Theophylline for the management of respiratory disorders in adults in the 21st century: A scoping review from the American College of Clinical Pharmacy Pulmonary Practice and Research Network.

Theophylline is an oral methylxanthine bronchodilator recommended as alternate therapy for the treatment of asthma and chronic obstructive pulmonary disease (COPD). However, it is not generally recommended for the treatment of other respiratory disorders such as obstructive sleep apnea (OSA) or hypoxia. Most clinical practice guidelines rely on evidence published prior to the year 2000 to make these recommendations. This scoping review aimed to gather and characterize evidence describing theophylline for the management of respiratory disorders in adults between January 1, 2000 and December 31, 2020. Databases searched included Ovid MEDLINE, Embase, CINAHL Complete, Scopus, and International Pharmaceutical Abstracts. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Studies were included if they were published in English, theophylline was used for any respiratory disorder, and the study outcomes were disease- or patient-oriented. After removal of duplicates, 841 studies were screened and 55 studies were included. Results aligned with current clinical guideline recommendations relegating theophylline as an alternative therapy for the treatment of respiratory disorders, in favor of inhaled corticosteroids and inhaled bronchodilators. This scoping review identified the need for future research including: theophylline versus other medications deemed alternative therapies for asthma and COPD, meta-analyses of low-dose theophylline, and studies evaluating evidence-based patient-oriented outcomes for OSA, hypoxia, ventilator-induced diaphragmatic dysfunction, and spinal cord injury-related pulmonary function.

Clinical efficacy and metabolomics study of Wendan Decoction in the treatment of phlegm-dampness obstructive sleep apnea-hypopnea syndrome with type 2 diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: Wendan Decoction (WDD) is one of the classic traditional Chinese prescriptions that has been used in the treatment of type 2 diabetes mellitus (T2DM), metabolic syndrome, obstructive sleep apnea-hypopnea syndrome (OSAHS) and so on. The therapeutic effects and mechanism of WDD remain to be explored, especially from the perspective of metabolomics, oxidative stress and inflammation. AIM OF THE STUDY: To investigate the therapeutic and metabolic regulatory effects and the underlying mechanism of WDD in OSAHS with T2DM patients. MATERIALS AND METHODS: All included patients were from Rudong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu Province, China. Both groups received lifestyle interventions; at the same time, all of them were administered metformin (1500 mg/day) and dapagliflozin (10 mg/day), and the treatment group was administered WDD orally. All patients were treated for two months. Before and after treatment, the changes in clinical symptoms and signs of the two groups of patients were evaluated, and the detection indicators such as body mass index (BMI), apnea-hypopnea index (AHI), lowest arterial oxygen saturation (LSaO2), Epworth sleepiness scale (ESS), percentage of total sleep time with oxygen saturation <90% (TST90), fasting plasma glucose (FPG), 2-h post-load glucose(2h-PG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)，hemoglobin A1c (HbA1c), blood lipid levels, as well as the adverse reactions and compliance of the patients were observed and detection of serum metabolites in patients to screen out specific biomarkers. The serum metabolic profile of WDD in OSAHS with T2DM patients was explored using ultra-high-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q Orbitrap HRMS). RESULTS: After treatment with WDD for 8 weeks, biochemical indicators, including BMI, FPG, 2h-PG, blood lipid, FINS, HbA1c, AHI, ESS, LSaO2, TST90, and HOMA-IR, were significantly improved. Serum metabolomic analysis showed that metabolites were differentially expressed before and after WDD-treated patients. Metabolomics results revealed that WDD regulated the biomarkers, such as DL-arginine, guaiacol sulfate, azelaic acid, phloroglucinol, uracil, L-tyrosine, cascarillin, Cortisol and L-alpha-lysophosphatidylcholine. Pathway enrichment analysis showed that the metabolites were associated with oxidative stress and inflammation. CONCLUSION: The study based on clinical research and metabolomics indicated that WDD can improve OSAHS with T2DM through multiple targets and pathways, and it may be a useful alternative therapy for the treatment of OSAHS with T2DM patients.

Continuous positive airway pressure as an accurate marker for non-24-hour sleep-wake rhythm disorder.

