Severe Obstructive Sleep Apnea Associated With Higher Risk of Mortality in Stage III and IV Lung Cancer

Hung-Yu Huang; Lin Shih-Wei; Li-Pang Chuang; Chih-Liang Wang; Ming-Hui Sun; Hsueh-Yu Li; Chee-Jen Chang; Shu-Chen Chang; Cheng-Ta Yang; Ning-Hung Chen

Severe Obstructive Sleep Apnea Associated With Higher Risk of Mortality in Stage III and IV Lung Cancer

J Clin Sleep Med. 2020 Mar 24. Online ahead of print.

Authors

Hung-Yu Huang^{1

2}, Lin Shih-Wei^{2

3

4}, Li-Pang Chuang^{2

3}, Chih-Liang Wang^{2

3}, Ming-Hui Sun⁵, Hsueh-Yu Li⁶, Chee-Jen Chang^{7

8}, Shu-Chen Chang^{7

8}, Cheng-Ta Yang^{2

3}, Ning-Hung Chen^{2

3

4}

Affiliations

¹ Division of Pulmonary and Critical Care, Department of Internal Medicine, Saint Paul's Hospital, Taoyuan, Taiwan.
² Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
³ Department of Respiratory Therapy, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, China.
⁵ Department of Ophthalmology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University, Taoyuan, Taiwan.
⁶ Department of Otorhinolaryngology - Head and Neck Surgery, Sleep Center, Linkou-Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁷ Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁸ Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan.

PMID: 32208133

Abstract

Study objectives: Obstructive sleep apnea (OSA) has been associated with increased cancer incidence and mortality. The aim of this study was to investigate cancer-related mortality, overall survival and progression free survival in patients with suspected OSA and lung cancer.

Methods: This was a case series analysis of lung cancer from a sleep cohort with suspected OSA between 2009 and 2014. The apnea- hypopnea index (AHI), Tsat90% (hypoxia index) and survival outcome were recorded. Immunohistochemistry was used to analyze HIF-1α and VEGF expression in tumor pathology.

Results: In the sleep cohort comprising 8261 patients, a total of 23 patients had lung cancer. The incidence of lung cancer was significantly higher in the sleep cohort than in the entire adult population in Taiwan (242.1 vs 51.5 per 10⁵ persons, P< 0.01). The 3-year cancer-related mortality was 25% in AHI < 15, 50% in AHI 15 to 29 and 80% in AHI ≥ 30 (chi-squared test for trend P =0.03). In Kaplan-Meier survival analysis, patients with stage III-IV lung cancer and AHI< 30 exhibited significantly better overall survival (P = 0.02) and progression free survival (P = 0.02) than patients with severe OSA. Overexpression of HIF-1α and VEGF was shown in 63 % and 45 % of lung tumor samples. Overexpression of HIF-1α was positively associated with AHI (P = 0.04).

Conclusions: In this preliminary case series, severe OSA is associated with an increased risk of cancer mortality in patients with stage III-IV lung cancer. AHI was significantly associated with HIF-1α overexpression.

Keywords: hypoxia-inducible factor; lung cancer; mortality; obstructive sleep apnea.