Prevalence of occupational hypersensitivity pneumonitis: a systematic review and meta-analysis.

In this meta-analysis, we aimed to evaluate the prevalence of occupational hypersensitivity pneumonitis (OHP) among different occupations globally. Our search was conducted on MEDLINE via PubMed, Scopus, Web of Science, and Cochrane CENTRAL from inception to September 2023. Eligible studies were observational in nature and focused on several specific occupations. A total of 46 articles were included (n = 2,826,420 participants). The overall prevalence of OHP was found to be 4.2% (95% CI: 2.1% to 8.0%), but this varied significantly based on occupation and geographic location. Printers had the highest OHP prevalence at 57.14%, followed by tobacco workers (26.32%), and water-related workers (24.10%). South America showed the highest prevalence of 16.71%, compared to Asia (15.19%), and North America (8.52%). Significant variations in OHP prevalence by occupation and region were found, with the highest rates in printers and tobacco workers. Age and smoking were identified as contributing factors to the prevalence variability.

Mechanisms underlying the health benefits of intermittent hypoxia conditioning.

Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well-characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia-activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure.

Impact of Hypoxia-Hyperoxia Exposures on Cardiometabolic Risk Factors and TMAO Levels in Patients with Metabolic Syndrome.

Along with the known risk factors of cardiovascular diseases (CVDs) constituting metabolic syndrome (MS), the gut microbiome and some of its metabolites, in particular trimethylamine-N-oxide (TMAO), are actively discussed. A prolonged stay under natural hypoxic conditions significantly and multi-directionally changes the ratio of gut microbiome strains and their metabolites in feces and blood, which is the basis for using hypoxia preconditioning for targeted effects on potential risk factors of CVD. A prospective randomized study included 65 patients (32 females) with MS and optimal medical therapy. Thirty-three patients underwent a course of 15 intermittent hypoxic-hyperoxic exposures (IHHE group). The other 32 patients underwent sham procedures (placebo group). Before and after the IHHE course, patients underwent liver elastometry, biochemical blood tests, and blood and fecal sampling for TMAO analysis (tandem mass spectrometry). No significant dynamics of TMAO were detected in both the IHHE and sham groups. In the subgroup of IHHE patients with baseline TMAO values above the reference (TMAO ≥ 5 µmol/l), there was a significant reduction in TMAO plasma levels. But the degree of reduction in total cholesterol (TCh), low-density lipoprotein (LDL), and regression of liver steatosis index was more pronounced in patients with initially normal TMAO values. Despite significant interindividual variations, in the subgroup of IHHE patients with MS and high baseline TMAO values, there were more significant reductions in cardiometabolic and hepatic indicators of MS than in controls. More research is needed to objectify the prognostic role of TMAO and the possibilities of its correction using hypoxia adaptation techniques.

Is fighting against COVID-19 enough?

Tools of empirical epidemiology have been and are indispensable to focus political power on blocking the spreading of coronavirus disease 2019 (COVID-19) by stopping transmission. The present paper is a comment on E. Gibney's article 'Whose coronavirus strategy worked best?' (Nature 2020;581:15-6). The strategy for phase 2 should be more complex and interdisciplinary than described in the paper in Nature, especially in the period before a vaccine and specific treatments are available. The focus on reducing the mortality of COVID-19 will have side effects, including excess mortality from other causes. A part of this excess mortality will be based on the reduction of health-care offers as a consequence of the pandemic, and on structural limitations of the health-care system. A special challenge is to understand the relationship between death from and death with COVID-19, and therefore the relevance of severe acute respiratory syndrome coronavirus 2 infection in people with pre-existing burdens, for example coronary heart disease, cancer or older age. There is a need to extend the recently used tools to all available instruments, including physiological principles of prevention and promotion. The way to integrate global solidarity into the strategies of the different countries is critical not only for global health but also for the peace and long-term success for each individual country. The consequences of efforts against COVID-19 and the impact on reduced air pollution and climate change are also important to analyse from a global health perspective.

Whole-body repeated hyperthermia increases irisin and brain-derived neurotrophic factor: A randomized controlled trial.

