Chronic Rhinosinusitis Disease Research Articles

Taste Receptor Polymorphisms and Immune Response: A Review of Receptor Genotypic-Phenotypic Variations and Their Relevance to Chronic Rhinosinusitis.

Bitter (T2R) and sweet taste (T1R) receptors have emerged as regulators of upper airway immune responses. Genetic variation of these taste receptors additionally confers susceptibility to infection and has been implicated in severity of disease in chronic rhinosinusitis (CRS). Ongoing taste receptor research has identified a variety of biologically active compounds that activate T1R and T2R receptors, increasing our understanding of not only additional receptor isoforms and their function but also how receptor function may contribute to the pathophysiology of CRS. This review will discuss the function of taste receptors in mediating airway immunity with a focus on recently described modulators of receptor function and directions for future research into the potential role of genotypic and phenotypic receptor variation as a predictor of airway disease and response to therapy.

Asthma onset pattern and patient outcomes in a chronic rhinosinusitis population.

Chronic rhinosinusitis (CRS) is strongly associated with comorbid asthma. This study compares early-onset and late-onset asthma in a CRS population using patient-reported and clinical characteristics. At enrollment into a clinical registry, CRS patients completed the 22-item Sino-Nasal Outcome Test (SNOT-22), Asthma Control Test (ACT), mini-Asthma Quality of Life Questionnaire (miniAQLQ), the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29), and medication use questionnaires. Patients also reported comorbid asthma and age at first asthma diagnosis. Early-onset (<18 years) and late-onset (>18 years) asthma groups were defined. Analysis of variance (ANOVA), chi-square, and Kruskal-Wallis tests were used to compare patient responses. A total of 199 non-asthmatic (56.1%), 71 early-onset asthmatic (20.0%), and 85 late-onset asthmatic (23.9%) CRS patients completed the survey. Body mass index (BMI) was significantly higher in late-onset asthmatic (p = 0.046) while age, gender, race, and smoking history did not differ with time of asthma onset. SNOT-22, ACT, and miniAQLQ were not different between asthma groups, but late-onset asthmatics had significantly lower physical function than non-asthmatics (p = 0.008). Compared to non-asthmatics, late-onset asthmatics showed increased rates of nasal polyps (p < 0.001), higher Lund-Mackay scores (p = 0.005), and had received more oral steroid courses (p < 0.001) and endoscopic surgeries (p = 0.008) for CRS management. Late-onset asthmatics compared to early-onset asthmatics showed increased nasal polyposis (p = 0.011) and oral steroid courses for CRS (p = 0.003). While CRS-specific and asthma-specific patient-reported outcome measures (PROMs) were not significantly different among groups, CRS patients with late-onset asthma had poorer physical function, more frequent nasal polyposis, and required increased treatment for CRS. Late-onset asthma may predict more severe disease in CRS.

Fungal Microbiota in Chronic Airway Inflammatory Disease and Emerging Relationships with the Host Immune Response.

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.

Air pollutants may be environmental risk factors in chronic rhinosinusitis disease progression.

Little is known about the role of environmental exposures in the pathophysiology of chronic rhinosinusitis (CRS). In this study, we measured the impact of air pollutants (particulate matter 2.5 [PM2.5 ] and black carbon [BC]) on CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP). Spatial modeling from pollutant monitoring sites was used to estimate exposures surrounding residences for patients meeting inclusion criteria (total patients, n = 234; CRSsNP, n = 96; CRSwNP, n = 138). Disease severity outcome measures included modified Lund-Mackay score (LMS), systemic steroids, number of functional endoscopic sinus surgeries (FESS), and 22-item Sino-Nasal Outcome Test (SNOT-22) score. PM2.5 and BC exposures were correlated with outcome measures. Mean PM2.5 and BC findings were not significantly different between CRSwNP and CRSsNP patients or patients with and without asthma. Among those with CRSsNP, PM2.5 was significantly associated with undergoing FESS. For each unit increase in PM2.5 , there was a 1.89-fold increased risk in the proportion of CRSsNP patients who required further surgery (p = 0.015). This association was not identified in CRSwNP patients (p = 0.445). BC was also significantly associated with SNOT-22 score in the CRSsNP group. For each 0.1-unit increase in BC, there was a 7.97-unit increase in SNOT-22 (p = 0.008). A similar, although not significant, increase in SNOT-22 was found with increasing BC in the CRSwNP group (p = 0.728). Air pollutants correlate with CRS symptom severity that may be influenced by exposure levels, with a more pronounced impact on CRSsNP patients. This study is the first to demonstrate the possible role of inhalant pollutants in CRS phenotypes, addressing a critical knowledge gap in environmental risk factors for disease progression.

