***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 Idiopathic pulmonary fibrosis ( IPF ) is a progressive lung disease with pulmonary vasculopathy . OBJECTIVE The purpose of this study was to determine whether sildenafil improves 6-min walk distance ( 6MWD ) in subjects with IPF and right ventricular dysfunction . METHODS The IPFnet , a network of IPF research centers in the United States , conducted a r and omized trial examining the effect of sildenafil on 6MWD in patients with advanced IPF , defined by carbon monoxide diffusing capacity < 35 % predicted . A sub study examined 119 of 180 r and omized subjects where echocardiograms were available for independent review by two cardiologists .  Right ventricular ( RV ) hypertrophy ( RVH ) , right ventricular systolic dysfunction ( RVSD ) , and right ventricular systolic pressure ( RVSP ) were assessed . Multivariable linear regression models estimated the relationship between RV abnormality , sildenafil treatment , and changes in 6MWD , St. George 's Respiratory Question naire ( SGRQ ) , the EuroQol instrument , and SF-36 Health Survey ( SF-36 ) from enrollment to 12 weeks . RESULTS The prevalence of RVH and RVSD were 12.8 % and 18.6 % , respectively . RVSP was measurable in 71 of 119 ( 60 % ) subjects ; mean RVSP was 42.5 mm Hg . In the subgroup of subjects with RVSD , subjects treated with sildenafil experienced less decrement in 6MWD ( 99.3 m ; P = .01 ) and greater improvement in SGRQ ( 13.4 points ; P = .005 ) and EuroQol visual analog scores ( 17.9 points ; P = .04 ) than subjects receiving placebo . In the subgroup with RVH , sildenafil was not associated with change in 6MWD ( P = .13 ) , but was associated with greater relative improvement in SGRQ ( 14.8 points ; P = .02 ) vs subjects receiving placebo . Sildenafil treatment in those with RVSD and RVH was not associated with change in SF-36 . CONCLUSIONS Sildenafil treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo . Sildenafil also improves quality of life in subjects with RVH and RVSD Background Pulmonary hypertension (PH)-targeted therapy in the setting of pulmonary fibrosis ( PF ) is controversial ; the main clinical concern is worsening of systemic hypoxaemia . We sought to determine the effects of gentle initiation and chronic administration of parenteral treprostinil on right heart function in patients with PF associated with an advanced PH phenotype . Methods Open-label , prospect i ve analysis of patients with PF-PH referred for lung transplantation ( LT ) . Advanced PH was defined as mean pulmonary artery pressure ( mPAP ) ≥35 mm Hg . We compared haemodynamics , Doppler echocardiography ( DE ) , oxygenation , dyspnoea and quality of life indices , and 6 min walk distance ( 6MWD ) before and 12 weeks after parenteral treprostinil . Results 15 patients were recruited in the study . After therapy , there were significant improvements in right heart haemodynamics ( right atrial pressure ( 9.5 ± 3.4 vs 6.0 ± 3.7 ) ; mPAP ( 47 ± 8 vs 38.9 ± 13.4 ) ; CI ( 2.3 ± 0.5 vs 2.7 ± 0.6 ) ; pulmonary vascular resistance ( 698 ± 278 vs 496 ± 229 ) ; transpulmonary gradient ( 34.7 ± 8.7 vs 28.5 ± 10.3 ) ; mvO2 ( 65 ± 7.2 vs 70.9 ± 7.4 ) ; and stroke volume index ( 29.2 ± 6.7 vs 33 ± 7.3 ) ) and DE parameters reflecting right heart function ( right ventricular ( RV ) end diastolic area ( 36.4 ± 5.2 vs 30.9 ± 8.2 cm2 ) , left ventricular eccentricity index ( 1.7 ± 0.6 vs 1.3 ± 0.5 ) , tricuspid annular planar systolic excursion ( 1.6 ± 0.5 vs 1.9 ± 0.2 cm ) ) . These changes occurred without significant alteration in systemic oxygenation , heart rate , or mean systemic arterial pressure . In addition , improvements were seen in 6MWD ( 171 ± 93 vs 230 ± 114 ) , 36-Item Short Form Health Survey Mental Component Summary aggregate ( 38 ± 11 vs 44.2 ± 10.7 ) , University of California , San Diego Shortness of Breath Question naire ( 87 ± 17.1 vs 73.1 ± 21 ) , and brain natriuretic peptide ( 558 ± 859 vs 228 ± 340 ) .  Conclusions PH-targeted therapy may improve right heart haemodynamics and echocardiographic function without affecting systemic oxygen saturation in an advanced PH phenotype associated with RV dysfunction in the setting of PF BACKGROUND Pulmonary hypertension ( PH ) is a well-known independent prognostic factor in chronic obstructive pulmonary disease ( COPD ) and a sufficient criterion for lung transplant c and idacy . Limited data are currently available on the hemodynamic and clinical effect of phosphodiesterase 5 inhibitors in patients with severe PH associated with COPD . This study assessed the effect of sildenafil on pulmonary hemodynamics and gas exchange in severe PH associated with COPD . METHODS After screening , this multicenter , r and omized , placebo-controlled double-blind trial r and omized patients to receive 20 mg sildenafil or placebo 3 times a day ( ratio 2:1 ) for 16 weeks . The