Non-24-h sleep-wake rhythm disorder is quite rare in sighted patients and frequently associated with psychiatric disorders. We report the case of a 46-year-old man with autism spectrum disorder (ASD) and agoraphobia who had been referred for a suspicion of obstructive sleep apnea syndrome (OSAS). Polysomnography and arterial blood gas confirmed moderate OSAS associated with hypoventilation. Continuous positive airway pressure (CPAP) was started on fixed mode with excellent results. At follow-up, his CPAP report data revealed an irregular sleep-wake rhythm with a progressive offset of sleep schedule and wake time delayed from 1 h from day to day. Melatonin (or agonist) is efficacious and safe for long-term treatment in ASD and circadian rhythm sleep-wake disorder (CRSWD) with light therapy and wakefulness promoting medication. This case underlines the importance to sensitise psychiatrists to sleep and CRSWD, and also that CPAP data offer a possible objective alternative to sleep diary.

Randomised, controlled crossover trial of intermittent and continuous transcutaneous electrical stimulation of the genioglossus muscle for obstructive sleep apnoea.

PURPOSE: Continuous transcutaneous electrical stimulation (CTES) of the genioglossus muscle may benefit patients with obstructive sleep apnoea (OSA). However, the therapeutic value of intermittent transcutaneous electrical stimulation (ITES) for OSA is unclear. METHODS: This was a randomised, controlled, crossover study to compare the effects of ITES and CTES of the genioglossus muscle. Over three single-night sessions, participants were alternately subjected to three genioglossus stimulation modalities during sleep (sham, CTES and ITES). The apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) were used for OSA diagnosis and to evaluate efficacy. A responder was defined as an individual with a ≥50% reduction in AHI together with <10 AHI events per hour and/or an ODI reduction of ≥25% between sham stimulation and electrical stimulation nights. RESULTS: Fifteen men with OSA completed the study. Compared with sham, the median AHI with ITES decreased by 13.3 events/hour (95% CI 3.1 to 23.5, p=0.030) and by 7.3 events/hour (95% CI -3.9 to 18.5, p=0.825) with CTES. The median ODI was reduced by 9.25 events/hour (95% CI 0.5 to 18.0) with ITES and 3.3 events/hour (95% CI -5.6 to 12.2) with CTES; however, there was no significant difference between groups. Furthermore, ITES outperformed CTES with respect to longest apnoea duration (median (95% CI), 9.5 (0.0 to 19.0), p=0.011)) and the highest sleep efficiency (12.2 (2.7 to 21.7), p=0.009). Of the 15 participants, 8 responded to ITES and 3 responded to CTES (p=0.058), of whom all eight cases and two out of three cases had ODIs <5 events/hour, respectively. All participants tolerated ITES well. CONCLUSIONS: ITES improved upper airway obstruction in patients with OSA, suggesting that further prospective validation of the intermittent approach is warranted. TRIAL REGISTRATION NUMBER: ChiCTR2100050138.

Transcutaneous electrical stimulation in obstructive sleep apnoea: current developments and concepts of the TESLA-home programme.

PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is a highly prevalent condition affecting about 1 billion people worldwide. The first line therapy for most patients with OSA is continuous positive airway pressure (CPAP) therapy. However, there are significant limitations with long-term adherence to CPAP therapy, which may be as low as 30-60%. RECENT FINDING: Electrical stimulation of the hypoglossal nerve has been studied in recent years. It achieves upper airway patency by causing a contraction of the genioglossus muscle, the strongest dilator of the upper airway, and by maintaining its neuromuscular tone in the asleep patient with OSA. Electrical stimulation can be delivered invasively, hypoglossal nerve stimulation (HNS), and noninvasively, transcutaneous electrical stimulation in OSA (TESLA). However, randomised controlled trials, the STAR and the TESLA trial, have provided promising results on efficacy and safety of the methods. SUMMARY: Patient and public involvement underlines the interest in TESLA and HNS and highlights the need to provide non-CPAP therapeutic options to those who may find it difficult to cope with first line therapies. The relatively low costs and the favourable safety profile of the TESLA approach provide the chance to offer this treatment to patients with OSA following further development of the evidence.

