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BackgroundEpithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell type shifts and their relationship to CRS endotypes and severity are incompletely described.ObjectiveThe purpose of this study was to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS.MethodsUsing cell type transcriptional signatures derived from epithelial single cell sequencing, we analyzed bulk RNA sequencing data from sinus epithelial brushes obtained from patients with CRS with and without nasal polyps in comparison to healthy controls.ResultsThe airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, chronic rhinosinusitis without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated (“polyp”) tuft cell score and a prostaglandin E2 (PGE2) activation signature. The Lund-McKay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, PGE2, and IL-13 and negatively with ciliated cell transcriptional signatures.ConclusionsThese results demonstrate that cell type alterations and PGE2 stimulation are key components of IL-13 induced epithelial remodeling in nasal polyposis, while IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13 induced epithelial remodeling.Key MessagesCell type signatures from single cell RNA sequencing, applied to bulk sequenced RNA sinus brushes, suggest increased tuft cells and mast cells and decreased ciliated cells in nasal polyp epithelium.IL-17 signaling rather than IL-13 signaling is observed in epithelium from CRSsNP.IL-13-drives epithelial remodeling and prostaglandin E2 signatures correlated with clinical measures of sinus opacification in CRS.Capsule SummaryMeasures of epithelial remodeling, including both IL-13 and PGE2 induced epithelial activation and cell type specific transcript alterations, correlate with a radiographic metric of disease severity in CRSwNP.

Granulomatous and vasculitic diseases of the airway may be part of more widespread systemic disease but can occur in isolation. They may present to the ear, nose, and throat (ENT) surgeon initially with vague symptoms that mimic more common chronic inflammatory unified airway conditions, such as rhinitis, chronic rhinosinusitis, and asthma. Early diagnosis is associated with better long-term outcomes, so a high index of suspicion is required. Bloody nasal discharge and crusting are highly suspicious for granulomatous disease, which should also be considered in atypical or recalcitrant disease. A combination of clinical findings, serologic tests, imaging, and histology may be required to confirm the diagnosis..

Upper airway cough syndrome (UACS), formerly known as postnasal drip syndrome, is one of the most common causes of chronic cough. UACS, asthma, and gastroesophageal reflux make up 90% of the cause of chronic cough. UACS is a clinical diagnosis of exclusion with no diagnostic testing or objective findings. UACS can be present with or without associated rhinitis and chronic rhinosinusitis. Treatment includes dual therapy with H1 receptor antihistamines and decongestants. Diagnosis is confirmed when therapeutic intervention results in symptom resolution.

To analyze published reports on the efficacy and safety of CSI in CRS and evaluate the clinical implications of current gaps in evidence. Corticosteroid irrigation (CSI) is commonly used for management of chronic rhinosinusitis (CRS) with nasal polyps; however, such use is not approved by the US Food and Drug Administration (FDA).Publications were obtained through PubMed searches through January 2022.Searches were conducted using 2 terms: "chronic rhinosinusitis" or "nasal polyps" as the first term and "corticosteroid irrigation," "steroid nasal lavage," or "sinus rinse" as the second term. We reviewed relevant, peer-reviewed literature (19 original research [9 controlled, 10 uncontrolled trials], 7 reviews, and 1 meta-analysis) reporting safety and efficacy of CSI in patients with CRS.Studies were difficult to compare because they used a variety of solution volumes (60 mL to 125 mL per nostril), corticosteroid agents (budesonide, betamethasone, mometasone, or fluticasone), corticosteroid doses, preparation protocols (by compounding pharmacy or by patient), and administration (frequency, time of day, body positioning). It is difficult to determine which parameters might substantially influence clinical effects because studies were generally small, showed marginal benefits, and rarely assessed safety. To date, no studies evaluating CSI have shown statistically significant differences in a type-I error-controlled primary end point over any comparator, possibly owing to small sample sizes.Designing more robust clinical trials may help determine whether CSI is a valid treatment option. Until more evidence supporting CSI use exists, health care professionals should strongly consider choosing FDA-approved therapies for the treatment of CRS.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear.We systematically synthesized the evidence addressing INCS for CRSwNP.We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach.We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others).Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

Chronic rhinosinusitis (CRS) is a common upper airways inflammatory disease requiring multidisciplinary care.To evaluate if African Americans (AA), Latinxs, and nonLatinx White (White) patients have different chronic rhinosinusitis outcomes and to identify associated factors impacting these outcomes.We conducted a large prospective cohort study of CRS patients who were evaluated and followed for several clinical variables at the initial encounter and after continuous management of CRS for a mean of 40 months. The Sinonasal Outcome Test (SNOT-22) and Lund-MacKay scores were measured on initial visits, and SNOT-22 was repeated at the end of follow-up. Logistic regression was used to compare outcomes between the different groups adjusted for comorbidities and demographics.Among the 977 enrolled CRS cases, 615 (63.0%), 235 (24.1%) and 138 (13.0%) were White, AA and Latinx respectively. There was no difference in severity of CRS based on Lund-MacKay scores and SNOT-22 scores, and frequency of other comorbidities at presentation among the 3 groups. During the follow-up period, compared with Whites, AA and Latinx were less frequently evaluated by an allergist. AAs had less frequent CRS related visits and lower final SNOT-22 score compared with Whites.Although our enrolled patients from the 3 ethnic groups had similar clinical characteristics and disease burden at baseline, AAs had less frequent follow-up visits and worse final SNOT-22 after 40 months of follow-up. The observed poorer outcomes in AAs are likely owing to inequity in healthcare access evidenced by differences in insurance and suboptimal management of CRS.

