Agnes S. Sundaresan

Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample.

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.

Five-year risk of incident disease following a diagnosis of chronic rhinosinusitis

Chronic rhinosinusitis (CRS) has a broad range of comorbidities. Due to a lack of longitudinal studies, it is not known whether these comorbidities cause CRS, are promoted by CRS, or share a systemic disease process with CRS.

Occupational and environmental risk factors for chronic rhinosinusitis: a systematic review

Chronic rhinosinusitis (CRS) is a prevalent and disabling paranasal sinus disease, with a likely multifactorial 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.

Identification of Four Novel Loci in Asthma in European American and African American Populations

Rationale: Despite significant advances in knowledge of the genetic architecture of asthma, specific contributors to the variability in the burden between populations remain uncovered. Objectives: To identify additional genetic susceptibility factors of asthma in European American and African American populations. Methods: A phenotyping algorithm mining electronic medical records was developed and validated to recruit cases with asthma and control subjects from the Electronic Medical Records and Genomics network. Genome‐wide association analyses were performed in pediatric and adult asthma cases and control subjects with European American and African American ancestry followed by metaanalysis. Nominally significant results were reanalyzed conditioning on allergy status. Measurements and Main Results: The validation of the algorithm yielded an average of 95.8% positive predictive values for both cases and control subjects. The algorithm accrued 21,644 subjects (65.83% European American and 34.17% African American). We identified four novel population‐specific associations with asthma after metaanalyses: loci 6p21.31, 9p21.2, and 10q21.3 in the European American population, and the PTGES gene in African Americans. TEK at 9p21.2, which encodes TIE2, has been shown to be involved in remodeling the airway wall in asthma, and the association remained significant after conditioning by allergy. PTGES, which encodes the prostaglandin E synthase, has also been linked to asthma, where deficient prostaglandin E2 synthesis has been associated with airway remodeling. Conclusions: 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.

Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network

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.

Identifying Asthma Exacerbation-Related Emergency Department Visit Using Electronic Medical Record and Claims Data

Background  Asthma exacerbation leading to emergency department (ED) visit is prevalent, an indicator of poor control of asthma, and is a potentially preventable clinical outcome. Objective  We propose to utilize multiple data elements available in electronic medical records (EMRs) and claims database to create separate algorithms with high validity for clinical and research purposes to identify asthma exacerbation-related ED visit among the general population. Methods  We performed a retrospective study with inclusion criteria of patients aged 4 to 40 years, a visit to Geisinger ED from January 1, 2006, to October 28, 2013, with asthma on their problem list. Different electronic data elements including chief complaints, vitals, season, smoking, medication use, and discharge diagnoses were obtained to create the algorithm. A stratified random sample was generated to select the charts for review. Chart review was performed to classify patients with asthma-related ED visit, that is, the gold standard. Two reviewers performed the chart review and validation was done on a small subset. Results  There were 966 eligible ED visits in the EMR sample and 731 in the claims sample. Agreement between reviewers was 95.45% and kappa statistic was 0.91. Mean age of the EMR sample was 22 years, and mostly white (93%). Multiple models conventionally used in studies were evaluated and the final model chosen included principal diagnosis, bronchodilator, and steroid use for both algorithms, chief complaints for EMR, and secondary diagnosis for claims. Area under the curve was 0.93 (95% confidence interval: 0.91–0.94) and 0.94 (0.93–0.96), respectively, for EMR and claims data, with positive predictive value of > 94%. The algorithms are visually presented using nomograms. Conclusion  We were able to develop two separate algorithms for EMR and claims to identify asthma exacerbation-related ED visit with excellent diagnostic ability and varying discrimination threshold for clinical and research purposes.

Longitudinal evaluation of clustering of chronic sinonasal and related symptoms using exploratory factor analysis

Sinonasal symptoms are common and can have several underlying causes. When symptoms occur in specified patterns lasting 3 months or more they meet criteria for chronic rhinosinusitis (CRS). Approaches to CRS symptom measurement do not specify how to measure symptoms and treat specified sinonasal symptoms as generally interchangeable, suggesting that such symptoms should cluster on 1 or 2 latent factors.

Prevalence, severity, and risk factors for acute exacerbations of nasal and sinus symptoms by chronic rhinosinusitis status

Nasal and sinus symptoms (NSS) are common to many health conditions, including chronic rhinosinusitis (CRS). Few studies have investigated the occurrence and severity of, and risk factors for, acute exacerbations of NSS (AENSS) by CRS status (current, past, or never met European Position Paper on Rhinosinusitis [EPOS] criteria for CRS).

Longitudinal Evaluation of Chronic Rhinosinusitis Symptoms in a Population-based Sample

BACKGROUND Chronic rhinosinusitis (CRS) is a prevalent and disabling condition of the nose and sinuses. The natural history of CRS symptoms in a general population sample has not been previously studied. OBJECTIVE In a general population-based sample from Pennsylvania, we used 2 questionnaires mailed 6 months apart to estimate the prevalence of, and identify predictors for, stability or change in symptoms over time. METHODS We mailed the baseline and 6-month follow-up questionnaires to 23,700 primary care patients and 7,801 baseline responders, respectively. We categorized nasal and sinus symptoms using European Position Paper on Rhinosinusitis (EPOS) epidemiologic criteria. We defined 6 symptom groups over time on the basis of the presence of CRS symptoms at baseline and follow-up. We performed multivariable survey logistic regression controlling for confounding variables comparing persistent versus nonpersistent, recurrent versus stable past, and incident versus never. RESULTS There were 4,966 responders at follow-up: 558 had persistent symptoms, 190 recurrent symptoms, and 83 new symptoms meeting EPOS criteria for CRS. The prevalence of persistent symptoms was 4.8% (95% CI, 3.8-5.8), whereas the annual cumulative incidence of new symptoms was 1.9% and of recurrent symptoms was 3.2%. More severe symptoms at baseline were associated with persistence, whereas minor symptoms, allergies, and multiple treatments were associated with the development of new symptoms. CONCLUSIONS 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.