Effects of respiratory training on obstructive sleep apnea: systematic review and meta-analysis.

PURPOSE: This systematic review sought to answer the following focused question: "What are the effects of respiratory training devices on obstructive sleep apnea (OSA) outcomes in adults?" METHODS : The acronym "PICOS" was used to determine eligibility criteria, which consists of (P population) = adults with mild to moderate OSA, (I intervention) = spirometry devices or breathing exercises, (C comparison) = compared to no breathing exercises in adults (> 18 years) with mild to moderate OSA, (O outcomes) = improved sleep quality (sleep quality indexes) and improved apnea-hypopnea indexes (AHI), (S study types) = randomized, pseudo-randomized, and non-randomized clinical trials. The search was performed in the following databases: PubMed/Medline, LILACS, Scopus, Web of Science, Scopus, and Cochrane Library, in addition to gray literature through Google Scholar, Proquest, and Open Grey. The risk of bias was assessed using the Cochrane Collaboration tool. The certainty of the evidence was assessed using the GRADE tool. Meta-analyses of random effects were performed for the outcomes of interest. RESULTS: A total of 1171 references were found. Applying the eligibility criteria, six studies were included in qualitative synthesis. Expiratory exercises showed a decrease in the apnea-hypopnea index (AHI) when compared to baseline (MD = - 8.4; 95% CI = - 12.4 to - 4.4; I2 = 19%). There was a decrease in values compared to baseline (MD = - 4.4; 95% CI = - 8.2 to - 0.6; I2 = 0%) for the Epworth Sleepiness Scale (ESS), when considering the inspiratory exercises. Both groups of breathing exercises showed a significant decrease in the mean index assessed by the Pittsburgh Sleep Quality Index (PSQI). CONCLUSION: Results of this meta-analysis suggests that breathing exercises lead to a measurable improvement in AHI for patients with mild to moderate OSA, as well as an improvement in sleep quality and daytime sleepiness. SYSTEMATIC REVIEW REGISTRATION: CRD42020148513 (PROSPERO).

Efficacy and safety of Chinese medicine for obstructive sleep apnea: A protocol for systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is significant public concern. Clinical practice indicates that Chinese medicine has certain therapeutic advantages, while there is a lack of evidence-based medicine support. The aim of this study is to synthesize related data to explore efficacy and safety of Chinese medicine for OSA. METHODS: Data in PubMed, Embase, Web of Science, CNKI, WanFang, VIP databases were comprehensively searched. All the randomized controlled trials (RCTs) in OSA children were identified, in which the effects of Chinese medicine on a range of outcomes were compared. The search had a deadline of January 1, 2020. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literature. RESULTS: The efficacy and safety of Chinese medicine for OSA were evaluated in terms of apnea hypopnea index (AHI, the average and lowest blood oxygen, the Epworth Sleep Scale [ESS], and adverse effects). CONCLUSIONS: This study provides reliable evidence-based support for the clinical application of Chinese medicine for OSA. PROSPERO REGISTRATION NUMBER: CRD42020154864.

The role of antioxidant vitamins and selenium in patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is a disorder characterized by recurrent episodes of obstruction of the upper respiratory tract during sleep often accompanied by oxygen desaturations. Antioxidant defense mechanisms are important to prevent OSA-associated diseases and decrease mortality. We aimed to determine the levels of selenium and vitamins A, C, and E in patients with OSA but without any comorbidities and compare the results with a control group, theorizing that the findings may be helpful to understand the antioxidant mechanisms in the pathogenesis of OSA and associated diseases. METHODS: We designed a case-control study with 146 subjects. Subjects were categorized into four groups by apnea-hypopnea index (AHI) scores: control (n = 32; AHI < 5), mild OSA (n = 32; 5 ≤ AHI < 15), moderate OSA (n = 34; 15 ≤ AHI < 30), and severe OSA (n = 48; AHI ≥ 30) groups. Serum levels of selenium were measured by atomic absorption spectrometer. Vitamin A, C, and E levels were measured by high-performance liquid chromatography and ultraviolet (HPLC-UV) detector. RESULTS: After adjusting for age, BMI, and gender, serum selenium and vitamin A levels were found to be higher in patients with OSA compared with controls (ANCOVA, p < 0.008, and p = 0.014 respectively), and levels of these markers increased with the severity of the disease. AHI was positively correlated with selenium (r = 0.289; p < 0.001), and vitamin A levels (r = 0.276; p < 0.001). CONCLUSION: These results demonstrated that antioxidant response with increased vitamin A, and selenium concentrations, may be important defense mechanisms in patients with OSA patients who do not have other comorbidities. Antioxidant nutrients or supplements may be implemented as a complementary treatment of OSA to support antioxidant defense.