Introduction High-volume corticosteroid nasal irrigation is a treatment option in patients with chronic rhinosinusitis. In Brazil, alternatives are used to optimize its cost and popularize its use, such as 1% compounded budesonide drops or betamethasone cream, and it is necessary to study these treatment modalities. Objective To evaluate the clinical response of nasal irrigation with 1% compounded budesonide drops or betamethasone cream compared to nasal sprays utilized in patients with chronic rhinosinusitis. Methods This was a retrospective observational study with 257 patients. One hundred and eight patients using corticosteroid nasal irrigation (292 treatment cycles) and 149 using corticosteroid nasal spray (300 treatment cycles) were included. Evaluation of subjective improvement, adverse events, exacerbations, and objective assessments with SNOT-22 and Lund–Kennedy endoscopic score were performed, in addition to sub-analyses related to nasal polyps and previous surgery. Results Corticosteroid nasal irrigation and corticosteroid nasal spray improved the Lund–Kennedy endoscopic score, with more adverse events in the corticosteroid nasal irrigation group. Previous surgery increased corticosteroid nasal irrigation improvement, with greater subjective improvement and fewer exacerbations. 1% compounded budesonide drops were better than betamethasone cream in the Lund–Kennedy endoscopic score, with fewer adverse events. A 1,000 µg dose of 1% compounded budesonide drops was more effective than 500 µg. Conclusion Corticosteroid nasal irrigation was effective in improving the Lund–Kennedy endoscopic score in chronic rhinosinusitis, especially in patients with nasal polyps and previous surgery, in addition to promoting a higher rate of subjective improvement and fewer exacerbations than corticosteroid nasal spray, but with more adverse events. 1% compounded budesonide drops improved the Lund–Kennedy endoscopic score with fewer adverse events than betamethasone cream, particularly at higher doses (1000 µg).

Transient increases in blood eosinophil counts have been observed in dupilumab clinical trials.To assess eosinophil counts and eosinophilia-related treatment-emergent adverse events (TEAEs) across 11 dupilumab clinical trials, comparing adult and adolescent patients with asthma and adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and eosinophilic esophagitis.Eosinophil counts, rates of eosinophilia-related TEAEs or treatment-emergent eosinophilia (1,500 cells/μL), discontinuations, clinical symptoms, and efficacy in patients with asthma or CRSwNP with treatment-emergent eosinophilia are presented.Transient increases in mean eosinophil counts were observed in dupilumab-treated patients with asthma (mean range across studies at baseline: 349-370 cells/μL; week 4: 515-578 cells/μL), CRSwNP (baseline: 440-448 cells/μL; week 16: 595 cells/μL), and atopic dermatitis (baseline: 434-600 cells/μL; week 4: 410-710 cells/μL), followed by a decline starting by week 24 to baseline or lower. No increases were seen in patients with eosinophilic esophagitis (baseline: 310 cells/μL; week 4: 230 cells/μL). In dupilumab-treated patients across all studies, rates of eosinophilia TEAEs were 0% to 13.6%. Clinical symptoms associated with increased eosinophils were rare (seven of 4,666 dupilumab-treated patients, including six cases of eosinophilic granulomatosis with polyangiitis) and occurred only in patients with asthma or CRSwNP. Eosinophilia was not associated with reduced dupilumab efficacy.Transient increases in eosinophil counts with dupilumab treatment did not affect efficacy and were rarely of clinical consequence. It remains important for physicians to base judgment on individual patient history and baseline eosinophil counts and to be alert to hypereosinophilic symptoms.

With improved survival in cystic fibrosis (CF) patients, it is crucial to evaluate the impact of chronic co-morbidities such as chronic rhinosinusitis (CRS). The objectives were 1) To determine the prevalence of CRS with a large series of CF patients 2) To evaluate the impact of CRS on the Health-Related Quality of Life (HRQoL) of CF patients and 3) To compare CRS-specific, CF-specific and general HRQoL instruments.Consecutive CF patients from the Toronto Adult Cystic Fibrosis Centre were recruited between March 2018 and January 2020. Participants completed the 22-Item Nasal Outcome Test (SNOT-22), Cystic Fibrosis Questionnaire-Revised for adolescents and adults over 14 years of age (CFQ-R), Cystic Fibrosis Quality of Life Evaluative Self-administered Test (CF-QUEST) and the 36-Item Short Form Survey (SF-36). HRQoL scores were correlated using Spearman's correlation coefficients.Out of 195 patients eligible for analysis, the prevalence of CRS with positive endoscopic findings was 42.6% (95% confidence interval: 35.5-49.8%). CRS patients reported significantly lower HRQoL with higher SNOT-22 scores and lower scores in the respiratory domain of CFQ-R and physical health domains of CF-QUEST and SF-36. The physical (ρ= -0.63) and mental (ρ= -0.66) domains of SF-36 and CF-QUEST (ρ= -0.76) had a strong correlation with SNOT-22. Higher scores of SNOT-22 nasal subdomains correlated with lower scores of SF-36, CFQ-R and CF-QUEST.CRS is a prevalent co-morbidity of CF patients, which significantly reduces HRQoL. SNOT-22, CFQ-R, CF-QUEST and SF-36 were strongly correlated. Severity of sinonasal symptoms have a strong correlation with HRQoL in CF patients.

Recent pandemic of COVID19 infection has witnessed a re-emergence of invasive fungal sinusitis especially of the Mucor species, which has been a rare entity in the pre covid era. Covid associated mucormycosis (CAM) is one of the dreaded and fatal complications which has surfaced up and early diagnosis is critical for management and survival .It is identified to affect both subset of patients, those with active COVID-19 infection and those who have recovered from the disease in the last 4-6 weeks. Imaging features suggestive of early invasion with supportive imaging examples and relevance of these findings in clinical decision making is presented.This paper reviews the various imaging signs of early invasion in CAM A comprehensive checklist for clinically relevant and quick reporting is also presented.Emphysematous or ulcerative mucosal changes in the nasal cavity is an early imaging feature of CAM. Periantral soft tissue and soft tissue within the pterygopalatine fossa are important imaging signs to indicate extrasinus invasion. Disease within pterygopalatine fossa may lead to multidirectional spread and is an important check site. These findings are seen even in absence of bony erosions owing to the neurovascular spread of disease. Intra orbital and intracranial extensions were found to be fairly common and must be sought for.The knowledge of early subtle signs of CAM on imaging can aid in prompt diagnosis of this fatal entity in the pertinent clinical setting. Imaging signs of spread of disease and delineation of its extent as inferred from CT imaging aids in prognosis and appropriate surgical management.

Cross-sectional imaging with computed tomography (CT) and MRI are diagnostic examinations useful in the diagnosis of painful ophthalmologic disorders and their potential complications. CT is a first-line imaging study for suspected orbital infections, particularly useful in differentiating preseptal cellulitis and orbital cellulitis and detecting complications such as orbital abscess. When compared with CT, MRI is better for orbital soft tissue evaluation, particularly useful for optic neuritis, ocular diseases such as endophthalmitis, and invasive fungal rhinosinusitis with orbital involvement. CT angiography is the preferred noninvasive imaging modality for the detection and classification of carotid cavernous fistula.

