Pulmonary emphysema and coronary artery calcifications at baseline LDCT and long-term mortality in smokers and former smokers of the ITALUNG screening trial.

OBJECTIVES: Cardiovascular disease (CVD), lung cancer (LC), and respiratory diseases are main causes of death in smokers and former smokers undergoing low-dose computed tomography (LDCT) for LC screening. We assessed whether quantification of pulmonary emphysematous changes at baseline LDCT has a predictive value concerning long-term mortality. METHODS: In this longitudinal study, we assessed pulmonary emphysematous changes with densitometry (volume corrected relative area below - 950 Hounsfield units) and coronary artery calcifications (CAC) with a 0-3 visual scale in baseline LDCT of 524 participants in the ITALUNG trial and analyzed their association with mortality after 13.6 years of follow-up using conventional statistics and a machine learning approach. RESULTS: Pulmonary emphysematous changes were present in 32.3% of subjects and were mild (6% ≤ RA950 ≤ 9%) in 14.9% and moderate-severe (RA950 > 9%) in 17.4%. CAC were present in 67% of subjects (mild in 34.7%, moderate-severe in 32.2%). In the follow-up, 81 (15.4%) subjects died (20 of LC, 28 of other cancers, 15 of CVD, 4 of respiratory disease, and 14 of other conditions). After adjusting for age, sex, smoking history, and CAC, moderate-severe emphysema was significantly associated with overall (OR 2.22; 95CI 1.34-3.70) and CVD (OR 3.66; 95CI 1.21-11.04) mortality. Machine learning showed that RA950 was the best single feature predictive of overall and CVD mortality. CONCLUSIONS: Moderate-severe pulmonary emphysematous changes are an independent predictor of long-term overall and CVD mortality in subjects participating in LC screening and should be incorporated in the post-test calculation of the individual mortality risk profile. KEY POINTS: • Densitometry allows quantification of pulmonary emphysematous changes in low-dose CT examinations for lung cancer screening. • Emphysematous lung density changes are an independent predictor of long-term overall and cardio-vascular disease mortality in smokers and former smokers undergoing screening. • Emphysematous changes quantification should be included in the post-test calculation of the individual mortality risk profile.

Lung ultrasound B-lines in systemic sclerosis: cut-off values and methodological indications for interstitial lung disease screening.

OBJECTIVES: Lung ultrasound (LUS), through assessment of B-lines and pleural line alterations, is able to evaluate interstitial lung disease (ILD), a frequent complication of SSc. Different scanning schemes and counting methods have been proposed but no clear cut-off values have been indicated for screening. We aimed to evaluate the accuracy of different LUS methodological approaches to detect ILD compared with high-resolution CT (HRCT) as the gold standard. METHODS: Sixty-nine SSc patients underwent LUS and chest HRCT on the same day. Both exams were scored by expert readers. The accuracy of different scanning schemes and counting methods was assessed and clinical and functional data were compared with imaging findings. RESULTS: B-lines were more numerous in patients with the diffuse skin subset and Scl70 autoantibody positivity. The number of B-lines correlated with the Scleroderma Lung Study (SLS) I HRCT score (R = 0.754, P < 0.0001). A total of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest showed 97% sensitivity for detecting even very early ILD signs (corresponding to an SLS I score of 1). Sensitivity increased to 100% when pleural line alterations were included in the analysis. CONCLUSIONS: LUS has a very high sensitivity in detecting SSc-related ILD. A cut-off value of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest can be used for the screening of SSc-ILD. Assessing only the postero-basal chest seems to be mostly effective, combining high sensitivity with a less time-consuming approach.

Low-dose CT for lung cancer screening: position paper from the Italian college of thoracic radiology.

