***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background High-altitude pulmonary edema ( HAPE ) is characterized by severe pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of inflammation . It is not known , however , whether the primary event is an increase in pressure or an increase in permeability of the pulmonary capillaries . Methods and Results We studied pulmonary hemodynamics , including capillary pressure determined by the occlusion method , and capillary permeability evaluated by the pulmonary transvascular escape of 67Ga-labeled transferrin , in 16 subjects with a previous HAPE and in 14 control subjects , first at low altitude ( 490 m ) and then within the first 48 hours of ascent to a high-altitude laboratory ( 4559 m ) . The HAPE-susceptible subjects , compared with the control subjects , had an enhanced pulmonary vasoreactivity to inspiratory hypoxia at low altitude and higher mean pulmonary artery pressures ( 37±2 versus 26±1 mm Hg , P < 0.001 ) and pulmonary capillary pressures ( 19±1 versus 13±1 mm Hg , P < 0.001 ) at high altitude . Nine of the susceptible subjects developed HAPE . All of them had a pulmonary capillary pressure > 19 mm Hg ( range 20 to 26 mm Hg ) , whereas all 7 susceptible subjects without HAPE had a pulmonary capillary pressure < 19 mm Hg ( range 14 to 18 mm Hg ) . The pulmonary transcapillary escape of radiolabeled transferrin increased slightly from low to high altitude in the HAPE-susceptible subjects but remained within the limits of normal and did not differ significantly from the control subjects . Conclusions HAPE is initially caused by an increase in pulmonary capillary pressure Aims The purpose of the current trial was to test the hypothesis that breathing oxygen-enriched air increases exercise performance of patients with pulmonary arterial or chronic thrombo-embolic pulmonary hypertension ( PAH/CTEPH ) and to investigate involved mechanisms . Methods and results Twenty-two patients with PAH/CTEPH , eight women , means ± SD 61 ± 14 years , resting mPAP 35 ± 9mmHg , PaO2 ambient air > 7.3 kPa , underwent four bicycle ergospirometries to exhaustion on different days , while breathing oxygen-enriched ( FiO2 0.50 , hyperoxia ) or ambient air ( FiO2 0.21 , normoxia ) using progressively increased or constant load protocol s ( with 75 % maximal work rate under FiO2 0.21 ) , according to a r and omized , sham-controlled , single-blind , cross-over design . ECG , pulmonary gas-exchange , arterial blood gases , cerebral and quadriceps muscle tissue oxygenation ( CTO and QMTO ) by near-infrared spectroscopy were measured . In ramp exercise , maximal work rate increased from 113 ± 38 W with normoxia to 132 ± 48 W with hyperoxia , mean difference 19.7 ( 95 % CI 10.5 - 28.9 ) W , P < 0.001 . Constant load exercise endurance increased from 571 ± 443 to 1242 ± 514 s , mean difference 671 ( 95 % CI 392 - 951 ) s , P < 0.001 . At end-exercise with hyperoxia PaO2 , CTO , QMTO , and PaCO2 were increased , and ventilatory equivalents for CO2 were reduced while the physiological dead space/tidal volume ratio remained unchanged . Conclusion In patients with PAH/CTEPH , breathing oxygen-enriched air provides major increases in exercise performance . This is related to an improved arterial oxygenation that promotes oxygen availability in muscles and brain and to a reduction of the excessive ventilatory response to exercise thereby enhancing ventilatory efficiency . Patients with PAH/CTEPH may therefore benefit from oxygen therapy during daily physical activities and training . Trial registration clinical trials.gov Identifier : NCT01748474 Reactive oxygen and nitrogen species have been reported to be increased due to hypobaric hypoxia . It was hypothesized that lowl and ers are more susceptible to protein nitration , lipid peroxidation and DNA damage at high altitude than highl and ers and formation of these biomarkers may have strong correlation with oxygen consumption . Male volunteers were r and omly selected and categorized into 3 groups , i.e.  lowl and ers at sea level ( LL-SL , n=10 ) , lowl and ers at an altitude of 4560 m ( LL-HA , n=10 ) and highl and ers ( HAN , n=10 ) . Volunteers performed maximal aerobic exercise . Resting and post-exercise blood sample s were taken at sea level and high altitude . Both resting and maximum oxygen consumption showed positive correlation with stress markers . LL-HA showed increased 3-nitrotyrosine and lipid hydroperoxide than LL-SL at rest . 