The severity of pediatric obstructive sleep apnea (OSA) can vary from mild to very severe (AHI ≥ 30 events/h) with the seasons. The efficacy of medical treatment has been investigated in cases of mild and moderate pediatric OSA, but not in severe cases thoroughly.Our prospective cohort study involved 205 children who visited our outpatient clinic between December 2014 and May 2020. We performed home sleep tests after the initial visit, and then polysomnography after optimizing the control of rhinitis, sinusitis, adenoid hypertrophy, and tonsillitis by using medical treatments.The respective proportions of patients who improved to obstructive AHI (O-AHI)1/h or who proceeded to surgery were 43.4% and 62.3% in mild cases; 43.3% and 52.2% in moderate cases; 30.2% and 68.4% in severe cases; and 0.0% and 100% in very severe cases. Additionally, nadir SaOMedical treatment instituted before a surgical decision is made can provide substantial benefits and avoid unnecessary surgery if there is time for such treatments. In contrast, it may be difficult to normalize the O-AHI in pediatric patients with very severe OSA or a nadir SaO

Dupilumab, a mAb targeting IL-4Rα, improves upper and lower airway symptoms in patients with aspirin-exacerbated respiratory disease (AERD), but the mechanisms leading to clinical improvement are not fully elucidated.Our aim was to identify the mechanistic basis of clinical improvement in patients with AERD treated with dupilumab.A total of 22 patients with AERD were treated with dupilumab for 3 months for severe asthma and/or chronic rhinosinusitis with nasal polyps. Clinical outcomes were assessed at baseline and at 1 and 3 months after initiation of dupilumab. Nasal fluid, urine, blood, and inferior turbinate scrapings were collected at the 3 time points for determination of mediator levels, cellular assays, and RNA sequencing.Participants had rapid improvement in clinical measures, including sense of smell, sinonasal symptoms, and lung function after 1 month of treatment with dupilumab; the improvements were sustained after 3 months of dupilumab. Baseline severity of smell loss was correlated with lower nasal prostaglandin EInhibition of IL-4Rα in AERD led to rapid improvement in respiratory symptoms and smell, with a concomitant improvement in epithelial barrier function, a decrease in inflammatory eicosanoid levels, and an increase in the anti-inflammatory eicosanoid prostaglandin E

The study objective was to assess the functional, endoscopic and tomodensitometric semiology of a cohort of patients with chronic respiratory rhinitis (CRR). The concept of CRR is based on the anatomical, pathophysiological and semiological individualization of the respiratory nose within the sinonasal organ, in which three noses are distinguished by the parallel study of evolution and development in the "evo-devo" theory of the origins of the nose, anterior base of the skull and middle third of the face.A single-center retrospective study included a cohort of 28 patients (16 men and 12 women, aged 19 to 69years) with CRR. The main objective was to describe symptoms clinically, endoscopically and on CT. The secondary objective was to compare clinical symptomatology and CT data between CRR and a control group of 31 patients with nasal polyposis (NP). The endoscopic semiology of CRR was analyzed consensually on video recordings using a pre-established grid. The DyNaChron self-administered questionnaire was used to compare symptom intensity and deterioration in quality of life. Olfaction was compared using the Sniffin' Sticks test. CT opacities were compared between CRR and NP on Lund-Mackay sinus score and a specific ethmoid opacities score.In CRR, endoscopy found a constant association of inflammatory or edematous signs in the inferior or middle turbinates with signs of hypersecretion. Ethmoid opacities in CRR were discrete and significantly smaller than in NP (P0.0001), and were mainly located in the medial compartment in contact with the olfactory cleft (P0.0001). Allergological assessment was positive in 17 of the 28 cases of CRR. Chronic nasal dysfunction was similar in CRR and NP, but olfactory impairment was significantly lower in CRR (P0.0001).The CRR entity clinically resembles atopic central compartment disease. In both entities, endoscopy reveals inflammatory lesions restricted to the nasal cavities without significant ethmoid opacity on CT, an observation which seems to contradict the pathophysiological united airway concept.

In the clinical assessment of chronic rhinosinusitis with nasal polyps (CRSwNP), evaluation of symptoms, nasoendoscopy findings and sinus computed tomography (CT) scan staging is employed in the management plan. Although prior studies have been done to assess the correlation of the three modalities in CRSwNP, such evaluation in patients with eosinophilic and non-eosinophilic types of CRSwNP requires further investigation. The aim of this study was to correlate the sinus CT scan staging to symptom and endoscopic scores in both types of CRSwNP.Patients with CRSwNP were classified into 2 types, eosinophilic and non-eosinophilic. Both types were assessed by Sino-Nasal Outcome Test 22 (SNOT-22) symptom score, nasal endoscopy Lund Kennedy grading (LK) score and sinus CT Lund Mackay (LM) staging score. All three modalities were correlated.Forty-four patients were recruited for this study. There was significant correlation between sinus CT and symptom scores in the eosinophilic (r=.51, p=.031) and the non-eosinophilic (r=.76, p.001) types. There was no significant correlation between symptom and nasoendoscopic scores in the eosinophilic (r=.12, p=.641) and the non-eosinophilic (r=.22, p=.276) types. There was also no significant correlation between sinus CT and nasoendoscopic scores in the eosinophilic (r=.20, p=.418) and the non-eosinophilic (r=.14, p=.508) types.Sinus CT staging correlates well with the symptom score for both the eosinophilic and the non-eosinophilic types of CRSwNP. The good correlation suggests both modalities are a reliable guide for their evaluation and management planning.

Chronic rhinosinusitis is characterized by persistent locoregional mucosal inflammation of the paranasal sinuses and upper airway that has substantial associated health care costs. Personalized approaches to care that incorporate use of molecular biomarkers, phenotypes, and inflammatory endotypes is a major focus of research at this time, and the concurrent rise of targeted therapeutics and biologic therapies has the potential to rapidly advance care and improve outcomes. Recent findings suggest that improved understanding of chronic rhinosinusitis phenotypic and endotypic heterogeneity, and incorporation of these characteristics into clinical care pathways, may facilitate more effective selection of surgical and/or therapeutic interventions. Ultimately, these personalized approaches have the potential to target specific inflammatory pathways, increase efficacy, reduce costs, and limit side effects. This review summarizes recent advances in the identification and characterization of chronic rhinosinusitis phenotypes, endotypes, and biomarkers and reviews potential implications for targeted therapeutics.

