Airway stenting for liberation from positive pressure ventilation in patients with central airway obstruction presenting with acute respiratory failure.

BACKGROUND: Central airway obstruction (CAO) can lead to acute respiratory failure (RF) necessitating positive pressure ventilation (PPV). The efficacy of airway stenting to aid liberation from PPV in patients with severe acute RF has been scarcely published. We present a systematic review and our recent experience. METHODS: A systematic review of PubMed was performed, and a retrospective review of cases performed at our two institutions from 2018 to 2022 in adult patients who needed stent insertion for extrinsic or mixed CAO complicated by RF necessitating PPV. RESULTS: Fifteen studies were identified with a total of 156 patients. The weighted mean of successful liberation from PPV post-stenting was 84.5% and the median survival was 127.9 days. Our retrospective series included a total of 24 patients. The most common etiology was malignant CAO (83%). The types of PPV used included high-flow nasal cannula (HFNC) (21%), non-invasive ventilation (NIV) (17%) and Invasive Mechanical Ventilation (62%). The overall rate of successful liberation from PPV was 79%, with 55% of HFNC and NIV cases being liberated immediately post-procedure. The median survival of the patients with MCAO that were successfully liberated from PPV was 74 days (n = 16, range 3-893 days), and for those with that failed to be liberated from PPV, it was 22 days (n = 4, range 9-26 days). CONCLUSION: In patients presenting with acute RF from extrinsic or mixed morphology CAO requiring PPV, airway stenting can successfully liberate most from the PPV. This may allow patients to receive pathology-directed treatment and better end-of-life care.

Evaluating the safety of intraprocedural chest tube removal during medical thoracoscopy.

BACKGROUND: Medical Thoracoscopy (MT) is a diagnostic procedure during which after accessing the pleural space the patient's negative-pressure inspiratory efforts draw atmospheric air into the pleural cavity, which creates a space to work in. At the end of the procedure this air must be evacuated via a chest tube, which is typically removed in the post-anesthesia care unit (PACU). We hypothesized that its removal intra-operatively is safe and may lead to lesser post-operative pain in comparison to its removal in the PACU. METHODS: A retrospective review was conducted of all the MT with intraprocedural chest tube removal done between 2019 to 2023 in adult patients in a single center in New York, NY by interventional pulmonology. RESULTS: A total of 100 MT cases were identified in which the chest tube was removed intra-operatively. Seventy-seven percent of cases were performed as outpatient and all these patients were discharged on the same day. Post procedure ex-vacuo pneumothorax was present in 42% of cases. Sixty-five percent of cases had some post-procedure subcutaneous emphysema, none reported any complaint of this being painful, and no intervention was needed to relieve the air. Seventy-three percent required no additional analgesia in PACU. Of the 27% that required any form of analgesia, 59% required no additional analgesia beyond the first 24 h. CONCLUSIONS: Intraprocedural CT removal for MT is safe and may decrease utilization of additional analgesia post procedure. Further prospective studies are necessary to validate these conclusions.

How risky is it to remove an airway stent?

BACKGROUND: Airway stent removal has traditionally been associated with a high complication rate. Most studies on stent removal are over a decade old, prior to newer anti-cancer therapies, and by including non-contemporary and uncovered metal stents, may not reflect the current practices. We review our experience at Mount Sinai Hospital to report outcomes of stent removal with more contemporary practices. METHODS: A retrospective review was carried out of all the airway stent removals performed between 2018 to 2022, in adult patients with benign or malignant airway diseases. Stents inserted and removal for stent trials for tracheobronchomalacia were excluded from the final analysis. RESULTS: Forty-three airway stents removals in 25 patients were included. Twenty-five (58%) stents were removed in 10 patients with benign diseases, and 18 (42%) stents were removed in the remaining 15 patients with malignant diseases. Patients with benign disease were more likely to have their stent removed (OR 3.88). 63% of the stents removed were silicone. The most common reasons for stent removal were migration (n = 14, 31.1%) and treatment response (n = 13, 28.9%). Rigid bronchoscopy was used in 86% of cases. Ninety-eight percent of removals were accomplished in a single procedure. The median time to removal of stents was 32.5 days. Three complications were noted: hemorrhage (n = 1, 2.3%) and stridor (n = 2, 4.6%); one not directly related to the stent removal. CONCLUSIONS: Covered metal or silicone airway stents, in the era of contemporary stents, better cancer-directed therapies and surveillance bronchoscopies, can be removed safely with the use of rigid bronchoscopy.