3-Nitrotyrosine and lipid hydroperoxide increased after exercise in 3 groups , but percentage increase was higher in HAN than LL-SL and LL-HA . LL-SL and HAN showed significant DNA damage after exercise . Results indicate that resting oxygen consumption is positively correlated with nitrosative and oxidative stress markers irrespective of environmental condition and adaptation levels . Lowl and ers have shown higher susceptibility to hypoxic insult than highl and ers at rest , but when subjected to exercise test , they showed better tolerance to hypoxia than highl and ers We aim ed to test effects of altitude acclimatization on pulmonary gas exchange at maximal exercise . Six lowl and ers were studied at sea level , in acute hypoxia ( AH ) , and after 2 and 8  wk of acclimatization to 4,100 m ( 2W and 8W ) and compared with Aymara high-altitude natives residing at this altitude . As expected , alveolar Po2 was reduced during AH but increased gradually during acclimatization ( 61 + /- 0.7 , 69 + /- 0.9 , and 72 + /- 1.4 mmHg in AH , 2W , and 8W , respectively ) , reaching values significantly higher than in Aymaras ( 67 + /- 0.6 mmHg ) . Arterial Po2 ( PaO2 ) also decreased during exercise in AH but increased significantly with acclimatization ( 51 + /- 1.1 , 58 + /- 1.7 , and 62 + /- 1.6 mmHg in AH , 2W , and 8W , respectively ) . PaO2 in lowl and ers reached levels that were not different from those in high-altitude natives ( 66 + /- 1.2 mmHg ) . Arterial O2 saturation ( SaO2 ) decreased during maximum exercise compared with rest in AH and after 2W and 8W : 73.3 + /- 1.4 , 76.9 + /- 1.7 , and 79.3 + /- 1.6 % , respectively . After 8W , SaO2 in lowl and ers was not significantly different from that in Aymaras ( 82.7 + /- 1 % ) . An improved pulmonary gas exchange with acclimatization was evidence d by a decreased ventilatory equivalent of O2 after 8W : 59 + /- 4 , 58 + /- 4 , and 52 + /- 4 l x min x l O2(-1 ) , respectively . The ventilatory equivalent of O2 reached levels not different from that of Aymaras ( 51 + /- 3 l x min x l O2(-1 ) ) . However , increases in exercise alveolar Po2 and PaO2 with acclimatization had no net effect on alveolar-arterial Po2 difference in lowl and ers ( 10 + /- 1.3 , 11 + /- 1.5 , and 10 + /- 2.1 mmHg in AH , 2W , and 8W , respectively ) , which remained significantly higher than in Aymaras ( 1 + /- 1.4 mmHg ) . In conclusion , lowl and ers substantially improve pulmonary gas exchange with acclimatization , but even acclimatization for 8 wk is insufficient to achieve levels reached by high-altitude natives AIM Sleep-disturbed breathing ( SDB ) is common in pre-capillary pulmonary hypertension ( PH ) and impairs daytime performance . In lack of proven effective treatments , we tested whether nocturnal oxygen therapy ( NOT ) or acetazolamide improve exercise performance and quality of life in patients with pre-capillary PH and SDB . METHODS This was a r and omized , placebo-controlled , double-blind , three period cross-over trial . Participants received NOT ( 3 L/min ) , acetazolamide tablets ( 2 × 250 mg ) , and sham-NOT/placebo tablets each during 1 week with 1-week washout between treatment periods . Twenty-three patients , 16 with pulmonary arterial PH , 7 with chronic thromboembolic PH , and with SDB defined as mean nocturnal oxygen saturation < 90 % or oxygen saturation dips > 10 h(-1 ) with daytime PaO2 ≥7.3 kPa participated . Assessment s at the end of the treatment periods included a 6 min walk distance ( MWD ) , SF-36 quality of life , polysomnography , and echocardiography . RESULTS Medians ( quartiles ) of the 6 MWD after NOT , acetazolamide , and placebo were 480 m ( 390;528 ) , 440 m ( 368;468 ) , and 454 m ( 367;510 ) , respectively , mean differences : NOT vs. placebo + 25 m ( 95 % CI 3 - 46 , P= 0.027 ) , acetazolamide vs. placebo -9 m ( -34 - 17 , P = 0.223 ) , and NOT vs. acetazolamide + 33 ( 12 - 45 , P < 0.001 ) . SF-36 quality of life was similar with all treatments . Nocturnal oxygen saturation significantly improved with both NOT and acetazolamide  . Right ventricular fractional area change was greater on NOT compared with placebo ( P = 0.042 ) and acetazolamide ( P = 0.027 ) . CONCLUSIONS In patients with pre-capillary PH and SDB on optimized pharmacological therapy , NOT improved the 6 MWD compared with placebo already after 1 week along with improvements in SDB and haemodynamics . CLINICAL TRIALSGOV NTC01427192 Few studies evidence d an enhancement in oxygen uptake ( VO2 ) during submaximal exercise in hyperoxia . This O2 " overconsumption " seems to increase above the lactate threshold . The aim of this study was to determine whether the hyperoxia-induced enhancement in VO2 may be related to a higher metabolism of lactate . Nine healthy males ( aged 23.1 years , mean VO2 max= 53.8 ml min-1 kg-1 ) were r and omized to two series of exercise in either normoxia or hyperoxia corresponding to an inspired O2 fraction ( FIO2 ) of 30 % . Each series consisted of 6 min cycling at 50 % VO2 max ( Moderate1 ) , 5 min cycling at 95%VO2 max ( Near Max ) and then 6 min at 50 % VO2 max ( Moderate2 ) . In both series Near Max was performed in normoxia . VO2 was significantly greater under hyperoxia than in normoxia during Moderate1 ( 2192 + /- 189 vs. 2025 + /- 172 ml min-1 ) and during Moderate2 ( 2352 + /- 173 vs. 2180 + /- 193 ml min-1 ) . However , the effect of the high FIO2 was not significantly different on VO2Moderate2 ( + 172+/-137 ml min-1 with [ La ] approximately 6 mmol l-1 ) compared to VO2Moderate1 ( + 166 + /- 133 ml min-1 with [ La ] approximately 2.4 mmol l-1 ) . [ La ] at the onset of Moderate2 was not different between normoxia and hyperoxia ( 10.1 + /- 2.2 vs. 10.9 + /- 1.6 mmol l-1 ) . The results show that VO2 is significantly increased during moderate exercise in hyperoxia . But this O2 overconsumption was not modified by a high [ La ] induced by a prior heavy exercise . It could be concluded that lactate accumulation is not directly responsible for the increase in O2 overconsumption with intensity during exercise in hyperoxia The present study examined the effect of oxygen fraction in inspired air ( FIO2 ) on exercise performance and maximum oxygen consumption ( VO2max ) .  Six national level male rowers exercised three 2500-m all-out tests on a Concept II rowing ergometer . Each subject performed one test in normoxia ( FIO2 20.9 % ) , one in simulated hyperoxia ( FIO2 62.2 % ) and one in simulated hypoxia ( FIO2 15.8 % ) in a r and omized single-blind fashion . The mean final rowing time was 2.3 + /- 0.9 % ( P < 0.01 ; 95 % CI  
    Output:
    
In studies performed near sea level in healthy subjects , as well as in patients with PH , maximal performance during progressive ramp exercise and endurance of submaximal constant-load exercise were substantially enhanced by breathing oxygen-enriched air .
Both in healthy individuals and in PH patients , these improvements were mediated by a better arterial , muscular , and cerebral oxygenation , along with a reduced sympathetic excitation , as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads , and an improved pulmonary gas exchange efficiency , especially in patients with PH .
In summary , in healthy individuals and in patients with PH , alterations in the inspiratory Po2 by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance , respectively , by modifying oxygen delivery to the muscles and the brain , by effects on cardiovascular and respiratory control , and by alterations in pulmonary gas exchange .