Anand Devaraj

Interstitial Lung Disease in Systemic Sclerosis A Simple Staging System

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 (HRCT) is uncertain. OBJECTIVES To construct a readily applicable prognostic algorithm in SSc-ILD, integrating PFTs and HRCT. METHODS The prognostic value of baseline PFT and HRCT variables was quantified in patients with SSc-ILD (n = 215) against survival and serial PFT data. MEASUREMENTS AND MAIN RESULTS Increasingly extensive disease on HRCT was a powerful predictor of mortality (P < 0.0005), with an optimal extent threshold of 20%. In patients with HRCT 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 HRCT or, in indeterminate cases, FVC >or= 70%) or extensive disease (severe disease on HRCT 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 HRCT 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 HRCT 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 HRCT and PFTs, provides discriminatory prognostic information.

Mortality in bronchiectasis: a long-term study assessing the factors influencing survival

There is little literature about the mortality associated with bronchiectasis. The aim of the present study was to investigate factors affecting mortality in patients with bronchiectasis. In total, 91 patients were examined for aetiology, pulmonary function tests, high-resolution computed tomography, sputum microbiology and quality of life scores and were then followed over 13 yrs. Overall, 29.7% of the patients died. On multivariate analysis, age, St George’s Respiratory Questionnaire activity score, Pseudomonas aeruginosa infection, total lung capacity (TLC), residual volume/TLC and the transfer factor coefficient were all independently associated with mortality. In patients with moderate to severe bronchiectasis, mortality is associated with a degree of restrictive and obstructive disease, poor gas transfer and chronic pseudomonas infection. These features should guide future research into disease progression, and identify those patients needing intensive treatment.

Detection of Pulmonary Hypertension with Multidetector CT and Echocardiography Alone and in Combination

PURPOSE To test the reliability of potentially new computed tomographic (CT) indicators of pulmonary hypertension (PH) and to establish whether a combination of CT and echocardiographic measurements was more predictive of PH than either test alone. MATERIALS AND METHODS The institutional review board approved this retrospective study; patient consent was not required. Seventy-seven patients undergoing right-sided heart catheterization were examined. CT diameters of the main pulmonary artery, ascending aorta, and thoracic vertebra and cross-sectional area of the main pulmonary artery were measured. Segmental and subsegmental arterial diameters were recorded, and segmental artery size was compared with adjacent bronchus size by using a semiquantitative scoring system. The relationship between CT measurements and mean pulmonary arterial pressure (mPAP) was tested with linear regression. Multivariate regression was used to establish a composite index of mPAP by using CT markers of PH with echocardiography-derived right ventricular systolic pressure (RVSP). Post hoc logistic regression and receiver operating characteristic curve analysis were performed to test the diagnostic ability of the CT-echocardiography composite. RESULTS The ratios of the diameter of the main pulmonary artery to the diameter of the ascending aorta (R(2) = 0.45; P < .001) and of the cross-sectional area of the pulmonary artery to the diameter of the ascending aorta (R(2) = 0.45; P < .001) correlated equally with mPAP. The ratio of the diameter of the main pulmonary artery to the diameter of the thoracic vertebra, the segmental arterial diameter, and the segmental artery-to-bronchus ratio were related to mPAP but did not strengthen correlations compared with the ratio of the diameter of the main pulmonary artery to the diameter of the ascending aorta alone. A composite index of the ratio of the diameter of the main pulmonary artery to the diameter of the ascending aorta and echocardiography-derived RVSP was more strongly related (R(2) = 0.55) to mPAP and was more significantly predictive of PH than either measure alone. CONCLUSION A combination of CT and echocardiographic markers of PH is more closely related to mPAP than either test in isolation.

The Effect of Diffuse Pulmonary Fibrosis on the Reliability of CT Signs of Pulmonary Hypertension