Diagnosis of tuberculous pleural effusions: A review.

Tuberculous pleural effusion (TPE) is the second most common presentation of extrapulmonary tuberculosis. The paucibacillary nature of the effusion poses diagnostic challenges. Biomarkers like adenosine deaminase and interferon-γ have some utility for diagnosing TPEs, as do cartridge-based polymerase chain reaction (PCR) methods. When these fluid studies remain indeterminate, pleural biopsies must be performed to confirm the diagnosis. This review article elaborates on the scientific evidence available for various diagnostic tests and presents a practical approach to the diagnosis of TPEs.

Randomization to Omega-3 Fatty Acid Supplementation and Endothelial Function in COPD: The COD-Fish Randomized Controlled Trial.

RATIONALE: Studies suggest a pathogenic role of endothelial dysfunction in chronic obstructive lung disease (COPD). Omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation improves endothelial function in other diseases but has not been examined in COPD. OBJECTIVE: We hypothesized that n-3 PUFA supplementation would improve systemic endothelial function in COPD. We performed a pilot randomized, placebo-controlled, double-blind, phase 2 superiority trial (NCT00835289). METHODS: Adults with moderate and severe stable COPD (79% with emphysema on computed tomography [CT]) were randomized to high-dose fish oil capsules or placebo daily for 6 months. The primary endpoint was percentage change in brachial artery flow-mediated dilation (FMD) from baseline to 6 months. Secondary endpoints included peripheral arterial tonometry, endothelial microparticles (EMPs), 6-minute walk distance, respiratory symptoms, and pulmonary function. RESULTS: Thirty-three of 40 randomized participants completed all measurements. Change in FMD after 6 months did not differ between the fish oil and placebo arms (-1.1%, 95% CI -5.0-2.9, p=0.59). CD31+ EMPs increased in the fish oil arm (0.9%, 95% CI 0.1-1.7, p=0.04). More participants in the fish oil arm reported at least a 4-point improvement in the St George's Respiratory Questionnaire (SGRQ) compared to placebo (8 versus 1; p=0.01). There were no significant changes in other secondary endpoints. There were 4 serious adverse events determined to be unrelated to the study (3 in the fish oil arm and 1 in the placebo arm). CONCLUSION: Randomization to n-3 PUFAs for 6 months did not change systemic endothelial function in COPD. Changes in EMPs and SGRQ suggest n-3 PUFAs might have biologic and clinical effects that warrant further investigation.

Rice Consumption and Subclinical Lung Disease in US Adults: Observational Evidence From the Multi-Ethnic Study of Atherosclerosis.

Rice accumulates arsenic, an established lung toxicant. Little is known about the association of rice consumption with arsenic-related health effects, particularly interstitial lung disease. Between 2000 and 2002, 6,814 white, black, Hispanic, and Chinese adults from 6 US cities were enrolled in the Multi-Ethnic Study of Atherosclerosis. We included 2,250 participants who had spirometry data, 2,557 with full-lung computed tomography (CT) scans, and 5,710 with cardiac CT scans. Rice consumption and 310 participants with urinary arsenic were assessed at baseline. Spirometry and full-lung CT-derived measures of total lung capacity and high attenuation area (HAA), and interstitial lung abnormalities were measured at examination 5. Cardiac CT-derived HAA was measured at 1-3 visits. Twelve percent of participants reported eating at least 1 serving of rice daily. Comparing data between that group with those who ate less than 1 serving weekly, the mean difference for forced vital capacity was -102 (95% confidence interval (CI): -198, -7) mL, and for forced expiratory volume in 1 second was -90 (95% CI: -170, -11) mL after adjustment for demographics, anthropometrics, dietary factors, and smoking. The cross-sectional adjusted percent difference for total lung capacity was -1.33% (95% CI: -4.29, 1.72) and for cardiac-based HAA was 3.66% (95% CI: 1.22, 6.15). Sensitivity analyses for urinary arsenic were consistent with rice findings. Daily rice consumption was associated with reduced lung function and greater cardiac-based HAA.