Chinese Herbs Medicine Huatan Huoxue Prescription for obstructive sleep apnea hypopnea syndrome as complementary therapy: A protocol for a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis is to assess effectiveness and safety of Chinese Herbs Medicine Huatan Huoxue Prescription (HTHXP) as complementary therapy in treating bronchiectasis. METHODS: The following databases will be searched: Embase, Cochrane, PubMed, China National Knowledge Infrastructure, Wan Fang, and VIP database from their inception to April 1, 2020. We performed and completed meta-analysis and methodologic evaluation by Review Manager 5.3.3 and statas 12.0 software. Study selection, data extraction, quality assessment, and assessment of risk bias will be performed by 2 reviewers independently. Odds ratios and correlative 95% confidence intervals will be calculated to present the association between the HTHXP and western medicine treatment using Review Manager version 5.3 when there is sufficient available data. RESULTS: The results will be disseminated through a peer-reviewed journal publication. CONCLUSION: These systematic review findings will summarize up-to-date evidence for that HTHXP is more effective and safe as adjunctive treatment for patients with bronchiectasis. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is a systematic review based on published articles. PROSPERO REGISTRATION NUMBER: INPLASY202050079.

Beneficial effects of estrogens in obstructive sleep apnea hypopnea syndrome.

Epidemiological studies showing the higher frequency of obstructive sleep apnea hypopnea syndrome in men, polycystic ovary syndrome (PCOS), and in post-menopausal women suggest the beneficial role of estrogen. These findings are well supported by the pre-clinical studies (ten research studies described in this review) showing that estrogen and phytoestrogens attenuate the deleterious effects of chronic intermittent hypoxia (obstructive apnea in animals) on the genioglossal muscles and on other organs (co-morbidities) in ovariectomized rodents. Moreover, clinical studies (four research studies described in this review) have also shown the beneficial role of estrogen therapy on the parameters of obstructive apnea in post-menopausal women. The beneficial effects of estrogen and phytoestrogens on obstructive sleep apnea and its co morbidities have been attributed to increase in thioredoxin, Nrf-2, activation of p38 MAP kinases, inhibition of vagal C fibers, and attenuation of HIF-1α. It is possible that estrogen-mediated activation of p38 MAP kinase may inhibit HIF-1α to attenuate lung inflammation, which may inhibit the activation of vagal C fibers to attenuate bronchoconstriction and prevent obstruction during sleep. Moreover, estrogen-mediated increase in thioredoxin and Nrf-2 may also contribute in increasing antioxidant defense and attenuating inflammation.

[Effects of rhodiola rosea on oxidative stress and negative emotional states in patients with obstructive sleep apnea].

