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BackgroundEvaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA).MethodsUsing previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus.ResultsThe ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated.ConclusionThis review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.

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.ObjectiveWe sought 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 brushings 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, CRS 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 activation signature. The Lund-Mackay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, prostaglandin E2, and IL-13 signatures and negatively with ciliated cell transcriptional signatures.ConclusionsThese results demonstrate that cell-type alterations and prostaglandin E2 stimulation are key components of IL-13-induced epithelial remodeling in nasal polyposis, whereas IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13-driven epithelial remodeling.

Chronic type 2 (T2) inflammatory diseases of the respiratory tract are characterized by mucus overproduction and disordered mucociliary function, which are largely attributed to the effects of IL-13 on common epithelial cell types (mucus secretory and ciliated cells). The role of rare cells in airway T2 inflammation is less clear, though tuft cells have been shown to be critical in the initiation of T2 immunity in the intestine. Using bulk and single-cell RNA sequencing of airway epithelium and mouse modeling, we found that IL-13 expanded and programmed airway tuft cells toward eicosanoid metabolism and that tuft cell deficiency led to a reduction in airway prostaglandin E2 (PGE2) concentration. Allergic airway epithelia bore a signature of PGE2 activation, and PGE2 activation led to cystic fibrosis transmembrane receptor-dependent ion and fluid secretion and accelerated mucociliary transport. These data reveal a role for tuft cells in regulating epithelial mucociliary function in the allergic airway.

ObjectiveDuring the COVID-19 pandemic, quaternary-care facilities continue to provide care for patients in need of urgent and emergent invasive procedures. Perioperative protocols are needed to streamline care for these patients notwithstanding capacity and resource constraints.MethodsA multidisciplinary panel was assembled at the University of California, San Francisco, with 26 leaders across 10 academic departments, including 7 department chairpersons, the chief medical officer, the chief operating officer, infection control officers, nursing leaders, and resident house staff champions. An epidemiologist, an ethicist, and a statistician were also consulted. A modified two-round, blinded Delphi method based on 18 agree/disagree statements was used to build consensus. Significant disagreement for each statement was tested using a one-sided exact binomial test against an expected outcome of 95% consensus using a significance threshold of p < 0.05. Final triage protocols were developed with unblinded group-level discussion.ResultsOverall, 15 of 18 statements achieved consensus in the first round of the Delphi method; the 3 statements with significant disagreement (p < 0.01) were modified and iteratively resubmitted to the expert panel to achieve consensus. Consensus-based protocols were developed using unblinded multidisciplinary panel discussions. The final algorithms 1) quantified outbreak level, 2) triaged patients based on acuity, 3) provided a checklist for urgent/emergent invasive procedures, and 4) created a novel scoring system for the allocation of personal protective equipment. In particular, the authors modified the American College of Surgeons three-tiered triage system to incorporate more urgent cases, as are often encountered in neurosurgery and spine surgery.ConclusionsUrgent and emergent invasive procedures need to be performed during the COVID-19 pandemic. The consensus-based protocols in this study may assist healthcare providers to optimize perioperative care during the pandemic.

Recent studies leveraging next-generation sequencing and functional approaches to understand the human microbiota have demonstrated the presence of diverse, niche-specific microbial communities at nearly every mucosal surface. These microbes contribute to the development and function of physiologic and immunological features that are key to host health status. Not surprisingly, several chronic inflammatory diseases have been attributed to dysbiosis of microbiota composition or function, including chronic rhinosinusitis (CRS). CRS is a heterogeneous disease characterized by inflammation of the sinonasal cavity and mucosal microbiota dysbiosis. Inflammatory phenotypes and bacterial community compositions vary considerably across individuals with CRS, complicating current studies that seek to address causality of a dysbiotic microbiome as a driver or initiator of persistent sinonasal inflammation. Murine models have provided some experimental evidence that alterations in local microbial communities and microbially-produced metabolites influence health status. In this perspective, we will discuss the clinical implications of distinct microbial compositions and community-level functions in CRS and how mucosal microbiota relate to the diverse inflammatory endotypes that are frequently observed. We will also describe specific microbial interactions that can deterministically shape the pattern of co-colonizers and the resulting metabolic products that drive or exacerbate host inflammation. These findings are discussed in the context of CRS-associated inflammation and in other chronic inflammatory diseases that share features observed in CRS. An improved understanding of CRS patient stratification offers the opportunity to personalize therapeutic regimens and to design novel treatments aimed at manipulation of the disease-associated microbiota to restore sinus health.

BackgroundChronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients.ResultsSinus brushings from patients with CRS (n = 59) and healthy individuals (n = 10) collected during endoscopic sinus surgery were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA profiling of the mucosal immune response. We show that CRS patients cluster into distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co-colonization (permutational multivariate analysis of variance (PERMANOVA); p = 0.001, r 2 = 0.318). Each sub-group was typically dominated by a pathogenic family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2 = 0.217) and encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI), tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR-γ signaling pathway [DSIII(a)]. Each is also associated with significantly distinct host immune responses; DSI, II, and III(b) invoked a variety of pro-inflammatory, TH1 responses, while DSIII(a), which exhibited significantly increased incidence of nasal polyps (Fisher's exact; p = 0.034, relative risk = 2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045).ConclusionsA large proportion of CRS patient heterogeneity may be explained by the composition of their sinus bacterial microbiota and related host immune response-features which may inform strategies for tailored therapy in this patient population.

BackgroundThe sinus lift (or sinus augmentation) is a common procedure to improve maxillary bone stock before dental implantation. Chronic rhinosinusitis (CRS) is a potential complication of this procedure and may be refractory to medical treatment. Functional endoscopic sinus surgery has previously been used to address CRS, however, results of previous studies indicated that implant removal is required. There are limited follow-up data available.ObjectiveThe purpose of this study was to characterize the long-term outcomes and efficacy of endoscopic sinus surgery for refractory CRS after sinus lift, including the ability to salvage dental implants.MethodsThis was a retrospective case series that described nine patients who, between June 2011 and September 2016, underwent endoscopic sinus surgery for CRS after a sinus lift procedure. The presenting symptoms of the patients, medical management, imaging results, operative procedures, and outcomes were reviewed.ResultsThe majority of patients developed symptoms (mucopurulent nasal drainage, facial pain and/or pressure, nasal congestion, and foul smell) within 3 months of implant placement and were treated with at least three courses of antibiotics before referral to an otolaryngologist. All the patients underwent wide endoscopic maxillary antrostomy, with no surgical complications or postoperative reports of infection. There was a statistically significant improvement in 22-item Sino-Nasal Outcome Test scores (t(8) = -2.908; p = 0.02) and discharge, inflammation, and polyps/edema endoscopic scores ([z = -2.539; p = 0.011) between pre- and postsurgical treatment. Four patients had their dental implants removed before presentation. Among the five patients who presented with intact dental implants, none required removal before or after functional endoscopic sinus surgery.ConclusionFunctional endoscopic sinus surgery was a reasonable and efficacious treatment option for patients who presented with paranasal sinus disease after a sinus lift. Dental implant removal may not be a requirement for successful treatment of CRS associated with sinus lift procedures.

ImportanceDespite the significant contribution of surgical spending to health care costs, most surgeons are unaware of their operating room costs.ObjectiveTo examine the association between providing surgeons with individualized cost feedback and surgical supply costs in the operating room.Design, setting, and participantsThe OR Surgical Cost Reduction (OR SCORE) project was a single-health system, multihospital, multidepartmental prospective controlled study in an urban academic setting. Intervention participants were attending surgeons in orthopedic surgery, otolaryngology-head and neck surgery, and neurological surgery (n = 63). Control participants were attending surgeons in cardiothoracic surgery, general surgery, vascular surgery, pediatric surgery, obstetrics/gynecology, ophthalmology, and urology (n = 186).InterventionsFrom January 1 to December 31, 2015, each surgeon in the intervention group received standardized monthly scorecards showing the median surgical supply direct cost for each procedure type performed in the prior month compared with the surgeon's baseline (July 1, 2012, to November 30, 2014) and compared with all surgeons at the institution performing the same procedure at baseline. All surgical departments were eligible for a financial incentive if they met a 5% cost reduction goal.Main outcomes and measuresThe primary outcome was each group's median surgical supply cost per case. Secondary outcome measures included total departmental surgical supply costs, case mix index-adjusted median surgical supply costs, patient outcomes (30-day readmission, 30-day mortality, and discharge status), and surgeon responses to a postintervention study-specific health care value survey.ResultsThe median surgical supply direct costs per case decreased 6.54% in the intervention group, from $1398 (interquartile range [IQR], $316-$5181) (10 637 cases) in 2014 to $1307 (IQR, $319-$5037) (11 820 cases) in 2015. In contrast, the median surgical supply direct cost increased 7.42% in the control group, from $712 (IQR, $202-$1602) (16 441 cases) in 2014 to $765 (IQR, $233-$1719) (17 227 cases) in 2015. This decrease represents a total savings of $836 147 in the intervention group during the 1-year study. After controlling for surgeon, department, patient demographics, and clinical indicators in a mixed-effects model, there was a 9.95% (95% CI, 3.55%-15.93%; P = .003) surgical supply cost decrease in the intervention group over 1 year. Patient outcomes were equivalent or improved after the intervention, and surgeons who received scorecards reported higher levels of cost awareness on the health care value survey compared with controls.Conclusions and relevanceCost feedback to surgeons, combined with a small departmental financial incentive, was associated with significantly reduced surgical supply costs, without negatively affecting patient outcomes.

