specific. Nanowires targeting integrins in the closed conformation increased epithelial permeability and caused zonula occludens-1 (ZO-1, also known as TJP1) to change from a linear to a ruffledmorphology. Claudin-2 and claudin-4 colocalized with ZO-1 and were also ruffled; however, claudin-1 and claudin-7 remained linear. Ruffling was dependent on myosin light chain kinases (MLCKs) and Rho kinases (ROCKs). Conversely, targeting integrins in the open conformation decreased epithelial permeability and made junctions more linearized. Anti-integrin β1 nanowires differentially affected actin and talin (analyzed using pan-talin antibodies), depending on whether they contained activating or inhibitory antibodies. Thus, apical integrins can act as a conformation-sensitive switch that regulates epithelial barrier function. [ABSTRACT FROM AUTHOR]

Aspirin-exacerbated respiratory disease (AERD) is characterized by the clinical triad of asthma, nasal polyposis and sensitivity to aspirin and other non-steroidal anti-inflammatory drugs. Across the spectrum of chronic rhinosinusitis, patients with AERD are among those with the most severe sinopulmonary inflammation, often refractory to standard treatments. Although AERD has a reputation as a recalcitrant disease, presentation and response to treatment is often along a spectrum. Yet, there have recently been significant advances in the management of both asthma and nasal polyposis, allowing for new treatment options and a shift in standard management algorithms. This article explores the prevalence and workup of AERD and reviews the latest evidence in both medical and surgical management. Furthermore, the results of on-going clinical trials are eagerly awaited. With a growing assortment of treatment options, especially with the addition of biologics to the clinician's armamentarium, it is paramount to individualize therapy alongside a stepwise algorithm for what is considered a difficult-to-treat disease. [ABSTRACT FROM AUTHOR]

Background: Eustachian tube dysfunction (ETD) may occur distinct from, or in conjunction with, chronic rhinosinusitis (CRS+ETD). Intranasal corticosteroid sprays are often prescribed for ETD, although ET distribution may be limited. To date, no anatomic studies compare nasopharynx (NP) distribution between conventional nasal sprays (NS) and exhalation delivery systems (EDS) after surgery. This study utilizes a cadaver model to examine topical NP delivery using EDS vs. NS before and after targeted endoscopic sinus surgery (ESS). Methods: Sixteen sinonasal cavities were administered fluorescein solution via NS and EDS before and after maxillary antrostomy and anterior ethmoidectomy, followed by nasal endoscopy of the NP and ET orifice. Seven blinded experts submitted staining ratings of endoscopy images on a 0‐ to 3‐point scale, with ratings averaged for analysis. Results: Interrater reliability was excellent (intraclass correlation, 0.956). EDS was associated with significantly greater NP staining vs. NS in a pooled cohort of nonsurgical and ESS specimens (1.19 ± 0.81 vs. 0.78 ± 1.06; p = 0.043). Using a logistic regression model, EDS significantly outperformed NS in nonsurgical (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.21–10.09; p = 0.021) and post‐ESS (OR, 9.00; 95% CI, 1.95–41.5; p = 0.005) specimens, with the greatest relative staining observed for EDS after targeted ESS (OR, 18.99; 95% CI, 3.44–104.85; p = 0.001). Conclusions: EDS is more effective than NS in topical delivery to the NP and ET orifices in cadavers. Targeted ESS may facilitate greater NP penetration by EDS compared with NS, with possible synergism after ESS for augmented delivery. These findings suggest a role for EDS delivery methods for ETD management and in CRS+ETD patients undergoing sinus surgery. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased β-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1β, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2. NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD. [ABSTRACT FROM AUTHOR]

