***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : Nonselective systemic vasodilators worsen ventilation perfusion ( V/Q ) matching and gas exchange in patients with chronic obstructive pulmonary disease ( COPD ) . Inhaled iloprost has the potential to act preferentially in ventilated regions of the lung , thereby reducing pulmonary hypertension ( PH ) while alveolar ventilation is still maintained . Objectives : To investigate the acute effects of inhaled iloprost on V/Q matching in patients with COPD and PH . Methods : Ten males with COPD and PH on echocardiography were evaluated before and after inhaling 2 doses of iloprost ( 2.5 µg ) . Measurements included lung function , arterial blood gas , 6-min walk test ( 6MWT ) as well as ventilatory equivalents for oxygen ( VE/VO2 ) and carbon dioxide ( VE/VCO2 ) taken at baseline , 30 min following each dose of iloprost , and 2 h after the second dose . Results : Mean differences in VE/VCO2 and VE/VO2 were –13.3 ( 95 % CI –36.5 to –2.7 ; p = 0.002 ) and –15.0 ( 95 % CI –36.7 to –0.4 ; p = 0.02 ) , respectively , and the mean change in ( A-a ) gradient was –3.7 mm Hg ( 95 % CI –6.1 to –1.0 ; p = 0.01 ) after a single dose of iloprost , whereas mean improvement in 6MWT was 49.8 m ( 95 % CI 14.8 to 84.7 ; p = 0.02 ) . Arterial blood gas , venous admixture , dead space fraction and lung functions were maintained after iloprost . The effects of iloprost were reproducible after the second dose . All measurements returned to baseline 2 h after the last dose . No adverse effects on systemic blood pressure or oxygen saturation were seen . Conclusions : Iloprost inhalation was safe in patients with COPD and PH , and was associated with improved V/Q matching and exercise tolerance Abstract Rationale : Pulmonary hypertension with exercise is common in chronic obstructive pulmonary disease ( COPD ) and may contribute to exercise limitation in this disease . We aim ed to determine the effects of treatment with sildenafil on exercise capacity in patients with COPD and emphysema . Methods : We performed a r and omized , double-blind , placebo-controlled 2-period crossover trial of sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without pulmonary hypertension . We r and omized study participants to 4 weeks of sildenafil ( or placebo ) followed by a 1-week washout and then 4 weeks of placebo ( or sildenafil ) . The 2 primary outcomes were the 6-minute walk distance and oxygen consumption at peak exercise . Results : Sildenafil had no effect on 6-minute walk distance ( placebo-corrected difference = -7.8 m , 95 % confidence interval , -23.2 to 7.5 m , p = 0.35 ) or oxygen consumption at peak exercise ( placebo-corrected difference = -0.1 ml/kg/min , 95 % confidence interval -2.1 to 1.8 ml/kg/min , p = 0.89 ) . Sildenafil increased the alveolar-arterial oxygen gradient ( p = 0.02 ) , worsened symptoms ( p = 0.04 ) , and decreased quality -of-life ( p = 0.03 ) . Adverse events were more frequent while receiving sildenafil ( p = 0.005 ) . Conclusions : Routine sildenafil administration did not have a beneficial effect on exercise capacity in patients with COPD and emphysema without pulmonary hypertension . Sildenafil significantly worsened gas exchange at rest and quality of life . ( clinical trials.gov NCT00104637 ) BACKGROUND Sildenafil inhibits phosphodiesterase type 5 , an enzyme that metabolizes cyclic guanosine monophosphate , thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells , including those in the lung . METHODS In this double-blind , placebo-controlled study , we r and omly assigned 278 patients with symptomatic pulmonary arterial hypertension ( either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts ) to placebo or sildenafil  ( 20 , 40 , or 80 mg ) orally three times daily for 12 weeks . The primary end point was the change from baseline to week 12 in the distance walked in six minutes . The change in mean pulmonary-artery pressure and World Health Organization ( WHO ) functional class and the incidence of clinical worsening were also assessed , but the study was not powered to assess mortality . Patients completing the 12-week r and omized study could enter a long-term extension study . RESULTS The distance walked in six minutes increased from baseline in all sildenafil groups ; the mean placebo-corrected treatment effects were 45 m ( + 13.0 percent ) , 46 m ( + 13.3 percent ) , and 50 m ( + 14.7 percent ) for 20 , 40 , and 80 mg of sildenafil , respectively ( P<0.001 for all comparisons ) . All sildenafil doses reduced the mean pulmonary-artery pressure ( P=0.04 , P=0.01 , and P<0.001 , respectively ) , improved the WHO functional class ( P=0.003 , P<0.001 , and P<0.001 , respectively ) , and were associated with side effects such as flushing , dyspepsia , and diarrhea . The incidence of clinical worsening did not differ significantly between the patients treated with sildenafil and those treated with placebo . Among the 222 patients completing one year of treatment with sildenafil monotherapy , the improvement from baseline at one year in the distance walked in six minutes was 51 m. CONCLUSIONS Sildenafil improves exercise capacity , WHO functional class , and hemodynamics in patients with symptomatic pulmonary arterial hypertension BACKGROUND Sildenafil has been found to improve exercise capacity and haemodynamic parameters in patients with various pulmonary disorders . This study was undertaken to evaluate its efficacy in severe chronic obstructive pulmonary disease ( COPD ) . METHODS In this double-blind , r and omised , placebo-controlled study , 37 patients with severe COPD received either sildenafil or placebo for 12 weeks . Distance covered in six-minute walk test ( 6MWD ) was taken as primary end-point . Pulmonary artery pressure ( PAP ) was measured as secondary end point . RESULTS Thirty-three patients ( 15 in sildenafil arm and 18 in placebo arm ) completed the study . Non-parametric tests were used for