Relationship between Occurrence and Progression of Lung Cancer and Nocturnal Intermittent Hypoxia, Apnea and Daytime Sleepiness

Abstract

The possible relationship between lung cancer and nocturnal intermittent hypoxia, apnea and daytime sleepiness, especially the possible relationship between the occurrence and progression of lung cancer and obstructive sleep apnea syndrome (OSAS) was explored. Forty-five cases of primary lung cancer suitable for surgical resection at the Third Affiliated Hospital of Kunming Medical University between January 2017 and December 2017 were recruited (lung cancer group), and there were 45 patients in the control group who had no significant differences in age, sex and other general data from lung cancer group. The analyzed covariates included general situation, snore score, the Epworth Sleeping Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), apnea and hypopneas index (AHI), oxygen desaturation index 4 (ODI₄), lowest arterial oxygen saturation [LSpO₂ (%)], oxygen below 90% of the time [T90% (min)], the percentage of the total recorded time spend below 90% oxygen saturation (TS90%), to explore the possible relationship between lung cancer and above indicators. The participants were followed up for one year. The results showed that: (1) There was significant difference in body mass index (BMI), ESS, AHI, T90% (min), TS90%, ODI₄, snore score and LSpO₂ (%) between lung cancer group and control group (P<0.05). There was no statistically significant difference in age, gender, PSQI score, incidence of concurrent hypertension, diabetes and coronary heart disease (CHD), and smoking history between the two groups (P>0.05); (2) Patients in the lung cancer group were divided into OSAS subgroup and non-OSAS subgroup according to the international standard for the diagnosis of OSAS. There was significant difference in BMI, age, staging, incidence of concurrent hypertension and concurrent CHD, snore score, ESS score, T90% (min), TS90%, ODI₄ and LSpO₂ (%) between OSAS subgroup and non-OSAS subgroup (P<0.05). There was no statistically significant difference in gender, PSQI score, incidence of concurrent diabetes, smoking history and lung cancer type between the two groups (P>0.05); (3) AHI was strongly negatively correlated with the LSpO₂ (%) and positively with ESS, staging, snoring score, T90% (min), TS90%, ODI₄ and BMI (P<0.05); (4) There were 3 deaths, 5 cases of recurrence, and 4 cases of metastasis in OSAS subgroup; and there was 1 death, 4 cases of recurrence and 2 cases of metastasis in non-OSAS subgroup during the follow-up period of one year, respectively. There was no significant difference in mortality, recurrence rate and metastasis rate between the two subgroups, and the total rate of deterioration in OSAS subgroup was significantly increased compared to the non-OSAS subgroup (P<0.05). It was concluded that the patients with lung cancer are prone to nocturnal hypoxemia, apnea, snoring and daytime sleepiness compared to control group. The incidence of OSAS in patients with lung cancer was higher, and the difference in the hypoxemia-related indicators was statistically significant. The mortality, recurrence rate, and metastasis rate increases in lung cancer patients with OSAS during the one-year follow-up period, suggesting that OSAS may be a contributing factor to the occurrence and progression of lung cancer.

References

[1] GarveyIF, PengoMF, DrakatosP, et al.. Epidemiological aspects of obstructive sleep apnea. J Thorac Dis, 2015, 7(5): 920-929

[2] KielyJL, McNicholasWT. Cardiovascular risk factors in patients with obstructive sleep apnoea syndrome. Eur Respir J, 2000, 16(1): 128-133

[3] RiceTB, FosterGD, SandersMH, et al.. The relationship between obstructive sleep apnea and self-reported stroke or coronary heart disease in overweight and obese adults with type 2 diabetes mellitus. Sleep, 2012, 35(9): 1293-1298

[4] Martinez-GarciaMA, Campos-RodriguezF, BarbeF. Cancer and OSA: Current Evidence From Human Studies. Chest, 2016, 150(2): 451-463