CONTEXT: Hyperthermia is known to be beneficial to patients affected by various diseases. Irisin is a key regulators of fat metabolism known to be released as response to cold. Brain Derived Neurotrophic Factor (BDNF) is a marker of neuroplasticity usually increased as response to acute exposure to human body stressors. OBJECTIVE: Effect of a repeated hyperthermia exposure programme on changes in circulating irisin and serum BDNF in healthy humans. DESIGN: Setting, Participants: Randomized, single-blind, cross-over trial in healthy humans conducted at Sechenov University Physiology Laboratory from April 2019. The treatment period was 2 weeks (wash-out 3 weeks). Researchers analysing serum biomarkers and questionnaires data were blinded to participants allocation. Participants were 20 healthy male (age 21.5 ± 2.1 years). INTERVENTION: Hyperthermia exposure programme (WBPH) versus sham exposure (SHAM) to hyperthermia (10 sessions in two weeks). MAIN OUTCOME MEASURE: Changes in irisin and BDNF before and after short hyperthermia exposure. RESULTS: Twenty participants were analyzed. Irisin increased significantly in group WBPH only: 6.3 µg/ml (mean with SD = 1.6) compared to 5.4 µg/ml (SD = 1.7) in SHAM group; This value was also higher than baseline (5.0 mean with SD = 1.1) in WBPH. After 10 sessions mean change in BDNF was higher in WBPH group vs SHAM: BDNF was 28,263 (SD = 4213) pg/ml in WBPH group and 24,064 (SD = 5600) pg/ml in SHAM group. BDNF concentrations were significantly higher than baseline values in WBPH group only, 28,263 (SD 4213) vs 25,888 (SD 4316) pg/ml. CONCLUSION: In healthy young humans a 2-week, ten sessions programme consisting of repeated exposure to hyperthermia resulted in a significantly higher increase of circulating Irisin and BDNF.

Repeated hyperthermia exposure increases circulating Brain Derived Neurotrophic Factor levels which is associated with improved quality of life, and reduced anxiety: A randomized controlled trial.

CONTEXT: Hyperthermia is known to be beneficial to patients affected by various diseases. Brain Derived Neurotrophic Factor (BDNF) is a marker of neuroplasticity usually increased as response to acute exposure to human body stressors. Little is known about BDNF changes after repeated exposure to hyperthermia. OBJECTIVE: To investigate the effect of a repeated hyperthermia exposure programme (HTC) on serum BDNF in healthy humans. DESIGN, SETTING, PARTICIPANTS: Randomized, single-blind, controlled trial in healthy humans conducted at Sechenov University Physiology Laboratory between December 2016 and November 2018. The treatment period was 10 weeks. Researchers analysing serum BDNF and questionnaires data were blinded to participants allocation. PARTICIPANTS: Were 34 healthy male (age 20.2 ± 1.6 years). INTERVENTION: Repeated Hyperthermia exposure programme, HTC, versus Light Intermittent Exercise, LIE, programme as control (10 weeks). MAIN OUTCOME MEASURE: Change in BDNF from baseline to final visit three days after treatment completion. RESULTS: 25 participants were analyzed. One participant withdrew before signing the informed consent and 8 participants (n = 3 in HTC and n = 5 in LIE) could not undertake the first assessment and were excluded. Mean change in BDNF was higher in HTC group vs LIE after both time points (after 12 and after 24 sessions). After 24 sessions BDNF was 30170 (SD 5268) pg/ml in HTC group a value that was significantly higher than 24104 (SD 2876) pg/ml measured in LIE group. BDNF concentrations were significantly higher than baseline values in HTC group only, 30170 (SD 5268) vs 26710 (SD 5437) pg/ml. CONCLUSION: A 10-week programme consisting of repeated exposure to hyperthermia resulted in a significantly higher increase of circulating BDNF compared to a programme consisting of intermittent light intensity exercise.

Effects of intermittent hypoxia-hyperoxia on mobility and perceived health in geriatric patients performing a multimodal training intervention: a randomized controlled trial.