Smoking is the main risk factor for lung cancer (LC), which is the leading cause of cancer-related death worldwide. Independent randomized controlled trials, governmental and inter-governmental task forces, and meta-analyses established that LC screening (LCS) with chest low dose computed tomography (LDCT) decreases the mortality of LC in smokers and former smokers, compared to no-screening, especially in women. Accordingly, several Italian initiatives are offering LCS by LDCT and smoking cessation to about 10,000 high-risk subjects, supported by Private or Public Health Institutions, envisaging a possible population-based screening program. Because LDCT is the backbone of LCS, Italian radiologists with LCS expertise are presenting this position paper that encompasses recommendations for LDCT scan protocol and its reading. Moreover, fundamentals for classification of lung nodules and other findings at LDCT test are detailed along with international guidelines, from the European Society of Thoracic Imaging, the British Thoracic Society, and the American College of Radiology, for their reporting and management in LCS. The Italian College of Thoracic Radiologists produced this document to provide the basics for radiologists who plan to set up or to be involved in LCS, thus fostering homogenous evidence-based approach to the LDCT test over the Italian territory and warrant comparison and analyses throughout National and International practices.

Smoking Cessation in the ITALUNG Lung Cancer Screening: What Does "Teachable Moment" Mean?

BACKGROUND: Changes in smoking habits and predictors of smoking cessation were examined in the randomized ITALUNG lung cancer screening trial. METHODS: In three centers, eligible smokers or ex-smokers (55-69 years, ≥20 pack-years in the last 10 years) were randomized to receive annual invitation for low-dose computed tomography for 4 years or usual care. At invitation, subjects received written information for a free smoking cessation program. Quitting outcome was assessed at year 4. RESULTS: Among participants who completed baseline assessments and year 4 screening, higher quitting (20.8% vs. 16.7%, p = .029) and lower relapse (6.41% vs. 7.56%, p = .50) rates were observed in the active screening group as compared to the usual-care control group. Corresponding figures in the intention-to-treat analysis were as follows: 16.04% versus 14.64% (p = .059) and 4.88% versus 6.43% (p = .26). Quitting smoking was significantly associated to male gender, lower pack-years, and having pulmonary nodules at baseline. Center-specific analyses showed a threefold statistically significant higher probability to quit associated with participating in the smoking cessation program. A subsample of smokers of the scan group from one center showed higher quitting rates over 12-month follow-up as compared to matched controls from the general population who underwent the same smoking cessation program. CONCLUSIONS: Consistently with previous reports, in the ITALUNG trial, screened subjects showed significantly higher quit rates than controls, and higher quit rates were associated with both the presence of pulmonary nodules and participating in a smoking cessation program. Maximal effect on quitting outcome was observed with the participation in the smoking cessation program. IMPLICATIONS: Participating in lung cancer screening promotes smoking cessation. An effective "teachable moment" may be achieved when the smoking cessation intervention is structured as integral part of the screening clinical visits and conducted by a dedicated team of health care professionals. Standardized guidelines for smoking cessation interventions in lung cancer screening are needed.

Multimodal lung cancer screening using the ITALUNG biomarker panel and low dose computed tomography. Results of the ITALUNG biomarker study.

Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1,406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1,356), in which samples of blood and sputum were analyzed for plasma DNA quantification (cut off 5 ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71 and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%.

Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.

BACKGROUND: ITALUNG is contributing to the European evaluation of low-dose CT (LDCT) screening for lung cancer (LC). METHODS: Eligible subjects aged 55-69 years, smokers or ex-smokers (at least 20 pack-years in the last 10 years), were randomised to receive an annual invitation for LDCT screening for 4 years (active group) or to usual care (control group). All participants were followed up for vital status and cause of death (at the end of 2014) and LC incidence (at the end of 2013). Pathological and clinical information was collected from the Tuscan Cancer Registry data. RESULTS: 1613 subjects were randomly assigned to the active group and 1593 to the control group. At the end of the follow-up period 67 LC cases were diagnosed in the active group and 71 in the control group (rate ratio (RR)=0.93; 95% CI 0.67 to 1.30). A greater proportion of stage I LC was observed in the active group (36% vs 11%, p<0.001). Non-significant reductions of 17% (RR=0.83; 95% CI 0.67 to 1.03) for overall mortality and 30% (RR=0.70; 95% CI 0.47 to 1.03) for LC-specific mortality were estimated. CONCLUSIONS: Despite the lack of statistical significance, the ITALUNG trial outcomes suggest that LDCT screening could reduce LC and overall mortality. Moreover, the comparison of the number of LC cases diagnosed in the two groups does not show overdiagnosis after an adequate follow-up period. A pooled analysis of all European screening trials is advocated to assess the benefit-to-harm ratio of LDCT screening and its implementation in public health settings. TRIAL REGISTRATION NUMBER: Results, NCT02777996.