The respiratory tract is a complex system that is inhabited by niche-specific communities of microbes including bacteria, fungi, and viruses. These complex microbial assemblages are in constant contact with the mucosal immune system and play a critical role in airway health and immune homeostasis. Changes in the composition and diversity of airway microbiota are frequently observed in patients with chronic inflammatory diseases including chronic rhinosinusitis (CRS), cystic fibrosis, allergy, and asthma. While the bacterial microbiome of the upper and lower airways has been the focus of many recent studies, the contribution of fungal microbiota to inflammation is an emerging research interest. Within the context of allergic airway disease, fungal products are important allergens and fungi are potent inducers of inflammation. In addition, murine models have provided experimental evidence that fungal microbiota in peripheral organs, notably the gastrointestinal (GI) tract, influence pulmonary health. In this review, we explore the role of the respiratory and GI microbial communities in chronic airway inflammatory disease development with a specific focus on fungal microbiome interactions with the airway immune system and fungal-bacterial interactions that likely contribute to inflammatory disease. These findings are discussed in the context of clinical and immunological features of fungal-mediated disease in CRS, allergy, and asthmatic patients. While this field is still nascent, emerging evidence suggests that dysbiotic fungal and bacterial microbiota interact to drive or exacerbate chronic airway inflammatory disease.

ObjectiveWe aimed to evaluate the impact of a novel noninvasive oral pressure therapy (OPT) (Winx®, ApniCure) system on polysomnographic measures of sleep-disordered breathing, sleep architecture, and sleep stability in obstructive sleep apnea (OSA).Subjects and methodsA 4-week, multicenter, prospective, open-label, randomized, crossover, first-night order of control vs treatment, single-arm trial was conducted in five American Academy of Sleep Medicine (AASM) - accredited sleep clinics and one research laboratory. Sixty-three subjects (analysis cohort) were studied from a screening cohort of 367 subjects. The analysis cohort was 69.8% men, ages 53.6±8.9 years (mean±SD), body mass index of 32.3±4.5kg/m(2), with mild to severe OSA. At treatment initiation, subjects received random assignment to one night with and one without (control) treatment, and they were assessed again following 28 nights of treatment. Breathing and sleep architecture were assessed each night based on blind scoring by a single centralized scorer using AASM criteria.ResultsAverage nightly usage across the take-home period was 6.0±1.4h. There were no severe or serious device-related adverse events (AEs). Median apnea-hypopnea index (AHI) was 27.5 events per hour on the control night, 13.4 events per hour on the first treatment night, and 14.8 events per hour after 28days of treatment. A clinically significant response (treatment AHI ⩽10/h and ⩽50% of control values) was seen in 20 of the 63 subjects evaluated. Rapid eye movement percentage (REM%) was significantly increased, and N1%, stage shifts to N1 sleep, overall stage shifts, total awakenings, and arousals per hour were all significantly reduced at both treatment nights compared to controls. Mean Epworth sleepiness scale (ESS) was significantly reduced from 12.1 to 8.6 (Cohen d effect size, 0.68) in those untreated for two or more weeks prior to OPT study participation and remained unchanged in subjects who directly switched from continuous positive airway pressure (CPAP) therapy to OPT.ConclusionClinically significant improvements in sleep quality and continuity, AHI, ODI, ESS, and overall clinical status were achieved in an easily identified subgroup. OPT was safe and well-tolerated and nightly usage was high.

Objectives/hypothesisTo evaluate the association between findings from drug-induced sleep endoscopy (DISE) and lateral cephalometry in obstructive sleep apnea (OSA) STUDY DESIGN: Cross-sectional.MethodsThis was a consecutive series of subjects with OSA who underwent DISE and lateral cephalometry. DISE findings were characterized according to the region/degree of obstruction as well as the VOTE classification (velum, oropharyngeal lateral walls, tongue, and epiglottis). The primary measurements from lateral cephalometry images were sella-nasion-point A angle, sella-nasion-point B angle, distance from the posterior nasal spine-tip of palate, posterior airway space, and mandibular plane to hyoid (MPH) distance, although additional airway measurements were taken. Descriptive statistics summarized DISE and lateral cephalometry findings, and χ(2) and t tests examined potential associations between their findings.ResultsAmong the 55 subjects, most demonstrated velum-related obstruction, although obstruction related to other structures was also common. Lateral cephalometry findings were within population norms with the exception of an increased MPH and decreased airway 4 and airway 5 measurements. There was little association between DISE and lateral cephalometry findings, although significant associations were identified between tongue-related obstruction and airway measurements posterior to the tongue base.ConclusionsDISE and lateral cephalometry are largely distinct airway evaluation techniques in OSA. The use of these techniques remains complementary.