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation fromthe full document. Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based reviewwith recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensuswas performed for each topic. The final document was then collated and includes the results of this work. Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) testing policies for symptomatic children attending US schools or daycare vary, and whether isolated symptoms should prompt testing is unclear. We evaluated children presenting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing to determine if the likelihood of having a positive SARS-CoV-2 test differed between participants with 1 symptom vs ≥2 symptoms, and to examine the predictive capability of isolated symptoms. Methods Participants aged < 18 years presenting for clinical SARS-CoV-2 molecular testing in 6 sites in urban/suburban/rural Georgia (July–October, 2021; Delta variant predominant) were queried about individual symptoms. Participants were classified into 3 groups: asymptomatic, 1 symptom only, or ≥2 symptoms. SARS-CoV-2 test results and clinical characteristics of the 3 groups were compared. Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for isolated symptoms were calculated by fitting a saturated Poisson model. Results Of 602 participants, 21.8% tested positive and 48.7% had a known or suspected close contact. Children reporting 1 symptom (n = 82; odds ratio [OR], 6.00 [95% confidence interval {CI}, 2.70–13.33]) and children reporting ≥2 symptoms (n = 365; OR, 5.25 [95% CI, 2.66–10.38]) were significantly more likely to have a positive COVID-19 test than asymptomatic children (n = 155), but they were not significantly different from each other (OR, 0.88 [95% CI,.52–1.49]). Sensitivity and PPV were highest for isolated fever (33% and 57%, respectively), cough (25% and 32%), and sore throat (21% and 45%); headache had low sensitivity (8%) but higher PPV (33%). Sensitivity and PPV of isolated congestion/rhinorrhea were 8% and 9%, respectively. Conclusions With high Delta variant prevalence, children with isolated symptoms were as likely as those with multiple symptoms to test positive for COVID-19. Isolated fever, cough, sore throat, or headache, but not congestion/rhinorrhea, offered the highest predictive value. [ABSTRACT FROM AUTHOR]

Importance: Despite the expansion of SARS-CoV-2 testing, available tests have not received Emergency Use Authorization for performance with self-collected anterior nares (nasal) swabs from children younger than 14 years because the effect of pediatric self-swabbing on SARS-CoV-2 test sensitivity is unknown.Objective: To characterize the ability of school-aged children to self-collect nasal swabs for SARS-CoV-2 testing compared with collection by health care workers.Design, Setting, and Participants: Cross-sectional study of 197 symptomatic children and adolescents aged 4 to 14 years old. Individuals were recruited based on results of testing in the Children's Healthcare of Atlanta system from July to August 2021.Exposures: Children and adolescents were given instructional material consisting of a short instructional video and a handout with written and visual steps for self-swab collection. Participants first provided a self-collected nasal swab. Health care workers then collected a second specimen.Main Outcomes and Measures: The primary outcome was SARS-CoV-2 detection and relative quantitation by cycle threshold (Ct) in self- vs health care worker-collected nasal swabs when tested with a real-time reverse transcriptase-polymerase chain reaction test with Emergency Use Authorization.Results: Among the study participants, 108 of 194 (55.7%) were male and the median age was 9 years (IQR, 6-11). Of the 196 participants, 87 (44.4%) tested positive for SARS-CoV-2 and 105 (53.6%) tested negative by both self- and health care worker-collected swabs. Two children tested positive by self- or health care worker-collected swab alone; 1 child had an invalid health care worker swab. Compared with health care worker-collected swabs, self-collected swabs had 97.8% (95% CI, 94.7%-100.0%) and 98.1% (95% CI, 95.6%-100.0%) positive and negative percent agreement, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups (mean [SD] Ct, self-swab: 26.7 [5.4] vs health care worker swab: 26.3 [6.0]; P = .65).Conclusions and Relevance: After hearing and seeing simple instructional materials, children and adolescents aged 4 to 14 years self-collected nasal swabs that closely agreed on SARS-CoV-2 detection with swabs collected by health care workers. [ABSTRACT FROM AUTHOR]

Viability of saliva samples stored for longer than 28 days has not been reported in the literature. The COVID-19 pandemic has spawned new research evaluating various sample types, thus large biobanks have been started. Residual saliva samples from university student surveillance testing were retested on SalivaDirect and compared with original RT-PCR (cycle threshold values) and quantitative antigen values for each month in storage. We conclude that saliva samples stored at -80°C are still viable in detecting SARS-CoV-2 after 12 months of storage, establishing the validity of these samples for future testing. [ABSTRACT FROM AUTHOR]

