Showing papers by "Anand Devaraj published in 2019"

Predicting outcomes in rheumatoid arthritis related interstitial lung disease.

Abstract: The aim of this study was to compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RAILD) to identify patients with a progressive fibrosis phenotype. RAILD patients had computed tomography (CT) scans scored visually and using CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques, as follows. 1) Scleroderma system evaluating visual interstitial lung disease extent and FVC values; 2) Fleischner Society idiopathic pulmonary fibrosis (IPF) diagnostic guidelines applied to RAILD; and 3) CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients. On univariable Cox analysis, all three staging systems strongly predicted outcome (scleroderma system hazard ratio (HR) 3.78, p=9×10−5; Fleischner system HR 1.98, p=2×10−3; and 4.4% VRS threshold HR 3.10, p=4×10−4). When the scleroderma and Fleischner systems were combined, termed the progressive fibrotic system (C-statistic 0.71), they identified a patient subset (n=36) with a progressive fibrotic phenotype and similar 4-year survival to IPF. On multivariable analysis, with adjustment for patient age, sex and smoking status, when analysed alongside the progressive fibrotic system, the VRS threshold of 4.4% independently predicted outcome (model C-statistic 0.77). The combination of two visual CT-based staging systems identified 23% of an RAILD cohort with an IPF-like progressive fibrotic phenotype. The addition of a computer-derived VRS threshold further improved outcome prediction and model fit, beyond that encompassed by RAILD measures of disease severity and extent.

Pleuroparenchymal Fibroelastosis. A Review of Clinical, Radiological, and Pathological Characteristics

Abstract: Pleuroparenchymal fibroelastosis (PPFE) is an unusual pulmonary disease with unique clinical, radiological, and pathological characteristics. Designated a rare idiopathic interstitial pneumonia in 2013, its name refers to a combination of fibrosis involving the visceral pleura and fibroelastotic changes predominating in the subpleural lung parenchyma. Although a number of disease associations have been described, no single cause of PPFE has been unequivocally identified. A diagnosis of PPFE is most commonly achieved by identifying characteristic abnormalities on computed tomographic scans. The earliest changes are consistently located in the upper lobes close to the lung apices, the same locations where subsequent disease progression is also most conspicuous. When sufficiently severe, the disease leads to progressive volume loss of the upper lobes, which, in combination with decreased body mass, produces platythorax. Once regarded as a slowly progressing entity, it is now acknowledged that some patients with PPFE follow an inexorably progressive course that culminates in irreversible respiratory failure and early death. In the absence of effective medical drug treatment, lung transplant remains the only therapeutic option for this disorder. This review focuses on improving early disease recognition and evaluating its pathophysiological impact and discusses working approaches for its management.

Variable utility of mosaic attenuation to distinguish fibrotic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis

Abstract: Background Mosaic attenuation on computed tomography (CT) has been identified in international guidelines as an important diagnostic feature of fibrotic hypersensitivity pneumonitis (FHP) as opposed to idiopathic pulmonary fibrosis (IPF). However, mosaic attenuation comprises several different radiological signs (low-density lobules, preserved lobules, air trapping and the so-called “headcheese sign”) which may have differing diagnostic utility. Furthermore, the extent of mosaic attenuation required to distinguish these two diagnoses is uncertain and thresholds of mosaic attenuation from international guidelines have not been validated. Methods Inspiratory and expiratory CT scans were evaluated by two readers in 102 patients (IPF n=57; FHP n=45) using a semiquantitative scoring system for mosaic attenuation. Findings were validated in an external cohort from a secondary referral institution (IPF n=34; FHP n=28). Results Low-density lobules and air trapping were a frequent finding in IPF, present in up to 51% of patients. A requirement for increasing extent of low-density lobules and air trapping based on guidelines (American Thoracic Society and Fleischner Society) was associated with increased specificity for the diagnosis of FHP (0.96 and 0.98, respectively) but reduced sensitivity (0.16 and 0.20, respectively). The headcheese sign was found to be highly specific (0.93) and moderately sensitive (0.49) for a high-confidence diagnosis of FHP. The high specificity of the headcheese sign was maintained in the validation cohort and when patients with other CT features of FHP were excluded. Conclusion Mosaic attenuation is a frequent finding in IPF. However, the headcheese sign can be confidently considered as being inconsistent with a diagnosis of IPF and specific for FHP.