Biofilms in chronic rhinosinusitis: Pathophysiology and therapeutic strategies.

BackgroundThere is increasing evidence that biofilms are critical to the pathophysiology of chronic infections including chronic rhinosinusitis (CRS). Until relatively recently, our understanding of biofilms was limited. Recent advances in methods for biofilm identification and molecular biology have offered new insights into the role of biofilms in CRS. With these insights, investigators have begun to investigate novel therapeutic strategies that may disrupt or eradicate biofilms in CRS.ObjectiveThis review seeks to explore the evidence implicating biofilms in CRS, discuss potential anti-biofilm therapeutic strategies, and suggest future directions for research.ResultsThe existing evidence strongly supports the role of biofilms in the pathogenesis of CRS. Several anti-biofilm therapies have been investigated for use in CRS and these are at variable stages of development. Generally, these strategies: 1) neutralize biofilm microbes; 2) disperse existing biofilms; or 3) disrupt quorum sensing. Several of the most promising anti-biofilm therapeutic strategies are reviewed.ConclusionsA better understanding of biofilm function and their contribution to the CRS disease process will be pivotal to the development of novel treatments that may augment and, potentially, redefine the CRS treatment paradigm. There is tremendous potential for future research.

General antibiotic exposure is associated with increased risk of developing chronic rhinosinusitis.

Antibiotic use and chronic rhinosinusitis (CRS) have been independently associated with microbiome diversity depletion and opportunistic infections. This study was undertaken to investigate whether antibiotic use may be an unrecognized risk factor for developing CRS. Case-control study of 1,162 patients referred to a tertiary sinus center for a range of sinonasal disorders. Patients diagnosed with CRS according to established consensus criteria (n = 410) were assigned to the case group (273 without nasal polyps [CRSsNP], 137 with nasal polyps [CRSwNP]). Patients with all other diagnoses (n = 752) were assigned to the control group. Chronic rhinosinusitis disease severity was determined using a validated quality of life (QOL) instrument. The class, diagnosis, and timing of previous nonsinusitis-related antibiotic exposures were recorded. Results were validated using a randomized administrative data review of 452 (38.9%) of patient charts. The odds ratio of developing CRS following antibiotic exposure were calculated, as well as the impact of antibiotic use on the subsequent QOL. Antibiotic use significantly increased the odds of developing CRSsNP (odds ratio: 2.21, 95% confidence interval, 1.66-2.93, P < 0.0001) as compared to nonusers. Antibiotic exposure was significantly associated with worse CRS QOL scores (P = 0.0009) over at least the subsequent 2 years. These findings were confirmed by the administrative data review. Use of antibiotics more than doubles the odds of developing CRSsNP and is associated with a worse QOL for at least 2 years following exposure. These findings expose an unrecognized and concerning consequence of general antibiotic use. 3b. Laryngoscope, 2016 127:296-302, 2017.

A role for auto-immunity in chronic rhinosinusitis? Lessons learned from sub-epidermal bullous disorders of the skin.

Chronic rhinosinusitis (CRS) is a frequent chronic condition, which has origins in complex interactions between genetic, immunological and microbial factors. The role of auto-immunity in CRS remains unclear, although recent studies have started to emerge in CRS patient refractory to maximal medical management. We discuss the possible auto-immunity link between CRS and other skin diseases, in particular acquired bullous dermatoses, and review the current evidence. We raise additional considerations for auto-immunity from both research and clinical standpoints.

Lack of correlation between patient reported location and severity of facial pain and radiographic burden of disease in chronic rhinosinusitis.

Facial pain is a cardinal symptom of chronic rhinosinusitis (CRS) with significant impacts on patient treatment selection, quality of life, and outcomes. The association between facial pain and CRS disease severity has not been systematically evaluated with validated, facial pain-specific questionnaires. Our objective was to measure pain location, severity, and interference in patients with CRS, and correlate these to the location and severity of radiographic evidence of disease. Patients with CRS were enrolled into a prospective, cross-sectional study. Patients completed the Brief Pain Inventory Short Form, which is a validated and widely used tool that measures pain location, severity, and interference with daily activities of living. The Lund-Mackay (L-M) computed tomography (CT) scoring system was used to operationalize the radiographic location and severity of inflammation. Facial pain location, severity, and interference scores were correlated to paranasal sinus opacification scores. Consecutive patients with CRS with nasal polyps (CRSwNP; n = 37) and CRS without nasal polyps (CRSsNP; n = 46) were enrolled. No significant relationship was found between the location and severity of reported facial pain and radiographic findings of disease for patients with either CRSwNP or CRSsNP. There was no difference in pain location between patients with and without radiographic disease in a given sinus. Facial pain in CRS is not predicted by the radiographic extent of disease. The location and severity of facial pain reported by the patient is not a reliable marker of the anatomic location and severity of sinonasal inflammation. Pain location should not necessarily be relied upon for guiding targeted therapy.

