***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 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)I2 caused preferential pulmonary vasodilatation with a decrease in mean pulmonary arterial pressure from 44.1 + /- 4.2 to 31.6 + /- 3.1 mmHg , and pulmonary vascular resistance ( RL ) from 810 + /- 226 to 386 + /- 69 dyn.s.cm-5 ( p < 0.005 , 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 PGI2 and CAAs were not pulmonary selective , result ing in a significant drop in arterial pressure . In addition PGI2 infusion caused a marked increase in shunt flow . Long-term therapy with aerosolized iloprost ( long-acting PGI2 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 PGI2 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 RATIONALE A previous trial of bosentan in idiopathic pulmonary fibrosis ( IPF ) showed a trend to delayed IPF worsening or death . Also , improvements in some measures of dyspnea and health-related quality of life were observed . OBJECTIVES To demonstrate that bosentan delays IPF worsening or death . METHODS Prospect i ve , r and omized ( 2:1 ) , double-blind ,  placebo-controlled , event-driven , parallel-group , morbidity-mortality trial of bosentan in adults with IPF of less than 3 years ' duration , confirmed by surgical lung biopsy , and without extensive honeycombing on high-resolution computed tomography . The primary endpoint was time to IPF worsening ( a confirmed decrease from baseline in FVC ≥ 10 % and diffusing capacity of the lung for carbon monoxide ≥ 15 % , or acute exacerbation of IPF ) or death up to End of Study . Effects of bosentan on health-related quality of life , dyspnea , and the safety and tolerability of bosentan were investigated . MEASUREMENTS AND MAIN RESULTS Six hundred sixteen patients were r and omized to bosentan ( n=407 ) or placebo ( = 209 ) . No significant difference between treatment groups was observed in the primary endpoint analysis ( hazard ratio , 0.85 ; 95 % confidence interval , 0.66 - 1.10 ; P=0.2110 ) . No treatment effects were observed on health-related quality of life or dyspnea . Some effects of bosentan treatment were observed in changes from baseline to 1 year in FVC and diffusing capacity of the lung for carbon monoxide . The safety profile for bosentan was similar to that observed in other trials . CONCLUSIONS The primary objective in the Bosentan Use in Interstitial Lung Disease-3 trial was not met . Bosentan was well tolerated . Clinical trial registered with www . clinical trials.gov ( NCT 00391443 ) 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 The aim of this study was to prospect ively evaluate the prevalence of pulmonary hypertension ( PH ) in patients with idiopathic pulmonary fibrosis ( IPF ) . One hundred thirty-nine patients ( 101 male , mean age = 68.6 ± 9 years ) , with confirmed IPF and who were admitted to eight Pulmonary Departments in Greece between November 2005 and December 2006 were included in the study . Pulmonary artery systolic pressure ( PASP ) was estimated by echocardiography , and PH was defined as PASP > 36 mmHg . We compared demographics , pulmonary function tests , NYHA functional status , 6-min walk distance ( 6MWD ) , B-type natriuretic peptide ( BNP ) , PaO2 , and P(A-a)O2 at rest data between patients with PH and without PH ( PASP ≤ 36 mmHg ) . Increased estimated right ventricular systolic pressure was present in 55 % of patients ( mean PASP = 47.1 ± 11.2 mmHg vs. 30.3 ± 3.8 mmHg , respectively ) . Patients with PH had a lower but not statistically significant DLCO ( 47.1 ± 18.8 vs. 52.5 ± 20.1 ) , lower PaO2 at rest ( 64.6 ± 12.2 vs. 71.1 ± 11.3 , P = 0.004 ) , and lower mean 6MWD ( 282 ± 118 vs. 338 ± 91 , P = 0.007 ) . Significant differences were also observed in the NYHA functional status between the two groups ( P = 0.02 ) . Statistically significant correlations were observed between PASP and PaO2 at rest ( r = −0.331 , P = 0.00 ) , P(A-a)O2 at rest ( r = 0.494 , P = 0.00 ) , 6MWD ( r = −0.264 , P = 0.01 ) , SpO2 at rest ( r = −0.293 , P = 0.00 ) , SpO2 at the end of exercise ( r = −0.364 , P = 0.00 ) , and also BNP values ( r = 0.319 , P = 0.01 ) . Moreover , PaO2 ( P = 0.02 ) , P(A-a)O2 ( P = 0.005 ) , and SpO2 at the end of exercise ( P = 0.023 ) were independent predictors of the presence of estimated PH . Using Doppler echocardiography as a screening tool for the estimation of PH , we found that PH is common in patients with IPF .  Gas exchange parameters at rest and exercise desaturation might indicate underlying PH in IPF Idiopathic pulmonary fibrosis is a progressive , fatal disease . This prospect i ve , r and omised , double-blind , multicentre , parallel-group , placebo-controlled phase II trial ( NCT00903331 ) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis . Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy . The primary objective was to demonstrate that macitentan ( 10 mg once daily ) positively affected forced vital capacity versus placebo . Using a central ised system , 178 subjects were r and omised ( 2:1 ) to macitentan ( n=119 ) or placebo ( n=59 ) . The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm . Overall , no differences between treatments were observed in pulmonary function tests or time to disease worsening or death . Median exposures to macitentan and placebo were 14.5 months and 15.0 months , respectively . Alanine and /or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4 % of macitentan-treated subjects and 5.1 % of placebo recipients . In conclusion , the primary objective was not met . Long-term exposure to macitentan was well tolerated with a similar , low incidence of elevated hepatic aminotransferases in each treatment group . Long-term exposure to macitentan was well tolerated in IPF in a trial that did not meet its primary end-point 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 The clinical course of pulmonary hypertension ( PH ) in idiopathic pulmonary fibrosis ( IPF ) is not known except in advanced disease 
    Output:
    
We found no significant changes from baseline in lung function , dyspnea , or exercise capacity .
Although PH-specific agents provided small health-related quality -of-life benefits , our meta- analysis provides insufficient evidence to support their use in IPF patients