BACKGROUND: Additional benefits of passive exposures to intermittent hypoxia and hyperoxia on cognitive performance and functional exercise capacity have been demonstrated in geriatric patients who performed a multimodal training program. The main goal of the present study was to evaluate effects of adding intermittent hypoxic-hyperoxic training (IHHT) to a multimodal training intervention (MTI) on mobility and perceived health in old individuals at a Geriatric Day Hospital. METHODS: Thirty-four patients between 64 and 92 years participated in the double blind, randomized and controlled clinical trial. The elderly patients attended in a 5-7 weeks lasting MTI (strength, endurance, balance, reaction, flexibility, coordination, and cognitive exercises) and performed IHHT (breathing 10-14% oxygen for 4-7 min followed by 2-4 min 30-40% oxygen) in the Hypoxic Group (HG) or placebo treatment with ambient air in the Normoxic Group (NG) in parallel. Before and after all treatments, mobility was assessed by the Tinetti Mobility Test (TMT), the Timed-Up-and-Go Test (TUG) and Barthel-Index, while perceived health was assessed by one part of the EQ-5D Test, the EQ visual analogue scale (EQ VAS). RESULTS: After the MTI plus IHHT or normoxia sessions, results of the TMT, TUG, Barthel Index and EQ-VAS revealed no significant difference between HG and NG (+ 14.9% vs + 15.4%, p = 0.25; - 21% vs - 26.3%, p = 0.51; + 4.2% vs + 3.6%, p = 0.56; + 37.9% vs + 33.9%, p = 0.24;). CONCLUSIONS: IHHT added to MTI did not elicit additional improvements in perceived health and mobility compared to MTI alone.

Brain-Derived neurotrophic factor and inflammatory biomarkers are unaffected by acute and chronic intermittent hypoxic-hyperoxic exposure in geriatric patients: a randomized controlled trial.

BACKGROUND: Animal and human studies have shown that exposure to hypoxia can increase brain-derived neurotrophic factor (BDNF) protein transcription and reduce systematic inflammatory cytokine response. Therefore, the aim of this study was to investigate the acute and chronic effects of intermittent hypoxic-hyperoxic exposure (IHHE) prior to aerobic exercise on BDNF, interleukin-6 (IL-6), and C-reactive protein (CRP) blood levels in geriatric patients. PATIENTS AND METHODS: Twenty-five geriatric patients (83.1 ± 5.0 yrs, 71.1 ± 10.0 kg, 1.8 ± 0.9 m) participated in a placebo-controlled, single-blinded trial and were randomly assigned to either an intervention (IG) or control group (CG) performing an aerobic cycling training (17 sessions, 20 min·session-1, 3 sessions·week-1). Prior to aerobic cycling exercise, the IG was additionally exposed to IHHE for 30 min, whereas the CG received continuous normoxic air. Blood samples were taken immediately before (pre-exercise) and 10 min (post-exercise) after the first session as well as 48 h (post-training) after the last session to determine serum (BDNFS) and plasma BDNF (BDNFP), IL-6, and CRP levels. Intervention effects were analyzed using a 2 x 2 analysis of covariance with repeated measures. Results were interpreted based on effect sizes with a medium effect considered as meaningful (ηp2 ≥ 0.06, d ≥ 0.5). RESULTS: CRP was moderately higher (d = 0.51) in the CG compared to the IG at baseline. IHHE had no acute effect on BDNFS (ηp2 = 0.01), BDNFP (ηp2 < 0.01), BDNF serum/plasma-ratio (ηp2 < 0.01), IL-6 (ηp2 < 0.01), or CRP (ηp2 = 0.04). After the 6-week intervention, an interaction was found for BDNF serum/plasma-ratio (ηp2 = 0.06) but not for BDNFS (ηp2 = 0.04), BDNFP (ηp2 < 0.01), IL-6 (ηp2 < 0.01), or CRP (ηp2 < 0.01). BDNF serum/plasma-ratio increased from pre-exercise to post-training (d = 0.67) in the CG compared to the IG (d = 0.51). A main effect of time was found for BDNFP (ηp2 = 0.09) but not for BDNFS (ηp2 = 0.02). Within-group post-hoc analyses revealed a training-related reduction in BDNFP in the IG and CG by 46.1% (d = 0.73) and 24.7% (d = 0.57), respectively. CONCLUSION: The addition of 30 min IHHE prior to 20 min aerobic cycling seems not to be effective to increase BDNFS and BDNFP or to reduce IL-6 and CRP levels in geriatric patients after a 6-week intervention.The study was retrospectively registered at drks.de (DRKS-ID: DRKS00025130).

