Obstructive Sleep Apnea and Smoking Increase the Risk of Cardiovascular Disease: Smoking Cessation Pharmacotherapy.

Tobacco smoking has been a recognized risk factor for cardiovascular diseases (CVD). Smoking is a chronic relapsing disease and pharmacotherapy is a main component of smoking cessation. Obstructive sleep apnea (OSA) and smoking both increase the risk of CVD and are associated with significant morbidity and mortality. There are few existing data examining how pharmacological treatment, such as nicotine replacement therapy (NRT), bupropion, and varenicline, affect smokers suffering with OSA and especially their cardiovascular effects. The aim of this review was to evaluate the effects of smoking cessation pharmacotherapy on OSA with a special emphasis on the cardiovascular system. Results: Only small studies have assessed the effect of NRTs on OSA. Nicotine gum administration showed an improvement in respiratory events but with no permanent results. No specific studies were found on the effect of bupropion on OSA, and a limited number evaluated varenicline's effects on sleep and specifically OSA. Varenicline administration in smokers suffering from OSA reduced the obstructive respiratory events, especially during REM. Studies on second-line medication (nortriptyline, clonidine, cytisine) are even more limited. There are still no studies evaluating the cardiovascular effects of smoking cessation medications on OSA patients. Conclusions: Sleep disturbances are common withdrawal effects during smoking cessation but could be also attributed to pharmacotherapy. Smokers should receive personalized treatment during their quitting attempts according to their individual needs and problems, including OSA. Future studies are needed in order to evaluate the efficacy and safety of smoking cessation medications in OSA patients.

Does Smoking Affect OSA? What about Smoking Cessation?

The connection between smoking and Obstructive sleep apnea (OSA) is not yet clear. There are studies that have confirmed the effect of smoking on sleep disordered breathing, whereas others did not. Nicotine affects sleep, as smokers have prolonged total sleep and REM latency, reduced sleep efficiency, total sleep time, and slow wave sleep. Smoking cessation has been related with impaired sleep. The health consequences of cigarette smoking are well documented, but the effect of smoking cessation on OSA has not been extensively studied. Smoking cessation should improve OSA as upper airway oedema may reduce, but there is limited data to support this hypothesis. The impact of smoking cessation pharmacotherapy on OSA has been studied, especially for nicotine replacement therapy (NRT). However, there are limited data on other smoking cessation medications as bupropion, varenicline, nortriptyline, clonidine, and cytisine. The aim of this review was to explore the current evidence on the association between smoking and OSA, to evaluate if smoking cessation affects OSA, and to investigate the possible effects of different pharmacologic strategies offered for smoking cessation on OSA.

Smoking and Obstructive Sleep Apnea: Is There An Association between These Cardiometabolic Risk Factors?-Gender Analysis.

Background and Objectives: Studies have tried to establish a relationship between Obstructive Sleep Apnea syndrome (OSA) and smoking but data still remain controversial. We aimed: 1. To evaluate the relationship between smoking and OSA; 2. To explore potential differences according to gender, and 3. To analyze the prevalence of cardiovascular disease (CVD) co-morbidities according to gender and smoking status. Materials and Methods: This retrospective study included 3791 (70.6% males) adult patients who visited a Sleep Clinic. All participants underwent nocturnal polysomnography. Daytime somnolence and insomnia were assessed by using the Epworth Sleepiness Scale (ESS) and the Athens Insomnia Scale (AIS). Ever-smokers completed the Fagerstrom Test for Nicotine Dependence (FTND). Results: OSA was confirmed in 72.1% of participants with 62.2% suffering from moderate-to-severe disease. The number of cigarettes/day, Pack/Years, and FTND were significantly higher in patients with more severe OSA. The prevalence of current smokers was higher in those without OSA or with mild disease, whereas the prevalence of former smokers was higher in moderate and severe OSA. In univariate analysis, current smokers were found to be 1.2 times more likely to have OSA compared with never and former smokers combined and former smokers 1.49 times more likely compared with never smokers. In the multiple regression analysis, after adjusting for BMI, gender, age and number of alcoholic drinks per week, smoking was not found to be significantly associated with OSA. In gender stratified multivariate analyses, no significant associations were observed. CVD co-morbidities were more frequent in more severe OSA. Hypertension, coronary disease and diabetes were more prevalent in former smokers with AHI ≥ 15, compared with current smokers, especially in men. Conclusions: Even if an independent effect of smoking on OSA was not found, the number of cigarettes/day, Pack/Years, and FTND were higher in patients with more severe OSA with more prevalent CVD co-morbidities.

