***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: 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 OBJECTIVE To investigate the use of high resolution computed tomography ( H RCT ) in diagnosis of patients with fibrosing alveolitis associated with systemic sclerosis ( FA-SSc ) , and to determine predictors of disease progression . METHODS We retrospectively studied 90 patients with SSc who had undergone an initial ( Time 1 ) and followup ( Time 2 ) clinical and H RCT evaluation , with a mean + /- SD interval of 5.14 + /- 2.98 years between T1 and T2 . RESULTS At T1 ,  H RCT  was normal in 40 patients ; at T2 , 34/40 ( 85 % ) continued to have a normal H RCT . For the 50 patients with FA-SSc on  H RCT scan at T1 , the overall disease progression comprised extension of lung changes toward the apices with worsening of lung fibrosis at T2 . Among the 37 patients who had areas of isolated ground-glass opacities at T1 , 25 ( 68 % ) had progression of lung fibrosis at T2 . These 25 patients were mostly men , who showed a more marked decrease of diffusing capacity and a longer interval between T1 and T2 . CONCLUSION The results emphasize the good longterm prognosis indicated by a normal initial H RCT in SSc . Patients with FA-SSc with abnormal H RCT experienced progressive replacement of ground-glass opacities by honeycombing and /or traction bronchiectasis/bronchiolectasis . Ground-glass opacity is probably the first step of lung fibrosis in SSc , and treatment should be discussed even at this early stage OBJECTIVE To evaluate the prognostic value of bronchoalveolar lavage ( BAL ) cellular profiles in patients with systemic sclerosis-associated interstitial lung disease ( SSc-ILD ) . METHODS  BAL cellularity was examined in relation to mortality ( n = 141 ) , serial pulmonary function findings ( n = 134 ) , and " progression-free survival " ( n = 134 ) , by proportional hazards analysis . Baseline severity was quantified according to the extent of disease on high-resolution computed tomography , the diffusing capacity for carbon monoxide , and the presence or absence of pulmonary hypertension . Mortality was subclassified into overall mortality ( during 10 years of followup ) , early mortality ( occurring within 2 years of presentation ) , and late mortality ( occurring 2 - 10 years after presentation ) . RESULTS Overall mortality was associated with neutrophilia on BAL ( hazard ratio 2.23 [ 95 % confidence interval 1.20 - 4.14 ] , P = 0.01 ) , but this effect was lost when disease severity was taken into account . Early mortality was associated with neutrophilia on BAL ( hazard ratio 8.40 [ 95 % confidence interval 1.91 - 36.95 ] , P = 0.005 ) , independent of disease severity . Late mortality was not associated with neutrophilia on BAL . The presence of neutrophilia on BAL was not associated with time to decline in pulmonary function or progression-free survival . Neither eosinophilia nor lymphocytosis on BAL was associated with mortality , rapidity of functional deterioration , or progression-free survival . These findings were unaltered when treatment status was taken into account . CONCLUSION BAL findings provide only limited prognostic information in SSc-ILD . Neutrophilia on BAL is linked to early mortality , but BAL findings are not linked to long-term survival or the rapidity of progression of lung disease . The usefulness of BAL to define alveolitis in SSc is question able RATIONALE In interstitial lung disease complicating systemic sclerosis ( SSc-ILD ) , the optimal prognostic use of baseline pulmonary function tests ( PFTs ) and high-resolution computed tomography ( H RCT ) is uncertain . OBJECTIVES To construct a readily applicable prognostic algorithm in SSc-ILD , integrating PFTs and H RCT . METHODS The prognostic value of baseline PFT and H RCT variables was quantified in patients with SSc-ILD ( n = 215 ) against survival and serial PFT data . MEASUREMENTS AND MAIN RESULTS Increasingly extensive disease on H RCT was a powerful predictor of mortality ( P < 0.0005 ) , with an optimal extent threshold of 20 % . In patients with H RCT extent of 10 - 30 % ( termed indeterminate disease ) , an FVC threshold of 70 % was an adequate prognostic substitute . On the basis of these observations , SSc-ILD was staged as limited disease ( minimal disease on H RCT or , in indeterminate cases , FVC > or= 70 % ) or extensive disease ( severe disease on H RCT or , in indeterminate cases , FVC < 70 % ) . This system ( hazards ratio [ HR ] , 3.46 ; 95 % confidence interval [ CI ] , 2.19 - 5.46 ; P < 0.0005 ) was more discriminatory than an H RCT threshold of 20 % ( HR , 2.48 ; 95 % CI , 1.57 - 3.92 ; P < 0.0005 ) or an FVC threshold of 70 % ( HR , 2.11 ; 95 % CI , 1.34 - 3.32 ; P = 0.001 ) . The system was evaluated by four trainees and four practitioners , with minimal and severe disease on H RCT defined as clearly < 20 % or clearly > 20 % , respectively , and the use of an FVC threshold of 70 % in indeterminate cases . The staging system was predictive of mortality for all scorers , with prognostic separation higher for practitioners ( HR , 3.39 - 3.82 ) than trainees ( HR , 1.87 - 2.60 ) . CONCLUSIONS An easily applicable limited/extensive staging system for SSc-ILD , based on combined evaluation with H RCT and PFTs , provides discriminatory prognostic information To evaluate the role and the prognostic value of bronchoalveolar lavage ( BAL ) in scleroderma patients with interstitial lung disease . We review ed the records of 79 patients with systemic sclerosis ( SSc ) who had dyspnea and pulmonary involvement and underwent BAL study .  