***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 Computed tomography ( CT ) lung densitometry has been demonstrated to be the most sensitive and specific outcome measure for the assessment of emphysema-modifying therapy , but the optimum densitometric index has yet to be determined and targeted sampling may be more sensitive than whole lung assessment . The EXAcerbations and CT scan as Lung Endpoints ( EXACTLE ) trial aim ed to clarify the optimum approach to the use of CT densitometry data for the assessment of alpha 1-antitrypsin ( AAT ) augmentation therapy on the progression of emphysema in AAT deficiency ( AATD ) . Methods Patients with AATD ( n = 77 ) were r and omised to weekly infusions of 60 mg/kg human AAT ( Prolastin ® ) or placebo over 2 to 2.5 years . Lung volume was included as a covariate in an endpoint analysis and a comparison was made of different CT densitometric indices ( 15th percentile lung density [ PD15 ] , mean lung density [ MLD ] and voxel index at a threshold of -910 [ VI-910 ] and -950 [ VI-950 ] Hounsfield Units ) obtained from whole lung scans at baseline and at 24 to 30 months . Targeted regional sampling was compared with whole lung assessment . Results Whole lung analysis of the total change ( baseline to last CT scan ) compared with placebo indicated a concordant trend that was suggestive of a treatment effect for all densitometric indices ( MLD [ 1.402 g/L , p = 0.204 ] ; VI-910 [ -0.611 , p = 0.389 ] ; VI-950 [ -0.432 , p = 0.452 ] ) and that was significant using PD15 ( 1.472 g/L , p = 0.049 ) . Assessment of the progression of emphysema in the apical , middle and basal regions of the lung by measurement with PD15 showed that this treatment effect was more evident when the basal third was sample d ( 1.722 g/L , p = 0.040 ) . A comparison between different densitometric indices indicated that the influence of inspiratory variability between scans was greatest for PD15 , but when adjustment for lung volume was made this index was the most sensitive measure of emphysema progression . Conclusion PD15 is the most sensitive index of emphysema progression and of treatment modification . Targeted sampling may be more sensitive than whole lung analysis .Trial registration Registered in Clinical Trials.gov as ' Antitrypsin ( AAT ) to Treat Emphysema in AAT-Deficient Patients ' ; Clinical Trials.gov Identifier : NCT00263887 Abstract The Dutch-Belgian R and omized Lung Cancer Screening Trial ( Dutch acronym : NELSON study ) was design ed to investigate whether screening for lung cancer by low-dose multidetector computed tomography ( CT ) in high-risk subjects will lead to a decrease in 10-year lung cancer mortality of at least 25 % compared with a control group without screening . Since the start of the NELSON study in 2003 , 7557 participants underwent CT screening  , with scan rounds in years 1 , 2 , 4 and 6 . In the current review , the design of the NELSON study including participant selection and the lung nodule management protocol , as well as results on validation of CT screening and first results on lung cancer screening are described PURPOSE To prospect ively evaluate airway wall thickness and lung attenuation at spirometrically gated thin-section computed tomography ( CT ) in patients with chronic obstructive pulmonary disease ( COPD ) and to correlate gated CT findings with pulmonary function test ( PFT ) results . MATERIAL S AND METHODS The ethical committee approved the study , and all patients gave informed consent . Forty-two consecutive patients with COPD ( 20 with and 22 without chronic bronchitis [ CB ] ) underwent gated thin-section CT and PFTs on the same day . The percentage wall area ( PWA ) and the thickness-to-diameter ratio ( TDR ) for all depicted bronchi that were round and larger than 2 mm in diameter , the mean lung attenuation ( MLA ) , and the pixel index ( PI ) at -950 HU were determined . The reproducibility of the airway measurements was preliminarily tested by performing a five-trial examination in a patient with COPD and in a control patient . Differences in airway and lung attenuation measurements between the patients with and those without CB were evaluated at Mann-Whitney U testing . Simple and multiple regression analyses were used to assess the correlation between thin-section CT and PFT measurements . RESULTS The mean intraoperator coefficient of variation for airway measurements was 7.8 % ( range , 3.8%-13.4 % ) . An average of nine bronchi per patient were assessed . Patients with CB had significantly higher PWAs , TDRs , and MLAs and significantly lower PIs than patients without CB ( P < .05 for all values ) . The combination of PWA , TDR , and PWA normalized to body weight correlated significantly ( P < .05 ) with the forced expiratory volume in 1 second-to-slow vital capacity ratio and the diffusing capacity of the lung for carbon monoxide in patients with but not in patients without CB . PFT results correlated better with MLA and PI in patients without CB . CONCLUSION Bronchial wall measurements differ between patients who have COPD with CB and those who have COPD without CB . The correlation between airway dimensions and indexes of airway obstruction in patients with COPD and CB indicates that the bronchial tree is the site of anatomic-functional alterations in this patient group Background The Korean Obstructive Lung Disease ( KOLD ) Cohort Study is a prospect i ve longitudinal study of patients with chronic obstructive pulmonary disease ( COPD ) , asthma , or other unclassified obstructive lung diseases . It was design ed to develop new classification models and biomarkers that predict clinical ly relevant outcomes for patients with obstructive lung diseases . Methods Patients over 18 years old who have chronic respiratory symptoms and airflow limitations or bronchial hyper-responsiveness were enrolled at 17 centers in South Korea . After a baseline visit , the subjects were followed up every 3 months for various assessment s. Results From June 2005 to October 2013 , a total of 477 subjects ( 433 [ 91 % ] males ; 381 [ 80 % ] diagnosed with COPD ) were enrolled . Analyses of the KOLD Cohort Study identified distinct phenotypes in patients with COPD , and predictors of therapeutic