Background: An ideal test for COVID-19 would combine the sensitivity of laboratory-based PCR with the speed and ease of use of point-of-care (POC) or home-based rapid antigen testing. We evaluated clinical performance of the Diagnostic Analyzer for Selective Hybridization (DASH) SARS-CoV-2 POC rapid PCR test. Methods: We conducted a cross-sectional study of adults with and without symptoms of COVID-19 at four clinical sites where we collected two bilateral anterior nasal swabs and information on COVID-19 symptoms, vaccination, and exposure. One swab was tested with the DASH SARS-CoV-2 POC PCR and the second in a central laboratory using Cepheid Xpert Xpress SARS-CoV-2 PCR. We assessed test concordance and calculated sensitivity, specificity, negative and positive predictive values using Xpert as the "gold standard". Results: We enrolled 315 and analyzed 313 participants with median age 42 years; 65% were female, 62% symptomatic, 75% had received ≥2 doses of mRNA COVID-19 vaccine, and 16% currently SARS-CoV-2 positive. There were concordant results for 307 tests indicating an overall agreement for DASH of 0.98 [95% CI 0.96, 0.99] compared to Xpert. DASH performed at 0.96 [95% CI 0.86, 1.00] sensitivity and 0.98 [95% CI 0.96, 1.00] specificity, with a positive predictive value of 0.85 [95% CI 0.73, 0.96] and negative predictive value of 0.996 [95% CI 0.99, 1.00]. The six discordant tests between DASH and Xpert all had high Ct values (>30) on the respective positive assay. DASH and Xpert Ct values were highly correlated (R = 0.89 [95% CI 0.81, 0.94]). Conclusions: DASH POC SARS-CoV-2 PCR was accurate, easy to use, and provided fast results (approximately 15 minutes) in real-life clinical settings with an overall performance similar to an EUA-approved laboratory-based PCR. [ABSTRACT FROM AUTHOR]

Among symptomatic outpatients, subgenomic RNA of severe acute respiratory syndrome coronavirus 2 in nasal midturbinate swab specimens was concordant with antigen detection but remained detectable in 13 (82.1%) of 16 nasopharyngeal swab specimens from antigen-negative persons. Subgenomic RNA in midturbinate swab specimens might be useful for routine diagnostics to identify active virus replication. [ABSTRACT FROM AUTHOR]

Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (n = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (<16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), P = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), P = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone. • Hemoglobinopathies have been reported as a risk factor for SARS-CoV-2 infection. • Age and race explain association between hemoglobinopathy and SARS-CoV-2. • CKD and diabetes higher odds of SARS-CoV-2 infection than heart and liver disease. [ABSTRACT FROM AUTHOR]

Objectives: Allergic fungal rhinosinusitis (AFRS) is an eosinophilic subtype of chronic rhinosinusitis with nasal polyposis (CRSwNP). This study aimed to investigate the transcriptome of AFRS nasal polyp epithelium., Methods: Sinonasal epithelial cells were harvested from healthy nasal mucosa and polyp tissue collected from participants undergoing elective sinonasal surgery. Primary epithelial cells were subsequently grown in air/liquid interface and subjected to RNA-seq analysis, RT-qPCR, immunoblotting, and immunostaining., Results: A total of 19 genes were differentially expressed between healthy and AFRS sample epithelium. The second top candidate gene, ranked by adjusted p-value, was prostaglandin E receptor 2 (PTGER2). The upregulation of PTGER2 was confirmed by RT-qPCR and immunoblot. The presence of the EP2 receptor, encoded by the PTGER2 gene, was confirmed by immunocytochemistry., Conclusion: PTGER2 is a potential novel therapeutic target for AFRS. EP2 dysregulation is associated with aspirin-exacerbated respiratory disease, potentially giving insight into common mechanisms of disease in severe CRSwNP., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Key Points: In patients with chronic rhinosinusitis and comorbid asthma, patients with surgical intervention required less asthma rescue medication, as compared to those who did not undergo surgery. Following sinus surgery, patients with chronic rhinosinusitis and asthma required more asthma medication, as compared to the time period prior to surgery., (© 2024 ARS‐AAOA, LLC.)