Sixty-two patients were prospect ively followed up for 12–36 months and re-evaluated by pulmonary function tests ( PFTs ) . Seventy-nine SSc patients were enrolled ( 71 F and 8 M ) , 55 with limited and 24 with a diffuse form ; mean age 55 ± 13 years ; mean disease duration 55.2 ± 59 months . All patients were ANA positive , of these 30 were anti-topoisomerase-1 positive ( anti-Topo1 ) and 22 were anti-centromere positive ( ACA ) . Thirty-one patients had alveolitis ( 39.2 % ) that was neutrophilic in 12 patients , eosinophilic in 3 and mixed ( neutrophilic and eosinophilic ) in 16 patients . Compared to patients without alveolitis , those with alveolitis had a significant reduction of carbon monoxide diffusing capacity ( DLCO ) , forced vital capacity ( FVC ) and more elevated lung high-resolution computed tomography ( H RCT ) scores . Furthermore , alveolar clearance was significantly accelerated . No differences were found between patients with and without alveolitis regarding disease subsets ( diffuse vs limited-SSc ) ; a significant predominance of anti-Topo1 antibodies was found in the alveolitis group and of ACA antibodies in the non-alveolitis cohort . During the follow-up , ( range : 12–36 months ) 62 patients , 26 with and 36 without alveolitis were re-evaluated with PFTs . In the alveolitis group , 12 patients ( 46.1 % ) showed stable lung function parameters and 14 had worsened ( 53.8 % ) . In this group , 20 patients ( 77 % ) received cyclophosphamide ( CYC ) :  11 ( 55 % ) worsened ( 5 of them died of cardio-pulmonary complications ) and 9 ( 45 % ) remained stable . Six patients could not be treated ; of these 3 remained stable and 3 worsened . Among 36 patients with normal BAL , 11 ( 30.5 % ) showed stable lung function parameters , 13 improved ( 36.1 % ) and 12 worsened ( 33.3 % ) ; in this last group , 2 patients died of extra-pulmonary complications . Six patients , with progression of lung fibrosis , were treated with CYC : 3 of them improved and 3 remained stable . Our study revealed a trend toward a more severe course in the SSc patients with BAL alveolitis ; probably the non-significant result is related to the low number of the examined subjects and to the selection criteria . However , BAL remains the only tool to exclude lung infections and , in our experience , a useful instrument to evaluate interstitial lung disease in SSc patients RATIONALE The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease . OBJECTIVES To evaluate whether lavage cellularity identifies distinct subsets of disease and /or predicts cyclophosphamide responsiveness . METHODS Patients underwent baseline lavage and /or high-resolution computed tomography as part of a r and omized placebo-controlled trial of cyclophosphamide versus placebo ( Scleroderma Lung Study ) to determine the effect of therapy on forced vital capacity . Patients with 3 % or greater polymorphonuclear and /or 2 % or greater eosinophilic leukocytes on lavage and /or ground-glass opacification on computed tomography were eligible for enrollment . MEASUREMENTS AND MAIN RESULTS  Lavage was performed in 201 individuals , including 141 of the 158 r and omized patients .  Abnormal cellularity was present in 101 of these cases ( 71.6 % ) and defined a population with a higher percentage of men ( P = 0.04 ) , more severe lung function , including a worse forced vital capacity ( P = 0.003 ) , worse total lung capacity ( P = 0.005 ) and diffusing capacity of the lung for carbon monoxide ( P = 0.004 ) , more extensive ground-glass opacity ( P = 0.005 ) , and more extensive fibrosis in the right middle lobe ( P = 0.005 ) . Despite these relationships , the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year ( P = not significant ) . CONCLUSIONS The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response . Clinical trial registered with www . clinical trials.gov ( NCT 000004563 ) 
    Output:
    
The extent of disease on H RCT scan was the only variable that independently predicted both mortality and ILD progression .
CONCLUSIONS Mortality and ILD progression were predicted by several patient-specific , ILD-specific , and SSc-specific factors .