Background The objective of this study was to describe the first US-based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis (CRS) in a general population sample. Methods A CRS symptom questionnaire was mailed to 23,700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups. Results We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50–59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Co-morbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms. Conclusions CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.

This study adds to understanding of the genetic architecture of asthma in European Americans and African Americans and reinforces the need to study populations of diverse ethnic backgrounds to identify shared and unique genetic predictors of asthma.

In this first longitudinal, population-based study of 3 AENSS definitions, NSS and AENSS were both common, sometimes severe, and differed by EPOS CRS status. Contrasting associations of risk factors for AENSS by the different definitions suggest a need for a standardized approach to definition of AENSS.

Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data.

Background Chronic rhinosinusitis (CRS) has a broad range of co-morbidities. Due to a lack of longitudinal studies, it is not known whether these co-morbidities cause CRS, are promoted by CRS, or share a systemic disease process with CRS. Objective To determine the risk of incident disease within five years after a new diagnosis of CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). Methods We conducted a case-control study nested within the longitudinal cohort of primary care patients in the Geisinger Clinic using electronic health record data. We evaluated incident disease over 5 years in newly diagnosed CRSwNP and CRSsNP cases compared to controls using multivariable Cox regression models. Results CRSsNP (n=3612) cases were at greater risk (HR, 95% confidence interval) than controls for incidence of: upper airway diseases, including adenotonsillitis (3.29, 2.41–4.50); lower aerodigestive tract diseases, including asthma (2.69, 2.14–3.38); epithelial conditions, including atopic dermatitis (2.75, 1.23–6.16); and hypertension (1.38, 1.19–1.61). CRSwNP (n=241) cases were at greater risk for obesity than controls (1.74, 1.08–2.80), but CRSwNP was not associated with other diseases. Conclusion The risk of other diseases associated with CRS adds to the burden of an already highly burdensome condition, and suggests either that CRS promotes onset of other diseases or is an indicator of systemic disease processes. Different patterns of association with diseases by CRS phenotype may be due to CRSwNP sample size imitations or reflect a different pattern of disease onset by phenotype. These findings have implications for screening guidelines and care of CRS patients.

Background Chronic rhinosinusitis (CRS) is a prevalent and disabling paranasal sinus disease, with a likely multi-factorial etiology potentially including hazardous occupational and environmental exposures. We completed a systematic review of the occupational and environmental literature to evaluate the quality of evidence of the role that hazardous exposures might play in CRS. Methods We searched PubMed for studies of CRS and following exposure categories: occupation, employment, work, industry, air pollution, agriculture, farming, environment, chemicals, roadways, disaster, or traffic. We abstracted information from the final set of articles across six primary domains: study design; population; exposures evaluated; exposure assessment; CRS definition; and results. Results We identified 41 articles from 1080 manuscripts: 37 occupational risk papers, 1 environmental risk paper, and 3 papers studying both categories of exposures. None of the 41 studies used a CRS definition consistent with current diagnostic guidelines. Exposure assessment was generally dependent on self-report or binary measurements of exposure based on industry of employment. Only grain, dairy and swine operations among farmers were evaluated by more than one study using a common approach to defining CRS, but employment in these settings was not consistently associated with CRS. The multiple other exposures did not meet quality standards for reporting associations or were not evaluated by more than one study. Conclusion The current state of the literature allows us to make very few conclusions about the role of hazardous occupational or environmental exposures in CRS, leaving a critical knowledge gap regarding potentially modifiable risk factors for disease onset and progression.

Allergy. 2020;75:911-920.wileyonlinelibrary.com/journal/all | 911 Abstract Background: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings.Objective: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample. Methods:We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRS S ) was based on guideline criteria, and objective radiologic inflammation (CRS O ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRS S+O . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRS S+O .Using weighted analysis, we calculated estimates for the source population. Results:The proportion of women with L-M scores ≥ 3, 4, or 6 (CRS O ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRS S+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRS S+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses. Conclusion:In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRS S+O . K E Y W O R D S chronic rhinosinusitis, CT scan, epidemiology, sex, sinus S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Hirsch AG, Nordberg C, Bandeen-Roche K, et al. Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population-based sample.Allergy. 2020;75:911-920. https ://doi.

Less than half with nasal and sinus symptoms meeting CRS EPOS criteria in our general, regional population had symptom persistence over time, with symptom profiles at baseline and age of onset being strongly associated with stability of symptoms.