Background: In the phase III SYNAPSE study, mepolizumab plus standard of care reduced total endoscopic nasal polyp score (NPS) versus that with placebo in patients with chronic rhinosinusitis with nasal polyps., Objective: Our aim was to investigate relationships between NPS and (1) peak nasal inspiratory flow (PNIF) and (2) patient-reported outcomes., Methods: In this post hoc analysis, patients randomized 1:1 received mepolizumab, 100 mg, or placebo subcutaneously every 4 weeks (plus standard of care). Changes from baseline in PNIF (week 52), visual analog scale scores (overall symptoms, nasal obstruction, and loss of smell [weeks 49-52]), and total 22-Item Sino-Nasal Outcome Test score (week 52) were assessed in patients with or without improvements in NPS (improvement of ≥1 point) or without (improvement of <1 point or worsening)., Results: Patients with improvements in NPS had greater improvements in PNIF (a median of 50 L per minute [interquartile range (IQR) = 10.5-87.5] with mepolizumab vs a median of 40 L per minute [IQR = 0-85.0] with placebo) than did those patients without improvements in NPS (a median of 0.0 L per minute [IQR = -10.0 to 45.0] with mepolizumab vs a median of 0.0 L per minute [IQR = -30.0 to 30.0] with placebo). Similar results were seen for the following: change from baseline in overall symptoms (a median of -5.8 [IQR = -8.1 to -3.80] with mepolizumab and a median of -4.1 [IQR = -7.0 to -1.2] with placebo with improvement in NPS vs a median of -1.3 [IQR = -6.3 to 0.0] with mepolizumab and a median of -0.1 [IQR = -3.4 to 0.0] with placebo without improvement in NPS); change in nasal obstruction (a median of -5.7 [IQR = -8.2 to -3.5] with mepolizumab and a median of -4.5 [IQR = -7.3 to -1.2] with placebo with improvement in NPS vs a median of -1.3 [IQR = -6.6 to 0.0] with mepolizumab and a median of 0.0 [IQR = -3.6 to 0.0] with placebo without improvement in NPS); change in loss of smell (a median of -2.8 [IQR = -7.9 to 0.0] with mepolizumab and a median of -0.7 [IQR = -4.0 to 0.0] with placebo with improvement in NPS vs a median of 0.0 [IQR = -2.4 to 0.0] with mepolizumab and a median of 0.0 [IQR = -0.3 to 0.0]) with placebo without improvement in NPS); and change in visual analog scale score and 22-Item Sino-Nasal Outcome Test total score (a median of -37.0 [IQR = -52.0 to -24.0] with mepolizumab and a median of -29.0 [IQR = -43.0 to -9.0] with placebo with improvement in NPS vs a median of -16.0 [IQR = -42.0 to 0.0] with mepolizumab and a median of 0.0 [IQR = -27.0 to 0.0] with placebo without improvement in NPS)., Conclusion: Improvement in NPS was associated with improvements in PNIF and patient-reported outcomes irrespective of treatment. PNIF could be a useful noninvasive tool for monitoring nasal polyp size., Competing Interests: This study and the post hoc analyses were funded by GSK (GSK identifier 205687/ClinicalTrials.gov NCT03085797). Medical writing and editorial support (in the form of writing assistance, including development of the initial draft based on author direction, assembly of tables and figures, collation and incorporation of authors’ comments on the drafts, grammatical editing, and referencing) was funded by GSK. The sponsor did not place any restrictions on access to the data or on the statements made in the article. Disclosure of potential conflict of interest: A. U. Luong serves as a consultant for Aerin Medical, GSK, Lyra Therapeutics, Medtronic, NeurENT Medical, Sanofi, and Stryker and also serves on scientific advisory boards for Maxwell Biosciences and SoundHealth. J. M. Levy reports serving as a consultant for 10.13039/100004325AstraZeneca, GSK, 10.13039/100019966Honeywell International, and Regeneron; receiving grants from Honeywell International, Sanofi/Regeneron, Genentech, and the 10.13039/100000002National Institutes of Health (grants 1R03TR004022-01 and HL-143541-02S2). L. Klimek reports grants and personal fees from 10.13039/100009946Allergopharma, Novartis, Bionorica, GSK, and Lofarma; personal fees from MEDA and Boehringer Ingelheim; and grants from AstraZeneca, Biomay, HAL, LETI Pharma, Roxall, Sanofi, and Bencard outside the submitted work. R. J. Harvey reports serving as a consultant/advisory board member with Medtronic, Novartis, Neilmed, Sanofi, GSK, and Viatris Pharmaceuticals; receiving research grant funding from GSK and Stallergenes; and having served on the speakers bureaus for Stallergenes, Sanofi, GSK, AstraZeneca, Viatris Pharmaceuticals, and Seqirus. A. Fuller is a contract resource for GSK. P. W. Hellings has received research grants and/or consultancy or lecture fees from Sanofi, Regeneron, GSK, Novartis, Viatris, and AstraZeneca. J. Silver, S. G. Smith, and R. Chan are employees of GSK and own stock/shares., (© 2024 The Authors.)