Varenicline administration for smoking cessation may reduce apnea hypopnea index in sleep apnea patients.

OBJECTIVE/BACKGROUND: Varenicline (VAR) is used for smoking cessation as it inhibits nicotine for binding on its receptors reducing nicotine dependence. VAR administration has been reported to affect sleep. The aim of this study was to evaluate possible changes in polysomnography (PSG) during VAR treatment (SmokeFreeBrain) in healthy smokers and smokers with obstructive sleep apnea (OSA). PATIENTS/METHODS: Thirty smokers (21 men) with 15.3 ± 10.2 PY, aged 32.8 ± 4.5 years, with BMI 28.6 ± 4 kg/m2, 16 without and 14 with OSA (92% males) were studied with PSG (Embletta MPR-Master) before treatment with VAR while smoking and 20-30 days during VAR administration and smoking cessation for at least 5 days. RESULTS: No significant differences were observed in sleep macro architecture (N1, N2, N3, REM, Sleep Efficiency, Total Sleep Time) during VAR treatment apart from prolongation of sleep latency, N2 and N3 latency in both smokers with and without OSA. Apnea hypopnea index (AHI) was reduced in OSA smokers and especially during REM with a borderline increase of arousal index (ArI) and reduction of sleep efficiency (SE). CONCLUSION: VAR treatment worsened sleep quality as a prolongation of sleep latency, N2 and N3 latency was observed. A marginal reduction of AHI was found in OSA patients, more significantly during REM. Due to the small sample size, further studies are needed to distinguish between the adverse reactions of VAR treatment and smoking cessation effects and to evaluate whether VAR may play a role in OSA treatment.

Gender Differences in Obstructive Sleep Apnea: The Value of Sleep Questionnaires with a Separate Analysis of Cardiovascular Patients.

BACKGROUND: Gender affects the clinical presentation of obstructive sleep apnea (OSA). The classic OSA symptoms, such as sleepiness, snoring, and apnea, are not so frequent in women. OBJECTIVES: To evaluate possible gender differences in questionnaires used for OSA prediction, such as the Epworth Sleepiness Scale (ESS), STOP, STOP Bang (SB), Berlin Questionnaire (BQ), Athens Insomnia Scale (AIS), and Fatigue Scale (FS). METHODS: 350 males were matched with 350 women referred to a sleep clinic, according to OSA severity. All responded to the questionnaires and underwent a sleep study. Cardiovascular disease (CVD) patients were separately analyzed. RESULTS: ESS did not differ between genders. SB was higher in males, whereas STOP, BQ, AIS, and FS were higher in females. BQ presented the highest sensitivity in both genders, whereas STOP exhibited the highest specificity in males and ESS in females. AIS and FS were more sensitive and SB more specific in females, whereas BQ was more specific in males. For severe OSA, the predictive values of SB and BQ were almost similar for both genders; however AIS and FS were higher in women. CVD patients presented higher scores, independent of gender, except for AIS, which was higher in females. CONCLUSION: Gender-specific evaluation of questionnaires is necessary to prevent OSA under-diagnosis.

Sleep questionnaires for the screening of obstructive sleep apnea in patients with type 2 diabetes mellitus compared with non-diabetic patients.

BACKGROUND: Several tools have been used to screen for obstructive sleep apnea (OSA). Evaluation of the predictive performance of different questionnaires is essential in patients with type 2 diabetes mellitus (T2DM) because the prevalence of OSA in this population is high. The aim of this study was to evaluate different sleep questionnaires to identify T2DM patients with OSA, and to compare the predictive values of these questionnaires with a matched sample of non-diabetic patients. METHODS: The study was a retrospective study of two patients groups (n = 350 with T2DM, n = 350 without T2DM) visiting a sleep clinic and matched by age, gender, body mass index, and the apnea-hypopnea index (AHI). Symptoms of OSA and Epworth Sleepiness Scale (ESS), STOP-Bang, Berlin questionnaire, and Athens insomnia scale (AIS) scores were compared, and sleep studies were performed. RESULTS: Diabetic patients with OSA complained more frequently of nocturia (P = 0.025), morning headaches (P = 0.04), restless sleep (P = 0.002), and leg movements (P = 0.01) than non-diabetic patients with OSA. Most predictive values of the sleep questionnaires did not differ significantly between the two groups; however, the AIS was higher only in T2DM women (P = 0.01). In both groups, the Berlin and STOP-Bang questionnaires had the highest sensitivity. The ESS had the highest specificity in T2DM patients and the STOP and S-B questionnaires had the highest specificity in non-diabetics. CONCLUSIONS: The predictive performance of the questionnaires was similar in both groups, especially in the case of moderate and severe OSA.