Human airway branch variation and chronic obstructive pulmonary disease.

Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.

Autoadjusted versus fixed CPAP for obstructive sleep apnoea: a multicentre, randomised equivalence trial.

BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) is conventionally treated by continuous positive airway pressure set at a fixed level (fCPAP). Automatic mask pressure adjustment (autoCPAP) is increasingly used during home therapy. We investigated whether autoCPAP is equivalent to fCPAP in improving sleepiness in patients with OSAS in the long-term. METHODS: In this multicentre equivalence trial, 208 patients with OSAS, with median Epworth sleepiness score (ESS) 13, apnoea/hypopnoea index 48.4/hour, were randomised to treatment with autoCPAP (5-15 mbar) or fCPAP (pressure set at the 90th percentile applied by autoCPAP during 2-4 weeks adaptation). Coprimary outcomes were changes in subjective and objective sleepiness from baseline to 2 years after treatment. Equivalence ranges were ±2 points in ESS and ±3 min sleep resistance time evaluated by recording responses to light signals. RESULTS: At 2 years, in the intention to treat analysis, the reduction in sleepiness versus pretreatment baseline was similar in patients using autoCPAP (n=113, mean ESS-change -6.3, 95% CI -7.1 to -5.5; sleep resistance time +8.3 min, +6.9 to +9.7) and fCPAP (n=95, mean ESS-change -6.2, 95% CI -7.0 to -5.3; sleep resistance time +6.3 min, +4.7 to +7.8). The 95% CI of difference in ESS-reduction between autoCPAP and fCPAP was -0.9 to +1.4 and the 95% CI of difference in increase in sleep resistance time was -2.6 to +1.0 min. Blood pressure reduction and OSAS-related costs were similar between groups. CONCLUSIONS: AutoCPAP and fCPAP are equivalent within prespecified ranges in improving subjective and objective sleepiness in patients with OSAS over the course of 2 years. Costs of these treatments are similar. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00280800.

Percent Emphysema and Daily Motor Activity Levels in the General Population: Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: COPD is associated with reduced physical capacity. However, it is unclear whether pulmonary emphysema, which can occur without COPD, is associated with reduced physical activity in daily life, particularly among people without COPD and never smokers. We hypothesized that greater percentage of emphysema-like lung on CT scan is associated with reduced physical activity assessed by actigraphy and self-report. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants free of clinical cardiovascular disease from the general population. Percent emphysema was defined as percentage of voxels < -950 Hounsfield units on full-lung CT scans. Physical activity was measured by wrist actigraphy over 7 days and a questionnaire. Multivariable linear regression was used to adjust for age, sex, race/ethnicity, height, weight, education, smoking, pack-years, and lung function. RESULTS: Among 1,435 participants with actigraphy and lung measures, 47% had never smoked, and 8% had COPD. Percent emphysema was associated with lower activity levels on actigraphy (P = .001), corresponding to 1.5 hour less per week of moderately paced walking for the average participant in quintile 2 vs 4 of percent emphysema. This association was significant among participants without COPD (P = .004) and among ever (P = .01) and never smokers (P = .03). It was also independent of coronary artery calcium and left ventricular ejection fraction. There was no evidence that percent emphysema was associated with self-reported activity levels. CONCLUSIONS: Percent emphysema was associated with decreased physical activity in daily life objectively assessed by actigraphy in the general population, among participants without COPD, and nonsmokers.