primary end point was the reduction in pulmonary vascular resistance . Secondary end points included BODE ( body mass index , airflow obstruction , dyspnea , and exercise capacity ) index , 6-minute walk test , and quality of life question naire . Changes in the partial pressure of arterial oxygen were evaluated as a safety parameter . RESULTS The final population included 28 patients , 18 in the sildenafil group and 10 in the placebo group . At 16 week , patients treated with sildenafil had a decrease in pulmonary vascular resistance ( mean difference with placebo -1.4 WU ; 95 % confidence interval , ≤ -0.05 ; p = 0.04 ) . Sildenafil also improved the BODE index , diffusion capacity of the lung for carbon monoxide percentage , and quality of life . Change from baseline in the partial pressure of arterial oxygen was not significantly different between the sildenafil and placebo groups . CONCLUSIONS This pilot study found that treatment with sildenafil  reduced pulmonary vascular resistance and improved the BODE index and quality of life , without a significant effect on gas exchange BACKGROUND Phosphodiesterase-5 ( PDE5 ) inhibitors improve exercise capacity and quality of life in patients with idiopathic pulmonary arterial hypertension . However , whether such beneficial effects take place in selected population s with chronic obstructive pulmonary disease ( COPD ) remains uncertain . We aim ed to assess the effects of tadalafil -- a PDE5 inhibitor -- on exercise capacity and quality of life in patients with COPD and mild pulmonary hypertension . METHODS We did a r and omised , double-blind , parallel-group , placebo-controlled trial at three centres in Scotl and , UK , between Sept 1 , 2010 , and Sept 1 , 2012 . Patients with moderate to severe COPD were r and omly assigned ( 1:1 ) , via central ised r and omisation with a computer-generated sequence and block sizes of four , to receive daily tadalafil 10 mg or placebo for 12 weeks . Patients , study investigators , outcome assessors , and those administering drugs were masked to group allocation . The primary endpoint was the mean placebo-corrected difference between the baseline and final 6 min walk distance after 12 weeks . We measured change in quality of life at baseline , 8 weeks , and 12 weeks , with st and ardised question naires . Analysis was per protocol and by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01197469 . FINDINGS 120 patients were r and omly assigned to receive tadalafil ( n=60 ) or placebo ( n=60 ) , of whom 56 ( 93 % ) versus 57 ( 95 % ) completed the study . At 12 weeks the difference in 6 min walking distance between the tadalafil and placebo groups was 0·5 m ( 95 % CI -11·6 to 12·5 ; p=0·937 ) . We recorded no statistically significant changes in quality of life ( between-group difference on the St George 's Respiratory Question naire -2·64 [ 95 % CI -6·43 to 1·15 ] ; Research and Development version 1 short-form-36 4·08 [ -1·35 to 9·52 ] ; Minnesota Living with Heart Failure question naire -2·31 [ -7·06 to 2·45 ] ) . 19 ( 32 % ) of 60 patients in the treatment group had dyspepsia ; the severity of dyspepsia ranged from mild to severe , with four ( 21 % ) of 19 patients needing a proton-pump inhibitor . Five ( 8 % ) of 60 participants had dyspepsia in the placebo group . Headache was noted in 17 ( 28 % ) patients in the treatment group versus 5 ( 8 % ) in the placebo group , but was mild in all patients . Two ( 3 % ) patients in the treatment group had facial flushing , which result ed in one withdrawal . Other withdrawals within the tadalafil group happened after a transient ischaemic attack and two deaths ( ruptured abdominal aortic aneurysm and pneumonia ) . INTERPRETATION Tadalafil does not improve exercise capacity or quality of life despite exerting pulmonary vasodilation . FUNDING Chief Scientist Office for Scotl and 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 ) Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce . METHODS In this event-driven , double-blind study , we r and omly assigned , in a 2:1:1 ratio , participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil ( combination-therapy group )  , 10 mg of ambrisentan plus placebo ( ambrisentan-monotherapy group )  , or 40 mg of tadalafil plus placebo ( tadalafil-monotherapy group ) , all administered once daily . The primary end point in a time-to-event analysis was the first event of clinical failure , which was defined as the first occurrence of a composite of death , hospitalization for worsening pulmonary arterial hypertension , disease progression , or unsatisfactory long-term clinical response . R 
    Output:
    
Treatment in both COPD -PH and ILD-PH did not worsen hypoxemia .
Symptomatic burden was not consistently reduced but there were trends for reduced pulmonary artery pressures and pulmonary vascular resistance with PAH-specific therapy .