Sleep disorders and health-related quality of life in patients with interstitial lung disease.

BACKGROUND: Interstitial lung diseases (ILD) are chronic and restrictive lung diseases with poor survival and quality of life. The aim of this study was to investigate the frequency of sleep disorders in idiopathic pulmonary fibrosis (IPF) and sarcoidosis and to assess patients' quality of life in relation to these disorders. METHODS: Forty patients, 19 with IPF, and 21 with sarcoidosis stage II/III were included. They were compared with 15 healthy subjects. All patients performed all-night polysomnography (PSG) and completed the Epworth, Berlin, and Stop-Bang questionnaires. In order to evaluate the quality of life, all patients completed the Short-Form 36 (SF-36) questionnaire. RESULTS: Of the IPF patients, 68% were diagnosed with mild obstructive sleep apnea (OSA), 5.2% with moderate to severe, 5.2% with severe OSA, and 21% with no OSA. Of patients with sarcoidosis, 52.4% were diagnosed with mild OSA and 4.8% with moderate severity OSA. The remaining 42.8% did not have OSA. The health-related quality of life in both patients with IPF and patients with sarcoidosis was impaired especially in the domains concerning physical health and the level of independence, compared to the control group. CONCLUSIONS: In this sample of patients with IPF and sarcoidosis, obstructive sleep apnea is common at least in a mild degree of severity. The SF-36 questionnaire may be a useful tool for the evaluation of the quality of life in these patients.

Evaluation of five different questionnaires for assessing sleep apnea syndrome in a sleep clinic.

BACKGROUND: Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a major cause of morbidity and mortality. Different clinical models and questionnaires have been used to evaluate patients with the highest OSAHS probability. OBJECTIVES: To evaluate the clinical utility of five different questionnaires--STOP, STOPBang (SB), Berlin Questionnaire (BQ), Epworth Sleepiness Scale (ESS), and 4-Variable Screening Tool (4-V) - in a sleep clinic in order to identify patients at risk for OSAHS and to assess the best possible combination of these tools. METHODS: 1853 (74.4% males) patients (mean age 52±14 years; mean body mass index 32.8±7 kg/m2) visiting a sleep clinic were studied retrospectively. RESULTS: SB had the highest sensitivity (97.6%), the largest area under the receiver operating characteristics curve (AUC) (0.73; 95% CI, 0.7-0.76) and best OR (5.9; 95% CI, 3.6-9.5), but the lowest specificity (12.7%) for AHI > or =15. The 4-V > or = 14 had the highest specificity (74.4%) followed by ESS (67%). BQ had good sensitivity (87%), worse specificity (33%) than 4-V and ESS but better than STOP (13%) and SB (12.7%). The combination of questionnaires did not improve their predictive value. CONCLUSIONS: SB had the highest sensitivity, OR, and AUC, but rather low specificity, and 4-V the highest specificity. The combination of different questionnaires did not improve their predictive value.

Targeted versus chrono-targeted chemotherapy for inhaled chemotherapy in non-small cell lung cancer.

Lung cancer long term survival still remains poor and early detection is still the best methodology to treatment. Therefore several novel approaches have been investigated for anticancer drug administration. Inhaled therapies for lung diseases are used since the ancient times. Inhaled anticancer treatment administration was firstly investigated almost 30 years ago. Since then the inclusion and exclusion criteria have been investigated in correlation with the safety and efficacy of cisplatin, 5-fluoracil, carboplatin, paclitaxel, docetaxel, 9-nitro camptothecine, gemcitabine, cetuximab, granulocyte-colony stimulating factor, interleukins and recently with bevasizumab. Along with the anticancer drug formulations administered, other aspects of this local treatment have been also investigated to improve the efficiency and safety, such as; proper nebulization system, drug formulation delivery system, setting of administration, aerosol protection measures, inhalation techniques and safety issues follow up. During the last years with the use of actigraphy wrist watches, an extended investigation of the circadian rhythm of animals and humans has been performed and new insights are included in lung cancer chemotherapy administration. The "personalized" therapy administration should not be considered only as a molecular pathway inhibition, but also as a chrono-targeted anticancer treatment.