[5] LiL, LuJ, XueW, et al.. Target of obstructive sleep apnea syndrome merge lung cancer: based on big data platform. Oncotarget, 2017, 8(13): 21567-21578

[6] DreherM, KrugerS, Schulze-OldenS, et al.. Sleep-disordered breathing in patients with newly diagnosed lung cancer. BMC Pulm Med, 2018, 18(1): 72

[7] AlmendrosI, WangY, BeckerL, et al.. Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. Am J Respir Crit Care Med, 2014, 189(5): 593-601

[8] CampilloN, TorresM, VilasecaA, et al.. Role of Cyclooxygenase-2 on Intermittent Hypoxia-induced Lung Tumor Malignancy in a Mouse Model of Sleep Apnea. Sci Rep, 2017, 7: 44693

[9] KhalyfaA, AlmendrosI, Gileles-HillelA, et al.. Circulating exosomes potentiate tumor malignant properties in a mouse model of chronic sleep fragmentation. Oncotarget, 2016, 7(34): 54676-54690

[10] NietoFJ, PeppardPE, FinnL, et al.. Reply: sleep-disordered breathing, hypoxemia, and cancer mortality. Am J Respir Cnt Care Med, 2013, 187(3): 331-332

[11] Campos-RodriguezF, Martinez-GarciaMA, MartinezM, et al.. Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort. Am JRespir Cnt Care Med, 2013, 187(1): 99-105

[12] ShimodaLA, SemenzaGL. HIF and the lung: role of hypoxia-inducible factors in pulmonary development and disease. Am J Respir Crit Care Med, 2011, 183(2): 152-156

[13] CorteseR, AlmendrosI, WangY, et al.. Mcroarray-based analysis of plasma cirDNA epigenetic modification profiling in xenografted mice exposed to intermittent hypoxia. Genom Data, 2015, 5: 17-20

[14] AlmendrosI, MontserratJM, TorresM, et al.. Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea. Sleep Med, 2012, 13(10): 1254-1260

[15] AlmendrosI, MontserratJM, TorresM, et al.. Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea. Respir Physiol Neurobiol, 2013, 186(3): 303-307

[16] FosterJG, WongSC, SharpTV. The hypoxic tumor microenvironment: driving the tumorigenesis of nonsmall-cell lung cancer. Future Oncol, 2014, 10(16): 2659-2674

[17] ColtenHR, AltevogtBM. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem, 2006, National Academies Press (US), Washington (DC)

[18] YoungT, PeppardPE, TaheriS. Excess weight and sleep-disordered breathing. J Appl Physiol, 1985, 99(4): 1592-1599

[19] GozalD, FarreR, NietoFJ. Putative Links Between Sleep Apnea and Cancer: From Hypotheses to Evolving Evidence. Chest, 2015, 148(5): 1140-1147

[20] GiovannettiE, WangQ, AvanA, et al.. Role of CYB5A in pancreatic cancer prognosis and autophagy modulation. J Natl Cancer Inst, 2014, 106(1): 346

[21] LiuY, SongX, WangX, et al.. Effect of chronic intermittent hypoxia on biological behavior and hypoxia-associated gene expression in lung cancer cells. J Cell Biochem, 2010, 111(3): 554-563

[22] MaceyPM, WooMA, RajeshK, et al.. Relationship between Obstructive Sleep Apnea Severity and Sleep, Depression and Anxiety Symptoms in Newly-Diagnosed Patients. PLoS One, 2010, 5(4): 10211

[23] MaoZF, ZhaoTT, WangZN, et al.. Influence of different hypoxia models on metastatic potential of SGC-7901 gastric cancer cells. Tumour Biol, 2014, 35(7): 6801-6808

[24] HakimF, WangY, ZhangSX, et al.. Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res, 2014, 74(5): 1329-1337

[25] ZielinskiMR, DavisJM, FadelJR, et al.. Influence of chronic moderate sleep restriction and exercise on inflammation and carcinogenesis in mice. Brain Behav Immun, 2012, 26(4): 672-679