Gastrointestinal Dysfunction in Patients with Duchenne Muscular Dystrophy.

BACKGROUND: In adult patients with Duchenne muscular dystrophy (DMD) life-threatening constipation has been reported. Since gastrointestinal function in DMD has not been rigorously studied we investigated objective and subjective manifestations of gastrointestinal disturbances in DMD patients. METHODS: In 33 patients with DMD, age 12-41 years, eating behavior and gastrointestinal symptoms were evaluated by questionnaires. Gastric emptying half time (T1/2) and oro-cecal transit time (OCTT) were evaluated by analyzing 13CO2 exhalation curves after ingestion of 13C labeled test meals. Colonic transit time (CTT) was measured by abdominal radiography following ingestion of radiopaque markers. RESULTS: The median (quartiles) T1/2 was 187 (168, 220) minutes, the OCTT was 6.3 (5.0, 7.9) hours, both substantially longer than normal data (Goetze 2005, T1/2: 107±10; Geypens 1999, OCTT 4.3±0.1 hours). The median CTT was 60 (48, 82) hours despite extensive use of laxative measures (Meier 1995, upper limit of normal: 60 hours). T1/2 and OCTT did not correlate with symptoms evaluated by the Gastroparesis Cardinal Symptom Index (GCSI) (Spearman r = -0.3, p = 0.1; and r = -0.15, p = 0.4, respectively). CTT was not correlated with symptoms of constipation assessed by ROME III criteria (r = 0.12, p = 0.5). CONCLUSIONS: DMD patients have a markedly disturbed gastrointestinal motor function. Since objective measures of impaired gastrointestinal transport are not correlated with symptoms of gastroparesis or constipation our findings suggest that measures assuring adequate intestinal transport should be taken independent of the patient's perception in order to prevent potentially life threatening constipation, particularly in older DMD patients.

Classifying Chronic Lower Respiratory Disease Events in Epidemiologic Cohort Studies.

RATIONALE: One in 12 adults has chronic obstructive pulmonary disease or asthma. Acute exacerbations of these chronic lower respiratory diseases (CLRDs) are a major cause of morbidity and mortality. Valid approaches to classifying cases and exacerbations in the general population are needed to facilitate prevention research. OBJECTIVES: To assess the feasibility, reproducibility, and performance of a protocol to identify CLRD cases and exacerbations triggering emergency department (ED) visits or hospitalizations in cohorts of patients derived from general populations of adults. METHODS: A protocol was developed to classify CLRD cases and severe exacerbations on the basis of review of medical records. ED and inpatient medical records were ascertained prospectively in the Hispanic Community Health Study/Study of Latinos, and inpatient records were retrospectively identified by administrative codes in the Multi-Ethnic Study of Atherosclerosis. "Probable" exacerbations were defined as a physician's diagnosis of CLRD with acute respiratory symptoms. "Highly probable" exacerbations additionally required systemic corticosteroid therapy, and "definite" exacerbations required airflow limitation or evidence of CLRD on imaging studies. Adjudicated results were compared with CLRD cases identified by spirometry and self-report, and with an administrative definition of exacerbations. MEASUREMENTS AND MAIN RESULTS: Protocol-based classification was completed independently by two physicians for 216 medical records (56 ED visits and 61 hospitalizations in the Hispanic Community Health Study/Study of Latinos; 99 hospitalizations in the Multi-Ethnic Study of Atherosclerosis). Reviewer disagreement occurred in 2-5% of cases and 4-8% of exacerbations. Eighty-nine percent of records were confirmed as at least probable CLRD cases. Fifty-six percent of confirmed CLRD cases had airflow limitation on the basis of baseline study spirometry. Of records that described CLRD as the primary discharge diagnosis code, an acute exacerbation was confirmed as at least probable for 96% and as highly probable or definite for 77%. Only 50% of records with CLRD as a secondary code were confirmed, although such records accounted for over half of all confirmed exacerbations. CONCLUSIONS: CLRD cases and severe exacerbations without preceding documentation of airflow limitation are identified frequently in population-based cohorts of persons. A primary discharge diagnosis of CLRD is specific but insensitive for defining exacerbations. Protocol-based classification of medical records may be appropriate to supplement and to validate identification of CLRD cases and exacerbations in general population studies. Clinical trials registered with www.clinicaltrials.gov (NCT00005487 and NCT02060344).