PURPOSE To determine whether pulmonary artery (PA) dilatation is a reliable indicator of pulmonary hypertension (PH) in patients with pulmonary fibrosis. MATERIALS AND METHODS This study had institutional review board approval. Patient consent was not required. Seventy-seven patients (39 men, 38 women) who underwent right heart catheterization were studied. The study population was divided into 30 patients with pulmonary fibrosis (group A), and 47 without (group B). The main PA diameter (dPA) and ascending aorta diameter (dAA) were measured by using computed tomography (CT), and the extent of fibrosis was recorded in group A. The dPA and the dPA/dAA ratio were correlated (Spearman rank) with mean PA pressure (mPAP) and pulmonary vascular resistance index (PVRi). The relationship between dPA and pulmonary fibrosis extent and total lung capacity (TLC) was examined by using multivariate linear regression. RESULTS There were strong correlations between dPA and both mPAP (r = 0.67, P < .0001) and PVRi (r = 0.78, P < .0001) in group B. In contrast, there were no significant correlations in group A (r = 0.23, P = .22 for mPAP and r = 0.23, P = .28 for PVRi). The dPA/dAA ratio had similar relationships to dPA alone in group B (r = 0.72, P < .0001 for mPAP and r = 0.71, P < .0001 for PVRi), but significantly strengthened the correlations in group A (r = 0.54, P < .005 for mPAP and r = 0.48, P = .04 for PVRi). PA dilatation occurred in group A in the absence of significant PH, and was unrelated to CT fibrosis score or TLC. CONCLUSION PA dilatation occurs in the absence of PH in patients with pulmonary fibrosis and is therefore an unreliable sign of PH in these patients.

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening

Background Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. Methods The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. Results 247 354 individuals aged 50–75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm3 or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm3 at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). Conclusions The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective—this needs to be confirmed using data on observed lung cancer mortality reduction. Trial registration ISRCTN 78513845.

Connective tissue disease related fibrotic lung disease: high resolution computed tomographic and pulmonary function indices as prognostic determinants

Purpose To determine high resolution computed tomography (HRCT) patterns and pulmonary function indices which are associated with increased mortality in patients with connective tissue disease related fibrotic lung disease (CTD-FLD). Methods HRCTs from 168 patients with CTD-FLD were scored by 2 observers for a variety of HRCT patterns and traction bronchiectasis. A radiological diagnosis of usual interstitial pneumonia (UIP), fibrotic non-specific interstitial pneumonia (NSIP) or indeterminate was also assigned. Using Cox regression analysis, associations with mortality were identified. Honeycombing and traction bronchiectasis scores were converted to binary absence/presence scores and also tested. A subgroup analysis of patients with biopsy material (n=51) was performed by classifying patients according to radiological and histopathological diagnoses, as concordant UIP, discordant UIP and fibrotic NSIP. The prognostic separation of this classification was also evaluated. Results Severity of traction bronchiectasis (HR 1.10, p=0.001, 95% CIs 1.04 to 1.17), increasing extent of honeycombing (HR 1.08, p=0.021, 95% CI 1.03 to 1.13) and reduction in DLco (HR 0.97, p=0.013, 95% CI 0.95 to 0.99) were independently associated with increased mortality. Interobserver agreement and prognostic strength were higher for binary traction bronchiectasis scores (weighted κ (κw)=0.69, HR 4.00, p=0.001, 95%CI 1.19 to 13.38), than binary honeycombing scores (κw=0.50, HR 2.87, p=0.022, 95% CI 1.53 to 5.43). The radiological-histopathological classification was strongly associated with increased mortality (HR 2.74, p<0.001, 95% CI 1.57 to 4.77) and patients with discordant UIP had a better prognosis than concordant UIP but worse prognosis than fibrotic NSIP. Conclusions Severity of traction bronchiectasis, extent of honeycombing and DLco are strongly associated with mortality in CTD-FLD. Interobserver agreement for traction bronchiectasis is higher than for honeycombing. In CTD-FLD, radiological diagnosis has survival implications in biopsy proven UIP.

Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants

AbstractObjectivesTo investigate high resolution computed tomography (HRCT) and pulmonary function indices (PFTs) for determining prognosis in patients with chronic fibrotic hypersensitivity pneumonitis (CHP).MethodsCase records, PFTs (FEV1, FVC and DLco) and HRCTs of ninety-two patients with chronic hypersensitivity pneumonitis were evaluated. HRCT studies were scored by two observers for total disease extent, ground-glass opacification, fine and coarse reticulation, microcystic and macrocystic honeycombing, centrilobular emphysema and consolidation. Traction bronchiectasis within each pattern was graded. Using Cox proportional hazards regression models the prognostic strength of individual HRCT patterns and pulmonary function test variables were determined.ResultsThere were forty two deaths during the study period. Increasing severity of traction bronchiectasis was the strongest predictor of mortality (HR 1.10, P < 0.001, 95%CI 1.04-1.16). Increasing global interstitial disease extent (HR 1.02, P = 0.02, 95%CI 1.00-1.03), microcystic honeycombing (HR 1.09, P = 0.019, 95%CI 1.01-1.17) and macrocystic honeycombing (HR 1.06, P < 0.01, 95%CI 1.01-1.10) were also independent predictors of mortality. In contrast, no individual PFT variable was predictive of mortality once HRCT patterns were accounted for.ConclusionHRCT patterns, in particular, severity of traction bronchiectasis and extent of honeycombing are superior to pulmonary function tests for predicting mortality in patients with CHP.Key Points• HRCT is increasingly used to assess chronic fibrotic hypersensitivity pneumonitis. • HRCT patterns are superior to pulmonary function tests for predicting mortality. • Extensive traction bronchiectasis strongly predicts poor survival in chronic hypersensitivity pneumonitis.