Chronic rhinosinusitis (CRS) is a common disease that affects10% of the adult population in Europe and the United States. It has been delineated phenotypically into CRS without nasal polyps and CRS with nasal polyps. Both have a high disease burden and an overlapping spectrum of symptoms such as nasal obstruction, olfactory dysfunction, facial pain, pressure, and nasal discharge. Primary assessment includes evaluation of patient symptoms and impact on quality of life, nasal endoscopic examination, and imaging. Significant progress has been made in the understanding of CRS pathophysiology. There is a move toward describing CRS in terms of the predominant endotype or inflammatory pattern pathomechanism rather than the traditional classification of patients with and without nasal polyps. An increased elucidation of the disease endotypes, as characterized by their inflammatory pathways and mediators, is leading to a tailored more personalized treatment approach to the different disease subtypes.

The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), latest version EPOS2020, and the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS), latest version ICAR-RS-2021, assimilate thousands of articles on the topic of rhinosinusitis. Encompassing scores of subtopics and relying on the perspectives of many international experts, EPOS2020 and ICAR-RS-2021 reduce the existing data into consumable formats and create evidence-based recommendations. The approaches and findings are similar in many respects but have significant differences. This clinical commentary, authored by some of the principal authors of these documents, compares and contrasts EPOS2020 and ICAR-RS-2021, examining methodology, diagnostic and treatment recommendations, and each document's emphases. This commentary demonstrates that, through somewhat differing methodologies, the 2 documents arrive at largely similar conclusions. Those who care for patients suffering from rhinosinusitis will find the documents complementary and valuable in their differences as much as in their similarities.

Novel medical devices are emerging as low-risk treatment options for patients suffering from sinus headaches. Early trends for the treatment of sinus headaches using medical devices are following the more established primary headache literature. There are two categories of devices with early data supporting use, which may serve as useful adjuncts to conventional pharmacotherapy in the management of sinus headaches not caused by sinusitis: transcutaneous electrical neurostimulation and acoustic vibration with oscillating expiratory pressure. There is currently a paucity of high-level evidence and further studies are needed. Initial reports suggest these interventions are low risk, but longer follow-up is necessary.

The COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of the most common causes of olfactory dysfunction. It can be classified into different phenotypes (ie, with and without nasal polyps) and endotypes (ie, type 2 and non-type 2 inflammation). However, scientific information regarding CRS within the context of COVID-19 is still scarce. This review focuses on (1) the potential effects of severe acute respiratory syndrome coronavirus 2 infection on CRS symptoms, including a loss of smell, and comorbidities; (2) the pathophysiologic mechanisms involved in the olfactory dysfunction; (3) CRS diagnosis in the context of COVID-19, including telemedicine; (4) the protective hypothesis of CRS in COVID-19; and (5) the efficacy and safety of therapeutic options for CRS within the context of COVID-19.

Aspirin-exacerbated respiratory disease (AERD) can be a frustratingly complex syndrome to treat. Until recently, standard medical and surgical therapies for patients' asthma and chronic rhinosinusitis with nasal polyposis were the primary treatment modalities available, combined with either complete avoidance of all aspirin and nonsteroidal anti-inflammatory medications, or aspirin desensitization and initiation of high-dose aspirin therapy. There are now several targeted respiratory biologics added to the available armament for patients with AERD and choosing between this ever-growing list of options can be daunting for both patients and their clinicians. This review includes our understanding and interpretation of the existing data for each option, along with our own approach to weighing the pros and cons of each treatment for individual patients.

This article presents guidelines for initial imaging utilization in patients presenting with sinonasal disease, including acute rhinosinusitis without and with suspected orbital and intracranial complications, chronic rhinosinusitis, suspected invasive fungal sinusitis, suspected sinonasal mass, and suspected cerebrospinal fluid leak. CT and MRI are the primary imaging modalities used to evaluate patients with sinonasal disease. Given its detailed depiction of bony anatomy, CT can accurately demonstrate the presence of sinonasal disease, bony erosions, and anatomic variants, and is essential for surgical planning. Given its superior soft tissue contrast, MRI can accurately identify clinically suspected intracranial and intraorbital complications, delineate soft tissue extension of tumor and distinguish mass from obstructed secretions.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

This review of aspirin-exacerbated respiratory disease (AERD) describes the clinical characteristics and pathophysiology of disease, highlighting its similarities and unique differences in comparison to classic IgE mediated hypersensitivity as well as AERD as a chronic disease. There is a specific focus on the comparison of mediator production over time and the use of desensitization in each diagnosis that serves to aid the clinician in differentiating aspirin reactions in AERD from those related to true immediate hypersensitivity.

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and is historically divided into two main phenotypes: CRS with nasal polyps (NPs) (CRSwNP) and CRS without NPs (CRSsNP). Inflammation in CRS is mainly characterized by three endotypes based on elevation of canonical lymphocyte cytokines; type 1 (T1) by Th1 cytokine IFN-γ, T2 by Th2 cutokines IL-4, IL-5 and IL-13 and T3 by Th17 cytokines including IL-17. Inflammation in both CRSsNP and CRSwNP is highly heterogeneous and the frequency of various endotypes varies geographically around the world. This finding complicates establishment of a unified understanding of the mechanisms of pathogenesis in CRS. Sinonasal epithelium acts as a passive barrier and epithelial barrier dysfunction is a common feature in CRS induced by endotype specific cytokines directly and indirectly. The sinonasal epithelium also participates in both innate immunity via recognition by innate pattern recognition receptors and promotes and regulates adaptive immunity via release of chemokines and innate cytokines including TSLP. The purpose of this review is to discuss the contribution of the epithelium to CRS pathogenesis and to update the field regarding endotypic heterogeneity and various mechanisms for understanding pathogenesis in CRS.