Nasal obstruction has a limited impact on sleep quality and quality of life in patients with chronic rhinosinusitis.

Nasal obstruction is a cardinal symptom in diagnosing chronic rhinosinusitis (CRS), and decreased sleep quality (SQ) and quality of life (QOL) are commonly reported in CRS. It is, however, unclear what role nasal obstruction severity plays in this decreased SQ and QOL. Using validated instruments, we evaluated the relationship between nasal obstruction severity, SQ, and QOL. Prospective case series. Patients with CRS refractory to standard medical therapy (n = 28) were prospectively enrolled and completed the Nasal Obstruction Symptom Evaluation (NOSE), Pittsburg Sleep Quality Index (PSQI), Rhinosinusitis Disability Index, and the 22-item Sinonasal Outcome Test. CRS disease severity was evaluated with computed tomography and endoscopy. NOSE scores were compared to SQ, QOL, and disease severity measures. Spearman correlations were used to identify significant associations between measures. All patients reported symptomatic nasal obstruction (NOSE score ≥ 30), whereas poor sleep (PSQI ≥ 5) was reported by 82%. The NOSE sleeping subdomain correlated strongly with the PSQI total score, whereas other elements of the NOSE instrument correlated weakly or not at all with this measurement of SQ. Nasal obstruction correlated weakly with disease-specific QOL and had no correlation with the PSQI total. Nasal obstruction appears to have a limited association with CRS-specific QOL and CRS-associated decrease in SQ. Further, the NOSE instrument, because it contains a question about sleep, may have overlap with the PSQI as a measure of SQ. The total NOSE score in CRS patients does not appear to be purely a measure of nasal obstruction. 4 Laryngoscope, 126:1971-1976, 2016.

Relationships among allergic rhinitis, asthma, and chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common disease in the United States. There are a significant number of patients with CRS who are refractory to standard medical and surgical therapy. Many of these patients also have comorbid allergic rhinitis (AR) and asthma, although the underlying pathophysiology that connects these three conditions remains unclear. The goal of this article is to review the relationships among CRS, AR and asthma. Scientific literature that addresses the prevalence of AR and asthma in CRS populations, the effect of AR and asthma on CRS disease severity, and whether treatment of AR and asthma can affect CRS outcomes was reviewed. The literature supports the relationship between AR and CRS, but there is no direct evidence of causality the between the two conditions. There is a high prevalence of CRS in patients with asthma and the presence of CRS is associated with worse asthma outcomes. There is weak evidence that treatment of CRS may improve asthma outcomes. Targeting type 2 inflammation via biologics is being investigated in the treatment of asthma and CRS. AR, asthma, and CRS are closed related and understanding the associations among these comorbid diseases will have significant clinical implication.

T2R38 genotype is correlated with sinonasal quality of life in homozygous ΔF508 cystic fibrosis patients.

Chronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment-refractory CRS in non-CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients. ΔF508 homozygous CF patients were recruited from the University of Pennsylvania Cystic Fibrosis Center and were genotyped for the TAS2R38 locus. To assess sinonasal symptom severity, a 22-item Sino-Nasal Outcome Test (SNOT-22) was collected from each patient. Additional demographic and medical history data was obtained at the time of patient enrollment. A total of 49 ΔF508 homozygous CF patients aged 18 to 32 years were included in the final SNOT-22 score analysis. Individuals with 2 functional T2R38 alleles (PAV/PAV) had significantly lower SNOT-22 scores (n = 49, p < 0.05). On further breakdown of SNOT-22 subcategories, rhinologic symptoms specifically were less severe in PAV/PAV patients than patients with other genotypes (n = 47, p < 0.05). Our investigation indicates that T2R38 genotype correlates both with SNOT-22 scores and rhinologic-specific QOL in ΔF508 homozygous CF patients.

