Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer–BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38–54) years and body mass index of 24·84 (22.6–28.51) kg/m² were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6–7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = −0.178, p < 0.001), poor sleep quality (r = −0.094, p < 0.05), insomnia (r = −0.098, p < 0.05), and nap frequency per week (r = −0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.     

CRP evolution pattern in CPAP-treated obstructive sleep apnea patients. Does gender play a role?

Background??aim

C-reactive protein (CRP) is directly implicated in atherogenesis and associated cardiovascular morbidity in patients with obstructive sleep apnea (OSA). Effective continuous positive airway pressure (CPAP) treatment has been shown to gradually decrease CRP levels and thus consequently improve disease-related cardiovascular morbidity. However, the influence of gender on the CRP evolution pattern has never been assessed before. The aim of our study was to investigate possible gender differences in CRP evolution in OSA patients 3 and 6?months after the start of effective CPAP treatment.

Methods

The study population consisted of 436 patients (252 males/184 females) with newly diagnosed moderate to severe OSA and good CPAP compliance assessed by a thorough follow up. High-sensitivity C-reactive protein (hs-CRP) was assessed before CPAP initiation and at the third and sixth month of the follow-up period.

Results

C-reactive protein values showed a statistically significant decrease at the third and sixth month of CPAP therapy [initial values 0.79?±?0.65?mg/dL versus 0.70?±?0.52?mg/dL (p?p?p?p?>?0.05). After 6?months?? treatment, CRP decreased significantly in both genders (males from 0.74?±?0.53?mg/dL to 0.28?±?0.32?mg/dL, p?p?Conclusion Our results suggest a delay in the normalization of CRP levels in females despite effective CPAP treatment. A time period of at least 6?months appeared to be required in women in order to reduce CRP levels and consequent cardiovascular risk. In contrast, CPAP??s protective role in males is achieved at an earlier time point. Gender-related hormonal and genetic factors may influence the above CRP evolution pattern.     

Pharmacological approaches to smoking cessation

Smoking, the most prominent nongenetic factor contributing to mortality, remains the major public health problem throughout the world. There are nearly 1.1 billion users of nicotine and tobacco products worldwide while approximately one third to half of them will die from smoking-related disease. The habit of smoking is mainly propelled by nicotine, a strongly addictive substance, to which the vast majority of smokers fall victim. Except for the general and specific support and counseling strategies there are now effective treatments for nicotine addiction. Two types of pharmacological therapies have been approved and are now licensed for smoking cessation. The first therapy consists of nicotine replacement, substituting the nicotine from cigarettes with safer nicotine formulations. The second therapy is bupropion, an antidepressant of the aminoketone class, which has been demonstrated to be effective in smoking cessation. However, although some cigarette smokers are able to quit, many are not, and standard medications to assist smoking cessation are ineffective. Several agents used for other indications (e.g. neurological diseases, depression, alcoholism) might be used to treat this subgroup. In conclusion, new more effective drugs are needed in order to fight the panepidemic of smoking globally.     

Tiotropium Respimat Soft Mist Inhaler versus HandiHaler to improve sleeping oxygen saturation and sleep quality in COPD

Purpose

Patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality as a result of various alterations in oxygenation parameters and sleep macro- and micro-architecture. There is a shortage of data to support the efficacy of long-acting inhaled anticholinergic agents in improving these adverse effects, which are known to have a negative impact on clinical outcomes. We aimed to compare the tiotropium Respimat Soft Mist Inhaler and the HandiHaler in terms of their effects on sleeping oxygen saturation (SaO₂) and sleep quality in patients with COPD.

Methods

In a randomized, open-label, parallel-group trial involving 200 patients with mild to moderate COPD (resting arterial oxygen tension >60 mmHg while awake), we compared the effects of 6 months’ treatment with the two devices on sleeping SaO₂ and sleep quality. Overnight polysomnography and pulmonary function testing were performed at baseline and after 6 months’ treatment.

Results

A total of 188 patients completed the trial. Both groups showed significant improvement in minimum sleep SaO₂ and time of sleep spent with SaO₂ below 90 (TST90) compared to baseline. The patients using the Respimat had significantly better TST90 than did those using the HandiHaler. Sleep disturbance was highly variable in these patients, but the sleep stage durations were significantly better in the Respimat group.

Conclusions

Sleeping SaO₂ can be improved by tiotropium delivered using either the HandiHaler device or the Respimat Soft Mist Inhaler. However, the patients who used the Respimat device had significantly better TST90 and sleep architecture parameters.