comparison . There was significant increase in 6MWD from baseline after three months of follow-up in sildenafil users ( median change in distance covered in six-minute walk test ( delta6MWD ) = 190 m ) as compared to placebo users ( delta6MWD = 0 m , p < 0.05 ) . The PAP decreased significantly ( chi2 = 14.94 , p < 0.05 ) in sildenafil group after three months , while it did not change significantly among placebo group ( chi2 = 3.84 , p > 0.05 ) . CONCLUSION Sildenafil improved 6MWD and PAP in patients with severe COPD Pulmonary hypertension is a life-threatening complication of lung fibrosis . Vasodilator therapy is difficult owing to systemic side effects and pulmonary ventilation-perfusion mismatch . We compared the effects of intravenous prostacyclin and inhaled NO and aerosolized prostacyclin in r and omized order and , in addition , tested for effects of oxygen and systemic calcium antagonists ( CAAs ) in eight patients with lung fibrosis and pulmonary hypertension .  Aerosolized prostagl and in (PG)I(2 ) caused preferential pulmonary vasodilatation with a decrease in mean pulmonary arterial pressure from 44.1 + /- 4.2 to 31.6 + /- 3.1 mm Hg , and pulmonary vascular resistance ( RL ) from 810 + /- 226 to 386 + /- 69 dyn . s. cm(-)(5 ) ( p < 0.05 , respectively ) . Systemic arterial pressure , arterial oxygen saturation , and pulmonary right-to-left shunt flow , measured by multiple inert gas analysis , were not significantly changed . Inhaled NO similarly result ed in selective pulmonary vasodilatation , with RL decreasing from 726 + /- 217 to 458 + /- 81 dyn . s. cm(-)(5 ) . In contrast , both intravenous PGI(2 ) and CAAs were not pulmonary selective , result ing in a significant drop in arterial pressure . In addition , PGI(2 ) infusion caused a marked increase in shunt flow . Long-term therapy with aerosolized iloprost ( long-acting PGI(2 ) analog ) result ed in unequivocal clinical improvement from a state of immobilization and severe resting dyspnea in a patient with decompensated right heart failure . We concluded that , in pulmonary hypertension secondary to lung fibrosis , aerosolization of PGI(2 ) or iloprost causes marked pulmonary vasodilatation with maintenance of gas exchange and systemic arterial pressure . Long-term therapy with inhaled iloprost may be life saving in decompensated right heart failure from pulmonary hypertension secondary to lung fibrosis Pulmonary hypertension is a serious complication of chronic obstructive pulmonary disease ( COPD ) that currently has no established pharmacological treatment . This study aim ed to assess whether concomitant treatment with sildenafil would enhance the results of pulmonary rehabilitation in patients with COPD and increased pulmonary arterial pressure ( PAP ) . In this double-blind , r and omised controlled trial patients received 20 mg sildenafil or placebo three times daily and underwent pulmonary rehabilitation for 3 months . The primary end-point was the gain in the cycle endurance time at a constant work-rate . Secondary end-points included performance in the incremental exercise test , 6-min walk distance and quality of life .  63 patients with severe COPD and moderately increased PAP were r and omised .  Cycle endurance time increased by 149 s ( 95 % CI 26–518 s ) in the sildenafil group and by 169 s ( 95 % CI 0–768 s ) in the placebo group ( median change difference -7 s , 95 % CI -540–244 s ; p=0.77 ) . Gains in the incremental exercise test , 6-min walk distance and quality of life at the end of the study did not differ between groups . Measurements of arterial oxygenation and adverse events were similar in both groups . In patients with severe COPD and moderately increased PAP , concomitant treatment with sildenafil does not improve the results of pulmonary rehabilitation in exercise tolerance . Sildenafil did not improve respiratory rehabilitation outcomes in patients with severe COPD and moderately increased PAP Pulmonary hypertension during exercise is common in severe chronic obstructive pulmonary disease ( COPD ) . It was hypothesised that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary haemodynamics during exercise , thus increasing exercise tolerance in patients with severe COPD . In the present double-blind , placebo-controlled study , 30 patients with severe or very severe COPD were r and omly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks . The primary end-point was change in the 6-min walking distance . Secondary end-points included changes in health-related quality of life , lung function , cardiac haemodynamics , maximal oxygen uptake and pulmonary perfusion patterns . Compared with placebo , patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by the 6-min walking distance ( mean±sd 331±123 versus 329±94 m ) . There was no change in lung function , pulmonary arterial pressure , maximal oxygen uptake or regional pulmonary perfusion pattern . In contrast , arterial oxygen pressure dropped , the alveolar – arterial gradient increased and quality of life deteriorated significantly in patients assigned bosentan . The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxaemia and functional status in severe chronic obstructive pulmonary disease patients without severe pulmonary hypertension at rest RATIONALE Sildenafil , a phosphodiesterase-5 inhibitor , could be useful for treating pulmonary hypertension ( PH ) in chronic obstructive pulmonary disease ( COPD ) . However , vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition . OBJECTIVES To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD -associated PH . METHODS We conducted a r and omized , dose comparison trial in 20 patients with COPD -associated PH . Eleven patients were assigned to 20 mg , and 9 patients to 40 mg , of sildenafil .  Pulmonary hemodynamics 
    Output:
    
In conclusion , PH specific drugs ( especially sildenafil ) could improve exercise capacity and decrease PAP in COPD patients with severe PH