Immune Mechanisms of Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common inflammatory disease that results in a significant decrease in patient quality of life and a large economic burden. However, the lack of population-based epidemiologic studies and robust model systems has made it difficult to fully elucidate the key inflammatory pathways that drive the chronic inflammatory responses observed in CRS. This review will highlight the wide variety of factors that likely contribute to CRS disease pathogenesis. Defects in the innate immune function of the airway epithelium, including decreases in barrier function, mucociliary clearance, and production of antimicrobial peptides, all likely play a role in the initial inflammatory response. Subsequent recruitment and activation of eosinophils, mast cells, and innate lymphoid cells (ILCs) further contributes to the chronic inflammatory response and directly activates adaptive immune cells, including T and B cells. However, development of new tools and model systems is still needed to further understand the chronicity of this inflammatory response and which specific factors are necessary or sufficient to drive CRS pathogenesis. Such studies will be critical for the development of improved therapeutic strategies aimed at treating this highly prevalent and costly disease.

Endoscopic sinus surgery for chronic rhinosinusitis in patients previously treated for sinonasal malignancy.

Patients with a history of sinonasal malignancy can develop chronic rhinosinusitis (CRS) as a consequence of their oncologic treatment. Some patients will fail medical management and require endoscopic sinus surgery (ESS). This study reviews the use of ESS in the management of CRS in patients previously treated for sinonasal malignancy. Retrospective review. All patients with a history of sinonasal malignancy who developed CRS and underwent ESS were reviewed. Preoperative and postoperative imaging and symptoms were collected. Major complications (bleeding, orbital injury, and cerebrospinal fluid leak) and minor complications (adhesion formation) and postoperative healing were reviewed. Eighteen patients were identified. All patients presented with symptoms of CRS and sinonasal crusting. Additionally, five patients presented with recurrent facial cellulitis, and six patients had mucoceles. No major complications were encountered. Postoperatively, all patients reported a subjective improvement in their sinonasal symptoms. Comparison of pre- and post-ESS imaging revealed a significant improvement in Lund-Mackay scores after ESS (P < 0.001) from 12.8 (range 5-22) to 7 (range). Despite symptomatic improvement, all patients continued to have nasal crusting. All patients who initially presented with recurrent facial cellulitis had no further episodes after ESS. None of the endoscopically drained mucoceles recurred. For patients previously treated for sinonasal malignancy with refractory CRS, ESS appears to be a safe and effective treatment option. ESS in these patients results in subjective improvement in sinonasal symptoms as well as objective improvement in radiographic CRS disease burden, although sinonasal crusting will likely not resolve. 4.

Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease

Epithelial barrier dysfunction is thought to play a role in many mucosal diseases, including asthma, chronic rhinosinusitis (CRS), and eosinophilic esophagitis. The objective of this study was to investigate the role of oncostatin M (OSM) in epithelial barrier dysfunction in human mucosal disease. OSM expression was measured in tissue extracts, nasal secretions, and bronchoalveolar lavage fluid. The effects of OSM stimulation on barrier function of normal human bronchial epithelial cells and nasal epithelial cells cultured at the air-liquid interface were assessed by using transepithelial electrical resistance and fluorescein isothiocyanate-dextran flux. Dual-color immunofluorescence was used to evaluate the integrity of tight junction structures in cultured epithelial cells. Analysis of samples from patients with CRS showed that OSM mRNA and protein levels were highly increased in nasal polyps compared with those seen in control uncinate tissue (P< .05). OSM levels were also increased in bronchoalveolar lavage fluid of allergic asthmatic patients after segmental allergen challenge and in esophageal biopsy specimens from patients with eosinophilic esophagitis. OSM stimulation of air-liquid interface cultures resulted in reduced barrier function, as measured by decreased transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran flux (P< .05). Alterations in barrier function by OSM were reversible, and the viability of epithelial cells was unaffected. OSM levels in lysates of nasal polyps and uncinate tissue positively correlated with levels of α2-macroglobulin, a marker of epithelial leak, in localized nasal secretions (r= 0.4855, P< .05). These results suggest that OSM might play a role in epithelial barrier dysfunction in patients with CRS and other mucosal diseases.

Superoxide dismutase reduces the inflammatory response to Aspergillus and Alternaria in human sinonasal epithelial cells derived from patients with chronic rhinosinusitis.

