Acute respiratory distress syndrome
(ARDS) is a life-threatening lung condition that affects approximately 200,000
people a year in the United States and has a higher mortality rate than breast
and prostate cancer combined. The condition most often occurs in people who are critically ill
or who have significant injuries; those who do survive it often experience
profound skeletal muscle weakness.
Over the past 30 years, efforts to fight ARDS with various drug therapies
aimed at the lungs have failed. However,
doctors at Wake Forest Baptist Medical Center have tried a different approach –
some earlier work done here, we’ve known that getting critically ill patients
up and moving around as soon as it’s medically feasible helps them get off of
ventilators sooner, increases their strength when they get out of intensive
care and improves overall outcomes,” said D. Clark Files, M.D., assistant
professor of pulmonary, critical care, allergy and immunologic medicine at Wake
Forest Baptist. “What we haven’t understood is why it helps.”
animal model that mimics what happens in people with ARDS, Files and a team of
researchers worked to understand how the mechanisms underlying early mobility
therapy improve the outcomes of patients with this illness. The study is
published in the March 11 edition of Science Translational Medicine.
study, mice with acute lung injury and the resulting muscle weakness were
exercised for two days. The researchers found that a short duration of moderate-
intensity exercise led to marked improvements in lung, limb and respiratory
at specific pathways involved in muscle wasting and found that early exercise
turns these pathways off,” Files said. “There is a complex immune response to
injury and it appears that exercise is acting on multiple different proteins
that involve the innate immune system and dampen this over-exuberant immune
researchers then confirmed their findings from the animal model by comparing them to banked plasma from patients who were enrolled in an earlier clinical trial
at Wake Forest Baptist in which patients were randomized to early mobility
versus usual control. They confirmed that at least one of the markers most
significantly changed in the regulation of the immune response in mice also
occurs in humans.
gives a lot of biological relevance to how and why early mobility tends to
work,” Files said. “We’ve identified some mechanisms that we think are very
Files said the next step will be to duplicate this study
in older animals (instead of the young mice used in current study) because most
people with ARDS are older with higher mortality.
“We want to know if therapies that work for younger ICU
patients should be the same or different for older patients,” he said.
Funding for the study was provided by Wake Forest School
of Medicine, the Claude D. Pepper Older Americans Independence Center, the
Parker B. Francis Foundation, the American Thoracic Society Foundation
Recognition Outstanding Early Career Investigator Award, the American Heart
Association and the National Institute on Aging.
Co-authors are Chun Liu, Sydney Philpott, (degree), Stephanie
Lussier, Lina Purcell, Michael Seeds, Ph.D., Peter E. Morris, M.D., and Osvaldo
Delbono, M.D., Ph.D., of Wake Forest Baptist; Andrea Pereyra, M.D., of National
Scientific and Technical Research Council and School of Medicine, National
University of La Plata, Argentina; Neil R. Aggarwal, M.D., Franco R. D’Alessio,
M.D., Brian T. Garibaldi, M.D., Jason R. Mock, M.D., Benjamin D. Singer, M.D., and
Landon S. King, M.D., of Johns Hopkins Asthma and Allergy Center.