[HRCT and LDCT in workers exposed to asbestos: a review of the literature in view of the Helsinki Criteria]. / HRCT e LDCT in esposti ad amianto: una revisione della letteratura alla luce della dichiarazione di Helsinki.

In approaching the asbestos-related diseases with CT, both the malignant diseases and the non-malignant disease are to be considered. In the recent publication of the Helsinki Criteria research activities are encouraged in the field of lung cancer screening with low-dose CT (LDCT) in exposed workers and initiatives of data pooling and study protocols standardization are stimulated. Herein, we propose a review of the literature in the light of the Helsinki statement focused on the different techniques of imaging with CT and on the different fields of application in the asbestos-related disease.

Idiopathic interstitial pneumonias: do HRCT criteria established by ATS/ERS/JRS/ALAT in 2011 predict disease progression and prognosis?

PURPOSE: The objective of the study was to determine whether HRCT criteria for Usual Interstitial Pneumonia (UIP), possible UIP or no-UIP pattern recommended by ATS/ERS/JRS/ALAT guidelines 2011 are able to predict progression and prognosis of the disease in a group of patients with fibrotic idiopathic interstitial pneumonia (IIP). MATERIALS AND METHODS: This was a retrospective study conducted with the approval of the ethics committee. Two radiologists at baseline HRCT distributed 70 patients with fibrotic IIP into three groups on the basis of the 2011 guidelines: UIP pattern (group 1), possible UIP pattern (group 2), inconsistent with UIP pattern (group 3). The different abnormalities (honeycombing, reticulation, ground-glass and traction bronchiectasis), fibrotic score (reticulation + honeycombing) and overall CT score were visually scored at baseline and during the follow-up (total HRCT 178). The mortality rate of the three groups was compared. The baseline abnormalities were then correlated with the mortality rate in the UIP group. RESULTS: The inter-observer agreement in the classification of the abnormalities in the three groups was almost perfect (k = 0.92). After consensus, 44 patients were classified into group 1, 13 into group 2 and 13 into group 3. During a mean follow-up of 1386 days, overall CT score, fibrotic score, honeycombing and traction bronchiectasis showed a significant progression in group 1. The mortality rate was significantly higher in group 1 (18 deaths) versus group 2 and 3 (1 death each). In group 1, baseline honeycombing rate higher than 25 %, fibrotic score higher than 30, overall CT score greater than 45 and traction bronchiectasis in more than 4 lobes defined the worst prognosis. CONCLUSION: HRCT classification based on 2011 guidelines showed high accuracy in stratifying fibrotic changes because in our study UIP, possible UIP and inconsistent with UIP pattern seem to be correlated with different disease progression and mortality rate.

Lung Cancer Screening with Low-Dose CT: What We Have Learned in Two Decades of ITALUNG and What Is Yet to Be Addressed.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer-aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover, ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as lung cancer associated with cystic airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs. biennial pace of LDCT, choice between opportunistic or population-based recruitment. and between uni or multi-centre screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema. and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention. and prospective validation of the biomarkers.

Low agreement of visual rating for detailed quantification of pulmonary emphysema in whole-lung CT.