Breast Cancer-related Lymphedema: Recent Updates on Clinical Efficacy of Therapies and Bioengineering Approaches for a Personalized Therapy.

BACKGROUND: Post-mastectomy lymphedema is a chronic progressive disease characterized by a significant reduction in quality of life and a range of complications. AIM: To this date, no single treatment method provides pathological correction of the mechanisms associated with tissue reorganization observed in later-stage breast cancer-related lymphedema (BCRL). METHODS: To define a personalized approach to the management of patients with iatrogenic lymphedema, we performed a systematic review of literature without a comprehensive meta-analysis to outline existing molecular- genetic patterns, overview current treatment methods and their efficacy, and highlight the specific tissue-associated changes in BCRL conditions and other bio-engineering approaches to develop personalized therapy. RESULTS: Our results show that several tissue-specific and pathological molecular markers may be found, yet current research does not aim to define them. CONCLUSION: As such, currently, a strong foundation for further research into molecular-genetic changes in lymphedema tissue exists, and further research should focus on finding specific targets for personalized treatment through bio-engineering approaches.

Effects of Intermittent Hypoxia-Hyperoxia Exposure Prior to Aerobic Cycling Exercise on Physical and Cognitive Performance in Geriatric Patients-A Randomized Controlled Trial.

Background: It was recently shown that intermittent hypoxic-hyperoxic exposure (IHHE) applied prior to a multimodal training program promoted additional improvements in cognitive and physical performance in geriatric patients compared to physical training only. However, there is a gap in the literature to which extent the addition of IHHE can enhance the effects of an aerobic training. Therefore, the aim of this study was to investigate the efficacy of IHHE applied prior to aerobic cycling exercise on cognitive and physical performance in geriatric patients. Methods: In a randomized, two-armed, controlled, and single-blinded trial, 25 geriatric patients (77-94 years) were assigned to two groups: intervention group (IG) and sham control group (CG). Both groups completed 6 weeks of aerobic training using a motorized cycle ergometer, three times a week for 20 min per day. The IG was additionally exposed to intermittent hypoxic and hyperoxic periods for 30 min prior to exercise. The CG followed the similar procedure breathing sham hypoxia and hyperoxia (i.e., normoxia). Within 1 week before and after the interventions, cognitive performance was assessed with the Dementia-Detection Test (DemTect) and the Clock Drawing Test (CDT), while physical performance was measured using the Timed "Up and Go" Test (TUG) and the Short-Physical-Performance-Battery (SPPB). Results: No interaction effect was found with respect to the DemTect (η p 2 = 0.02). An interaction effect with medium effect size (η p 2 = 0.08) was found for CDT performance with a higher change over time for IG (d = 0.57) compared to CG (d = 0.05). The ANCOVA with baseline-adjustment indicated between-group differences with a large and medium effect size at post-test for the TUG (η p 2 = 0.29) and SPPB (η p 2 = 0.06) performance, respectively, in favour of the IG. Within-group post-hoc analysis showed that the TUG performance was worsened in the CG (d = 0.65) and remained unchanged in the IG (d = 0.19). Furthermore, SPPB performance was increased (d = 0.58) in IG, but no relevant change over time was found for CG (d = 0.00). Conclusion: The current study suggests that an additional IHHE prior to aerobic cycling exercise seems to be more effective to increase global cognitive functions as well as physical performance and to preserve functional mobility in geriatric patients in comparison to aerobic exercise alone after a 6-week intervention period.

Influence of acute and chronic intermittent hypoxic-hyperoxic exposure prior to aerobic exercise on cardiovascular risk factors in geriatric patients-a randomized controlled trial.

