High-Resolution CT Scan Fibrotic Patterns in Stage IV Pulmonary Sarcoidosis: Impact on Pulmonary Function and Survival.

BACKGROUND: Different patterns of fibrosis on high-resolution CT scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT scan patterns and survival in sarcoidosis. RESEARCH QUESTION: Will a detailed description of the extent and pattern of HRCT scan fibrosis in patients with stage IV pulmonary sarcoidosis impact pulmonary function and survival? STUDY DESIGN AND METHODS: Two hundred forty patients with stage IV sarcoidosis at two large tertiary institutions were studied. The earliest HRCT scan with fibrosis was reviewed for extent of fibrosis (< 10%, 10%-20%, and > 20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground-glass opacities (GGOs), large bullae, and mycetomas. Presence of sarcoidosis-associated pulmonary hypertension (SAPH) and pulmonary function testing performed within 1 year of HRCT were recorded. Patients were followed up until last clinic visit, death, or lung transplantation. RESULTS: The mean age was 58.4 years. Seventy-four percent were Black, 63% were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). Thirty-one percent had > 20% fibrosis, 25% had 10%-20% fibrosis, and 44% had < 10% fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). Twelve percent had basal subpleural honeycombing, and 32% had SAPH. Patients with > 20% fibrosis had more severe pulmonary impairment, were more likely to have SAPH (53%), and had worse survival (44% mortality; P < .001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55% mortality; P < .001). GGOs were associated with worse pulmonary function but not worse survival, and mycetomas were associated with worse survival but not worse pulmonary function. A Cox proportional hazards model indicated that basal subpleural honeycombing (hazard ratio, 7.95), diffusion capacity for carbon monoxide < 40% (HR, 5.67) and White race (hazard ratio, 2.61) were independent predictors of reduced survival. INTERPRETATION: HRCT scan features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20% fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.

Application and impact of Lasso regression in gastroenterology: A systematic review.

Least absolute shrinkage and selection operator (Lasso) regression is a statistical technique that can be used to study the effects of clinical variables in outcome prediction. In this study, we aimed at systematically reviewing the application of Lasso regression in gastroenterology for developing predictive models and providing a method of performing Lasso regression. A comprehensive search strategy was conducted in PubMed, Embase and Cochrane CENTRAL databases (Keywords: lasso regression; gastrointestinal tract/diseases) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were screened for eligibility based on pre-defined selection criteria and the data was extracted using a standardized form. Total 16 studies were included, comprising a diverse range of gastroenterological disease-related outcomes. Sample sizes ranged from 134 to 8861 subjects. Eleven studies reported liver disease-related prediction models, while five focused on non-hepatic etiology models. Lasso regression was applied for variable selection, risk prediction and model development, with various validation methods and performance metrics used. Model performance metrics included Area Under the Receiver Operating Characteristics (AUROC), C-index and calibration plots. In gastroenterology, Lasso regression has been used in various diseases such as inflammatory bowel disease, liver disease and esophageal cancer. It is valuable for complex scenarios with many predictors. However, its effectiveness depends on high-quality and complete data. While it identifies important variables, it doesn't provide causal interpretations. Therefore, cautious interpretation is necessary considering the study design and data quality.