Evaluation of cardiovascular risk in a lung cancer screening cohort

Abstract: Introduction Lung cancer screening (LCS) by low-dose computed tomography (LDCT) offers an opportunity to impact both lung cancer and coronary heart disease mortality through detection of coronary artery calcification (CAC). Here, we explore the value of CAC and cardiovascular disease (CVD) risk assessment in LCS participants in the Lung Screen Uptake Trial (LSUT). Methods In this cross-sectional study, current and ex-smokers aged 60–75 were invited to a ‘lung health check’. Data collection included a CVD risk assessment enabling estimation of 10 year CVD risk using the QRISK2 score. Participants meeting the required lung cancer risk underwent an ungated, non-contrast LDCT. Descriptive data, bivariate associations and a multivariate analysis of predictors of statin use are presented. Results Of 1005 individuals enrolled, 680 were included in the final analysis. 421 (61.9%) had CAC present and in 49 (7.2%), this was heavy. 668 (98%) of participants had a QRISK2≥10% and QRISK2 was positively associated with increasing CAC grade (OR 4.29 (CI 0.93 to 19.88) for QRISK2=10%–20% and 12.29 (CI 2.68 to 56.1) for QRISK2≥20% respectively). Of those who qualified for statin primary prevention (QRISK2≥10%), 56.8% did not report a history of statin use. In the multivariate analysis statin use was associated with age, body mass index and history of hypertension and diabetes. Conclusions LCS offers an important opportunity for instituting CVD risk assessment in all LCS participants irrespective of the presence of LDCT-detected CAC. Further studies are needed to determine whether CAC could enhance uptake and adherence to primary preventative strategies.

Visual and Automated CT Measurements of Lung Volume Loss in Idiopathic Pulmonary Fibrosis.

Abstract: OBJECTIVE. The purpose of this study is to establish the relationship between CT markers of lung volume and pulmonary function test (PFT) parameters of lung volume in idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS. The relationships between PFT-derived parameters of lung volume (forced vital capacity [FVC] and total lung capacity [TLC]) and both CT-derived automated lung volume and manually derived surrogate measurements of lung volume on CT were evaluated in 273 patients (212 men and 61 women; median age, 67 years) with a multidisciplinary diagnosis of IPF. All patients underwent unenhanced volumetric high-resolution CT of the thorax. Automated lung volume was extracted using commercially available software. Three manual CT surrogate measurements of lung volume previously tested in the setting of radiation-induced lung fibrosis were evaluated by two raters. These measurements were lung height, aortosternal distance, and oblique fissure retraction distance. Fibrosis extent on CT was scored by two observers. Correlation coefficients and multivariable regression analyses were performed to assess the relationship between CT measurements and percentage of predicted FVC (hereafter referred to as "percentage FVC") and TLC. Interobserver agreement for CT markers was evaluated on the basis of the intraclass correlation coefficient. RESULTS. There was a strong correlation between CT-derived automated lung volume and TLC (rP = 0.92; p < 0.0005). There was excellent interobserver agreement for all manual CT measurements (intraclass correlation coefficient, 0.82-0.96). There were significant correlations between manual CT measurements and percentage FVC. Lung height had the strongest relationship with percentage FVC (rP = 0.44; p < 0.0005). In multivariable analysis, the CT measurements were independent determinants of lung volumes, after adjustment for fibrosis and emphysema (R2 = 0.48; p < 0.0005 and p < 0.003, respectively). Lung height had the most significant impact on the fit against lung volumes. CONCLUSION. Automated and manual CT measurements of lung volume are significantly related to PFT-derived parameters of lung volume, independent of fibrosis and emphysema.

Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial

Abstract: Background Estimation of the clinical probability of malignancy in patients with pulmonary nodules will facilitate early diagnosis, determine optimum patient management strategies and reduce overall costs. Methods Data from the UK Lung Cancer Screening trial were analysed. Multivariable logistic regression models were used to identify independent predictors and to develop a parsimonious model to estimate the probability of lung cancer in lung nodules detected at baseline and at 3-month and 12-month repeat screening. Results Of 1994 participants who underwent CT scan, 1013 participants had a total of 5063 lung nodules and 52 (2.6%) of the participants developed lung cancer during a median follow-up of 4 years. Covariates that predict lung cancer in our model included female gender, asthma, bronchitis, asbestos exposure, history of cancer, early and late onset of family history of lung cancer, smoking duration, FVC, nodule type (pure ground-glass and part-solid) and volume as measured by semiautomated volumetry. The final model incorporating all predictors had excellent discrimination: area under the receiver operating characteristic curve (AUC 0.885, 95% CI 0.880 to 0.889). Internal validation suggested that the model will discriminate well when applied to new data (optimism-corrected AUC 0.882, 95% CI 0.848 to 0.907). The risk model had a good calibration (goodness-of-fit χ[8] 8.13, p=0.42). Conclusions Our model may be used in estimating the probability of lung cancer in nodules detected at baseline and at 3 months and 12 months from baseline, allowing more efficient stratification of follow-up in population-based lung cancer screening programmes. Trial registration number 78513845.

Diffuse alveolar haemorrhage associated with subsequent development of ANCA positivity and emphysema in three young adults

Abstract: Diffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement. Patient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis. We believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as “idiopathic”. Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.

Multidisciplinary Evaluation in Patients with Lung Disease Associated with Connective Tissue Disease.

Abstract: Multidisciplinary diagnosis is now viewed as the diagnostic reference standard in interstitial lung disease (ILD). This process consists of the integration of the evidence base with clinical reasoning in the formulation of a diagnosis and requires input from clinicians, radiologists, and, in selected cases, histopathologists. In ILD associated with connective tissue disease (CTD-ILD), multidisciplinary evaluation is especially helpful when CTD is suspected but cannot be diagnosed using strict criteria. In this context, the integration of systemic clinical data, serologic information, and computed tomography and biopsy findings may allow CTD-ILD to be diagnosed. However, the value of multidisciplinary evaluation in CTD-ILD is not confined to diagnosis. The frequent coexistence of pulmonary processes other than ILD, including pulmonary vascular disease, extrapulmonic restriction, and airways disease, often has a major impact on symptoms and pulmonary function tests (PFTs). In this review, we highlight the value of multidisciplinary discussion (MDD) in reconciling clinical data, PFT, and imaging data in the accurate staging of disease severity, baseline prognostic evaluation, and the identification of progression of ILD. MDD also provides a means to combine the views of respiratory physicians and rheumatologists in formulating a treatment strategy. It is often possible to reach a robust view as to whether management should be driven by systemic disease, pulmonary disease, or both. When treatment needs to be introduced or modified for both systemic and pulmonary reasons, face-to-face discussion facilities the selection of therapeutic agents that are likely to be efficacious for both systemic and pulmonary diseases.

Longitudinal prediction of outcome in idiopathic pulmonary fibrosis using automated CT analysis.