Impaired postural control in healthy men at moderate altitude (1630 m and 2590 m): data from a randomized trial.

OBJECTIVES: Intact postural control is essential for safe performance of mountain sports, operation of machinery at altitude, and for piloting airplanes. We tested whether exposure to hypobaric hypoxia at moderate altitude impairs the static postural control of healthy subjects. METHODS: In 51 healthy men, median age 24 y (quartiles 20;28), static control was evaluated on a balance platform in Zurich, 490 m, and during a 4-day sojourn in Swiss mountain villages at 1630 m and 2590 m, 2 days each. The order of altitude exposure was randomized. Total center of pressure path length (COPL) and sway amplitude measured in two directions by a balance platform, and pulse oximetry were recorded. Data were compared between altitudes. RESULTS: Median (quartiles) COPL during standing on both legs with eyes open at 490 m and in the evenings on the first and second days at 1630 and 2590 m, respectively were: 50 (45;57), 55 (48;62), 56 (49;61), 53 (47;59), 54 (48;60) cm, P<0.001 ANOVA. Corresponding arterial oxygen saturation was 97% (96;97), 95% (94;96), 95%(94;96), 92%(90;93), 93%(91;93), P<0.001. Anterior-posterior sway amplitudes were larger at 1630 and 2590 m compared to 490 m, P<0.001. Multiple logistic regression analysis confirmed that higher altitudes (1630 and 2590m) were independently associated with increased COPL when controlled for the order of altitude exposure and age (P=0.001). CONCLUSIONS: Exposure to 1630 and 2590m was associated with impaired static postural control even when visual references were available. TRIAL REGISTRATION: ClinicalTrials.gov NCT01130948.

Ascent to moderate altitude impairs overnight memory improvements.

Several studies showed beneficial effects of sleep on memory performance. Slow waves, the electroencephalographic characteristic of deep sleep, reflected on the neuronal level by synchronous slow oscillations, seem crucial for these benefits. Traveling to moderate altitudes decreases deep sleep. In a randomized cross-over design healthy male subjects performed a visuo-motor learning task in Zurich (490 m) and at Davos Jakobshorn (2590 m) in random order. Memory performance was assessed immediately after learning, before sleep, and in the morning after a night of sleep. Sleep EEG recordings were performed during the nights. Our findings show an altitude induced reduction of sleep dependent memory performance. Moreover, this impaired sleep dependent memory performance was associated with reduced slow wave derived measures of neuronal synchronization. Our results are consistent with a critical role of slow waves for the beneficial effects of sleep on memory that is susceptible to natural environmental influences.

Severe metabolic acidosis in adult patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential.

Circulating levels of cell-derived microparticles are reduced by mild hypobaric hypoxia: data from a randomised controlled trial.

PURPOSE: Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. METHODS: Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. RESULTS: Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ -221/µl 95 % CI -370.8/-119.0, lactadherin+ -202/µl 95 % CI -372.2/-93.1), platelet-derived microparticles (-114/µl 95 % CI -189.9/-51.0) and red blood cell-derived microparticles (-81.4 µl 95 % CI -109.9/-57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. CONCLUSIONS: In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential.

Sleep respiratory disturbances and arousals at moderate altitude have overlapping electroencephalogram spectral signatures.