Objective: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care., Purpose: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients., Action Statements: The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens., (© 2024 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objective: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care., Purpose: The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients., Action Statements: The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens., (© 2024 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Limited data highlight the need to understand differences in SARS-CoV-2 omicron (B.1.1.529) variant viral load between the gold standard nasopharyngeal (NP) swab, mid-turbinate (MT)/anterior nasal swabs, oropharyngeal (OP) swabs, and saliva. MT, OP, and saliva samples from symptomatic individuals in Atlanta, GA, in January 2022 and longitudinal samples from a small familial cohort were tested by both RT-PCR and ultrasensitive antigen assays. Higher concentrations in the nares were observed in the familial cohort, but a dominant sample type was not found among 39 cases in the cross-sectional cohort. The composite of positive MT or OP assay for both RT-PCR and antigen assay trended toward higher diagnostic yield but did not achieve significant difference. Our data did not identify a singular preferred sample type for SARS-CoV-2 testing, but higher levels of saliva nucleocapsid, a trend toward higher yield of composite OP/MT result, and association of apparent MT or OP predominance with symptoms warrant further study., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wilbur Lam, Greg Martin reports financial support was provided by 10.13039/100000070National Institute of Biomedical Imaging and Bioengineering. Wilbur Lam, Greg Martin reports administrative support was provided by 10.13039/100006108National Center for Advancing Translational Sciences. This research was supported by funds from the NIDCD Division of Intramural Research to Joshua Levy (DC000097).

Background and objective Chronic rhinosinusitis (CRS) is an inflammatory condition affecting the nasal mucosa, and it causes olfactory dysfunction (OD) in up to 78.2% of patients. Corticosteroids are the mainstay of treatment to shrink nasal polyposis, reduce inflammation, and improve olfactory function. While many delivery methods for topical nasal corticosteroids exist, there is scarce data on the efficacy of the various medication delivery methods to the olfactory cleft (OC). In light of this, this study aimed to compare the following delivery methods to the OC: conventional nasal spray (NS), nasal drops in the Kaiteki position (KP), and exhalation delivery system (EDS). Methods We evaluated 16 sinonasal cavities from eight cadaver specimens in this study. Each sinonasal cavity was administered fluorescein dye solution via NS, KP, and EDS. Following administration, nasal endoscopy was employed to capture staining patterns in the OC. OC staining was rated with scores ranging from 0 (no staining) to 3 (heavy staining) after each administration of dye solution. Mean OC staining ratings were calculated and compared using the Kruskal-Wallis rank sum test and the Wilcoxon signed-rank test. Results The mean OC staining score for the different delivery methods was as follows - NS: 1.095 ± 1.008, EDS: 0.670 ± 0.674, and KP: 2.038 ± 1.097. Nasal drops in the KP had a significantly higher staining score compared to NS (p=0.041) and EDS (p=0.003). However, there was no significant difference in staining scores between NS and EDS. Conclusions Nasal drops in the KP are more effective at reaching the OC than NS or EDS and should be considered as a first-line modality for administering topical medications when treating OD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Jacobson et al.)

