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Asthma is a complex syndrome in which bronchial inflammation and smooth muscle hyperactivity lead to labile airflow obstruction. The commonest form of asthma is that due to atopy, which is an immune disorder where production of IgE to inhaled antigens leads to bronchial mucosal inflammation. The ultimate origins of asthma are interactive environmental and genetic factors. The genetics is acknowledged to be heterogeneous, and one chromosomal region of interest and controversy has been 11q13. To clarify the nature of the chromosome 11q13 effect in atopy and asthma, we conducted a genetic association study in subjects with marked atopic asthma and matched controls, which incorporated the study of 13 genetic variants over a distance of 10-12 cM and which took account of detailed immune and clinical phenotyping. Association with high IgE levels was limited to the interval flanked by D11S1335 and CD20 in a 0.8-Mb interval and was greatest for variants of Fc epsilonRIbeta and HTm4; these variants also associated with asthma (recurrent wheeze with labile airflow obstruction and need for regular inhaler treatment). At the more telomeric marker, D11S480, variants associated with asthma, but not with high IgE levels. The data might support the possibility of multiple loci relevant to atopic asthma on chromosome 11q13.

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Patients with CRS developed OSA at a lower BMI; patients CRS and OSA had similar sleep-related breathing patterns but higher risks for PLMs compared with patients with OSA and without CRS.

RATIONALE: It is well established that most patients with chronic rhinosinusitis(CRS) suffer from poor sleep, which is associated with impaired quality of life. However, this has not been studied objectively and the risk factors for sleep disruption in CRS remain unknown. This prospective study aimed to investigate the extent of disturbances and breathing disorders during sleep by using polysomnography(PSG). METHODS: Thirty randomly selected CRS patients underwent overnight PSG and completed 2 sleep-related questionnaires including the Pittsburgh Sleep Quality Index(PSQI) and Munich Circadian Rhythm. CRS characteristics including presence of nasal polyps, sinus tissue histopathology, Lund-Mackay Score(LMS), sinonasal outcome test scores(SNOT-22) and comorbid diseases (asthma, aspirin exacerbated respiratory disease, allergic rhinitis and gastroesophageal reflux[GERD]) were also investigated. PSG results were recorded and compared in association with these variables. RESULTS: Overall, 58.6 % of the patients had apnea-hypopnea index above 5 indicative of obstructive sleep apnea(OSA): 27.6% mild, 13.8% moderate and 17.2% severe. 68% of patients had hypoxemic episodes during sleep. The mean6SD O2 nadir was 77.5623.03 in the whole series. Male gender and GERD were associated with OSA, after adjusting for BMI. Patients with nasal polyp had a trend toward increased supine AHI(adjusted p50.09). OSA was associated with poor sleep quality measured by PSQI and circadian rhythm disruption measured by Munich. CONCLUSIONS: Our prospective study screening with PSG showed that more than half of the CRS patients have OSA, which suggests that all CRS patients potentially need to be screened using PSG, especially male patients and those with comorbid GERD. Further research on cost effectiveness is warranted. J ALLERGY CLIN IMMUNOL FEBRUARY 2019 AB284 Abstracts MONDAY

RATIONALE: This study found Cystatin SN (CST1), a type 2 cystatin subfamily member, to be highly expressed in nasal polyps from patients with intractable chronic rhinosinusitis with nasal polyps (CRSwNP), using a whole transcript analysis with next-generation sequencing. Eosinophilic chronic rhinosinusitis (ECRS) involves nasal polyps that are refractory and recurrent immediately after endoscopic sinus surgery. We hypothesized that CST1 may contribute to the pathogenesis of ECRS. METHODS: The expression of CST1 in nasal polyps from patients with ECRS was examined by mRNA expression levels, using real-time PCR and immunohistochemistry. We examined the function of CST1 using nasal epithelial cells and nasal fibroblasts. RESULTS: CST1 was significantly expressed in the epithelial cells of the nasal polyps from patients with ECRS, compared with patients who did not have ECRS (non-ECRS). Particularly, CST1 showed very strong expression in patients with severe ECRS. The expression of CST1 may be correlated with the recurring and refractory nature of ECRS. Stimulation by a combination of IL-4 plus dsRNA plus CST1 significantly elevated mRNA expression levels and protein levels of TSLP in nasal epithelial cells. Stimulation by TSLP or IL-33 significantly elevated mRNA expression levels of CST1 in nasal epithelial cells. Stimulation of CST1 significantly elevated mRNA expression levels of CCL11 and POSTN in nasal fibroblasts. CONCLUSIONS: CST1 could amplify eosinophilic infiltration and Th2 inflammation by interacting with epithelial-derived cytokines and fibroblasts on nasal polyps. CST1 may be involved in the pathogenesis of ECRS, and may contribute to the severity and recurrence of CRSwNP after ESS.

For patients with asthma, self-reported inhaled corticosteroid (ICS) adherence and Short Acting Beta 2 Agonist (SABA) use may be inaccurate. This may lead to inappropriate clinical decision-making, keep patients from achieving their treatment goals and adversely impact healthcare costs. This study compares self-reported ICS and SABA use with objective data from electronic medication monitors (EMM). METHODS: Adults with uncontrolled asthma (defined by Asthma Control Test Scores of <19 and/or NHLBI NAEPP EPR3 guideline criteria) and prescribed ICS and SABA by their asthma specialist (allergist/immunologist/pulmonologist) were enrolled. At visit one, participants' ICS and SABA inhalers were fitted with EMMs (Propeller Health, Madison, WI) to track real-time medication usage over 14 days. Participants were asked to complete paper diaries to self-report medication usage over the same period. Self-reported vs. objective ICS adherence and SABA use was compared using paired t-tests and Wilcoxon signed-rank tests. RESULTS: One hundred participants (80% female, mean age 48.5 years, 60% completed college, 80% privately insured) had complete data. Selfreported mean (standard deviation) daily ICS adherence (79% [31]) and median (interquartile range) SABA use (0.7 puffs [0-1.9]) was higher than objectively measured ICS adherence (69% [29], P50.01) and SABA use (0.3 puffs [0.1-1.1], P<0.001). CONCLUSIONS: There was significant over-reporting of inhaler use, which may result in inappropriate changes to therapy and medication regimen complexity. Use of EMMs can increase the accuracy of medication usage reporting and allow healthcare providers to make more informed clinical decisions for patients.

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