Background: Intermittent hypoxic-hyperoxic exposure (IHHE) and aerobic training have been proposed as non-pharmacological interventions to reduce age-related risk factors. However, no study has yet examined the effects of IHHE before aerobic exercise on cardiovascular risk factors in the elderly. Therefore, the aim of this study was to investigate the acute and chronic effects of IHHE prior to aerobic cycling exercise on blood lipid and lipoprotein concentrations as well as blood pressure in geriatric patients. Methods: In a randomized, controlled, and single-blinded trial, thirty geriatric patients (72-94 years) were assigned to two groups: intervention (IG; n = 16) and sham control group (CG; n = 14). Both groups completed 6 weeks of aerobic cycling training, 3 times a week for 20 min per day. The IG and CG were additionally exposed to IHHE or sham IHHE (i.e., normoxia) for 30 min prior to aerobic cycling. Blood samples were taken on three occasions: immediately before the first, ∼10 min after the first, and immediately before the last session. Blood samples were analyzed for total (tCh), high-density (HDL-C), and low-density lipoprotein cholesterol (LDL-C), and triglyceride (Tgl) serum concentration. Resting systolic (SBP) and diastolic blood pressure (DBP) was assessed within 1 week before, during (i.e., at week two and four), and after the interventions. Results: The baseline-adjusted ANCOVA revealed a higher LDL-C concentration in the IG compared to the CG after the first intervention session (ηp 2 = 0.12). For tCh, HDL-C, Tgl, and tCh/HDL-C ratio there were no differences in acute changes between the IG and the CG (ηp 2 ≤ 0.01). With regard to the chronic effects on lipids and lipoproteins, data analysis indicated no differences between groups (ηp 2 ≤ 0.03). The repeated measures ANOVA revealed an interaction effect for SBP (ηp 2 = 0.06) but not for DBP (ηp 2 ≤ 0.01). Within-group post-hoc analysis for the IG indicated a reduction in SBP at post-test (d = 0.05). Conclusion: Applying IHHE prior to aerobic cycling seems to be effective to reduce SBP in geriatric patients after 6 weeks of training. The present study suggests that IHHE prior to aerobic cycling can influence the acute exercise-related responses in LDL-C concentration but did not induce chronic changes in basal lipid or lipoprotein concentrations.

Intermittent Hypoxic-Hyperoxic Exposures Effects in Patients with Metabolic Syndrome: Correction of Cardiovascular and Metabolic Profile.

The aim of this study was to evaluate efficacy and applicability of the "intermittent hypoxic-hyperoxic exposures at rest" (IHHE) protocol as an adjuvant method for metabolic syndrome (MS) cardiometabolic components. A prospective, single-center, randomized controlled clinical study was conducted on 65 patients with MS subject to optimal pharmacotherapy, who were randomly allocated to IHHE or control (CON) groups. The IHHE group completed a 3-week, 5 days/week program of IHHE, each treatment session lasting for 45 min. The CON group followed the same protocol, but was breathing room air through a facial mask instead. The data were collected 2 days before, and at day 2 after the 3-week intervention. As the primary endpoints, systolic (SBP) and diastolic (DBP) blood pressure at rest, as well as arterial stiffness and hepatic tissue elasticity parameters, were selected. After the trial, the IHHE group had a significant decrease in SBP and DBP (Cohen's d = 1.15 and 0.7, p < 0.001), which became significantly lower (p < 0.001) than in CON. We have failed to detect any pre-post IHHE changes in the arterial stiffness parameters (judging by the Cohen's d), but after the intervention, cardio-ankle vascular indexes (RCAVI and LCAVI) were significantly lowered in the IHHE group as compared with the CON. The IHHE group demonstrated a medium effect (0.68; 0.69 and 0.71 Cohen's d) in pre-post decrease of Total Cholesterol (p = 0.04), LDL (p = 0.03), and Liver Steatosis (p = 0.025). In addition, the IHHE group patients demonstrated a statistically significant decrease in pre-post differences (deltas) of RCAVI, LCAVI, all antropometric indices, NTproBNP, Liver Fibrosis, and Steatosis indices, TC, LDL, ALT, and AST in comparison with CON (p = 0.001). The pre-post shifts in SBP, DBP, and HR were significantly correlated with the reduction degree in arterial stiffness (ΔRCAVI, ΔLCAVI), liver fibrosis and steatosis severity (ΔLFibr, ΔLS), anthropometric parameters, liver enzymes, and lipid metabolism in the IHHE group only. Our results suggested that IHHE is a safe, well-tolerated intervention which could be an effective adjuvant therapy in treatment and secondary prevention of atherosclerosis, obesity, and other components of MS that improve the arterial stiffness lipid profile and liver functional state in MS patients.