Persistent mucosal inflammation and microbial infection are characteristics of chronic rhinosinusitis (CRS). Mucosal microbiota dysbiosis is found in other chronic inflammatory diseases; however, the relationship between sinus microbiota composition and CRS is unknown. Using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, we demonstrate that the sinus microbiota of CRS patients exhibits significantly reduced bacterial diversity compared with that of healthy controls. In our cohort of CRS patients, multiple, phylogenetically distinct lactic acid bacteria were depleted concomitant with an increase in the relative abundance of a single species, Corynebacterium tuberculostearicum. We recapitulated the conditions observed in our human cohort in a murine model and confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, Lactobacillus sakei, which was identified from our comparative microbiome analyses as a potentially protective species, defended against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota as well as identify both a new sino-pathogen and a strong bacterial candidate for therapeutic intervention.

Objectives/hypothesisThe objectives of this study were to determine the mycology of the middle meatus using an endoscopically guided brush sampling technique and polymerase chain reaction laboratory processing of nasal mucous; to compare the mycology of the middle meatus in patients with sinus disease with subjects without sinus disease; to compare the responses on two standardized quality-of-life survey forms between patients with and without sinusitis; and to determine whether the presence of fungi in the middle meatus correlates with responses on these data sets.Study designThe authors conducted a single-blind, prospective, cross-sectional study.MethodsPatients with sinus disease and a control group without sinus disease were enrolled in the study. A disease-specific, validated Sinonasal Outcomes Test survey (SNOT-20) was completed by the subjects and a generalized validated Medical Outcomes Short Form 36 Survey (SF-36) was also completed. An endoscopically guided brush sampling of nasal mucous was obtained from the middle meatus. Fungal specific quantitative polymerase chain reaction (QPCR) was performed on the obtained sample to identify one of 82 different species of fungus in the laboratory. Statistical analysis was used to categorize the recovered fungal DNA and to crossreference this information with the outcomes surveys.ResultsThe fungal recovery rate in the study was 45.9% in patients with sinus disease and 45.9% in control subjects. Patients with chronic rhinosinusitis had a mean SNOT-20 score of 1.80 versus the control group mean score of 0.77 (P < .0001). SF-36 data similarly showed a statistically significant difference between diseased and control populations with controls scoring a mean of 80.37 and patients with chronic rhinosinusitis scoring a mean of 69.35 for a P value of .02. However, no statistical significance could be ascribed to the presence or absence of fungi recovered, the type of fungi recovered, or the possible impact of fungi on the quality-of-life survey results.ConclusionThe recovery rate of fungi from the middle meatus of patients with chronic rhinosinusitis and a control population without chronic rhinosinusitis is 45.9% using QPCR techniques. No direct causation with regard to fungal species or presence was proven; however, a species grouping for future studies is proposed based on trends in this data and other reports. Disease-specific outcomes surveys revealed a statistically significant difference between the two groups.

Background: Acute invasive fungal sinusitis (AIFS) is an aggressive and dangerous disease of the paranasal sinuses with high morbidity and mortality. The immune response at the level of the nasal mucosa, the site of entry, has not been previously evaluated. Objective: To evaluate differential gene expression in the sinonasal mucosa of AIFS patients as compared to control patients using RNA sequencing. Methods: Sinonasal tissue samples were prospectively obtained from consenting patients undergoing surgery between November, 2020 and November, 2021. RNA extraction and sequencing were performed and differential expression was analyzed to detect transcriptional differences between patient groups. Results: Tissue samples were collected from 4 patients with active AIFS diagnoses, 2 patients with recovered AIFS, 1 patient with a diagnosis of non-invasive fungal ball, and 4 healthy controls. 255 genes were differentially expressed in AIFS patients as compared to control patients. Specific Gene Ontology (GO) biological processes that were identified as differentially expressed in AIFS patients as compared to controls included the following: 1. GO:0007155 (cell adhesion), 2. GO:0030199 (collagen fibril organization) and 3. GO:0001525 (angiogenesis). Conclusion: Transcriptional differences were noted between AIFS and control patients in sinonasal tissue samples. Future work is necessary to determine causes of the differential gene expressions between AIFS and control patients, specifically those who are immunosuppressed, or with preexisting non-invasive forms of fungal sinusitis, to guide treatment and prevention strategies. [ABSTRACT FROM AUTHOR]