IMPORTANCE In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency. OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels. DESIGN, SETTING, AND PARTICIPANTS The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute’s AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized. INTERVENTIONS Oral vitamin D3 (100 000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained. MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care). RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28%[95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%–35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6–1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2–120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2–135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1–27.7 µg/d]). CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01248065

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Background Immunotherapy is emerging as the cornerstone for treatment of patients with advanced cancer, but significant toxicity (immune-related adverse events [irAEs]) associated with unbridled T cell activity remains a concern. Patients and methods A retrospective review of the electronic medical records of 290 patients with advanced cancer treated on an immunotherapy-based clinical trial in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center between February 2010 and September 2015 was performed. Clinical and laboratory parameters were collected to determine the incidence of irAEs, risk factors, and their association with treatment outcomes. Results Ninety eight of 290 patients (34%) experienced any grade irAEs. Among the 15 (5.2%) patients with grade ≥ 3 irAEs, the most common irAEs were dermatitis and enterocolitis. Although 80% of the patients with grade ≥ 3 irAEs required systemic corticosteroids, all the 15 patients recovered from the irAEs. On re-challenge, 4 of the 5 patients who had received systemic corticosteroids for irAE continued to respond. There were no irAE-related deaths. Importantly, patients with grade ≥ 3 irAEs had improved overall response rate (25 vs. 6%; p = 0.039) and longer median time to progression (30 weeks vs. 10 weeks; p = 0.0040) when compared to those without grade ≥ 3 irAEs. Conclusion Incidence of irAEs with immunotherapeutic agents indicates an active immune status, suggestive of potential clinical benefit to the patient. Further validation of this association in a large prospective study is warranted.

).q RSNA, 2014 Purpose:To quantify regional lung ventilation in healthy volunteers and patients with severe asthma (both before and after thermoplasty) by using a combination of helium 3 ( 3 He) magnetic resonance (MR) imaging and computed tomography (CT), with the intention of developing more effective image-guided treatments for obstructive lung diseases. Materials andMethods:With approval of the local institutional review board, informed consent, and an Investigational New Drug Exemption, six healthy volunteers and 10 patients with severe asthma were imaged in compliance with HIPAA regulations by using both multidetector CT and 3He MR imaging. Individual bronchopulmonary segments were labeled voxel by voxel from the CT images and then registered to the Results:Ventilation measures for healthy volunteers yielded smaller segment-to-segment variation (mean SVP, 100% 6 18 [standard deviation]) than did the measures for patients with severe asthma (mean SVP, 97% 6 23). Patients with asthma also demonstrated larger segmental defect percentages (median, 13.5%; interquartile range, 8.9%-17.8%) than healthy volunteers (median, 6%; interquartile range, 5.6%-6.3%). These quantitative results confirm what is visually observed on the 3 He images. A Spearman correlation of r = 20.82 was found between the change in whole-lung defect percentage and the number of days between final treatment and second 3 He imaging. Conclusion:Regional quantification of lung ventilation is indeed feasible and may be a useful technique for image-guided treatment of obstructive lung diseases, such as bronchial thermoplasty for severe asthma. In these patients, ventilation defects decreased as a function of time after treatment.q RSNA, 2014

We present the first reported work that explores the potential of radiomics to predict patients who are at risk for developing immunotherapy-induced pneumonitis. Despite promising results with immunotherapies, immune-related adverse events (irAEs) are challenging. Although less common, pneumonitis is a potentially fatal irAE. Thus, early detection is critical for improving treatment outcomes; an urgent need to identify biomarkers that predict patients at risk for pneumonitis exists. Radiomics, an emerging field, is the automated extraction of high fidelity, high-dimensional imaging features from standard medical images and allows for comprehensive visualization and characterization of the tissue of interest and corresponding microenvironment. In this pilot study, we sought to determine whether radiomics has the potential to predict development of pneumonitis. We performed radiomic analyses using baseline chest computed tomography images of patients who did (N = 2) and did not (N = 30) develop immunotherapy-induced pneumonitis. We extracted 1860 radiomic features in each patient. Maximum relevance and minimum redundancy feature selection method, anomaly detection algorithm, and leave-one-out cross-validation identified radiomic features that were significantly different and predicted subsequent immunotherapy-induced pneumonitis (accuracy, 100% [p = 0.0033]). This study suggests that radiomic features can classify and predict those patients at baseline who will subsequently develop immunotherapy-induced pneumonitis, further enabling risk-stratification that will ultimately lead to better treatment outcomes.

Airway remodelling in asthma remains poorly understood. This study aimed to determine the association of airway remodelling measured on bronchial biopsies with i) lung function impairment and ii) quantitative thoracic CT (QCT)-derived morphometry and densitometry measures of proximal airway remodelling and air-trapping. Subjects were recruited from a single centre Bronchial biopsy remodelling features that were the strongest predictors of lung function impairment and QCT-derived proximal airway morphometry and air-trapping markers were determined by step-wise multiple regression. The best predictor of air-trapping was validated in an independent replication group. Airway smooth muscle percentage (ASM %) was the only predictor of post-bronchodilator FEV1 % predicted, while both ASM % and vascularity were predictors of FEV1/FVC. Epithelial thickness and ASM % were predictors of mean segmental bronchial luminal area (R2=0.12; p=0.02 and R2=0.12; p=0.015). Whereas epithelial thickness was the only predictor of % wall area (R2=0.13; p=0.018). Vascularity was the only significant predictor of air-trapping (R2=0.24; p=0.001), which was validated in the replication group (R2=0.19; p=0.031). In asthma, airway smooth muscle content and vascularity were both associated with airflow obstruction. QCT-derived proximal airway morphometry was most strongly associated with epithelial thickness and airway smooth muscle content, whereas air-trapping was related to vascularity.

BackgroundRadiologic severity may predict adverse outcomes after lower respiratory tract infection (LRI). However, few studies have quantified radiologic severity of LRIs. We sought to evaluate whether a semi-quantitative scoring tool, the Radiologic Severity Index (RSI), predicted mortality after parainfluenza virus (PIV)-associated LRI.MethodsWe conducted a retrospective review of consecutively-enrolled adult patients with hematologic malignancy or hematopoietic stem cell transplantation and with PIV detected in nasal wash who subsequently developed radiologically-confirmed LRI. We measured RSI (range 0–72) in each chest radiograph during the first 30 days after LRI diagnosis. We used extended Cox proportional hazards models to identify factors associated with mortality after onset of LRI with all-cause mortality as our failure event.ResultsAfter adjustment for patient characteristics, each 1-point increase in RSI was associated with an increased hazard of death (HR 1.13, 95% confidence interval [CI] 1.05–1.21, p = 0.0008). Baseline RSI was not predictive of death, but both peak RSI and the change from baseline to peak RSI (delta-RSI) predicted mortality (odds ratio for mortality, peak: 1.11 [95%CI 1.04–1.18], delta-RSI: 1.14 [95%CI 1.06–1.22]). A delta-RSI of ≥19.5 was 89% sensitive and 91% specific in predicting 30-day mortality.ConclusionsWe conclude that the RSI offers precise, informative and reliable assessments of LRI severity. Progression of RSI predicts 30-day mortality after LRI, but baseline RSI does not. Our results were derived from a cohort of patients with PIV-associated LRI, but can be applied in validated in other populations of patients with LRI.

Mortality is similarly high among HM patients without HCT and HCT recipients. High-grade immunodeficiency and detection of RSV from BAL fluid are associated with higher 60-day mortality.