Background: A definitive diagnosis of eosinophilic chronic rhinosinusitis (eCRS) requires invasive surgical tissue sampling and histologic enumeration of intact eosinophils. Eosinophil peroxidase (EPX) is an accurate biomarker of sinonasal tissue eosinophilia in CRS regardless of polyp status. A less invasive and rapid method that accurately identifies tissue eosinophilia would be of great benefit to patients., Objective: We sought to evaluate a new clinical tool that uses a nasal swab and colorimetric EPX activity assay to predict a diagnosis of eCRS., Methods: A prospective, observational cohort study was conducted using nasal swabs and sinonasal tissue biopsies obtained from patients with CRS electing endoscopic sinus surgery. Patients were classified as non-eCRS (n = 19) and eCRS (n = 35) on the basis of pathologically determined eosinophil counts of less than 10 or greater than or equal to 10 eosinophils/HPF, respectively. Swab-deposited EPX activity was measured and compared with tissue eosinophil counts, EPX levels, and CRS-specific disease metrics., Results: EPX activity was significantly increased in patients with eCRS than in patients without eCRS (P < .0001). With a relative absorbance unit cutoff value of greater than or equal to 0.80, the assay demonstrated high sensitivity (85.7%) and moderate specificity (79.0%) for confirming eCRS. Spearman correlations between EPX activity and tissue eosinophil counts (r s  = 0.424), EPX levels (r s  = 0.503), and Lund-Kennedy endoscopy scores (r s  = 0.440) in eCRS were significant (P < .05)., Conclusions: This investigation evaluates a nasal swab sampling method and EPX activity assay that accurately confirms eCRS. This method could potentially address the unmet need to identify sinonasal tissue eosinophilia at the point-of-care, as well as to longitudinally monitor eosinophil activity and treatment response., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: The endogenous cannabinoid (endocannabinoid) system is an emerging target for the treatment of chronic inflammatory disease with the potential to advance treatment for many respiratory illnesses. The varied effects of endocannabinoids across tissue types makes it imperative that we explore their physiologic impact within unique tissue targets. The aim of this scoping review is to explore the impact of endocannabinoid activity on eicosanoid production as a measure of human airway inflammation. Methods: A scoping literature review was conducted according to PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Search strategies using MeSH terms related to cannabinoids, eicosanoids, cyclooxygenase (COX), and the respiratory system were used to query Medline, Embase, Cochrane, CINAHL, Web of Science, and Biosis Previews in December 2021. Only studies that investigated the relationship between endocannabinoids and the eicosanoid system in mammalian respiratory tissue after 1992 were included. Results: Sixteen studies were incorporated in the final qualitative review. Endocannabinoid activation increases COX-2 expression, potentially through ceramide-dependent or p38 and p42/44 Mitogen-Activated Protein Kinase pathways and is associated with a concentration-dependent increase in prostaglandin (PG)E 2 . Inhibitors of endocannabinoid hydrolysis found either an increase or no change in levels of PGE 2 and PGD 2 and decreased levels of leukotriene (LT)B 4 , PGI 2 , and thromboxane A 2 (TXA 2 ). Endocannabinoids increase bronchial epithelial cell permeability and have vasorelaxant effects in human pulmonary arteries and cause contraction of bronchi and decreased gas trapping in guinea pigs. Inhibitors of endocannabinoid hydrolysis were found to have anti-inflammatory effects on pulmonary tissue and are primarily mediated by COX-2 and activation of eicosanoid receptors. Direct agonism of endocannabinoid receptors appears to play a minor role. Conclusion: The endocannabinoid system has diverse effects on the mammalian airway. While endocannabinoid-derived PGs can have anti-inflammatory effects, endocannabinoids also produce proinflammatory conditions, such as increased epithelial permeability and bronchial contraction. These conflicting findings suggest that endocannabinoids produce a variety of effects depending on their local metabolism and receptor agonism. Elucidation of the complex interplay between the endocannabinoid and eicosanoid pathways is key to leveraging the endocannabinoid system as a potential therapeutic target for human airway disease.

