Nightly nicotine withdrawal as well as other respiratory and pulmonary effects of smoking may result in sleep-disordered breathing, especially obstructive sleep apnea (OSA). We hypothesize that there is higher prevalence of smoking in patients with OSA. We also hypothesize that smoking is an independent risk factor for OSA. The aim of this study is to determine whether there is a higher prevalence of smoking in patients with OSA compared with patients who do not have OSA. To investigate this, we randomly selected a group of 108 patients who were diagnosed as having OSA, defined by an apnea-hypopnea index (AHI) of greater than 10 events per hour. We compared their smoking history with another randomly selected group of 106 patients without OSA, defined by an AHI of less than five events per hour. The prevalence of smoking in patients with OSA was found to be 35%, whereas it was only 18% in patients without OSA. Logistic regression analyses were performed to investigate the effects of smoking while adjusting for age, gender, body mass index (BMI), and number of alcoholic drinks per week. While holding fixed the BMI, gender, age, and number of alcoholic drinks per week, current smokers were found to be 2.5 times more likely to have OSA than former smokers and nonsmokers combined (odds ratio = 2.5, CI 1.3-4.7, p = 0.0049), and 2.8 times more likely to have OSA than former smokers alone (odds ratio = 2.8, CI = 1.4-5.4, p = 0.0028). Adjusted for BMI, gender, age, and number of alcoholic drinks per week, former smokers were not more likely than never smokers to have OSA (odds ratio = 1.2, CI = 0.55-2.7, p = 0.64). We conclude that cigarette smoke may be an independent risk factor for OSA in this referral population.

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Nightly nicotine withdrawal as well as other respiratory and pulmonary effects of smoking may result in sleep-disordered breathing, especially obstructive sleep apnea (OSA). We hypothesize that there is higher prevalence of smoking in patients with OSA. We also hypothesize that smoking is an independent risk factor for OSA. The aim of this study is to determine whether there is a higher prevalence of smoking in patients with OSA compared with patients who do not have OSA. To investigate this, we randomly selected a group of 108 patients who were diagnosed as having OSA, defined by an apnea-hypopnea index (AHI) of greater than 10 events per hour. We compared their smoking history with another randomly selected group of 106 patients without OSA, defined by an AHI of less than five events per hour. The prevalence of smoking in patients with OSA was found to be 35%, whereas it was only 18% in patients without OSA. Logistic regression analyses were performed to investigate the effects of smoking while adjusting for age, gender, body mass index (BMI), and number of alcoholic drinks per week. While holding fixed the BMI, gender, age, and number of alcoholic drinks per week, current smokers were found to be 2.5 times more likely to have OSA than former smokers and nonsmokers combined (odds ratio = 2.5, CI 1.3-4.7, p = 0.0049), and 2.8 times more likely to have OSA than former smokers alone (odds ratio = 2.8, CI = 1.4-5.4, p = 0.0028). Adjusted for BMI, gender, age, and number of alcoholic drinks per week, former smokers were not more likely than never smokers to have OSA (odds ratio = 1.2, CI = 0.55-2.7, p = 0.64). We conclude that cigarette smoke may be an independent risk factor for OSA in this referral population.

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Introduction: Formalin-fixed paraffin-embedded (FFPE) tissue is commonly used for molecular analysis, including for next generation sequencing (NGS). In an effort to improve the quality of molecular results in small tissue samples, we developed a novel biopsy transport device that splits the biopsy sample longitudinally for dual-mode preservation by freezing (for biomolecular analysis) and formalin (for the evaluation of histologic features without freezing artifact). In this feasibility study we compared NGS results from samples acquired by the new device with those obtained using standard biopsy handling procedures. Methods: Following informed consent, biopsy samples were obtained ex-vivo by a breast imaging radiologist under ultrasound guidance from invasive cancers in two mastectomy specimens using a standard biopsy needle (Mission 14G, CR Bard). A reference sample (REF) was placed directly into 10% neutral buffered formalin. An experimental sample (EXP) was placed in the new device, ink marked on one end for orientation and sectioned longitudinally. After sectioning, one half-sample was formalin fixed and one half was frozen and then stored at -80 degrees until further processing. The REF samples and one half of the EXP samples were fixed for 24 hours then processed routinely into FFPE blocks. DNA was extracted from the REF sample and the frozen EXP half-sample and evaluated using NGS Oncopanel (targeted exome sequencing, Illumina) at 25ng, 50ng and 100ng input template. Results: The formalin-fixed EXP halves maintained high quality of tissue histology with minimal artifacts. The number of unique, aligned, high-quality reads was on average 1.85-fold greater in the EXP specimens relative to the paired REF samples for all three template amounts in both tumors that were analyzed (range 1.58-fold to 2.29-fold; p=0.0016). More than twice as many high-quality reads were present in the EXP specimens for Tier 2 and Tier 3 mutations (TP53, PIK3CA and GATA3) at the lowest template amounts (average 2.40-fold at 25ng). Copy number reads showed lower cutoff scores (a measure of signal variability across segments) in EXP samples than in REF samples (p=0.0052). Conclusions: Dual-mode preservation of core biopsy samples by freezing and formalin can be done with the new device and it provides equivalent quality of histology sections. Preservation of biopsy samples by freezing rather than formalin improved the quality of NGS evaluation in all samples down to 25ng input template, both for single variant analysis and for copy number detection. Longitudinal sectioning of the tissue samples allows for assessment of tumor purity and for macrodissection of the oriented frozen half-sample as needed. These improvements allow for greater confidence in variant and copy number calls with lower input template amounts. Citation Format: Deborah A. Dillon, Elizabeth P. Garcia, Michele Baltay, Krishan Taneja, Teri Bowman, Eva C. Gombos, Tom Gal, Stuart G. Silverman, Erez Nevo, Shoshan Nevo. High quality next generation sequencing results for breast cancer using dual-mode biopsy tissue preservation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1611.