Background/purpose In this study we aimed to investigate the prevalence of abnormal nasality in patients with unilateral rhinosinusitis and their nasality outcomes following functional endoscopic sinus surgery (FESS). Methods A total of 42 patients with unilateral chronic rhinosinusitis who underwent unilateral FESS between April 2016 and November 2017 were enrolled. Questionnaires on sinonasal symptoms and nasality were recorded. The change in the nasalance score of vowels [a], [i] [u], nasal consonant [m], 2 nasal syllable repetitions, and 2 Chinese sentences were measured. The patients were evaluated preoperatively, 6 months, and 12 months after the operation. The patients were divided into two groups, wide opening surgery and limited surgery, according to the severity of the disease. Results Among 42 patients, the subjective reports showed that one-third of unilateral chronic rhinosinusitis (CRS) patients had abnormal nasality preoperatively and significant improvement following FESS. The Lund–Mackay score was significantly negatively correlated with preoperative nasalance of [i] and positively correlated with change of nasalance of [i]. The increase in the value of [i] is statistically significant (p = 0.01) following FESS. In the further subgroup analysis, the change in nasalance was significant in the wide opening surgery group, but not in the limited surgery group. Conclusion Although only one side of the nasal airway was involved, one-third of the patients reported abnormal nasality. In patients with more disease severity who underwent wide opening surgery, the nasalance significantly increased 1 year after FESS. The increase in the objective nasalance score was corresponded to a significant improvement of subjective self-reported nasality assessment postoperatively.

BACKGROUND: Patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP) experience recurrent respiratory tract infections. Dupilumab targets type 2 inflammation, a common underlying pathophysiology of both conditions, with proven efficacy. OBJECTIVE: To examine investigator-reported respiratory infection adverse events and anti-infective medication use with dupilumab versus placebo in patients with moderate-to-severe asthma or severe CRSwNP. METHODS: We performed a post hoc analysis of the pivotal phase 3 trials LIBERTY ASTHMA QUEST (NCT02414854) and LIBERTY NP SINUS-52 (NCT02898454) in moderate-to-severe asthma and severe CRSwNP, respectively. RESULTS: Investigator-reported respiratory infection events occurred at a significantly lower incidence in patients treated with dupilumab versus placebo, in both asthma (22% lower; P < .0001; 95% CI 0.71-0.85) and CRSwNP (38% lower; P

In the last 2 decades, an increasing understanding of pathophysiological mechanisms in chronic rhinosinusitis (CRS) opened an avenue from phenotyping to endotyping, from eosinophilic inflammation to type 2 immunity, and from the ventilation and drainage paradigm to the mucosal concept for therapeutic considerations. With the advent of type 2 endotyping and targeted biomarkers, precise endotype-driven therapeutic options are possible including biologics and adapted surgical approaches. We here aim to focus on the complexity and heterogeneity of the features of CRS endotypes, especially for those with nasal polyps, including its history, latest developments, clinical associations, and endotype-driven solutions. In order to better manage uncontrolled severe CRS in clinical practice, medical decisions based on a profound understanding of the pathology and immunology of this heterogeneous disease, aiding a precision-medicine based approach for patient's treatment, are pivotal.

Background Elexacaftor-tezacaftor-ivacaftor (ETI) improves pulmonary health and chronic rhinosinusitis (CRS) for people with cystic fibrosis (PwCF), however its impact on olfaction has not been investigated. Olfactory dysfunction impairs quality-of-life (QOL). This study evaluated the impact of ETI on multiple olfactory metrics. Methods Adult PwCF/CRS with CF transmembrane conductance regulator genotype F508del/F508del or F508del/minimal function who clinically initiated ETI participated in a prospective, observational study. Endpoints included changes after 6 months of ETI in quantitative olfactory function (Smell Identification Test, SIT), olfactory QOL (Questionnaire of Olfactory Disorders, QOD) and percent olfactory cleft opacification (%OCO), representing superior nasal cavity inflammation where afferent olfactory neurons are concentrated. Results 30 PwCF/CRS met inclusion criteria; 25 completed the study. Mean ETI adherence was 93%. At baseline, participants were hyposmic (mean SIT 31.3), had significant %OCO (mean 65.6%), yet reported non-impaired olfactory QOL (mean QOD 6.1). At follow-up, mean SIT worsened mildly (p=0.009), mean %OCO remained stable (p=0.46), and mean QOD improved modestly (p=0.008). No outcomes were impacted by prior modulator use, genotype, nasal polyps, or CF-related diabetes. Prior sinus surgery was associated with QOD improvement (p=0.04). Increased (worse) baseline QOD scores and %OCO were associated with greater improvements (p Conclusions ETI was not associated with improvement in quantitative olfaction or olfactory cleft opacification after 6 months. PwCF/CRS have hyposmia but do not report impairment in olfactory QOL. Further study to investigate mechanisms explaining olfactory dysfunction and whether olfaction improves with greater duration of ETI or in younger age groups is warranted.

Assessment of asthma comorbidities, conditions that adversely affect the pathobiology of asthma or impair its response to therapies, is a fundamental step in the evaluation and management of patients with difficult-to-treat asthma. Identifying and effectively treating asthma comorbidities, such as obesity, obstructive sleep apnea, and chronic sinusitis with nasal polyps may improve asthma control and reduce exacerbations. Additionally, identifying comorbid T2 inflammatory conditions may help guide optimal selection of biologic therapies. Here, we describe common comorbid conditions found in adult and pediatric difficult-to-control asthma, discuss evidence for the association with asthma morbidity and treatment benefit, and provide information on how and when to assess comorbidities.

Chronic rhinosinusitis (CRS) is an inflammatory condition of the paranasal sinuses defined by classic symptoms, imaging findings, and/or endoscopic findings. There are a growing number of emerging pharmacologic therapies being evaluated to treat patients with CRS, some of which have gained indication status in the United States. There have not been updated treatment guidelines published in the United States however since 2014. This document is meant to serve as an updated expert consensus document for the pharmacologic management of patients with CRS We review available data focusing on prospective clinical trials on oral and intranasal corticosteroids, nasal irrigation, biologics, antibiotics, and allergy immunotherapy for CRS both with and without nasal polyposis, as well as specific therapies for aspirin exacerbated respiratory disease associated CRS and allergic fungal CRS. There are multiple options to treat CRS, and clinicians should be knowledgeable about the efficacy and risks of these available therapies. Allergists/Immunologists now have various therapies available to treat patients with CRS.

