MD Conference Express ATS 2011 - (Page 11)
(FVC) also improved with sirolimus, but exercise tolerance and measures of gas exchange did not change. There was a 50% reduction in serum levels of vascular endothelial growth factor-D (VEGF-D), which stimulates pathological growth in LAM. Functional and symptomatic improvement lasted only so long as patients remained on sirolimus. LAM is a rare cystic lung disease that affects women. The condition arises from mutations in the tuberous sclerosis complex (TSC) genes that regulate mammalian target of rapamycin (mTOR) [Carsillo and Henske. Proc Natl Acad Sci 2000]. Additionally, lung lesions that are associated with LAM exhibit abnormal mTOR activation, providing a rationale to investigate treatment with sirolimus, which inhibits mTOR [Goncharova et al. J Biol Chem 2002]. In a small open-label trial, tumors that were associated with TSC or LAM shrunk by 50% during treatment with sirolimus, and lung function improved by as much as 13% [Bissler et al. N Engl J Med 2008]. The accumulation of clinical and preclinical evidence led to the multicenter trial, reported by Dr. McCormack. Investigators at 13 sites in the United States, Canada, and Japan randomized 89 patients with moderate lung impairment to sirolimus or placebo for 12 months, followed by an additional 12 months of follow-up. The primary endpoint was the change in FEV1 from baseline to 12 months. Baseline characteristics did not differ significantly between treatment groups. The patients had an FEV1 of 49% of predicted, FVC of 80%, total lung capacity of 105%, functional residual capacity of 113%, residual volume of 141%, and carbon monoxide diffusion capacity of 43%, consistent with moderately severe obstructive lung impairment, air trapping, and reduced diffusing capacity. Patients who were randomized to active therapy received sirolimus 2 mg. Sirolimus levels were measured at every visit after baseline, and the dose was adjusted to maintain a serum level of 5 to 15 ng/ml. The observation period of the trial was truncated after a planned interim analysis in February 2010 showed that the stopping rule for efficacy had been met. Among patients in the sirolimus arm, FEV1 had stabilized or improved in 46% of patients compared with 12% in the placebo group (p<0.001). Moreover, the change in FEV1 averaged -134 ml in the placebo group versus an increase of 19 ml with sirolimus, resulting in a between-group difference of 153 ml (p<0.001). “The clinical relevance of an FEV1 difference of 153 ml is important to consider,” said Dr. McCormack. “It represents more than a 10% increase from baseline mean FEV1 of 1.37
liters for these patients. It exceeds the estimated minimal clinically important difference in FEV1 for COPD of 100 to 140 ml, which can be perceived by patients and is typical for bronchodilator response. Another reason that a 153-ml difference might be important is that in any patient with advanced disease, any stabilization that may delay transplantation and associated risk is of value.” The change in FVC averaged a decrease of 129 ml in the placebo group versus an increase of 97 ml in the sirolimus group. Sirolimus was associated with significant improvement in functional performance and QoL versus placebo (p=0.03). FEV1 began to decrease soon after patients stopped treatment, although the mean value in the sirolimus group exceeded that of the placebo group through the end of the 12-month follow-up period. Sirolimus was associated with a higher incidence of adverse events. The most common adverse events were stomatitis, diarrhea, nausea, hypercholesterolemia, acneiform rash, and lower-extremity edema. “Therapy with sirolimus may be useful in selected LAM patients,” concluded Dr. McCormack. “Longer-term studies are needed to determine if benefit can be sustained with continued therapy.”
Intensive Care Physician- Versus Qualified Nurse-Based Critical Care Transport
Qualified nurses can safely accompany selected critical care patients during ground transport, minimizing the need for physician assistance, suggest the results of a randomized controlled (IQ transport) trial, presented by Erik van Lieshout, MD, University of Amsterdam, Amsterdam, The Netherlands. Transport time and the incidence of clinical events were similar whether critical nurses or physicians accompanied patients during transport. Additionally, the frequency and magnitude of adjustments in inotropic or vasoactive medication did not differ between groups. Regionalization of health care delivery has increased the need for interhospital transport of critically ill patients. The level of clinical expertise that is required to ensure safe ground transport of intensive care patients remains unclear, and the Society of Critical Care Medicine has provided no guidance on the issue [Crit Care Med 2004]. In an effort to resolve some of the uncertainty, participants in the Mobile Intensive Care Unit in the Amsterdam
Peer-Reviewed Highlights from the American Thoracic Society 2011 International Conference
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Table of Contents for the Digital Edition of MD Conference Express ATS 2011
MD Conference Express ATS 2011
Contents
Obesity: Implications for the Clinical Practice of the Pulmonary, Critical Care and Sleep Physician
Asthma Phenotypes: Understanding Distinct Subgroups of Asthma Patients
Evaluation of a Rifapentine-Containing Regimen for Intensive Phase Treatment of Pulmonary Tuberculosis: TBTC Study 29
Asthma Exacerbations During Pregnancy Are Reduced By Inflammatory Guided Asthma Management
TESRA Study Results
Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus Trial
Intensive Care Physician Versus Qualified Nurse Based Critical Care Transport
Chronic Azithromycin Decreases the Frequency of COPD Exacerbations
Drug Development
Sleep Medicine
Critical Care
Advances in NSCLC
Mechanisms and Advances in COPD Therapy
MD Conference Express ATS 2011
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