In-hospital mortality trends among patients with idiopathic pulmonary fibrosis in the United States between 2013-2017: a comparison of academic and non-academic programs.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating condition characterized by progressive lung function decline and early mortality. While early accurate diagnosis is essential for IPF treatment, data evaluating the impact of hospital academic status on IPF-related mortality remains limited. Here we examined in-hospital mortality trends for patients with IPF from 2013 to 2017. We hypothesized that in-hospital IPF mortality would be influenced by hospital academic setting. METHODS: Hospitalization data was extracted from the National Inpatient Sample (NIS) for subjects with an international classification of disease code for IPF. In-hospital mortality stratified by hospital setting (academic versus non-academic) was the primary outcome of interest, with secondary analyses performed for subgroups with and without respiratory failure and requiring mechanical ventilation. Predictors of mortality were then assessed. RESULTS: Among 93,680 patients with IPF requiring hospitalization, 58,450 (62.4%) were admitted to academic institutions. In-hospital mortality decreased significantly in those admitted to an academic hospital (p < 0.001) but remained unchanged in patients admitted to a non-academic hospital. A plateau in-hospital mortality was observed among all hospitalized patients (p = 0.12), with a significant decrease observed for patients with admitted respiratory failure (p < 0.001) and those placed on mechanic ventilation (p < 0.001). CONCLUSION: In-hospital mortality decreased significantly for patients with IPF admitted to an academic hospital, suggesting that management strategies may differ by hospital setting. Mortality among those with respiratory failure and those requiring mechanical ventilation has dropped significantly. Our findings may underscore the importance of promoting early referral to an academic institution and adherence to international treatment guidelines.

Circulating Plasma Biomarkers of Survival in Antifibrotic-Treated Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND: A number of circulating plasma biomarkers have been shown to predict survival in patients with idiopathic pulmonary fibrosis (IPF), but most were identified before the use of antifibrotic (AF) therapy in this population. Because pirfenidone and nintedanib have been shown to slow IPF progression and may prolong survival, the role of such biomarkers in AF-treated patients is unclear. RESEARCH QUESTION: To determine whether plasma concentration of cancer antigen 125 (CA-125), C-X-C motif chemokine 13 (CXCL13), matrix metalloproteinase 7 (MMP7), surfactant protein D (SP-D), chitinase-3-like protein-1 (YKL-40), vascular cell adhesion protein-1 (VCAM-1), and osteopontin (OPN) is associated with differential transplant-free survival (TFS) in AF-exposed and nonexposed patients with IPF. STUDY DESIGN AND METHODS: A pooled, multicenter, propensity-matched analysis of IPF patients with and without AF exposure was performed. Optimal thresholds for biomarker dichotomization were identified in each group using iterative Cox regression. Longitudinal biomarker change was assessed in a subset of patients using linear mixed regression modeling. A clinical-molecular signature of IPF TFS was then derived and validated in an independent IPF cohort. RESULTS: Three hundred twenty-five patients were assessed, of which 68 AF-exposed and 172 nonexposed patients were included after propensity matching. CA-125, CXCL13, MMP7, YKL-40, and OPN predicted differential TFS in AF-exposed patients but at higher thresholds than in AF-nonexposed individuals. Plasma biomarker level generally increased over time in nonexposed patients but remained unchanged in AF-exposed patients. A clinical-molecular signature predicted decreased TFS in AF-exposed patients (hazard ratio [HR], 5.91; 95% CI, 2.25-15.5; P < .001) and maintained this association in an independent AF-exposed cohort (HR, 3.97; 95% CI, 1.62-9.72; P = .003). INTERPRETATION: Most plasma biomarkers assessed predicted differential TFS in AF-exposed patients with IPF, but at higher thresholds than in nonexposed patients. A clinical-molecular signature of IPF TFS may provide a reliable predictor of outcome risk in AF-treated patients but requires additional research for optimization and validation.