Safety and Efficacy of Intermittent Hypoxia Conditioning as a New Rehabilitation/ Secondary Prevention Strategy for Patients with Cardiovascular Diseases: A Systematic Review and Meta-analysis.

BACKGROUND: Once used by mountaineers to facilitate rapid adaptations to altitude and by athletes to improve their aerobic capacity, exposure to hypoxia has been proven to affect various physiological, clinically relevant parameters. A form of conditioning known as Intermittent Hypoxia Conditioning (IHC) consists of repeated exposures to intermittent hypoxia, combined with normoxia and hyperoxia, which has been shown to have potential as a treatment to improve cardio- metabolic risks profile in cardiac patients but results across studies are inconsistent. This systematic review and meta-analysis aimed to evaluate the clinical effectiveness of IHC. METHODS: Four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) were searched (from inception to December 2019) to retrieve all studies focused on IHC in elderly patients with cardiovascular disease. A meta-analysis of functional, efficacy and safety outcomes in cardiac patients was completed to compare IHC to sham treatments. RESULTS: Fourteen studies with 320 patients in the Interval Hypoxia-normoxia Group (IHNG) or Interval Hypoxia-hyperoxia training Group (IHHG) and 111 patients in the control group were included in our meta-analysis. IHNT and IHHT were associated with significant reduction in heart rate, SBP, and DBP at rest after treatment [MD= -5.35 beat/min, 95% CI (-9.19 to -1.50), p=0.006], [MD= -13.72 mmHg, 95% CI (-18.31 to -9.132), p<0.001], and [MD= -7.882 mmHg, 95% CI (-13.163 to -2.601), p=0.003], respectively. There were no significant complications or serious adverse events related to IHNT/IHHT. CONCLUSION: The current evidence suggested that the use of the IHNT/IHHT program in elderly patients with CVDs can be safe and effective in terms of heart rate and elevated blood pressure. However, currently, there is no supporting evidence that IHNT/IHHT can significantly improve hematological parameters or lipid profile. Exercise tolerance increased at the end of the course of hypoxic conditioning within IHC group, but did not differ from controls. Further research is needed.

Redox Homeostasis in Humans Exposed to Intermittent Hypoxia-Normoxia and to Intermittent Hypoxia-Hyperoxia.

Aim: Exposure to hypoxia is known to increase oxidative stress and to impair antioxidant defenses in humans. The aim of the study was to measure oxidative stress and antioxidant capacity in healthy humans after being acutely exposed to both intermittent hypoxia-normoxia (IHN) and intermittent hypoxia-hyperoxia (IHH). Methods: Twenty-one healthy, young male participants were exposed to both IHN and IHH (fraction of inspired oxygen [FIO2] 0.11 for up to 7 minutes followed by 3-5 minutes of exposure to normoxia (room air) or hyperoxia, FIO2 0.3-0.35) in a crossover design study. In each participant, oxidative stress and antioxidant capacity were measured before and after each exposure in both experimental conditions. Results: After IHN, compared with baseline, neither oxidative stress (289.1 ± 63.2 vs. 262.2 ± 85.2 UCarr) nor antioxidant capacity (2376.1 ± 452.9 vs. 2525.0 ± 400.7 UCor) was significantly different. After IHH, neither oxidative stress (285.1 ± 94.2 vs. 277.5 ± 86.7 UCarr) nor antioxidant capacity (2653.6 ± 492.7 vs. 2568.4 ± 427.4 UCor) was significantly different compared with baseline. When the two studied exposure modalities were compared, there was no significant difference between groups with respect to both oxidative stress and antioxidant capacity. Conclusions: These data suggest that exposing healthy individuals to short-term IHN and IHH does not increase oxidative stress and it does not impair antioxidant defenses.