Objective:The aim of this study is to investigate the effects of rhodiola rosea on oxidative stress, anxiety and depression in patients with OSA. Method:Ninety patients with moderate and severe OSA patients with negative emotions diagnosed by PSG, self-rating depression scale （SDS） and self-rating anxiety scale （SAS） were selected from the respiratory department of our hospital from February 2015 to February 2018. According to the random number table method, the patients were randomly divided into non-invasive ventilator group, rhodiola rosea+non-invasive ventilator group and rhodiola rosea group, with 30 cases in each group. Patients in the non-invasive ventilator group were treated with continuous positive airway pressure （CPAP） for 3 months, and those in the rhodiola rosea+non-invasive ventilator group were treated with oral rhodiola capsules for 3 months on the basis of CPAP, and those in the rhodiola rosea treatment group were treated with pure oral rhodiola capsules for 3 months. The changes of SDS and SAS before and after the three groups were compared, and the changes of serum SOD and MDA were detected by immunoenzyme-linked adsorption for comparative analysis. Result:There were no significant differences in SDS and SAS scores between the three groups （P>0.05）. SDS and SAS scores of patients in the rhodiola rosea+non-invasive ventilator group decreased after treatment （P<0.05） compared with those in the non-invasive ventilator group. SDS and SAS scores of patients in the rhodiola treatment group increased after treatment （P<0.05）. Compared with those in the rhodiola treatment group, SDS and SAS scores of patients in the rhodiola+non-invasive breathing group decreased after treatment （P<0.05）. Three group patients were no significant difference in serum SOD and malondialdehyde （MDA） before treatment （P>0.05）. Compared with before treatment, serum SOD level were all increased and MDA level were all decreased in the three groups after treatment （P<0.05）. Compared with noninvasive breathing unit after treatment, rhodiola+noninvasive breathing unit after treatment in patients with elevated levels of serum SOD, MDA level decreased （P<0.05）, and for the treatment group after treatment in patients with serum SOD levels drop, the MDA levels （P<0.05）, and the after rhodiola rosea treatment group compared, rhodiola+noninvasive breathing unit after treatment in patients with elevated levels of serum SOD, MDA level decreased （P<0.05）. Conclusion:Rhodiola may improve the negative emotions such as anxiety and depression by inhibiting oxygen free radicals and lipid peroxidation in patients with OSA.

Influence of the TLR4-mediated p38MAPK signaling pathway on chronic intermittent hypoxic-induced rat's oxidative stress and inflammatory cytokines in rats.

OBJECTIVE: To investigate the influence of the TOLL-like receptor 4 (TLR4)-mediated p38MAPK signaling pathway on chronic intermittent hypoxic (CIH)-induced oxidative stress and inflammatory cytokines in rats. MATERIALS AND METHODS: A total of 120 healthy male Sprague Dawley (SD) rats, aged between 8-10 weeks, were randomly divided into 9 groups (normoxia control group, CIH 2 weeks group, CIH 4 weeks group, CIH 6 weeks group, CIH 8 weeks group, CIH 6 weeks + p38MAPK receptor inhibit group, CIH 6 weeks + Tempol group, CIH 8 weeks + p38MAPK receptor inhibitor group and CIH 8 weeks + Tempol group). The expression of TLR4 and p38MAPK in the adipose tissue was evaluated, as well as the level of serum oxidative stress markers (SOD, TRx-1, MDA) and inflammatory cytokines (adiponectin, TNF-α, hsCRP and IL-6). RT-PCR and Western-blot were conducted to detect the expression of TLR4 and p38MAPK mRNA. RESULTS: With increased hypoxia, the levels of SOD and adiponectin in the serum of the CIH group decreased significantly, and the levels of TNF-α, hsCRP, IL-8 and IL-6 in serum increased significantly. After the intervention of antioxidant Tempol and p38MAPK inhibitor SB203580, SOD increased significantly but with significant MDA reduction. The levels of TNF-α, hsCRP, IL-8 and IL-6 in serum significantly decreased. The results of RT-PCR and Western-Blot indicated that the P-p38 and TLR4 proteins related to the MAPK pathway were expressed in rat adipose tissue. With the hypoxia intensity, expression of P-p38 decreased after initially increasing. The expression of TLR4 showed a continuously growing trend. After Tempol treatment, the expression of p38MAPK protein decreased, and the expression of TLR4 did not change significantly, indicating the inhibiting effect of Tempol on p38MAPK, without a significant inhibiting effect on TLR4. CONCLUSIONS: The TLR4-mediated p38MAPK signaling pathway was active in adipose tissue and the expression of the corresponding molecules increased as the duration of intermittent hypoxia increased. The expression of TLR4 and p38MAPK components regulated the level of oxidative stress and inflammatory cytokines; the application of p38MAPK inhibitors and antioxidant free radical scavengers improved the levels of oxidative stress and inflammatory cytokines.

Combination of Broccoli Sprout Extract and Zinc Provides Better Protection against Intermittent Hypoxia-Induced Cardiomyopathy Than Monotherapy in Mice.

