***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 Decline in forced vital capacity ( FVC ) over time reliably predicts mortality in patients with idiopathic pulmonary fibrosis . The use of this measure in clinical practice is recommended by current evidence -based guidelines . It is unknown if the method of calculating decline in FVC ( relative vs absolute change ) impacts its frequency or its ability to predict mortality . Methods Patients with idiopathic pulmonary fibrosis from two prospect i ve cohorts were included if they had a baseline and 12-month follow-up FVC . A ≥10 % decline in FVC from baseline was calculated in two ways : a relative decline of 10 % ( eg , from 60 % predicted to 54 % predicted ) and an absolute decline of 10 % ( eg , from 60 % predicted to 50 % predicted ) . The frequency of a ≥10 % decline in FVC and its ability to predict 2-year transplant-free survival were compared between these two methods . Declines in FVC of ≥5 % and ≥15 % were similarly compared . Analyses were performed unadjusted and adjusted for age , gender , use of oxygen , baseline FVC and baseline diffusion capacity for carbon monoxide . Results The frequency of any given FVC decline was significantly greater using the relative change in FVC method . For ≥10 % decline , both methods predicted 2-year transplant-free survival with similar accuracy , and remained significant predictors after adjusting for baseline characteristics . The absolute change method appeared more predictive for ≥5 % decline . Conclusions Using the relative change in FVC maximises the chance of identifying a ≥10 % decline in FVC without sacrificing prognostic accuracy . This may not hold true for ≥5 % decline in FVC . These findings have important implication s for clinical practice and the design of clinical trials OBJECTIVE Patients with systemic sclerosis-associated interstitial lung disease ( SSc-ILD ) are thought to have the greatest decline in lung function ( forced vital capacity [FVC]% predicted ) in the early years after disease onset . The aim of this study was to assess the natural history of the decline in FVC% predicted in patients receiving placebo in the Scleroderma Lung Study and to evaluate possible factors for cohort enrichment in future therapeutic trials . METHODS Patients r and omized to receive placebo ( n=79 ) were divided into 3 groups based on the duration of SSc ( 0 - 2 years , 2 - 4 years , and > 4 years ) . Descriptive statistics and a mixed-effects model were used to analyze the rate of decline in the FVC% predicted over a 1-year period . Additional analyses stratified according to the severity of fibrosis on high-resolution computed tomography ( H RCT ) were performed , and interactions between disease severity and disease duration were explored . RESULTS The mean±SD decline in the unadjusted FVC% predicted during the 1-year period was 4.2±12.8 % . At baseline , 28.5 % , 43.0 % , and 28.5 % of patients were in the groups with disease duration s of 0 - 2 years , 2 - 4 years , and > 4 years , respectively . The rate of decline in the FVC% predicted was not significantly different across the 3 disease groups ( P=0.85 ) . When stratified by baseline fibrosis on H RCT , the rate of decline in the FVC% predicted was statistically significantly greater in the group with severe fibrosis ( mean annualized decline in the FVC% predicted 7.2 % versus 2.7 % in the groups with no or moderate fibrosis ; P=0.008 ) . The decline observed in the group with severe fibrosis was most pronounced in those with a relatively short disease duration ( 0 - 2 years ; annualized decline 7.0 % ) . CONCLUSION Among patients with SSc-ILD in the Scleroderma Lung Study , the rates of progression of lung disease were similar irrespective of disease duration . The baseline H RCT fibrosis score is a predictor of a future decline in the FVC% predicted in the absence of effective treatment Pulse cyclophosphamide is more effective than prednisone alone in preventing  renal failure in lupus nephritis . We undertook a r and omised , controlled trial to find out whether pulse methylprednisolone could equal pulse cyclophosphamide in preserving renal function in patients with lupus nephritis , and whether there was a difference between long and short courses of pulse cyclophosphamide in preventing exacerbations . 