Obliterative paranasal sinusitis is a rare sequela and end stage of chronic rhinosinusitis, which is often overlooked on imaging. It is an exuberant form of neo-osteogenesis characterized by complete or partial obliteration of the sinus cavity by new bone formation. This article presents a series of cases of obliterative sinusitis involving the sphenoid and maxillary sinuses. It is important to comment on the presence of obliterative sinusitis in the radiology report and not confuse it for native bone, fibro-osseous lesion, or arrested pneumatization, as this may have clinical implications for patients being considered for surgery. Given its potential implications for severity of sinusitis as well as prognostic significance for outcomes following endoscopic sinus surgery, awareness and timely identification of this entity is important to guide referring clinicians.

To document incidence rate and severity of specific sub-categories of respiratory tract illness (RTill) in rugby players during the Super Rugby tournament.Cross-sectional study.Team physicians completed daily illness logs in 537 professional male rugby players from South African teams participating in the Super Rugby Union tournaments (2013-2017) (1141 player-seasons, 102,738 player-days). The incidence rate (IR: illness episodes/1000 player-days) and severity [%RTill resulting in time-loss, illness burden (IB: days lost to illness/1000 player-days) and days until return-to-play (DRTP)/single illness (mean: 95% Confidence Intervals)] are reported for the following specific sub-categories of RTill: non-infective respiratory tract illness (RTnon-inf), respiratory tract infections (RTinf), influenza-like illness, infective sinusitis, upper respiratory tract infections (URTinf), lower respiratory tract infections (LRTinf).The overall IR of RTill was 2.9 (2.6-3.3). IR was higher for RTinf (2.5; 2.2-2.9) vs. RTnon-inf (0.4; 0.3-0.6) (p 0.001). For sub-categories the highest IR was in URTinf (1.9; 1.7-2.2), while the % illness causing time-loss was influenza-like illness (100%), LRTinf (91.7%), infective sinusitis (55.6%), and URTinf (49.0%). IB was highest for URTinf (2.0; 1.6-2.5), and the DRTP/single illness was highest for LRTinf (3.2; 2.3-4.4), and influenza-like illness (2.1; 1.6-2.8).RTinf accounted for57% of all illness during the Super Rugby tournament, and mostly URTinf. Influenza-like illness. LRTinf caused time-loss in90% cases. URTinf, LRTinf and influenza-like illness resulted in the highest burden of illness and LRTinf caused the highest DRTP. Prevention strategies should focus on mitigating the risk of RTinf, specifically URTinf, LRTinf and influenza-like illness.

Patients with severe chronic rhinosinusitis with nasal polyps represent an unmet clinical need in terms of recurrent disease despite current medical and surgical therapy. Targeting type 2 inflammatory cytokines (IL4/5/13) appears to be a promising therapeutic approach for such patients akin to what has already been seen in severe asthma. An indirect comparison from phase 3 placebo-controlled trials has shown relative improvements in the coprimary end point of nasal polyp score (NPS) ranging from a 15% reduction (-0.8 units) with mepolizumab, 18% with omalizumab (-1.14 units), and 35% (-2.06 units) with dupilumab. This trend was mirrored by relative improvements in health status with the 22-item Sinonasal Outcome Test score showing a 21% reduction (-13.7 units) with mepolizumab, 27% (-16.1 units) with omalizumab, and 43% (-21.1 units) with dupilumab, all exceeding the minimal clinically important difference of 8.9 units. All biologics improved the coprimary end point of nasal airway blockage and also reduced the need for rescue medical and/or surgical polypectomy. We advocate performing real-life studies looking at the response to biologics in patients who are at increased risk for disease recurrence, including initial optimal medical and surgical polyp clearance before commencing biologics.

Multisystem involvement has not been uncommon in SARS-CoV-2 infection. There has been reports of devastating neurological complication both during the infection and after the virus clears out. Here we present a rare case of sino-orbital mucormycosis, diagnosis of which was confirmed only on histopathology. Our patient presented with headache, 18 days after her recovery from SARS-CoV-2 infection and was extensively worked up for the cause. Initially she was treated as a severe sinusitis but failure to response to antibiotics treatment warranted for further investigations and imaging. Our patient had to undergo right eye enucleation plus debridement under general anesthesia under the care of ENT, Ophthalmology, Neurosurgery and Neurology. She is currently on anti-fungal treatment as advised by infectious disease department.

Epidemiology and potential risk factors for cystic fibrosis arthropathy (CFA) were studied in a relevant cystic fibrosis (CF) patient cohort.Cohort study of patients included in the German CF registry in 2016-2017. Descriptive analysis, exploratory tests and multivariable logistic regression were used to assess prevalence of CFA and associated potential risk factors for adult patients with/without chronic Pseudomonas aeruginosa infection.6069 CF patients aged from 0 to 78 years were analysed. CFA was observed in 4.9% of the patients. Prevalence was significantly higher in adult patients (8.4%) compared to patients18 years (0.7%; p0.0001). Logistic regression analyses in adult patients (n=3319) showed that CFA was significantly associated with increasing age (OR=1.04; 95% CI: 1.02-1.05; p0.0001), female gender (OR=2.10; 95%CI:1.52-2.90; p0.0001), number of hospitalizations (OR=1.24; 95%CI:1.12-1.36; p0.0001), chronic P. aeruginosa infection (OR=1.83; 95%CI:1.28-2.61; p=0.0009), CF-related diabetes (OR=1.69; 95%CI:1.23-2.33; p=0.0013), pancreatic insufficiency (OR=2.39; 95%CI:1.28-4.46; p=0.0060) and sinusitis/polyps (OR=1.91; 95%CI:1.39-2.62; p0.0001). In a subgroup analysis of adults without chronic P. aeruginosa infection (n=1550) CFA was also significantly associated with increasing age, female gender, increasing number of hospitalizations, pancreatic insufficiency as well as sinusitis/polyps; antimycotic treatment associated only in this subgroup while association with CF-related diabetes was not significant.CFA is a frequent and clinically relevant co-morbidity particularly in adult CF patients. CFA is significantly more common in patients with chronic P. aeruginosa colonization but associations with other indicators for a more severe disease course were identified regardless of P. aeruginosa colonization status.