Abstract: The advent of antifibrotic agents [1, 2] as standard of care in idiopathic pulmonary fibrosis (IPF) requires that new non-inferiority IPF drug trials will need to identify smaller declines of forced vital capacity (FVC). Marginal annualised FVC declines (between 5.00 and 9.99%) are particularly challenging to interpret as they might reflect measurement variation or genuine clinical deterioration [3]. Following on from previous baseline-only CT analyses [4], the current study examined whether changes in computer features (CALIPER) across serial CT examinations could be considered as a trial co-endpoint, particularly with regard to adjudicating marginal FVC declines, and therefore improve the sensitivity of IPF drug trials. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Jacob reports personal fees from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr. Bartholmai reports grants from Royal Brompton Hospital, personal fees from Promedior, personal fees from Boehringer Ingelheim, during the conduct of the study; other from Imbio, LLC, outside the submitted work; In addition, Dr. Bartholmai has a patent SYSTEMS AND METHODS FOR ANALYSING IN VIVO TISSUE VOLUMES USING MEDICAL IMAGING DATA licensed to Imbio, LLC. Conflict of interest: Dr. van Moorsel has nothing to disclose. Conflict of interest: Dr. RAJAGOPALAN reports grants from , Royal Brompton Hospital, during the conduct of the study; other from Imbio, LLC, outside the submitted work; In addition, Dr. RAJAGOPALAN has a patent SYSTEMS AND METHODS FOR ANALYSING IN VIVO TISSUE VOLUMES USING MEDICAL IMAGING DATA licensed to Imbio, LLC. Conflict of interest: Dr. Devaraj reports personal fees from Boehringer Ingelheim, personal fees from Roche, outside the submitted work. Conflict of interest: Dr. van Es has nothing to disclose. Conflict of interest: Dr. Moua has nothing to disclose. Conflict of interest: Dr. van Beek has nothing to disclose. Conflict of interest: Dr. Clay has nothing to disclose. Conflict of interest: Dr. Veltkamp has nothing to disclose. Conflict of interest: Dr. Kokosi has nothing to disclose. Conflict of interest: Dr. De Lauretis has nothing to disclose. Conflict of interest: Dr. Judge has nothing to disclose. Conflict of interest: Dr. Burd has nothing to disclose. Conflict of interest: Dr. Peikert has nothing to disclose. Conflict of interest: Dr. Karwoski reports grants from Royal Brompton Hospital, during the conduct of the study; other from Imbio, LLC, outside the submitted work; In addition, Dr. Karwoski has a patent SYSTEMS AND METHODS FOR ANALYSING IN VIVO TISSUE VOLUMES USING MEDICAL IMAGING DATA licensed to Imbio LLC. Conflict of interest: Dr. Maldonado has nothing to disclose. Conflict of interest: Dr. Renzoni reports personal fees from Roche, personal fees from Boehringher, personal fees from Takeda, outside the submitted work. Conflict of interest: Dr. Maher reports other from Gilead, grants and personal fees from GSK, grants from Novartis, personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from InterMune, personal fees from Lanthio, personal fees from Sanofi Aventis, grants, personal fees and non-financial support from UCB, personal fees from Astra Zeneca, personal fees from Roche, personal fees from Bayer, personal fees from Biogen Idec, personal fees from Cipla, personal fees from Prometic, personal fees from Apellis, outside the submitted work. Conflict of interest: Dr. Altmann has nothing to disclose. Conflict of interest: Dr. Wells reports personal fees from Intermune, personal fees from Boehringer Inlgeheim, personal fees from Gilead, personal fees from MSD, personal fees from Roche, personal fees from Bayer, personal fees from Chiesi, outside the submitted work.

Quantitative CT-derived vessel metrics in idiopathic pulmonary fibrosis: A structure-function study.

Abstract: BACKGROUND AND OBJECTIVE This study aimed to investigate whether quantitative lung vessel morphology determined by a new fully automated algorithm is associated with functional indices in idiopathic pulmonary fibrosis (IPF). METHODS A total of 152 IPF patients had vessel volume, density, tortuosity and heterogeneity quantified from computed tomography (CT) images by a fully automated algorithm. Separate quantitation of vessel metrics in pulmonary arteries and veins was performed in 106 patients. Results were evaluated against readouts from lung function tests. RESULTS Normalized vessel volume expressed as a percentage of total lung volume was moderately correlated with functional indices on univariable linear regression analysis: forced vital capacity (R2 = 0.27, P < 1 × 10-6 ), diffusion capacity for carbon monoxide (DLCO ; R2 = 0.12, P = 3 × 10-5 ), total lung capacity (TLC; R2 = 0.45, P < 1 × 10-6 ) and composite physiologic index (CPI; R2 = 0.28, P < 1 × 10-6 ). Normalized vessel volume was correlated with vessel density but not with vessel heterogeneity. Quantitatively derived vessel metrics (and artery and vein subdivision scores) were not significantly linked with the transfer factor for carbon monoxide (KCO ), and only weakly with DLCO . On multivariable linear regression analysis, normalized vessel volume and vessel heterogeneity were independently linked with DLCO , TLC and CPI indicating that they capture different aspects of lung damage. Artery-vein separation provided no additional information beyond that captured in the whole vasculature. CONCLUSION Our study confirms previous observations of links between vessel volume and functional measures of disease severity in IPF using a new vessel quantitation tool. Additionally, the new tool shows independent linkages of normalized vessel volume and vessel heterogeneity with functional indices. Quantitative vessel metrics do not appear to reflect vasculopathic damage in IPF.