Intermittent Hypoxia-Hyperoxia Conditioning Improves Cardiorespiratory Fitness in Older Comorbid Cardiac Outpatients Without Hematological Changes: A Randomized Controlled Trial.

AIM: To compare a program based on intermittent hypoxia-hyperoxia training (IHHT) consisting of breathing hypoxic-hyperoxic gas mixtures while resting to a standard exercise-based rehabilitation program with respect to cardiorespiratory fitness (CRF) in older, comorbid cardiac outpatients. MATERIALS AND METHODS: Thirty-two cardiac patients with comorbidities were randomly allocated to IHHT and control (CTRL) groups. IHHT completed a 5-week program of exposure to hypoxia-hyperoxia while resting, CTRL completed an 8-week tailored exercise program, and participants in the CTRL were also exposed to sham hypoxia exposure. CRF and relevant hematological biomarkers were measured at baseline and after treatment in both groups. RESULTS: After intervention, CRF in the IHHT group was not significantly different (n = 15, 19.9 ± 6.1 mlO2 minutes-1 kg-1) compared with the CTRL group (n = 14, 20.6 ± 4.9 mlO2 minutes-1 kg-1). CRF in IHHT increased significantly from baseline (6.05 ± 1.6 mlO2 minutes-1 kg-1), while no difference was found in CTRL. Systolic and diastolic blood pressures were not significantly different between groups after treatment. Hemoglobin content was not significantly different between groups. Erythrocytes and reticulocytes did not change pre/post interventions in both experimental groups. CONCLUSIONS: IHHT is safe in patients with cardiac conditions and common comorbidities and it might be a suitable option for older patients who cannot exercise. A 5-week IHHT is as effective as an 8-week exercise program in improving CRF, without hematological changes. Further studies are needed to clarify the nonhematological adaptations to short, repeated exposure to normobaric hypoxia-hyperoxia.

Intermittent systemic hypoxic-hyperoxic training for myocardial protection in patients undergoing coronary artery bypass surgery: first results from a single-centre, randomised controlled trial.

Background: Although remote ischaemic preconditioning (RIP) provides protection against myocardial ischaemia and reperfusion injury during cardiac surgery, it is not widely used. Systemic intermittent hypoxic-hyperoxic training (IHHT) may be a suitable alternative. Methods: This is a prospective, single-centre, randomised controlled trial. 127 patients with ischaemic heart disease and indication for coronary artery bypass graft (CABG) surgery from the Cardiology Clinic IM Sechenov First Moscow State Medical University were randomly assigned to IHHT, IHHT-control or RIP. Primary endpoint was serum concentration of troponin I and lactate 2 and 24 hours after surgery. Results: Median value for troponin I 24 hours after surgery was 1.068 (0.388-1.397) ng/mL in the IHHT group and was significantly lower compared with IHHT-controls with 1.980 (1.068-3.239) ng/mL (p=0.012) and to the RIP group with 1.762 (1.288-2.186) ng/mL (p=0.029), while there was no significant difference between RIP and the IHHT-control. Serum lactate after surgery was 1.74 (1.23-2.04) mmol/L in the IHHT group and was also significantly lower compared with IHHT-controls with 2.10 (1.80-2.29) mmol/L (p=0.045) and RIP with 2.12 (1.91-2.33) mmol/L (p=0.032). No significant complications or serious adverse events were observed during IHHT. Intraoperative and early postoperative complications did not differ significantly between groups. Conclusions: The results of this first trial using IHHT for myocardial protection against perioperative ischaemic myocardial injury in patients undergoing CABG surgery are promising and further larger trials should be done with adequate power to detect clinical rather than surrogate marker benefits.

A programme based on repeated hypoxia-hyperoxia exposure and light exercise enhances performance in athletes with overtraining syndrome: a pilot study.