Objectives: Understanding the incidence and characteristics that influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections (VBIs) is imperative for developing public health policies to mitigate the coronavirus disease of 2019 (COVID-19) pandemic. We examined these factors and post-vaccination mitigation practices in individuals partially and fully vaccinated against SARS-CoV-2., Materials and Methods: Adults >18 years old were voluntarily enrolled from a single metro-based SARS-CoV-2 testing network from January to July 2021. Participants were categorized as asymptomatic or symptomatic, and as unvaccinated, partially vaccinated, or fully vaccinated. All participants had confirmed SARS-CoV-2 infection based on standard of care (SOC) testing with nasopharyngeal swabs. Variant analysis by rRT-PCR was performed in a subset of time-matched vaccinated and unvaccinated individuals. A subgroup of partially and fully vaccinated individuals with a positive SARS-CoV-2 rRT-PCR was contacted to assess disease severity and post-vaccination mitigation practices., Results: Participants ( n = 1,317) voluntarily underwent testing for SARS-CoV-2 during the enrollment period. A total of 29.5% of the population received at least one SARS-CoV-2 vaccine ( n = 389), 12.8% partially vaccinated ( n = 169); 16.1% fully vaccinated ( n = 213). A total of 21.3% of partially vaccinated individuals tested positive ( n = 36) and 9.4% of fully vaccinated individuals tested positive ( n = 20) for SARS-CoV-2. Pfizer/BioNTech mRNA-1273 was the predominant vaccine received (1st dose = 66.8%, 2nd dose = 67.9%). Chronic liver disease and immunosuppression were more prevalent in the vaccinated (partially/fully) group compared to the unvaccinated group ( p = 0.003, p = 0.021, respectively). There were more asymptomatic individuals in the vaccinated group compared to the unvaccinated group [ n = 6 (10.7%), n = 16 (4.1%), p = 0.045]. C T values were lower for the unvaccinated group (median 24.3, IQR 19.1-30.5) compared to the vaccinated group (29.4, 22.0-33.7, p = 0.004). In the vaccinated group ( n = 56), 18 participants were successfully contacted, 7 were lost to follow-up, and 2 were deceased. A total of 50% ( n = 9) required hospitalization due to COVID-19 illness. Adherence to nationally endorsed mitigation strategies varied post-vaccination., Conclusion: The incidence of SARS-CoV-2 infection at this center was 21.3% in the partially vaccinated group and 9.4% in the fully vaccinated group. Chronic liver disease and immunosuppression were more prevalent in the vaccinated SARS-CoV-2 positive group, suggesting that these may be risk factors for VBIs. Partially and fully vaccinated individuals had a higher incidence of asymptomatic SARS-CoV-2 and higher C T values compared to unvaccinated SARS-CoV-2 positive individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Strickler, Esper, Wells, Wood, Frediani, Nehl, Waggoner, Rebolledo, Levy, Figueroa, Ramachandra, Lam and Martin.)

Objective: To compare systemic allergen sensitivity and local allergen sensitivity in the sinonasal tissue of patients with a recently identified subtype of chronic rhinosinusitis strongly associated with allergy: central compartment atopic disease (CCAD)., Study Design: Prospective cohort study., Setting: Academic tertiary care rhinology clinic., Methods: Fifteen participants with endoscopic and radiographic evidence of CCAD underwent systemic allergy testing with skin testing and measurement of serum specific immunoglobulin E (sIgE) to 15 regionally common aeroallergens. Local allergen sensitivity was determined by measuring sIgE to these same 15 allergens in their sinonasal tissue. sIgE testing was performed by ImmunoCAP assay., Results: Of the 15 participants, 14 were sensitive to at least 1 allergen locally in the central compartment and systemically on skin or serum testing. Among all participants, 4 were sensitive to allergens on central compartment sIgE testing that they were not sensitive to on skin and serum sIgE testing (range, 1-8 discordant allergens). Comparisons between local and systemic aeroallergen sensitivity results showed statistically significant correlations ( P < .05) ranging from weak to strong., Conclusion: Systemic allergy testing is recommended in the initial workup for CCAD. Local allergen sensitivities may be present in a subset of patients with CCAD. Further study of the clinical significance of these sensitivities should be undertaken in CCAD, with evaluation of the role of medical therapies and allergen immunotherapy in the treatment of CCAD.