An ascent to altitude has been shown to result in more central apneas and a shift towards lighter sleep in healthy individuals. This study employs spectral analysis to investigate the impact of respiratory disturbances (central/obstructive apnea and hypopnea or periodic breathing) at moderate altitude on the sleep electroencephalogram (EEG) and to compare EEG changes resulting from respiratory disturbances and arousals. Data were collected from 51 healthy male subjects who spent 1 night at moderate altitude (2590 m). Power density spectra of Stage 2 sleep were calculated in a subset (20) of these participants with sufficient artefact-free data for (a) epochs with respiratory events without an accompanying arousal, (b) epochs containing an arousal and (c) epochs of undisturbed Stage 2 sleep containing neither arousal nor respiratory events. Both arousals and respiratory disturbances resulted in reduced power in the delta, theta and spindle frequency range and increased beta power compared to undisturbed sleep. The similarity of the EEG changes resulting from altitude-induced respiratory disturbances and arousals indicates that central apneas are associated with micro-arousals, not apparent by visual inspection of the EEG. Our findings may have implications for sleep in patients and mountain tourists with central apneas and suggest that respiratory disturbances not accompanied by an arousal may, none the less, impact sleep quality and impair recuperative processes associated with sleep more than previously believed.

Are nocturnal breathing, sleep, and cognitive performance impaired at moderate altitude (1,630-2,590 m)?

STUDY OBJECTIVES: Newcomers at high altitude (> 3,000 m) experience periodic breathing, sleep disturbances, and impaired cognitive performance. Whether similar adverse effects occur at lower elevations is uncertain, although numerous lowlanders travel to moderate altitude for professional or recreational activities. We evaluated the hypothesis that nocturnal breathing, sleep, and cognitive performance of lowlanders are impaired at moderate altitude. DESIGN: Randomized crossover trial. SETTING: University hospital at 490 m, Swiss mountain villages at 1,630 m and 2,590 m. PARTICIPANTS: Fifty-one healthy men, median (quartiles) age 24 y (20-28 y), living below 800 m. INTERVENTIONS: Studies at Zurich (490 m) and during 4 consecutive days at 1,630 m and 2,590 m, respectively, 2 days each. The order of altitude exposure was randomized. Polysomnography, psychomotor vigilance tests (PVT), the number back test, several other tests of cognitive performance, and questionnaires were evaluated. MEASUREMENTS AND RESULTS: The median (quartiles) apnea-hypopnea index at 490 m was 4.6/h (2.3; 7.9), values at 1,630 and 2,590 m, day 1 and 2, respectively, were 7.0/h (4.1; 12.6), 5.4/h (3.5; 10.5), 13.1/h (6.7; 32.1), and 8.0/h (4.4; 23.1); corresponding values of mean nocturnal oxygen saturation were 96% (95; 96), 94% (93; 95), 94% (93; 95), 90% (89; 91), 91% (90; 92), P < 0.05 versus 490 m, all instances. Slow wave sleep on the first night at 2,590 m was 21% (18; 25) versus 24% (20; 27) at 490 m (P < 0.05). Psychomotor vigilance and various other measures of cognitive performance did not change significantly. CONCLUSIONS: Healthy men acutely exposed during 4 days to hypoxemia at 1,630 m and 2,590 m reveal a considerable amount of periodic breathing and sleep disturbances. However, no significant effects on psychomotor reaction speed or cognitive performance were observed. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov: NCT01130948.

Quantitative changes in the sleep EEG at moderate altitude (1630 m and 2590 m).