Overtraining syndrome (OTS) is a major concern among endurance athletes and is a leading cause in preventing them to perform for long periods. Intermittent exposure to hypoxia has been shown to be an effective way of improving performance without exercising. Aim of this pilot study was to evaluate intermittent hypoxia-hyperoxia training combined with light exercise as an intervention to facilitate athletes with OTS to restore their usual performance level. Thirty-four track and field athletes were recruited: 15 athletes with OTS volunteered to participate and undertook a conditioning programme consisting of repeated exposures to hypoxia (O2 at 10%) and hyperoxia (O2 at 30%) (6-8 cycles, total time 45 min-1 h), three times a week, delivered 1·5-2 h after a low-intensity exercise session (2 bouts of 30 min, running at 50% of VO2max with 10 min rest between bouts) over 4 weeks. Nineteen healthy track and field athletes volunteered to participate as a control group and followed their usual training schedule. Measurements before and after the intervention included exercise capacity, analysis of heart rate variability and hematological parameters. In athletes with OTS, a 4-week light exercise combined with intermittent hypoxia-hyperoxia training improved exercise performance (191·9 ± 26·9 W versus 170·8 ± 44·8 W in exercise capacity test, P = 0·01). Heart rate variability analysis revealed an improved sympatho-parasympathetic index (low frequency/high frequency ratio, 8·01 ± 7·51 before and 1·45 ± 1·71 after, P = 0·007). Hematological parameters were unchanged. Our pilot study showed that intermittent hypoxia-hyperoxia training and low-intensity exercise can facilitate functional recovery among athletes with OTS in a relatively short time.

Adaptations following an intermittent hypoxia-hyperoxia training in coronary artery disease patients: a controlled study.

BACKGROUND: Repeated exposure to intermittent normobaric hypoxia improves exercise tolerance in cardiac patients. Little is known on the effects of intermittent normobaric hypoxia-hyperoxia exposure in coronary artery disease (CAD) patients (New York Heart Association II-III). HYPOTHESIS: IHHT improves exercise tolerance, cardiometabolic profile, and quality of life in CAD patients. METHODS: The study design was a nonrandomized, controlled, before-and-after trial. Forty-six CAD patients volunteered to take part in the study: a group of 27 patients undertook the intermittent hypoxia (O2 at 10%)-hyperoxia (O2 at 30%) training (IHHT), whereas a control group (CTRL) of 19 patients, who already completed an 8-week standard cardiac rehabilitation program, was allocated to sham-IHHT treatment (breathing room air, O2 at 21%). Exercise performance, blood and metabolic profiles, and quality of life (Seattle Angina Questionnaire [SAQ]) were measured before and after in the IHHT group (IHHG) and sham-IHHT in the CTRL group. RESULTS: The IHHG showed improved exercise capacity, reduced systolic and diastolic blood pressures, enhanced left ventricle ejection fraction, and reduced glycemia, but only at 1-month follow-up. Angina as a reason to stop exercising was significantly reduced after treatment and at 1-month follow-up. The IHHT SAQ profile was improved in the IHHG and not significantly different to the CTRL group after standard rehabilitation. The IHHG was also compared to the CTRL group at 1-month follow-up, and no differences were found. CONCLUSIONS: In CAD patients, an IHHT program is associated with improved exercise tolerance, healthier risks factors profile, and a better quality of life. Our study also suggests that IHHT is as effective as an 8-week standard rehabilitation program.

Intermittent hypoxic-hyperoxic training on cognitive performance in geriatric patients.

INTRODUCTION: Intermittent hypoxic-hyperoxic training (IHHT) may complement a multimodal training intervention (MTI) for improving cognitive function and exercise tolerance in geriatric patients. METHODS: Thirty-four patients (64-92 years) participated in this randomized controlled trial. Before and after the 5- to 7-week intervention period (MTI + IHHT vs. MTI + ambient air), cognitive function was assessed by the Dementia-Detection Test (DemTect) and the Sunderland Clock-Drawing Test (CDT), and functional exercise capacity by the total distance of the 6-Minute Walk Test (6MWT). RESULTS: DemTect and CDT indicated significantly larger improvements after MTI + IHHT (+16.7% vs. -0.39%, P < .001) and (+10.7% vs. -8%, P = .031) which was also true for the 6MWT (+24.1% vs. +10.8%, P = .021). DISCUSSION: IHHT turned out to be easily applicable to and well tolerated by geriatric patients up to 92 years. IHHT contributed significantly to improvements in cognitive function and functional exercise capacity in geriatric patients performing MTI.