Nuclear factor-E2-related factor 2 (Nrf2) and metallothionein have each been reported to protect against chronic intermittent hypoxia- (IH-) induced cardiomyopathy. Sulforaphane-rich broccoli sprout extract (BSE) and zinc can effectively induce Nrf2 and metallothionein, respectively, to protect against IH-induced cardiomyopathy via antioxidative stress. However, whether the cardiac protective effects of the combination of BSE and zinc can be synergistic or the same has not been evaluated. In this study, we treated 8-week-old C57BL/6J mice with BSE and/or zinc during exposure to IH for 8 weeks. Cardiac dysfunction, as determined by echocardiography, and pathological remodeling and abnormalities, including cardiac fibrosis, inflammation, and oxidative damage, examined by histopathology and western blotting, were clearly observed in IH mice but were not significant in IH mice treated with either BSE, zinc, or zinc/BSE. Furthermore, the effects of the combined treatment with BSE and zinc were always greater than those of single treatments. Nrf2 function and metallothionein expression in the heart increased to a greater extent using the combination of BSE and zinc than using BSE or zinc alone. These findings for the first time indicate that the dual activation of Nrf2 and metallothionein by combined treatment with BSE and zinc may be more effective than monotherapy at preventing the development of IH-induced cardiomyopathy.

Medical Cannabis and the Treatment of Obstructive Sleep Apnea: An American Academy of Sleep Medicine Position Statement.

ABSTRACT: The diagnosis and effective treatment of obstructive sleep apnea (OSA) in adults is an urgent health priority. Positive airway pressure (PAP) therapy remains the most effective treatment for OSA, although other treatment options continue to be explored. Limited evidence citing small pilot or proof of concept studies suggest that the synthetic medical cannabis extract dronabinol may improve respiratory stability and provide benefit to treat OSA. However, side effects such as somnolence related to treatment were reported in most patients, and the long-term effects on other sleep quality measures, tolerability, and safety are still unknown. Dronabinol is not approved by the United States Food and Drug Administration (FDA) for treatment of OSA, and medical cannabis and synthetic extracts other than dronabinol have not been studied in patients with OSA. The composition of cannabinoids within medical cannabis varies significantly and is not regulated. Synthetic medical cannabis may have differential effects, with variable efficacy and side effects in the treatment of OSA. Therefore, it is the position of the American Academy of Sleep Medicine (AASM) that medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA due to unreliable delivery methods and insufficient evidence of effectiveness, tolerability, and safety. OSA should be excluded from the list of chronic medical conditions for state medical cannabis programs, and patients with OSA should discuss their treatment options with a licensed medical provider at an accredited sleep facility. Further research is needed to understand the functionality of medical cannabis extracts before recommending them as a treatment for OSA.

The Effect of Montelukast on Mild Persistent OSA after Adenotonsillectomy in Children: A Preliminary Study.

This study sought to evaluate the treatment effect of montelukast in children with obstructive sleep apnea (OSA) after tonsillectomy and/or adenoidectomy (T&A). Fifty-eight children with persistent OSA after T&A were included and randomly divided into 2 groups: one group was administered montelukast for 12 weeks, and the other received no treatment. Clinical information, such as the apnea-hypopnea index (AHI) and nadir oxyhemoglobin saturation (nadir SpO2), was recorded. Symptoms of OSA were evaluated using the validated Pediatric Sleep Questionnaire (PSQ). After surgery, there was no difference in terms of AHI, nadir SpO2, and PSQ scores between 2 groups. After the 12-week course of montelukast administration, the treatment group had significant improvement in the AHI, nadir SpO2, and PSQ scores ( P < .001), while the no-treatment group had no change over time ( P > .05). In summary, montelukast as a complementary therapy can improve sleep disturbances in children with OSA after T&A.

Evaluation of oxidative stress markers in obstructive sleep apnea syndrome and additional antioxidant therapy: a review article.