BACKGROUND: Multidetector spiral computed tomography (CT) has opened the possibility of quantitative evaluation of emphysema extent in the whole lung. Visual assessment can be used for such a purpose, but its reproducibility has not been established. PURPOSE: To assess agreement of detailed assessment of pulmonary emphysema on whole-lung CT using a visual scale. MATERIAL AND METHODS: Thirty patients with chronic obstructive pulmonary disease underwent whole-lung inspiratory CT. Four chest radiologists rated the same 22 ± 2 thin sections using a visual scale which defines a range of emphysema extent between 0 and 100. Two of them repeated the rating two months later. Inter- and intra-operator agreement was evaluated with the Bland and Altman method. In addition, the percentage of emphysema at -950 Hounsfield units in the whole lung was determined using fully automated commercially available software for 3D densitometry. RESULTS: In three of six operator pairs and in one of two intra-operator pairs the Kendall τ test showed a significant correlation between the difference and the average magnitude of visual scores. Among different operators the half-width of 95% limits of agreement (95% LoA) was wide ranging between a score of 14.2-27.7 for an average visual score of 20 and between 18.5-36.8 for an average visual score of 80. Within the same operator the half-width of 95% LoA ranged between a score of 10.9-21.0 for an average visual score of 20 and between 25.1-30.1 for an average visual score of 80. The visual scores of the four radiologists were correlated with the results of densitometry (P < 0.001; r = 0.65-0.81). CONCLUSION: The inter- and intra-operator agreement of detailed assessment of emphysema in the whole lung using a visual scale is low and decreases with increasing emphysema extent.

Automatic lung segmentation in CT images with accurate handling of the hilar region.

A fully automated and three-dimensional (3D) segmentation method for the identification of the pulmonary parenchyma in thorax X-ray computed tomography (CT) datasets is proposed. It is meant to be used as pre-processing step in the computer-assisted detection (CAD) system for malignant lung nodule detection that is being developed by the Medical Applications in a Grid Infrastructure Connection (MAGIC-5) Project. In this new approach the segmentation of the external airways (trachea and bronchi), is obtained by 3D region growing with wavefront simulation and suitable stop conditions, thus allowing an accurate handling of the hilar region, notoriously difficult to be segmented. Particular attention was also devoted to checking and solving the problem of the apparent 'fusion' between the lungs, caused by partial-volume effects, while 3D morphology operations ensure the accurate inclusion of all the nodules (internal, pleural, and vascular) in the segmented volume. The new algorithm was initially developed and tested on a dataset of 130 CT scans from the Italung-CT trial, and was then applied to the ANODE09-competition images (55 scans) and to the LIDC database (84 scans), giving very satisfactory results. In particular, the lung contour was adequately located in 96% of the CT scans, with incorrect segmentation of the external airways in the remaining cases. Segmentation metrics were calculated that quantitatively express the consistency between automatic and manual segmentations: the mean overlap degree of the segmentation masks is 0.96 ± 0.02, and the mean and the maximum distance between the mask borders (averaged on the whole dataset) are 0.74 ± 0.05 and 4.5 ± 1.5, respectively, which confirms that the automatic segmentations quite correctly reproduce the borders traced by the radiologist. Moreover, no tissue containing internal and pleural nodules was removed in the segmentation process, so that this method proved to be fit for the use in the framework of a CAD system. Finally, in the comparison with a two-dimensional segmentation procedure, inter-slice smoothness was calculated, showing that the masks created by the 3D algorithm are significantly smoother than those calculated by the 2D-only procedure.

Prognostic selection and long-term survival analysis to assess overdiagnosis risk in lung cancer screening randomized trials.

OBJECTIVES: Overdiagnosis in low-dose computed tomography randomized screening trials varies from 0 to 67%. The National Lung Screening Trial (extended follow-up) and ITALUNG (Italian Lung Cancer Screening Trial) have reported cumulative incidence estimates at long-term follow-up showing low or no overdiagnosis. The Danish Lung Cancer Screening Trial attributed the high overdiagnosis estimate to a likely selection for risk of the active arm. Here, we applied a method already used in benefit and overdiagnosis assessments to compute the long-term survival rates in the ITALUNG arms in order to confirm incidence-excess method assessment. METHODS: Subjects in the active arm were invited for four screening rounds, while controls were in usual care. Follow-up was extended to 11.3 years. Kaplan-Meyer 5- and 10-year survivals of "resected and early" (stage I or II and resected) and "unresected or late" (stage III or IV or not resected or unclassified) lung cancer cases were compared between arms. RESULTS: The updated ITALUNG control arm cumulative incidence rate was lower than in the active arm, but this was not statistically significant (RR: 0.89; 95% CI: 0.67-1.18). A compensatory drop of late cases was observed after baseline screening. The proportion of "resected and early" cases was 38% and 19%, in the active and control arms, respectively. The 10-year survival rates were 64% and 60% in the active and control arms, respectively (p = 0.689). The five-year survival rates for "unresected or late" cases were 10% and 7% in the active and control arms, respectively (p = 0.679). CONCLUSIONS: This long-term survival analysis, by prognostic categories, concluded against the long-term risk of overdiagnosis and contributed to revealing how screening works.