responses and exacerbations as well as the factors related to pulmonary hypertension in COPD . In addition , several genotypes were associated with radiological phenotypes and therapeutic responses among Korean COPD patients . Conclusion The KOLD Cohort Study is one of the leading long-term prospect i ve longitudinal studies investigating heterogeneity of the COPD and is expected to provide new insights for pathogenesis and the long-term progression of COPD Background Emphysema on CT is common in older smokers . We hypothesised that emphysema on CT predicts acute episodes of care for chronic lower respiratory disease among older smokers . Material s and Methods Participants in a lung cancer screening study age ≥60 years were recruited into a prospect i ve cohort study in 2001–02 . Two radiologists independently visually assessed the severity of emphysema as absent , mild , moderate or severe . Percent emphysema was defined as the proportion of voxels ≤ −910 Hounsfield Units . Participants completed a median of 5 visits over a median of 6 years of follow-up . The primary outcome was hospitalization , emergency room or urgent office visit for chronic lower respiratory disease . Spirometry was performed following ATS/ERS guidelines . Airflow obstruction was defined as FEV1/FVC ratio < 0.70 and FEV1<80 % predicted . Results Of 521 participants , 4 % had moderate or severe emphysema , which was associated with acute episodes of care ( rate ratio 1.89 ; 95 % CI : 1.01–3.52 ) adjusting for age , sex and race/ethnicity , as was percent emphysema , with similar associations for hospitalisation . Emphysema on visual assessment also predicted incident airflow obstruction ( HR 5.14 ; 95 % CI 2.19–21.1 ) . Conclusion Visually assessed emphysema and percent emphysema on CT predicted acute episodes of care for chronic lower respiratory disease , with the former predicting incident airflow obstruction among older smokers Background Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease ( COPD ) , although factors influencing the length and frequency of each episode are poorly understood . This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin ( AAT ) deficiency ( PiZ phenotype ) and COPD . Methods Daily diary cards were collected over 2 years . Patients had emphysema visualized and quantified by computed tomography scan , and had at least one documented exacerbation in the previous year . Results The patients ( n = 23 ) had a mean age of 52.5 years , forced expiratory volume in one second ( FEV1 ) of 1.2 L ( 38.4 % predicted ) , corrected gas transfer ( KCO ) of 0.90 mmol/min/kPa/L ( 59.7 % predicted ) , and 15th percentile lung density of 44.55 g/L. Two hundred and sixty-three exacerbations ( 164 treated ) were identified . The frequency of treated exacerbations correlated negatively with KCO% predicted ( r = −0.432 ; P = 0.022 ) . Exacerbation length ( determined for 17 of the patients for whom diary card data through the episode were available ) correlated negatively with baseline 15th percentile lung density ( r = −0.361 ; P = 0.003 ) , and increased the longer treatment was delayed ( r = 0.503 ; P < 0.001 ) . Treatment delay was shorter with higher day 1 symptom score , lower baseline FEV1 , FEV1/forced vital capacity , and lower 15th percentile lung density ( r = −0.368 , 0.272 , 0.461 , and 0.786 ; P = 0.004 , 0.036 , < 0.001 , and < 0.001 , respectively ) . Time to resolution of exacerbation after treatment initiation was not affected by treatment delay , but correlated negatively with KCO% predicted ( r = −0.647 ; P = 0.007 ) . Conclusion In alpha-1 antitrypsin deficiency , the frequency and length of resolution of exacerbation were related to baseline gas transfer . Treatment delay adversely affected exacerbation length , and lung density was the best independent predictor of delay in starting treatment Chronic obstructive pulmonary disease ( COPD ) is a heterogeneous disease and responses to therapies are highly variable . The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD . A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease ( KOLD ) Cohort , which were prospect ively recruited from June 2005 to September 2009 , were analyzed retrospectively . The prediction models for the FEV1 , FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple , stepwise , linear regression analysis . The prediction model for the FEV1 change after 3 months of treatment included wheezing history , pre-bronchodilator FEV1 , post-bronchodilator FEV1 change and emphysema extent on CT ( R = 0.578 ) . The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC , post-bronchodilator FVC change ( R = 0.533 ) , and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV1 change ( R = 0.401 ) . Wheezing history , pre-bronchodilator pulmonary function , bronchodilator responsiveness , and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD BACKGROUND Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema . METHODS One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema , defined by diffusing capacity of the lung for carbon monoxide ( Dlco ) [ 37.1 + /- 12.0 % of predicted ] and CT density mask ( 38.5 + /- 12.8 % of voxels < - 910 Hounsfield units ) [ mean + /- SD ] were enrolled into a r and omized , double-blind , feasibility study at five university hospitals . Participants received all-trans retinoic acid ( ATRA ) at either a low dose ( LD ) [ 1 mg/kg/d ] or high dose ( HD ) [ 2 mg/kg/d ] , 13-cis retinoic acid ( 13-cRA ) [ 1 mg/kg/d ] , or placebo for 6 months followed by a 3-month crossover period . RESULTS No treatment was associated with an overall improvement in pulmonary function , CT density mask score , or health-related quality of life ( QOL ) at the end of 6 months . However , time-dependent changes in 
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There was marked heterogeneity between studies secondary to large variety of disease severity within commonly included cohorts and differences in CT acquisition parameters .
Conclusion CT density shows a good relationship to clinical ly relevant parameters ; however , study heterogeneity and lack of longitudinal data mean that it is difficult to compare studies or derive a minimal clinical ly important difference .