PURPOSE: The hypoxia and reoxygenation cycles in obstructive sleep apnea syndrome (OSAS) cause a change in the oxidative balance, leading to the formation of reactive oxygen species capable of reacting with other organic molecules impairing their functions. This study aimed to determine the best markers of oxidative stress in OSAS and what better antioxidant agent to be used to treat the disease. METHODS: Searches were conducted in three different databases (PubMed, LILACS, SCIELO), using as descriptors the terms obstructive sleep apnea, oxidative stress, and antioxidant therapy. A total of 120 articles were found but only those considered of interest to the research were selected. Thus, 10 articles were included for further analysis regarding the biomarkers of oxidative stress in OSAS, and 6 articles to evaluate the antioxidant most often used for demonstration of efficacy. RESULTS: The thioredoxin, malondialdehyde, superoxide dysmutase, and reduced iron were the most commonly used biomarkers and showed a more consistent relationship between increased oxidative stress and OSAS. As antioxidant therapy, vitamin C and N-acetylcysteine (NAC) presented interesting results as a reduction of oxidative stress, which may become an alternative to the complementary treatment of OSAS. CONCLUSIONS: This review's findings agree mostly to measure that the markers of oxidative stress in OSAS may be a contributing aspect to assessment and monitoring of patient, and the antioxidant therapy appears to be beneficial in the treatment of OSAS.

A systematic review of the pharmacological approaches against snoring: can we count on the chickens that have hatched?

BACKGROUND: Snoring is the sound produced by the vibration of the soft tissues caused by the air passing through a narrow upper airway during sleep. It is usually associated with the conditions that increase upper airway resistance, but can occur in their absence too (primary snoring). Considering its sheer prevalence, the associated comorbidities, like carotid atherosclerosis and the social disorder that it can represent, treatment for snoring must be considered even in the absence of any other medical condition. Treatment options include conservative approaches like weight reduction, smoking and alcohol cessation, sleep positioning, mechanical nasal dilators, and continuous positive airway pressure (CPAP) to more radical approaches like surgery. Till date, we have no drugs for treating the primary pathology of snoring. METHODS: A systematic literature search was carried out in PUBMED and EMBASE, and we found only nine randomized control trial's and one interventional study focusing on the pharmacotherapy of snoring per se, even as the literature is replete with studies evaluating drug therapy for obstructive sleep apnea. RESULT: Drugs evaluated include protriptyline, pseudoephedrine and domperidone, mometasone, nasal surfactant, Botulinum toxin type A, and some homeopathic and oil-based nasal sprays. The selected studies showed no strength in data and had a great methodological heterogeneity, so it is impossible to compare the analyzed studies. DISCUSSION: Even though there are no consistent data to support pharmacologic treatment for primary snoring, through the critical analysis of these studies, we have discussed about the future directions for clinical trials in this area to arrive at a clinically meaningful decision.

Antiinflammatory therapy outcomes for mild OSA in children.

BACKGROUND: OSA is highly prevalent in children and usually initially treated by adenotonsillectomy. Nonsurgical alternatives for mild OSA primarily consisting of antiinflammatory approaches have emerged, but their efficacy has not been extensively assessed. METHODS: A retrospective review of clinically and polysomnographically diagnosed patients with OSA treated between 2007 and 2012 was performed to identify otherwise healthy children ages 2 to 14 years who fulfilled the criteria for mild OSA and who were treated with a combination of intranasal corticosteroid and oral montelukast (OM) for 12 weeks (ICS + OM). A subset of children continued OM treatment for 6 to 12 months. RESULTS: A total of 3,071 children were diagnosed with OSA, of whom 836 fulfilled mild OSA criteria and 752 received ICS + OM. Overall, beneficial effects occurred in > 80% of the children, with nonadherence being documented in 61 children and adenotonsillectomy being ultimately performed in 12.3%. Follow-up polysomnography in a subset of 445 patients showed normalization of sleep findings in 62%, while 17.1% showed either no improvement or worsening of their OSA. Among the latter, older children (aged > 7 years; OR, 2.3; 95% CI, 1.43-4.13; P < .001) and obese children (BMI z-score > 1.65; OR: 6.3; 95% CI, 4.23-11.18; P < .000001) were significantly more likely to be nonresponders. CONCLUSIONS: A combination of ICS + OM as initial treatment of mild OSA appears to provide an effective alternative to adenotonsillectomy, particularly in younger and nonobese children. These results support implementation of multicenter randomized trials to more definitively establish the role of ICS + OM treatment in pediatric OSA.