Lung magnetic resonance imaging in systemic sclerosis: a new promising approach to evaluate pulmonary involvement and progression.

INTRODUCTION/OBJECTIVES: Interstitial lung disease (ILD) is frequent and highly disabling in systemic sclerosis (SSc). Magnetic resonance imaging (MRI) is not routinely used to evaluate the lung, due to poorer spatial resolution compared to high-resolution computed tomography (HRCT). We aimed to compare lung MRI signal with HRCT and evaluate the role of MRI in predicting ILD progression. METHODS: Thirty SSc patients underwent lung MRI and HRCT. STIR and T1 mapping sequences were acquired before and after gadolinium injection. Patients were classified as normal (group 1 with normal HRCT and MRI), discordant (group 2 without ILD signs on HRCT but areas of hyperintensity on MRI), and abnormal (group 3 with ILD signs on HRCT and areas of hyperintensity on MRI). Patients were followed up for ILD progression. RESULTS: Mean STIR and T1 values were different between the three groups (p < 0.0001). STIR values correlated with HRCT score (R = 0.79, p < 0.0001), lung ultrasound B-lines (R = 0.73, p < 0.0001), and %DLco (R = - 0.63, p = 0.0001). Nine events were recorded during a follow-up of 25 ± 20 months. Continuous STIR values were independently associated with events (HR 1.018; CI 1.005-1.031, p = 0.005). A STIR value >90 ms discriminated patients at a higher risk of worsening pulmonary involvement (HR 8.80; CI 1.81-42.74; p < 0.007). CONCLUSIONS: Lung MRI can detect SSc-related ILD, with good correlations with other ILD markers. STIR values, independently of HRCT appearance, may predict worsening lung involvement. Lung MRI, although very preliminary, is a promising tool that in a near future could help selecting patients for an early treatment of SSc-related ILD and a more appropriate use of HRCT. Key points • Lung MRI has the potential to differentiate inflammation-predominant versus fibrosis-predominant lesions, but it is not currently used in routine clinical practice to assess SSc-related ILD. • Lung MRI STIR and T1 values are significantly different between patients with and without SSc-related ILD. STIR values, independently of HRCT appearance, are also able to predict worsening lung involvement over time. • These preliminary data suggest that, in a near future, MRI could support the choice for an early treatment of SSc-related ILD, as well as a more appropriate use of HRCT.

Moderate-severe coronary calcification predicts long-term cardiovascular death in CT lung cancer screening: The ITALUNG trial.

PURPOSE: Coronary artery calcifications (CAC) are very strong indicators for increased cardio-vascular (CV) risk and can be evaluated also in low-dose computed tomography (LDCT) for lung cancer screening. We assessed whether a simple and fast CAC visual score is associated with CV mortality. METHODS: CAC were retrospectively assessed by two observers using a 4-score (absent, mild, moderate and severe) scale in baseline LDCT obtained in 1364 participants to the ITALUNG trial who had 55-69 years of age and a smoking history ≥20 pack-years. Correlations with CV risk factors at baseline and with CV mortality after 11 years of follow-up were investigated. RESULTS: CAC were absent in 470 (34.5%), mild in 433 (31.7%), moderate in 357 (26.2%) and severe in 104 (7.6%) subjects. CAC severity correlated (≤0.001) with age, male sex, pack-years, history of arterial hypertension or diabetes, obesity and treated hypercholesterolemia. Twenty-one CV deaths occurred. Moderate or severe CAC were significantly associated with higher CV mortality after adjustment for all other known risk factors (ARR = 2.72; 95 %CI:1.04-7.11). Notably, also in subjects with none or one only additional CV risk factor, the presence of moderate-severe CAC allowed to identify a subgroup of subjects with higher CV death risk (RR = 3.66; CI95%:1.06-12.6). CONCLUSIONS: Moderate or severe CAC visually assessed in LDCT examinations for lung cancer screening are independently associated with CV mortality.