The UK Lung Screen (UKLS): demographic profile of first 88,897 approaches provides recommendations for population screening.

The UK Lung Cancer Screening trial (UKLS) aims to evaluate low-dose computed tomography (LDCT) lung cancer population screening in the United Kingdom. In UKLS, a large population sample ages 50 to 75 years is approached with a questionnaire to determine lung cancer risk. Those with an estimated risk of at least 5% of developing lung cancer in the next 5 years (using the Liverpool Lung project risk model) are invited to participate in the trial. Here, we present demographic, risk, and response rate data from the first 88,897 individuals approached. Of note, 23,794 individuals (26.8% of all approached) responded positively to the initial questionnaire; 12% of these were high risk. Higher socioeconomic status correlated positively with response, but inversely with risk (P < 0.001). The 50- to 55-year age group was least likely to participate, and at lowest cancer risk. Only 5% of clinic attendees were ages ≤60 years (compared with 47% of all 88,897 approached); this has implications for cost effectiveness. Among positive responders, there were more ex-smokers than expected from population figures (40% vs. 33%), and fewer current smokers (14% vs. 17.5%). Of note, 32.7% of current smokers and 18.4% of ex-smokers were designated as high risk. Overall, 1,452 of 23,794 positive responders (6.1%) were deemed high risk and attended a recruitment clinic. UKLS is the first LDCT population screening trial, selecting high-risk subjects using a validated individual risk prediction model. Key findings: (i) better recruitment from ex- rather than current smokers, (ii) few clinic attendees ages early 50s, and (iii) representative number of socioeconomically deprived people recruited, despite lower response rates. Cancer Prev Res; 7(3); 362–71. ©2014 AACR.

An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study

BACKGROUND Mortality in pulmonary sarcoidosis is highly variable and a reliable prognostic algorithm for disease staging and for guiding management decisions is needed. The objective of this study is to derive and test a staging system for determining prognosis in pulmonary sarcoidosis. METHODS We identified the prognostic value of high-resolution computed tomography (HRCT) patterns and pulmonary function tests, including the composite physiological index (CPI) in patients with pulmonary sarcoidosis. We integrated prognostic physiological and HRCT variables to form a clinical staging algorithm predictive of mortality in a test cohort. The staging system was externally validated in a separate cohort by the same methods of discrimination used in the primary analysis and tested for clinical applicability by four test observers. FINDINGS The test cohort included 251 patients with pulmonary sarcoidosis in the study referred to the Sarcoidosis clinic at the Royal Brompton Hospital, UK, between Jan 1, 2000, and June 30, 2010. The CPI was the strongest predictor of mortality (HR 1·04, 95% CI 1·02-1·06, p<0·0001) in the test cohort. An optimal CPI threshold of 40 units was identified (HR 4·24, 2·84-6·33, p<0·0001). The CPI40, main pulmonary artery diameter to ascending aorta diameter ratio (MPAD/AAD), and an extent of fibrosis threshold of 20% were combined to form a staging algorithm. When assessed in the validation cohort (n=252), this staging system was strikingly more predictive of mortality than any individual variable alone (HR 5·89, 2·68-10·08, p<0·0001). The staging system was successfully applied to the test and validation cohorts combined, by two radiologists and two physicians. INTERPRETATION A clear prognostic separation of patients with pulmonary sarcoidosis is provided by a simple staging system integrating the CPI and two HRCT variables.

Computed tomographic imaging in connective tissue diseases.

The connective tissue diseases are a group of autoimmune mediated disorders characterized by multiorgan damage. High-resolution computed tomography (HRCT) plays an important role in identifying patients with respiratory involvement. Although there is some overlap, typical HRCT appearances are increasingly recognized for each of the major connective tissue diseases and are described in detail in this review (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, polymyositis/dermatomyositis, mixed connective tissue disease). The clinical utility of HRCT is discussed with respect to the detection of disease, diagnosis, staging of disease severity, prognostic evaluation, and monitoring of disease progression. The difficult problem of establishing the clinical significance of CT abnormalities is also addressed.