Aspergillus fumigatus and Alternaria alternata are ubiquitous environmental fungal allergens that can exacerbate airway inflammation and contribute to the disease process in patients with chronic rhinosinusitis (CRS). These antigens have been shown to induce human sinonasal epithelial cells (HSNECs) to promote a proinflammatory response, but what is unclear is a means by which to reduce these effects. Inhaled pathogens can induce HSNECs to produce reactive oxygen species (ROS) that trigger cytokine production. This study aimed to determine whether the free radical scavenger superoxide dismutase (SOD) could reduce HSNEC-derived inflammation, as measured by interleukin (IL)-6 and IL-8 production, in response to Aspergillus or Alternaria exposure. Sinus tissue explants were collected at the time of surgery from control patients (n = 7) and patients with CRS with nasal polyps (CRSwNP) (n = 9). HSNECs were cultured from the explants and treated with Aspergillus, Alternaria, and SOD for 24 hours. Cell supernatants and lysates were collected, and IL-6 and IL-8 concentrations were measured using enzyme-linked immunosorbent assay. In control and CRSwNP HSNECs, Aspergillus and Alternaria both increased cytokine production (p < 0.05), as measured by IL-6 and IL-8 concentration. SOD treatment reduced the inflammatory response to fungal antigen exposure from CRSwNP HSNECs but not control HSNECs. In CRSwNP patients, SOD significantly decreased IL-6 and IL-8 production after Alternaria exposure and IL-8 after Aspergillus exposure (p < 0.05). When HSNECs from CRSwNP patients are treated with SOD concurrently with Aspergillus or Alternaria, SOD treatment decreases the fungal antigen-induced inflammatory response. The ability to attenuate inflammation induced by common fungal allergens with SOD treatment could provide a novel therapeutic or preventative approach for patients with CRS or other allergic inflammatory airway diseases.

Outcomes of Surgical Treatment of Chronic Rhinosinusitis

Since the introduction of endoscopic sinus surgery (ESS) for treatment of chronic rhinosinusitis (CRS) over 25 years ago, there has been an effort to quantify the effectiveness of this intervention. Within the last few years, the field has matured to a point where study designs are able to accurately capture the impact of ESS relative to continued medical therapy on the CRS disease process and quality-of-life (QOL). These comparative effectiveness studies demonstrate superior effectiveness of ESS over medical therapy at mean reduction of disease burden as measured by comprehensive disease-specific QOL questionnaires. As outcomes from large comparative effectiveness studies accumulates, and a more complete understanding of the many variables that contribute to and influence CRS, the potential to build predictive models based on baseline characteristics might allow for forecasting of treatment successes and failures.

Coagulase-negative Staphylococcus culture in chronic rhinosinusitis.

Coagulase-negative Staphylococcus (CoNS) is commonly isolated from patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS remains controversial. We aimed to determine the association between positive CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity. Adult CRS patients who underwent FESS between October 1, 2007 to December 31, 2011 were recruited. Patient demographics, disease characteristics, medication use, Lund-Mackay computed tomography (CT) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were collected at baseline before FESS. Intraoperative cultures were obtained in a standard manner. Patients were placed into 2 groups based on culture findings: patients with CoNS as the sole positive culture result and patients with all other positive culture results, including CoNS, as part of a polymicrobial culture. A total of 376 CRS patients met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%) had other positive cultures, and 10 (3%) had no bacterial growth. Compared to patients with other positive cultures, patients with the sole result of CoNS were significantly less likely to have a history of FESS (52% vs 65%, p = 0.019), nasal polyps (50% vs 65%, p = 0.006), and had a better Lund-Mackay CT score (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple logistic regression model, CoNS as the sole positive culture result was independently associated with having no history of FESS (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.22 to 0.94; p = 0.034). Positive intraoperative CoNS cultures alone do not result in increased CRS disease burden by objective or subjective measures as compared to patients with other bacterial or polymicrobial culture isolates.

Sleep and quality of life improvements after endoscopic sinus surgery in patients with chronic rhinosinusitis.

