Jared T. Hagaman

Vitamin D deficiency and reduced lung function in connective tissue-associated interstitial lung diseases.

BACKGROUND Vitamin D is a steroid hormone with pleiotropic effects including immune system modulation, lung tissue remodeling, and bone health. Vitamin D deficiency has been implicated in the development of autoimmune diseases. We sought to evaluate the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease (ILD) and hypothesized that vitamin D deficiency would be associated with an underlying connective tissue disease (CTD) and reduced lung function. METHODS Patients in the University of Cincinnati ILD Center database were evaluated for serum 25-hydroxyvitamin D levels as part of a standardized protocol. Regression analysis evaluated associations between 25-hydroxyvitamin D levels and other variables. RESULTS One hundred eighteen subjects were included (67 with CTD-ILD, 51 with other forms of ILD). The overall prevalence of vitamin D deficiency and insufficiency in the study population was 38% and 59%, respectively. Those with CTD-ILD were more likely to have vitamin D deficiency (52% vs 20%, P < .0001) and insufficiency (79% vs 31%, P < .0001) than other forms of ILD. Diminished FVC was associated with lower 25-hydroxyvitamin D(3) levels (P = .01). The association between vitamin D insufficiency and CTD-ILD persisted (OR, 11.8; P < .0001) after adjustment for potential confounders. Among subjects with CTD-ILD, reduced 25-hydroxyvitamin D(3) levels were strongly associated with reduced lung function (FVC, P = .015; diffusing capacity for carbon monoxide, P = .004). CONCLUSIONS There is a high prevalence of vitamin D deficiency in patients with ILD, particularly those with CTD-ILD, and it is associated with reduced lung function. Vitamin D may have a role in the pathogenesis of CTD-ILD.

Screening for lymphangioleiomyomatosis by high-resolution computed tomography in young, nonsmoking women presenting with spontaneous pneumothorax is cost-effective.

RATIONALE Women with pulmonary lymphangioleiomyomatosis (LAM) who present with a sentinel spontaneous pneumothorax (SPTX) will experience an average of 2.5 additional pneumothoraces. The diagnosis of LAM is typically delayed until after the second pneumothorax. OBJECTIVES We hypothesized that targeted screening of an LAM-enriched population of nonsmoking women between the ages of 25 and 54 years, who present with a sentinel pneumothorax indicated by high-resolution computed tomography (HRCT), will facilitate early identification, definitive therapy, and improved quality of life for patients with LAM. METHODS We constructed a Markov state-transition model to assess the cost-effectiveness of screening. Rates of SPTX and prevalence of LAM in populations stratified by age, sex, and smoking status were derived from the literature. Costs of testing and treatment were extracted from 2007 Medicare data. We compared a strategy based on HRCT screening followed by pleurodesis for patients with LAM, versus no HRCT screening. MEASUREMENTS AND MAIN RESULTS The prevalence of LAM in nonsmoking women, between the ages of 25 and 54 years, with SPTX is estimated at 5% on the basis of the available literature. In our base case analysis, screening for LAM by HRCT is the most cost-effective strategy, with a marginal cost-effectiveness ratio of

Predictors for clinical trial participation in the rare lung disease lymphangioleiomyomatosis.

32,980 per quality-adjusted life-year gained. Sensitivity analysis showed that HRCT screening remains cost-effective for groups in which the prevalence of LAM in the population subset screened is greater than 2.5%. CONCLUSIONS Screening for LAM by HRCT in nonsmoking women age 25-54 that present with SPTX is cost-effective. Physicians are advised to screen for LAM by HRCT in this population.