65 patients ( 60 female , 5 male ; median [ range ] age 29 [ 10 - 48 ] years ) with severe lupus nephritis were assigned r and omly to monthly pulse methylprednisolone for 6 months ( 25 patients ) , monthly pulse cyclophosphamide for 6 months ( 20 ) , or monthly cyclophosphamide for 6 months followed by quarterly pulse cyclophosphamide for 2 additional years ( 20 ) . Patients treated with pulse methylprednisolone had a higher probability of doubling serum creatinine than those treated with long-course cyclophosphamide ( p less than 0.04 ) . Risk of doubling creatinine was not significantly different between short and long course cyclophosphamide . However , patients treated with short-course cyclophosphamide had a higher probability of exacerbations than those treated with long-course cyclophosphamide ( p less than 0.01 ) . An extended course of pulse cyclophosphamide is more effective than 6 months of pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis . Addition of a quarterly maintenance regimen to monthly pulse cyclophosphamide reduces the rate of exacerbations OBJECTIVE The lack of r and omized controlled trials ( RCTs ) in pulmonary fibrosis in systemic sclerosis ( SSc ) has hampered an evidence -based approach to treatment . This RCT was undertaken to investigate the effects of intravenous ( IV ) cyclophosphamide ( CYC ) followed by azathioprine ( AZA ) treatment in pulmonary fibrosis in SSc . METHODS Forty-five patients were r and omized to receive low-dose prednisolone and 6 infusions ( monthly ) of CYC followed by oral AZA , or placebo . Primary outcome measures were change in percent predicted forced vital capacity ( FVC ) and change in single-breath diffusing capacity for carbon monoxide ( DLCO ) . Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores . An intent-to-treat statistical analysis was performed . RESULTS At baseline , there were no significant group differences in factors linked to outcome , including severity of pulmonary fibrosis and autoantibody status . Sixty-two percent of the patients completed the first year of treatment . Withdrawals included 9 patients ( 6 from the placebo group ) with significant decline in lung function , 2 with treatment side effects ( both from the active treatment group ) , and 6 with non-trial-related comorbidity . No hemorrhagic cystitis or bone marrow suppression was observed . Estimation of the relative treatment effect ( active treatment versus placebo ) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19 % ; this between-group difference showed a trend toward statistical significance ( P = 0.08 ) . No improvements in DLCO or secondary outcome measures were identified . CONCLUSION This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo . However , for FVC there was a trend toward statistical significance between the 2 groups . This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease . Therapy was well tolerated with no increase in serious adverse events Introduction The objective of the present study was to examine the association of baseline demographic and clinical characteristics with sequentially obtained measurements of  forced vital capacity ( FVC ) , expressed as a percentage of the predicted value , and to identify predictors of the decline rate in FVC over time in the Genetics versus Environment in Scleroderma Outcome Study ( GENISOS ) . Methods To date , 266 patients have been enrolled in GENISOS , a prospect i ve , observational cohort of patients with early systemic sclerosis . In addition to pulmonary function tests ( PFTs ) , clinical and laboratory data were obtained from each patient . We analyzed 926 FVC measurements utilizing generalized linear mixed models . The predictive significance of baseline variables for the decline rate in FVC was investigated by the interaction term between the variable and the follow-up time within the first 3 years after enrollment as well as throughout the entire follow-up time . Results The cohort consisted of 125 white , 54 African American , and 77 Hispanic patients with average disease duration of 2.5 years at enrollment . The mean follow-up time was 3.8 years , ranging up to 11.4 years . A number of baseline variables , including antibody status , African American ethnicity , disease type , baseline PFT values , modified Rodnan Skin Score , fibrosis on chest radiograph , and lung and skin subscores of the Severity Index , were associated with serially measured FVC levels . However , only the presence of anti-topoisomerase I antibodies ( ATA ) was associated with lower FVC levels ( P < 0.001 ) as well as accelerated decline rate in FVC within the first 3 years of follow-up ( P = 0.02 ) . None of the baseline variables predicted the rate of decline in FVC on long-term follow-up . Patients with rapidly progressive ILD , however , were under-represented in the long-term follow-up group because the accelerated rate of decline