Kartagener's syndrome (KS) is a rare genetic disease characterised by the triad of sinusitis, bronchiectasis, and situs inversus. This syndrome is associated with an increased risk of respiratory complications. Therefore, both the anaesthetic technique and the agents used must be carefully chosen according to the type of intervention and the patient's baseline condition. We present the case of a 48-year-old woman with KS, scheduled for functional endoscopic sinus surgery (FESS) and septoplasty under general anaesthesia. The main anaesthetic considerations in patients with KS are related to anatomical variations, pulmonary and cardiac functions, and respiratory infections. In this case, measures that reduce perioperative complications in KS are reviewed together with the special anaesthetic management in FESS, derived primarily from the need to maintain a bloodless surgical field and the use of induced hypotension techniques.

Septic cavernous sinus thrombosis (SCST) is a rare, yet severe, process typically arising from infections of the paranasal sinuses (predominately ethmoid and/or sphenoid sinusitis) and less commonly, otogenic, odontogenic, and pharyngeal sources. Clinical symptoms of SCST arise from obstruction of venous drainage from the orbit and compression of the cranial nerves within the cavernous sinus. In the preantibiotic era SCST was considered universally fatal (80-100%); however, with the introduction of antibiotics the overall incidence, morbidity, and mortality of SCST have greatly declined. In spite of dramatic improvements, morbidity and mortality remain high, with the majority of patients experiencing neurological sequalae, highlighting the severity of the disease and the need for prompt recognition, diagnosis, and treatment. Here we review of the literature on SCST with a focus on the current recommendations and recent evidence for diagnostic and medical management of this condition.

The present study aimed to investigate the effects of oral steroids on olfactory disturbances in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).This is a prospective randomized non-blinded study. Selected CRSwNP patients (n=140), with hyposmia, were devided into two groups; group A received a 7-day course of oral steroids with a 12-weeks course of nasal steroids and douching; group B received a 12-weeks course of nasal steroids and douching. Assessment included Sniffin' Sticks scores, visual analogue scale score for olfaction and discomfort (VASsmell, VASdis), the Sinonasal Outcome Test-22, Greek-version (SNOT22-Gr) and the endoscopic appearance (EAS).The main objective was to compare the olfactory effect of the different therapy in group A and group B, at 2, 12 and 24 weeks. Accessory objectives included the comparison of EAS, VASdis and SNOT22-Gr between groups, the evaluation of the therapeutic outcome duration, and, the investigation of potential correlation between the evaluated parameters.The 2-weeks evaluation showed a significant statistical difference (P0.001) for all parameters except VASdis. Olfactory outcomes (Sniffin' Sticks and VASsmell scale scores) were found significantly better in group A at the 24-weeks evaluation (P0.001). Within groups, the therapeutic result remained stable between the 12-weeks and 24-weeks evaluation (P0.05). Sniffin' Sticks score was strongly correlated at 12-weeks evaluation with EAS (rho=0.58, P0.001).Our results suggest that a combination treatment of oral and nasal steroids in well-selected patients with CRSwNP may result in early olfaction restoration with a possible long-term effect.

The present article reviews the molecular and cellular mechanisms involved in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwCRSwNP) and underlying the action mechanisms of biotherapies. Biotherapy uses substances naturally produced by the organism or their specific antagonists targeting a proinflammatory mechanism. CRSwCRSwNP is a form of chronic rhinosinusitis (CRS), which is classically subdivided in to 2 types according to the presence of polyps. In recent years, the concept of endotypes emerged, with a more exhaustive definition of the types of CRS according to inflammatory mechanism, with a view to developing personalized treatments. CRSwNP pathophysiology is poorly understood. Polyps arise from a primary epithelial lesion in a context of chronic local inflammation, mainly type 2 in Europe, implicating eosinophils, IgE, Th2 cytokines (IL-4/IL-13, IL-5) and T and B cells. Biotherapy seems promising in CRSwNP. The present review details the various pathophysiological pathways underlying the action mechanisms of biotherapies, and the various published studies, assessing efficacy and mode of action in the treatment of CRSwNP.

Case Presentation A 30-year-old woman was referred with increasing shortness of breath and cough in the setting of GATA2 deficiency. She initially presented 9 years previously with recurrent episodes of pneumonia and sinusitis. Genetic testing revealed a heterozygous GATA2 mutation (c.988C>T). She has since had multiple infections that have included necrotizing fasciitis of the right thumb, recurrent pilonidal infections (which required 23 procedures), esophageal candidiasis, and human papillomavirus-positive high-grade squamous intraepithelial lesion of the cervix. Serial bone marrow biopsy specimens showed persistent hypocellularity (20% to 60%) with intermittent erythroid atypia and variable detection of trisomy 8, which were concerning for evolving myelodysplastic syndrome. One year before the current admission, she was diagnosed with disseminated Mycobacterium avium complex and was treated with rifabutin, ethambutol, and azithromycin. She was taking voriconazole, acyclovir, and trimethoprim-sulfamethoxazole prophylaxis.

Recently, depleted tissue zinc levels were found in nasal mucosa from patients with chronic rhinosinusitis (CRS) in correlation with tissue eosinophilia, however, no clinical biomarkers for tissue zinc levels have been identified. Metallothionein-3 (MT3) is an intracellular zinc chelator and previous data showed MT3 mRNA levels to be reduced in CRS patients with nasal polyps (CRSwNP). In this study, we examined the correlation between MT3 expression and zinc levels in nasal mucosa and primary human nasal epithelial cells (HNECs) to investigate whether MT3 could be a clinical biomarker for tissue zinc levels.Tissue was harvested from 36 patients and mounted on tissue micro-array (TMA) slides. MT3 expression and tissue zinc fluorescence intensity were measured at different areas within the mucosa (surface epithelium and lamina propria) and compared between controls, CRSwNP and CRS without nasal polyps (CRSsNP) patients. MT3 mRNA and protein expression were examined in zinc-depleted HNECs by qPCR and immunofluorescence microscopy.MT3 expression in CRSwNP was significantly decreased in both surface epithelium (p0.001 to controls) and lamina propria (p = 0.0491 to controls). There was a significant positive correlation between tissue zinc levels and MT3 expression in nasal mucosa (r = 0.45, p = 0.007). In zinc-deplete HNECs, MT3 expression was significantly decreased at mRNA (p = 0.02) and protein level (p0.01). There was a significant positive correlation between tissue zinc levels and MT3 expression within individual HNECs (r = 0.59, p0.001).MT3 expression reflects intramucosal zinc levels in both nasal mucosa and HNECs indicating MT3 could be used as a clinical biomarker for monitoring intracellular zinc levels in the nasal mucosa.