Derivation and Validation of a Diagnostic Prediction Tool for Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) results in high morbidity and health-care utilization. Diagnostic delays remain common and often occur in nonpulmonology settings. Screening for ILD in these settings has the potential to reduce diagnostic delays and improve patient outcomes. RESEARCH QUESTION: This study sought to determine whether a pulmonary function test (PFT)-derived diagnostic prediction tool (ILD-Screen) could accurately identify incident ILD cases in patients undergoing PFT in nonpulmonology settings. STUDY DESIGN AND METHODS: Clinical and physiologic PFT variables predictive of ILD were identified by using iterative multivariable logistic regression models. ILD status was determined by using a multi-reader approach. An ILD-Screen score was generated by using final regression model coefficients, with a score ≥ 8 considered positive. ILD-Screen test performance was validated in an independent external cohort and applied prospectively to PFTs over 1 year to identify incident ILD cases at our institution. RESULTS: Variables comprising the ILD-Screen were age, height, total lung capacity, FEV1, diffusion capacity, and PFT indication. The ILD-Screen showed consistent test performance across cohorts, with a sensitivity of 0.79 and a specificity of 0.83 when applied prospectively. A positive ILD-Screen strongly predicted ILD (OR, 18.6; 95% CI, 9.4-36.9) and outperformed common ILD clinical features, including cough, dyspnea, lung crackles, and restrictive lung physiology. Prospective ILD-Screen application resulted in a higher proportion of patients undergoing chest CT imaging compared with a historical control cohort (74% vs 56%, respectively; P = .003), with a significantly shorter median time to chest CT imaging (5.6 vs 21.1 months; P < .001). INTERPRETATION: The ILD-Screen showed good test performance in predicting ILD across diverse geographic settings and when applied prospectively. Systematic ILD-Screen application has the potential to reduce diagnostic delays and facilitate earlier intervention in patients with ILD.

Interstitial lung abnormality is prevalent and associated with worse outcome in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Interstitial lung abnormality (ILA) is found in 5-10% of the general population and is associated with increased mortality risk. Risk factors for ILA, including advanced age and smoking history also increase the risk for aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become an increasingly utilized intervention for patients with severe AS, and requires a high-resolution computed tomography (HRCT) of the chest to assess aortic valve dimensions. OBJECTIVES: To determine the prevalence and clinical significance of ILA on HRCT performed in patients referred for TAVR. METHODS: Consecutive pre-TAVR HRCTs performed over a 5-year period were reviewed. ILA was defined as bilateral, nondependent reticular opacities. All-cause mortality among TAVR recipients was compared between ILA cases and non-ILA controls matched 2:1 by age and gender using Cox proportional hazards regression and the Kaplan Meier estimator. RESULTS: Of 623 HRCTs screened, ILA was detected in 92 (14.7%), including 62 patients that underwent TAVR. Among ILA cases, 17 (27.4%) had a typical or probable usual interstitial pneumonia pattern, suggesting a diagnosis of idiopathic pulmonary fibrosis. Survival was worse in ILA cases compared to non-ILA controls (p = 0.008) and ILA was an independent predictor of mortality after multivariable adjustment (HR 3.29, 95% CI 1.34-8.08; p = 0.009). CONCLUSIONS: ILA is a common finding among patients with severe AS and is associated with increased mortality in those undergoing TAVR. Further research is needed to elucidate the biology underpinning this observation and determine whether ILA evaluation and risk stratification modulates this mortality risk.

Cocaine induced pleural and pericardial effusion syndrome.

A 42-year-old African American female with chronic cocaine use for 20 years, presented with two-day history of exertional shortness of breath and pleuritic chest pain. She was admitted three years back with acute kidney injury and skin rashes. At that time, skin biopsy was consistent with leukocytoclastic vasculitis and renal biopsy revealed proliferative glomerulonephritis. She responded to oral prednisone and mycophenolate with complete recovery of her kidney functions. Skin rash was waxing and waning over the last two years. On the second admission, patient was found to have large pleural effusion on computerized tomography scan and pericardial effusion on echocardiogram as shown in the figures. Pleural fluid analysis was exudative. Her serology was negative for ANA (antineutrophilic antibody) and anti-dsDNA (double stranded DNA). Complements levels were normal. She had positive low titers of ANCA levels. The patient was started on a course of prednisone for 6 months. Her pleural and pericardial effusion resolved completely on follow-up imaging with computerized tomography scan and echocardiogram. This case is unique since the pericardial and pleural effusions developed without any other etiology in the setting of cocaine; hence, we describe this clinical syndrome as cocaine induced pleural and pericardial effusions syndrome (CIPP).