in FVC was associated with poor survival ( P = 0.001 ) . Conclusions Presence of ATA was the only baseline variable associated with differential FVC levels , predicting the rate of decline in FVC within the first 3 years of follow-up . The association of faster decline in FVC with poor survival further emphasizes the need for identification of predictive biomarkers by collection of genetic information and serial blood sample s in cohort studies Objective : To estimate minimally important differences ( MIDs ) in scores for the modified Rodnan Skin Score ( mRSS ) and Health Assessment Question naire — Disability Index ( HAQ-DI ) in a clinical trial on diffuse systemic sclerosis ( SSc ) . Participants and methods : 134 people participated in a 2-year , double-blind , r and omised clinical trial comparing efficacy of low-dose and high-dose d-penicillamine in diffuse SSc . At 6 , 12 , 18 and 24 months , the investigator was asked to rate the change in the patient ’s health since entering the study : markedly worsened , moderately worsened , slightly worsened , unchanged , slightly improved , moderately improved or markedly improved . Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved . Results : The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 ( 0.40–0.66 effect size ) and for the HAQ-DI from 0.10 to 0.14 ( 0.15–0.21 effect size ) . Patients who were rated to improve more than slightly were found to improve by 6.9–14.2 ( 0.86–1.77 effect size ) on the mRSS and 0.21–0.55 ( 0.32–0.83 effect size ) on the HAQ-DI score . Conclusion : MID estimates are provided for improvement in the mRSS and HAQ-DI scores , which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc Background The assessment of treatment response in idiopathic pulmonary fibrosis ( IPF ) is complicated by the variable clinical course . We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment . Methods The source population included patients enrolled in the ASCEND and CAPACITY trials ( N=1247 ) . Pearson 's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population . Outcomes following a ≥10 % decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10 % decline in FVC or death during the subsequent 6 months . Results A weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population ( coefficient , −0.146 , p<0.001 ) , indicating substantial variability . Thirty-four ( 5.5 % ) and 68 ( 10.9 % ) patients in the pirfenidone and placebo groups , respectively , experienced a ≥10 % decline in FVC by month 6 . During the subsequent 6 months , fewer patients in the pirfenidone group compared with placebo experienced a ≥10 % decline in FVC or death ( 5.9 % vs 27.9 % ; relative difference , 78.9 % ) . There was one ( 2.9 % ) death in the pirfenidone group and 14 ( 20.6 % ) deaths in the placebo group ( relative difference , 85.7 % ) . Conclusions Longitudinal FVC data from patients with IPF showed substantial intrasubject variability , underscoring the inability to reliably assess therapeutic response using serial FVC trends . In patients who progressed during treatment , continued treatment with pirfenidone result ed in a lower risk of subsequent FVC decline or death . Trial registration numbers NCT01366209 , NCT00287729 , NCT00287716 OBJECTIVES To assess the safety and 
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Trialists reported no significant impact on lung function when cyclophosphamide was used compared with mycophenolate at 12 months ( FVC % MD -0.82 , 95 % CI -3.95 to 2.31 ; P = 0.61 ; two trials , 149 participants ; DLCO % MD -1.41 , 95 % CI -10.40 to 7.58 ; P = 0.76 ; two trials , 149 participants ) .Risk of side effects was increased with cyclophosphamide versus mycophenolate , in particular , leukopenia and thrombocytopenia .
The data demonstrates no significant impact on health-related quality of life , all-cause mortality , dyspnoea , or cough severity in the  cyclophosphamide  group compared with the mycophenolate group .
No trials reported outcomes associated with functional exercise tests .
This review , which is based on studies of varying method ological quality , demonstrates that overall , in this population , small benefit may be derived from the use of cyclophosphamide in terms of mean difference in % FVC when compared with placebo , but not of the difference in % DLCO , or when compared with mycophenolate .
Modest clinical improvement in dyspnoea may be noted with the use of cyclophosphamide .
Clinical practice guidelines should advise clinicians to consider individual patient characteristics and to expect only modest benefit at best in preserving FVC .