In patients with idiopathic pulmonary fibrosis the presence of hiatus hernia is associated with disease progression and mortality.

Abstract: For IPF patients, the presence of hiatus hernia is associated with lung function decline and increased mortality. This observation supports the view that hiatus hernia may influence pathogenic mechanisms involved in IPF disease progression.http://ow.ly/hPAY30omE9o

Perinodular Vascularity Distinguishes Benign Intrapulmonary Lymph Nodes From Lung Cancer on Computed Tomography

Abstract: Purpose:A common diagnostic dilemma in the assessment of small pulmonary nodules on computed tomography (CT) is in distinguishing benign intrapulmonary lymph nodes (IPLNs) from small primary pulmonary malignancies. Several CT features have been described of IPLNs, including attachment to a pleural s

Quantitative Evaluation of Lobar Pulmonary Function of Emphysema Patients with Endobronchial Coils.

Abstract: Background Recent advances in bronchoscopic lung volume reduction offer new therapies for patients with emphysema and hyperinflation. Pulmonary lobe segmentation with quantification of lobar volumes and emphysema severity plays a pivotal role in treatment planning and post-interventional assessment. Computed tomography (CT)-derived lobar volumes could reflect more accurate regional changes in pulmonary function. Objectives The aim of our study is to validate the reliability of an in-house CT Lung Segmentation software (LungSeg; the Hamlyn Centre, Imperial College London, UK) for lung lobar volume and emphysema quantification for chronic obstructive pulmonary disease (COPD) patients. Methods A total of 108 CT scans from subjects who participated in an endobronchial coil treatment trial were included. Lobar volume and emphysema quantification were performed using the LungSeg and Syngo CT Pulmo 3D package (Siemens Healthcare GmbH, Germany). The inter-user reliability of the LungSeg program was investigated. Correlation coefficients and Bland-Altman analyses were used to quantify the inter-software variability. The agreement between CT volume analysis and plethysmography analysis was also examined. Results The high intraclass correlation coefficients (mean ICC = 0.98) of the lobar volumes and emphysema indices measured by LungSeg suggest its excellent reproducibility. The LungSeg and Syngo program have good correlation (rho ≥0.94) and agreement for both lobar volume (median difference = 94 mL and LOAnp = 214.6 mL) and emphysema index (median difference ≤1.5% and LOAnp ≤2.03%) calculations. CT analysis provides a higher estimation of total lung capacity (TLCCT) than body plethysmography (TLCpleth), while there is a fair agreement on residual volume (RVCT) by LungSeg as compared with body plethysmography (RVpleth). Conclusions CT-derived lobar volume and emphysema quantification using the LungSeg program is efficient and reliable in allowing lobar volume assessment. LungSeg has low inter-user variability and agrees better with plethysmography for COPD assessment in our study.

Evaluation of inter-observer variation for computed tomography identification of childhood interstitial lung disease.

Abstract: Making chILD diagnoses on CT is poorly reproducible, even amongst sub-specialists. CT might best improve diagnostic confidence in a multidisciplinary team setting when augmented with clinical, functional and haematological results. http://bit.ly/327jRCw.

Nintedanib in patients with chronic fibrosing interstitial lung diseases with progressive phenotype: the INBUILD trial

Abstract: Introduction: Nintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF). Pre-clinical data suggest that nintedanib inhibits processes fundamental to progression of lung fibrosis irrespective of the aetiology. Aim: The INBUILD trial was designed to investigate the efficacy and safety of nintedanib in patients with various non-IPF chronic fibrosing ILDs with progressive phenotype. Methods: Eligible patients had diffuse fibrosing lung disease of >10% extent on HRCT, FVC ≥45% predicted, DLco ≥30– Results: 663 patients were randomised and treated (Table). Mean (±SD) age was 65.8±9.8 years, FVC was 69.0±15.7% predicted, DLco was 47.6±32.2% predicted. Conclusions: The INBUILD trial will provide insights into the natural history and role of nintedanib in treating patients with various progressive fibrosing ILDs. Results will be presented at the congress.