Research and Strategies to Improve Patient Quality of Life Within
Pulmonary and Critical Care Medicine
Over the course of the past year faculty, fellows, residents and staff from the Division of Pulmonary and Critical Care Medicine have participated in a wealth of research endeavors. From designing bench and translational research studies to creating assessment tools to partnering with pharmaceutical sponsors, our team strives to advance scientific knowledge to better the health outcomes of our patients. Concurrent with this pursuit we have developed numerous research-based projects and programs to improve the quality of life of our patients. As we continue to grow our research programs in such areas as interstitial pulmonary fibrosis, sleep medicine, smoking cessation, and critical care medicine we highlight select research accomplishments from the last 12 months.
The research activities at Dr. Elizabeth Jacobs’ lab entail determining the mechanism of lung injury due to ischemia/reperfusion (IR). Lung tissue IR can occur during crush injury to the chest or in diseases such as pneumonitis and sepsis. Ischemia followed by reperfusion increases reactive oxygen (ROS) species which is injurious to the lung. Increase in ROS is usually the first event that leads to inflammation of the lungs and results in acute lung injury (ALI). If the inflammation is not resolved, ALI can lead to life threatening acute respiratory distress syndrome (ARDS). Dr. Jacobs has discovered that a cytochrome P450 metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), protects the lungs from ROS-mediated lung injury. 20-HETE’s protective effects arise from lowering the ROS produced during IR. The mechanism for lowering ROS by 20-HETE is not known. Recent studies indicate that the source of increase in ROS during IR is the mitochondria. These studies also suggest that increased ROS from the mitochondria may be due to dysfunction of the mitochondrial electron chain. Studies using IR in vivo animal models, ex vivo tissue models and cultured cells are currently under way to determine precisely the mechanism involving mitochondrial dysfunction and lung injury. Such studies are valuable in determining the mechanisms for the development of lung injury and in the future may be instrumental in developing strategies for controlling IR-induced inflammation and lung injury leading to expedited recovery.
In the area of clinical critical care research, we have had a myriad of research projects amongst our faculty and fellows in the past year. Dr. Rahul Nanchal and colleagues oversaw a pivotal trial of Calfactant for Direct ARDS and Direct ALI in adults. He is also collaborating with John Densmore of Children’s Hospital of Wisconsin and the Children’s Research Institute to study the role of elevations in human endothelial microparticle (EMP) concentrations in adults with ALI. The goal is to determine whether EMP can be used as a biomarker for severity, timing, or type of lung injury. Our MICU investigators also formed the Milwaukee Initiative in Critical Care Outcomes Research (MICCOR) group, presenting and publishing data from more than 10 investigations already this year.
The Adult Cystic Fibrosis (CF) program has been in existence for 6 years under the direction of Dr. Julie Biller. Together with Children’s Hospital of Wisconsin we form a CF Center following 300 individuals, and comprised of a multidisciplinary team including physicians, nurses, respiratory therapists, dietitians, research coordinators and administrative staff. Accredited by the CF Foundation’s Care Center Network in 2008 as one of only 80 Therapeutics Development Centers in the nation, we have partnered with numerous industry sponsors to elucidate the safety, effectiveness and tolerability of a variety of therapies. Over the past year we have offered individuals with CF the opportunity to participate in 10 clinical trials and 2 longitudinal observational studies. In this timeframe our investigators have also developed genetic research projects funded by the National Institutes of Health as well as tools to improve patient quality of life via pulmonary health, nutritional intake, adherence to appointments, and medication usage. In recognition of “Outstanding Quality Improvement Processes and Accomplishments” our Center was honored with a Quality Care Award after being visited by the national Cystic Fibrosis Foundation in 2010. Thus far in 2011 we have already been selected to conduct 3 new clinical trials to research both novel and existing inhaled antimicrobials dispersed via traditional and investigational modalities. Moreover, we continue to focus efforts on improving the quality of care we provide to our patients via 1) developing new projects and interventions, 2) offering monthly evening clinics, 3) writing a quarterly newsletter for those impacted by CF in our community, and 4) hosting quarterly CF Education Nights featuring expert speakers and patient panels.
In the specialty of pulmonary hypertension (PH), two industry sponsored trials under the direction of Dr. Kenneth Presberg are examining the role of Bosentan in disease course and management. The first study is an ongoing trial of the effects of a combination of Bosentan and Sildenafil versus Sildenafil monotherapy on morbidity and mortality in symptomatic patients with pulmonary arterial hypertension. We have followed these participants since 2006 and anticipate the trial to be completed in 2013. The second study, just completed, was an exploratory, open-label, multi-center trial employing a targeted 6-minute walk test distance threshold approach to guide Bosentan-based therapy, and to assess the utility of MRI on cardiac remodeling. Additionally, our PH nurse practitioner and nurse have recently developed a monthly support group for individuals diagnosed with pulmonary hypertension and their caregivers. With the backing of the Pulmonary Hypertension Association, meetings are held the third Monday of every month in our Community Conference Center. Serving as an opportunity for those impacted by PH to share their experiences, improve quality of life, and identify additional resources, future meetings will focus on topics such as nutrition and traveling with oxygen. For more information about this group, please visit: www.phassociation.org/SouthWisconsin, email WI-Southeast@PHAsupportgroups.org or call 414.955.7040.
Article collaboratively written by Randi Rothman & Dana Soetaert, Clinical Research Coordinators and Irshad Ali, PhD, Research Scientist in the Division of Pulmonary, Critical Care and Sleep Medicine