Getting Physicians to Make “The Switch”: The Role of Clinical Guidelines in the Management of Community-Acquired Pneumonia

BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare, progressive and frequently lethal cystic lung disease that almost exclusively affects women and has no proven therapies. An improved understanding of the pathogenesis has identified promising molecular targets for clinical trials. Although barriers, modifiers, and benefits for clinical trial participation in common diseases such as cancer have been studied, we are unaware of such evaluations concerning rare diseases. METHODS We performed a survey of a population-based registry of 780 LAM subjects in North America to identify predictors of trial participation. Logistic regression analysis evaluated the association of demographic and clinical features with trial participation. RESULTS 41 of 263 (16%) LAM patient respondents in North America had participated in a clinical trial. Age, disease duration, lack of any college education, use of oxygen therapy, and presentation without chest pain were associated with trial participation in unadjusted analyses. Multivariate analyses indicate that patient age was the strongest independent predictor for trial participation (OR=2.07, p=0.004 per decade greater of patient age). Common reasons reported against trial participation included not meeting enrollment criteria (44%), drug toxicity (25%), and stable disease (20%). The most frequent reason reported for trial participation was to help future patients (85%). CONCLUSIONS Study entry criteria, drug toxicity, and stability of disease are barriers to trial enrollment among subjects with LAM. Older LAM patients and those with more advanced disease are more likely to have participated in clinical trials. Altruism is commonly a motivating factor.

Could combating vitamin D deficiency reduce the incidence of autoimmune disease

The authors sought to assess physician awareness and usage of American Thoracic Society guidelines for early conversion from intravenous to oral antibiotics (“switch therapy”) in those with community-acquired pneumonia (CAP). We then determined if adoption of a CAP guideline would improve either. Patients (N = 510) hospitalized with CAP from June 2002 to May 2003 were identified retrospectively, and chart reviews were done on a random sample (130 [25%]) of these. Physicians were surveyed before and after guideline adoption. Community-acquired pneumonia guideline implementation increased physician awareness of American Thoracic Society recommendations (5% to 40%) and use of switch therapy (60% to 86%). Such use resulted in decreased overall length of stay from 3.6 to 2.4 days ( P < .05) and from 2.91 to 2.41 days ( P < .05) among early-switch candidates. Early-switch therapy was not optimally used prior to implementation of this CAP guideline. Adoption of the guideline increased awareness and reduced length of stay among inpatients with CAP.

Endobronchial Carcinoid Tumor in an HIV-infected Patient.

Vitamin D is a steroid hormone with pleiotropic effects. In addition to its essential role in calcium homeostasis, vitamin D has many nonskeletal effects that are important in health and disease [1]. Although some foods are fortified with vitamin D, the primary source for humans is exposure of skin to ultraviolet B radiation in sunlight. There is increasing evidence that vitamin D may have a role in immunoregulation. 1,25-(OH) 2 D is the biologically active form of vitamin D. Cells of the adaptive immune system express vitamin D receptors and are sensitive to the action of 1,25-(OH) 2 D. High levels of 1,25-(OH) 2 D inhibits dendritic cell maturation with lower expression of MHC class II molecules, downregulation of costimulatory molecules and lower production of proinflammatory cytokines [2,3]. In mouse models, 1,25-(OH) 2 D drives the adaptive immune system from a Th1/Th17 response toward a Th2 and regulatory T-cell response, suggesting potential beneficial effects of supplementary dietary vitamin D on the occurrence and progression of Th1-mediated autoimmune diseases in humans [4]. The immune system of vitamin D receptor-deficient mice is grossly normal but shows increased susceptibility to autoimmune diseases such as inflammatory bowel disease or Type 1 diabetes [5]. In addition, there is some evidence that vitamin D might play a regulatory role in autoanti body production by B cells, inhibiting the ongoing proliferation of activated B cells and inducing their apoptosis [6]. A common theme in the proposed immunomodulatory functions of vitamin D is that higher levels are immunosuppressive, consistent with a role for vitamin D insufficiency in the pathogenesis of autoimmune disorders.

Thiopurine S-Methyltranferase Testing in Idiopathic Pulmonary Fibrosis: A Pharmacogenetic Cost-Effectiveness Analysis

Endobronchial carcinoid is an uncommon pulmonary neoplasm. In this brief report, we present a case of an HIV-infected patient with an incidentally identified endobronchial carcinoid. This case illustrates the importance of a broad differential diagnosis for lung lesions in HIV-infected patients.