Objective To investigate evidence for maxillary sinusitis and pulmonary inflammation in archaeological skeletons dating to the Late Intermediate Period (AD 1000-1476) at the site of Pachacamac, Peru. Materials Thirty-nine individuals (male, female, and unknown sex; 16+ years age-at-death) were analyzed for inflammatory periosteal reaction (IPR) on the visceral (inner) surfaces of the ribs, and 16 individuals were analyzed for evidence of maxillary sinusitis. Methods All individuals were macroscopically examined for bony changes in the maxillary sinuses and new bone formation on the ribs according to pre-established criteria. Results Some 33.3% (13/39) of individuals had IPR on the ribs and 93.8% (15/16) had bony changes in the maxillary sinuses. Conclusions Respiratory disease was likely prevalent in people buried at Pachacamac during the Late Intermediate Period. A number of factors may have increased the risk of developing respiratory disease, including exposure to poor air quality and increased crowding and social mixing, resulting from pilgrimage to this important ritual center. Significance This paper represents one of the first systematic analyses of evidence for respiratory disease in Peruvian and South American human skeletal remains, demonstrating the suitability of the region for further study. Limitations A limited sample was available for analysis. Additionally, the site’s skeletal preservation was excellent, meaning the sample available for assessment of maxillary sinusitis was smaller, being limited to individuals with post-mortem breakage. Further Research The results of this study should stimulate further much needed systematic investigation of evidence for respiratory disease in other Peruvian and South American populations.

OBJECTIVE: Regulatory and payment changes associated with COVID-19 facilitated wide-spread use of telehealth within pediatric primary care starting in March 2020. Given prior quality concerns about antibiotic management for children during telemedicine visits outside of primary care, we sought to examine acute respiratory tract infection (ARTI) visit volume and antibiotic management for children via telemedicine integrated within pediatric primary care. METHODS: Using electronic health record data from 47 practices within a large pediatric primary care network, we identified visits for ARTI from April to September 2020. For these visits, we categorized antibiotic management consistent with clinical guidelines as guideline concordant. We compared telemedicine and in-person visit guideline-concordant antibiotic management, diagnoses, and antibiotic prescribing using chi-square tests and examined trends over time using descriptive statistics. Antibiotic stewardship during the study period included learning collaborative videoconferences and sharing of clinic and clinician-level metrics through an interactive dashboard. RESULTS: During the 6-month period, 8332 ARTI visits were identified, with 3003 (36%) via telemedicine. Guideline-concordant antibiotic management occurred in 92.5% of telemedicine visits compared to 90.7% of in-person office visits (P = .004). Telemedicine ARTI visits receiving diagnoses of acute otitis media or streptococcal pharyngitis declined from peak of 52% (May) to 7% (September). Guideline-concordant antibiotic management of sinusitis and viral ARTI during telemedicine visits increased from 88% (April) to 97% (September). CONCLUSION: With active antibiotic stewardship, pediatricians practicing within certified medical homes consistently delivered highly guideline-concordant care for ARTIs to their patient population via telemedicine integrated into primary care.

Graphical abstract, Background The incidence of devastating opportunistic coinfections in patients with COVID-19 infection, their imaging features and their morbidity and mortality consequences need to be unraveled. Methods This is a case series presenting the radiologic features and clinical presentation of acute invasive fungal rhino-orbital-cerebral sinusitis (AIFS) in eight hospitalized patients with confirmed COVID-19 infection. Results Our patient cohort presented with symptoms of the invasive fungal disease within 12–35 days from their initial presentation with COVID-19 infection. The cross-sectional imaging features of AIFS associated with COVID-19 infection do not differ from those reported in the literature for AIFS associated with other risk factors, yet our patients had features of aggressive late-stage forms with high morbidity and mortality rate. Conclusion AIFS is a possible encounter in patients with COVID-19 patients and radiologists should be familiar with its imaging features.

The allergic airway diseases chronic rhinosinusitis (CRS), allergic fungal rhinosinusitis (AFRS), asthma, allergic bronchopulmonary mycosis/aspergillosis (ABPM/A), and cystic fibrosis (CF) share a common immunological signature marked by T H 2 and TH 17 cell predominant immune responses, the production of IgE antibody, and atypical inflammatory cell infiltrate that includes eosinophils and other innate immune effector cells. Severe forms of these disorders have long been recognized as being related to hypersensitivity reactions to environmental fungi. Increasingly however,environmental fungi are assuming a more primary role in the etiology of these disorders, with airway mycosis, a type of non-invasive airway fungal infection,recognized as an essential driving factor in at least severe subsets of allergic airway diseases. In this review, we consider recent progress made in understanding the immune mechanisms that drive airway mycosis-related diseases, improvements in immune-based diagnostic strategies, and therapeutic approaches that target key immune pathways.

There are many phenotypes of chronic sinusitis and clinical variables that differ between patients. The ability to accurately diagnose, predict prognosis, and select the appropriate treatment depends on the understanding of disease endotypes. Chronic sinusitis is in the early stages of disease endotyping. The ability to identify endotypes is at the forefront of clinical research. Endotyping of chronic sinusitis uses clinical information, radiographic studies, and pathophysiologic data. Understanding of the full spectrum of chronic sinusitis is in its infancy. A personalized approach to treatment will consider standard medical therapies, sinus surgeries, and targeted use of biologic agents.

Biologic agents are emerging for chronic rhinosinusitis with nasal polyposis (CRSwNP) patients with recalcitrant disease. Although early work has shown promise, and several trials are ongoing, there is significant work to be done in this field. CRS patients form a heterogeneous group, and identification of appropriate patients for the use of biologic agents is critical. The determination of endotype-specific biomarkers will help define patient selection and predict treatment response. As more biologic agents become approved, head-to-head trials will be needed to compare them with similar products. Ultimately, cost-effectiveness analyses and further quality of life studies will guide treatment recommendations.