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 $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.

Thiopurine S- methyltransferase [corrected] testing in idiopathic pulmonary fibrosis: a pharmacogenetic cost-effectiveness analysis.

Azathioprine in combination with N-acetylcysteine (NAC) and steroids is a standard therapy for idiopathic pulmonary fibrosis (IPF). Its use, however, is limited by its side effects, principally leukopenia. A genotypic assay, thiopurine S-methyltransferase (TPMT), has been developed that can potentially identify those at risk for developing leukopenia with azathioprine, and thereby limit its toxicity. In those with abnormal TPMT activity, azathioprine can be started at lower dose or an alternate regimen selected. Determine the cost-effectiveness of a treatment strategy using TPMT testing before initiation of azathioprine, NAC, and steroids in IPF by performing a computer-based simulation. We developed a decision analytic model comparing three strategies: azathioprine, NAC and steroids with and without prior TPMT testing, and conservative therapy, consisting of only supportive measures. Prevalence of abnormal TPMT alleles and complication rates of therapy were taken from the literature. We assumed a 12.5% incidence of abnormal TPMT alleles, 4% overall incidence of leukopenia while taking azathioprine, and that azathioprine, NAC, and steroids in combination reduced IPF disease progression by 14% during 12 months. TPMT testing before azathioprine, NAC, and steroids was the most effective and most costly strategy. The marginal cost-effectiveness of the TPMT testing strategy was $49,156 per quality adjusted life year (QALY) gained versus conservative treatment. Compared with azathioprine, NAC and steroids without prior testing, the TPMT testing strategy cost only $29,662 per QALY gained. In sensitivity analyses, when the prevalence of abnormal TPMT alleles was higher than our base case, TPMT was "cost-effective." At prevalence rates lower than our base case, it was not. TPMT testing before initiating therapy with azathioprine, NAC, and steroids is a cost-effective treatment strategy for IPF.

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

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.