Recent investigation has demonstrated that approximately 75% of patients with medically refractory chronic rhinosinusitis (CRS) report abnormal sleep quality, with strong correlation between worse sleep quality and more severe CRS disease severity. It remains unknown whether the treatment effect of endoscopic sinus surgery (ESS) for CRS results in appreciable sleep quality improvements. Adult patients (aged ≥18 years) with a current diagnosis of recalcitrant chronic rhinosinusitis (CRS), who voluntarily elected ESS as the next treatment modality (n = 301), were prospectively evaluated within 4 academic, tertiary care centers using treatment outcome instruments: the Rhinosinusitis Disability Index, the 22-item Sinonasal Outcome Test, the 2-item Patient Health Questionnaire, and the Pittsburgh Sleep Quality Index (PSQI) both before and after ESS. Seventy-two percent (72%) of patients with CRS were found to have poor sleep (PSQI > 5) at baseline with a mean (standard deviation) global PSQI score of 9.4 (4.6). Surgery improved overall mean global PSQI scores (by 2.2 points), and all 7 subdomain scores of the PSQI. Similarly, the odds of good sleep quality (PSQI ≤ 5) in patients treated with sinus surgery increased significantly (odds ratio [OR] 5.94; 95% confidence interval [CI], 3.06 to 11.53; p < 0.001). Stepwise multivariate linear regression found that acetylsalicylic acid (ASA) intolerance (β [standard error], -1.94 [0.93]; 95% CI, -3.77 to -0.11; p = 0.038), history of prior sinus surgery (β [standard error], 1.10 (0.54); 95% CI, 0.03 to 2.16; p = 0.044), and frontal sinusotomy (β [standard error], -1.03 [0.62]; 95% CI, -2.26 to 0.20; p = 0.099) were found to significantly associate with improvement in PSQI sleep scores. Among patients with CRS, reduced sleep quality, poor disease-specific quality of life, and greater disease severity were improved following ESS.

One airway: Biomarkers of protection from upper and lower airway injury after World Trade Center exposure

Firefighters exposed to World Trade Center (WTC) dust have developed chronic rhinosinusitis (CRS) and abnormal forced expiratory volume in 1s(FEV1). Overlapping but distinct immune responses may be responsible for the clinical manifestations of upper and lower airway injury. We investigated whether a panel of inflammatory cytokines, either associated or not associated with WTC-LI, can predict future chronic rhinosinusitis disease and its severity. Serum obtained within six months of 9/11/2001 from 179 WTC exposed firefighters presenting for subspecialty evaluation prior to 3/2008 was assayed for 39 cytokines. The main outcomes were medically managed CRS (N=62) and more severe CRS cases requiring sinus surgery (N=14). We tested biomarker-CRS severity association using ordinal logistic regression analysis. Increasing serum IL-6, IL-8, GRO and neutrophil concentration reduced the risk of CRS progression. Conversely, increasing TNF-α increased the risk of progression. In a multivariable model adjusted for exposure intensity, increasing IL-6, TNF-α and neutrophil concentration remained significant predictors of progression. Elevated IL-6 levels and neutrophil counts also reduced the risk of abnormal FEV1 but in contrast to CRS, increased TNF-α did not increase the risk of abnormal FEV1. Our study demonstrates both independent and overlapping biomarker associations with upper and lower respiratory injury, and suggests that the innate immune response may play a protective role against CRS and abnormal lung function in those with WTC exposure.

Antisomnogenic cytokines, quality of life, and chronic rhinosinusitis: A pilot study

Sleep disturbance, reduced quality of life (QOL), and other components of "sickness behavior" in patients with chronic rhinosinusitis (CRS) are poorly understood. These complex changes in central behavior are due to the effects of immune mediators acting in the brain. We hypothesized that immune mediators that have been associated with CRS are also associated with sickness behavior, somnifacient complaints, and CRS disease-specific QOL. Pilot study. Twenty patients with CRS were prospectively enrolled and completed the Pittsburgh Sleep Quality Index (PSQI), disease-specific QOL, and olfactory instruments. Ethmoid mucosa was obtained and reverse transcription-polymerase chain reaction was performed for the cytokines interleukin (IL)-4, -13, and transforming growth factor-β (TGF-β). Average change in crossover threshold was calculated, and differences in gene expression were correlated with sleep quality, CRS-specific QOL, and disease severity. Patients with CRS reported overall poor sleep quality and poor CRS-specific QOL with significant correlations between them. Increased expression of TGF-β (r = -0.443; P = .050) and IL-4 (r = -0.548; P = .012) correlated with sleep dysfunction, whereas IL-13 expression was linearly associated with worse sleep quality (PSQI scores r = -0.417; P = .075). IL-4 and TGF-β expression was not associated with CRS disease severity or QOL, whereas significantly higher levels of IL-13 expression correlated with worse CRS disease severity and QOL. Patients with CRS exhibited behavioral changes commonly referred to as sickness behavior, which include poor sleep quality and reduced QOL. The upregulation of IL-4 and TGF-β may contribute to inflammatory brain-mediated effects on sleep quality, whereas IL-13 may be a pleiotropic signaling molecule influencing sleep, QOL, and CRS disease severity. 2b.