BACKGROUND: Previous studies have observed an altitude-dependent increase in central apneas and a shift towards lighter sleep at altitudes >4000 m. Whether altitude-dependent changes in the sleep EEG are also prevalent at moderate altitudes of 1600 m and 2600 m remains largely unknown. Furthermore, the relationship between sleep EEG variables and central apneas and oxygen saturation are of great interest to understand the impact of hypoxia at moderate altitude on sleep. METHODS: Fourty-four healthy men (mean age 25.0 ± 5.5 years) underwent polysomnographic recordings during a baseline night at 490 m and four consecutive nights at 1630 m and 2590 m (two nights each) in a randomized cross-over design. RESULTS: Comparison of sleep EEG power density spectra of frontal (F3A2) and central (C3A2) derivations at altitudes compared to baseline revealed that slow-wave activity (SWA, 0.8-4.6 Hz) in non-REM sleep was reduced in an altitude-dependent manner (~4% at 1630 m and 15% at 2590 m), while theta activity (4.6-8 Hz) was reduced only at the highest altitude (10% at 2590 m). In addition, spindle peak height and frequency showed a modest increase in the second night at 2590 m. SWA and theta activity were also reduced in REM sleep. Correlations between spectral power and central apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation revealed that distinct frequency bands were correlated with oxygen saturation (6.4-8 Hz and 13-14.4 Hz) and breathing variables (AHI, ODI; 0.8-4.6 Hz). CONCLUSIONS: The correlation between SWA and AHI/ODI suggests that respiratory disturbances contribute to the reduction in SWA at altitude. Since SWA is a marker of sleep homeostasis, this might be indicative of an inability to efficiently dissipate sleep pressure.

Effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.

BACKGROUND: Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. OBJECTIVES: To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. METHODS: In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. RESULTS: Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides -0.14 mmol/l, p=0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio -0.25, p=0.001), LDL particle size increased (median difference +0.45 nm, p=0.048) and hsCRP decreased (median difference -0.18 mg/l, p=0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. CONCLUSIONS: Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT01130948.

Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial.

CONTEXT: Many patients with obstructive sleep apnea syndrome (OSA) living near sea level travel to altitude, but this may expose them to hypoxemia and exacerbation of sleep apnea. The treatment in this setting is not established. OBJECTIVE: To evaluate whether acetazolamide and autoadjusted continuous positive airway pressure (autoCPAP) control breathing disturbances in OSA patients at altitude. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, double-blind, crossover trial involving 51 patients with OSA living below an altitude of 800 m and receiving CPAP therapy who underwent studies at a university hospital at 490 m and resorts in Swiss mountain villages at 1630 m and 2590 m in summer 2009. INTERVENTIONS: Patients were studied during 2 sojourns of 3 days each in mountain villages, 2 days at 1630 m, 1 day at 2590 m, separated by a 2-week washout period at less than 800 m. At altitude, patients either took acetazolamide (750 mg/d) or placebo in addition to autoCPAP. MAIN OUTCOME MEASURES: Primary outcomes were nocturnal oxygen saturation and the apnea/hypopnea index; secondary outcomes were sleep structure, vigilance, symptoms, adverse effects, and exercise performance. RESULTS: Acetazolamide and autoCPAP treatment was associated with higher nocturnal oxygen saturation at 1630 m and 2590 m than placebo and autoCPAP: medians, 94% (interquartile range [IQR], 93%-95%) and 91% (IQR, 90%-92%) vs 93% (IQR, 92%-94%) and 89% (IQR, 87%-91%), respectively. Median increases were 1.0% (95% CI, 0.3%-1.0%) and 2.0% (95% CI, 2.0%-2.0). Median night-time spent with oxygen saturation less than 90% at 2590 m was 13% (IQR, 2%-38%) vs 57% (IQR, 28%-82%; P < .001). Acetazolamide and autoCPAP resulted in better control of sleep apnea at 1630 m and 2590 m than placebo and autoCPAP: median apnea/hypopnea index was 5.8 events per hour (5.8/h) (IQR, 3.0/h-10.1/h) and 6.8/h (IQR, 3.5/h-10.1/h) vs 10.7/h (IQR, 5.1/h-17.7/h) and 19.3/h (IQR, 9.3/h-29.0/h), respectively; median reduction was 3.2/h (95% CI, 1.3/h-7.5/h) and 9.2 (95% CI, 5.1/h-14.6/h). CONCLUSION: Among patients with OSA spending 3 days at moderately elevated altitude, a combination of acetazolamide and autoCPAP therapy, compared with autoCPAP alone, resulted in improvement in nocturnal oxygen saturation and apnea/hypopnea index. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00928655.