MR cholangiography in orthotopic liver transplantation: sensitivity and specificity in detecting biliary complications.

BACKGROUND: To assess the diagnostic value of magnetic resonance cholangiography (MRC) when evaluating biliary complications in a large series of liver transplants. METHODS: One hundred and twenty-nine patients prospectively underwent magnetic resonance (MR) imaging and MR cholangiography at 1.5-T device after orthotopic liver transplantation (OLT). After the preliminary acquisition of axial T1- and T2-weighted images, MRC involved respiratory-triggered, thin-slab (2 mm), heavily T2-weighted fast spin-echo and breath-hold, thick-slab (10-50 mm), single-shot T2-weighted sequences. MR images were blindly evaluated by two experienced readers in conference to determine the biliary anatomy and the presence of complications, whose final diagnosis was based on endoscopic retrograde cholangiography, percutaneous trans-hepatic cholangiography, and by integrating clinical follow-up with ultrasound and/or MR findings. RESULTS: Biliary complications were found in 60 patients (46.5%) and were represented by ischemic-type biliary lesions (n=21); anastomotic strictures (n=13); non-anastomotic strictures (n=5); anastomotic strictures associated to lithiasis (n=6); lithiasis (n=6); papillary dysfunctions (n=9). The sensitivity, specificity, positive predictive value, and negative predictive value of the reviewers for the detection of all types of biliary complications in patients with OLT were 98%, 94%, 94%, and 98%, respectively. CONCLUSIONS: MRC is a reliable technique for detecting post-OLT biliary complications and should be recommended before planning therapeutic interventions.

Automated Computed Tomography analysis in the assessment of Idiopathic Pulmonary Fibrosis severity and progression.

PURPOSE: To investigate the role of a quantitative analysis software (CALIPER) in identifying HRCT thresholds predicting IPF patients' survival and lung function decline and its role in detecting changes of HRCT abnormalities related to treatment and their correlation with Forced Vital Capacity (FVC). METHODS: This retrospective study included 105 patients with a multidisciplinary diagnosis of IPF for whom one HRCT at baseline and concomitant FVC were available. HRCTs were evaluated with CALIPER and the correlation between FVC and radiological features were assessed. Radiological thresholds for survival prediction and functional decline were calculated for all patients. Fifty-nine patients with at least 2 serial HRCTs were classified into two groups based on treatment. For patients for whom a FVC within 3 months of the HRCT was available (n = 44), the correlation of radiological and clinical progression was evaluated. RESULTS: The correlation between FVC and CALIPER-derived features at baseline was significant and strong. A baseline CALIPER-derived interstitial lung disease (ILD%) extent higher than 20 % and pulmonary vascular related structures (PVRS%) score greater than 5 % defined a worse prognosis. A significant progression of CALIPER-derived features in all patients was found with a faster increase in untreated patients. ILD% and PVRS% changes during follow-up demonstrated strong correlations with FVC changes. CONCLUSIONS: CALIPER quantification of fibrosis and vascular involvement could distinguish disease progression in treated versus untreated patients and predict the survival. The changes in CALIPER-derived variables over time were significantly correlated to changes in FVC.

Prognostic Value of Lung Ultrasound B-Lines in Systemic Sclerosis.