     

Unique sleep‐stage transitions determined by obstructive sleep apnea severity,age and gender

In obstructive sleep apnea, patients’ sleep is fragmented leading to excessive daytime sleepiness and co‐morbidities like arterial hypertension. However, traditional metrics are not always directly correlated with daytime sleepiness, and the association between traditional sleep quality metrics like sleep duration and arterial hypertension is still ambiguous. In a development cohort, we analysed hypnograms from mild (n = 209), moderate (n = 222) and severe (n = 272) obstructive sleep apnea patients as well as healthy controls (n = 105) from the European Sleep Apnea Database. We assessed sleep by the analysis of two‐step transitions depending on obstructive sleep apnea severity and anthropometric factors. Two‐step transition patterns were examined for an association to arterial hypertension or daytime sleepiness. We also tested cumulative distributions of wake as well as sleep‐states for power‐laws (exponent α) and exponential distributions (decay time τ) in dependency on obstructive sleep apnea severity and potential confounders. Independent of obstructive sleep apnea severity and potential confounders, wake‐state durations followed a power‐law distribution, while sleep‐state durations were characterized by an exponential distribution. Sleep‐stage transitions are influenced by obstructive sleep apnea severity, age and gender. N2 → N3 → wake transitions were associated with high diastolic blood pressure. We observed higher frequencies of alternating (symmetric) patterns (e.g. N2 → N1 → N2, N2 → wake → N2) in sleepy patients both in the development cohort and in a validation cohort (n = 425). In conclusion, effects of obstructive sleep apnea severity and potential confounders on sleep architecture are small, but transition patterns still link sleep fragmentation directly to obstructive sleep apnea‐related clinical outcomes like arterial hypertension and daytime sleepiness.     

Obstructive sleep apnea syndrome and cardiovascular disease: The influence of C-reactive protein

Obstructive sleep apnea syndrome(OSAS) is a common medical condition, associated with atherosclerosis and cardiovascular disease(CVD). The underlying pathophysiologic mechanisms of this association have not been completely understood and may be multifactorial in origin. A number of studies suggest that inflammatory processes have emerged critical in the pathogenesis of CVD in OSAS. A range of circulating inflammatory molecules has been identified and measured, with a view to assess inflammation and predict vascular damage risk, such as plasma cytokines, adhesion molecules, and C-reactive protein(CRP). CRP is a relevant marker worthy of further study, because not only is elevated in patients with OSAS, but also is rapidly becoming a risk factor for cardiac disease. Furthermore, in selected OSAS patients, aggressive treatment of the disorder may lead to retarding or even improvement of CVD progression. However, still there is a debate on the true correlation between CRP and OSAS, as well as the clinical effect of any reduction after OSAS treatment. Further research is required to define those OSAS patients who will have a considerable reduction with treatment, as well as to understand the significance of the interaction between cardiovascular risk factor and CRP reduction in patients with OSAS.     

Carbonic anhydrase,obstructive sleep apnea and hypertension: Effects of intervention

Whole blood carbonic anhydrase activity (CAa) is increased in patients with obstructive sleep apnea (OSA). Our study investigated the influence of positive airway pressure (PAP) or CA inhibitor acetazolamide (ACT) therapy on CAa, OSA and blood pressure. Thirty‐three OSA patients (21 hypertensive, body mass index (BMI) 37 ± 7 kg/m² and apnea–hypopnea index (AHI) of 47 ± 31 events/hr) were followed‐up after PAP treatment (compliance, 4.7 ± 1.5 hr/day; duration, median 6 [IQR 6,6] months) (Cohort A). A second OSA Cohort (B) contained nine hypertensive patients (BMI, 29 ± 4 kg/m²; AHI, 39 ± 20 events/hr) with 2‐week treatment of ACT, PAP or ACT + PAP in an open crossover study. CAa was assessed at baseline and at the end of each treatment period. In Cohort A, baseline CAa was higher in hypertensive, compared with normotensive, patients (1,033 ± 204 versus 861 ± 201 units, p = .028). PAP treatment reduced systolic/diastolic blood pressure but not CAa (?9 ± 11/?5 ± 7 mmHg and ?20 ± 289 units, p < .001, <.001 and .70). In Cohort B, blood pressure was reduced in both ACT‐treated groups (?10 ± 10/?5 ± 7 mmHg, p = .043 and .019; and ?5 ± 5/?13 ± 13 mmHg, p < .001 and .009). AHI was reduced in both groups: ACT only, ?17 ± 9 events/hr p = .001; and ACT + PAP, ?39 ± 19 events/hr, p < .001. PAP did not change CAa (p = .98) but activity tended to decrease after ACT with or without PAP (p = .081 and .056). CAa is elevated in hypertensive OSA patients. Long‐term PAP reduced blood pressure without affecting CAa. ACT reduced blood pressure and CAa. Increased CAa may constitute a physiological characteristic in OSA, contributing to comorbid hypertension.