BACKGROUND: A high percentage of systemic sclerosis (SSc) patients experience interstitial lung disease (ILD) during the disease course. Recent data have shown that lung ultrasound (LUS) can assess ILD by the evaluation of B-lines, the sonographic sign of pulmonary interstitial involvement. RESEARCH QUESTION: To establish the prognostic value of B-lines in a large number of patients with SSc. STUDY DESIGN AND METHODS: A total of 396 consecutive patients with SSc, who were enrolled at three Rheumatology Departments, underwent a comprehensive LUS examination on the anterolateral and posterior chest for a total of 58 scanning sites. All available clinical, imaging, and functional data were recorded. Patients were followed after enrolment to establish the prognostic role of LUS. RESULTS: The median number of B-lines was higher in patients with the diffuse cutaneous subset (44 vs 17 B-lines; P < .0001), topoisomerase I autoantibodies (39 vs 16 B-lines; P < .0001), and the presence of ILD at chest high-resolution CT (45 vs 9 B-lines; P < .0001). At multivariable analysis, the number of posterior B-lines ≥5 was associated with new development or worsening ILD (hazard ratio, 3.378; 95% CI, 1.137-9.994; P = .028), with additional value over topoisomerase I positivity. The prognostic value was further confirmed in the subgroup of patients with known ILD at baseline (hazard ratio, 1.010; 95% CI, 1.003-1.018; P = .008). INTERPRETATION: Lung ultrasound B-lines are associated with worsening or development of pulmonary deterioration. In the near future, LUS might become part of the diagnostic and prognostic armamentarium in patients with SSc, which would allow a more sustainable and user-friendly approach to this very fragile population.

Design, recruitment and baseline results of the ITALUNG trial for lung cancer screening with low-dose CT.

BACKGROUND: Results of randomized clinical trials (RCTs) are needed to assess the efficacy of lung cancer screening with low-dose chest computed tomography (CT) in reducing lung cancer mortality. We report design and results of enrolment and baseline screening test in the ITALUNG trial, a RCT. METHODS: Invitation letters were sent to subjects of 55-69 years of age clients of 269 general practitioners. Smokers or former smokers of at least 20 pack/years were eligible and after written consent were randomized in an active arm undergoing a low-dose CT annually for 4 years and in a control arm receiving no screening. Management of positive screening test was carried out using follow-up low-dose CT, fluorodeoxyglucose positron emission tomography, fine needle aspiration cytology and fiber optic bronchoscopy. RESULTS: A sample of 3206 eligible subjects was achieved by sending 71,232 letters (enrolment efficacy = 4.5%). Subjects in control (n = 1593) and active (n = 1613) arm were balanced for age, gender and smoking history. Two-hundred and seven (12.8%) subjects did not undergo CT after randomization. The baseline screening test was positive in 426 (30.3%) of 1406 subjects. Twenty-one lung cancers (prevalence = 1.5%) were found in 20 subjects: 18 non-small cell lung cancer (NSCLC), 2 small cell lung cancer (SCLC) and a case of typical carcinoid. Ten NSCLC (47.6%) were in Stage I. Sixteen fine needle aspirations were performed in 15 lung cancers, with a positive result in 12 (75%) cases. One biopsy only (6.3%) was performed on a benign lesion. Seventeen lung cancers (81%) were treated with surgical resection in 16 subjects. One subject underwent surgery for a benign lesion (5.5% of all surgical resections). CONCLUSIONS: Recruitment by mail of high risk subjects for a lung cancer screening RCT is feasible but not efficient. Results of the baseline screening test in the active arm of the ITALUNG trial are substantially in line with those of RCT and observational studies.

Prevalence and correlates of pulmonary emphysema in smokers and former smokers. A densitometric study of participants in the ITALUNG trial.

We assessed with computed tomography (CT) densitometry the prevalence of emphysema in 266 (175 men and 91 women; mean age 64 +/- 4 years) smokers and former smokers enrolled in the ITALUNG trial of lung cancer screening with low-dose thin-slice CT. Whole-lung volume and the relative area at -950 Hounsfield units (RA(950)) and mean lung attenuation (MLA) in 1 of every 10 slices (mean, 24 slices per subject) were measured. Lung volume, MLA and RA950 significantly correlated each other and with age. Average RA950 >6.8% qualifying for emphysema was present in 71 (26.6%) of 266 subjects, with a higher prevalence in men than in women (30.3% vs 19.8%; p = 0.003). Only in smokers was a weak (r = 0.18; p = 0.05) correlation between RA950 and packs/year observed. In multiple regression analysis, the variability of RA950 (R2 = 0.24) or MLA (R2 = 0.34) was significantly, but weakly explained by age, lung volume and packs/year. Other factors besides smoking may also have a significant role in the etiopathogenesis of pulmonary emphysema.