UAB MEDICINE PULMONARY SERVICES
RANKED NO. 17
NATIONALLY BY
U.S. News &
World Report
NEW PHYSICIANS
Sheetal Gandotra, MD
Assistant Professor
Dr. Gandotra earned her
medical degree from Saba
University School of Medicine
in 2012, completed residency
training at Rochester
University Hospital in 2015, and finished her
fellowship at Wake Forest School of Medicine
in 2018. Her research and clinical interests
include coagulation, thrombosis, and pulmonary
embolism. Dr. Gandotra’s recent publications
include work in lymphoma diagnosis and acute
respiratory failure.
Daniel Kelmenson, MD
Assistant Professor
Dr. Kelmenson attended
medical school at Case
Western Reserve School of
Medicine and completed his
residency at Massachusetts
General Hospital. After completing his
pulmonary fellowship at the University of
Colorado, he joined UAB Medicine in 2018. Dr.
Kelmenson’s research focuses on critical care
medicine, with recent publications examining
diagnostic accuracy in the ICU, recovery from
critical illness, and ICU discharge outcomes.
David Page, MD
Assistant Professor
After completing his initial
medical training at Florida
State University College of
Medicine, Dr. Page studied
emergency medicine at UAB
Medicine, followed by a critical care medicine
fellowship at Washington University in St.
Louis. He next joined UAB Medicine, seeing
patients in both the medical ICU and emergency
medicine settings. Dr. Page currently researches
ventilation and emergency medicine.
SUMMER 2019
To learn more, please visit uabmedicine.org/referpulm
TRIPLE-COMBINATION DRUG BENEFITS 90% OF CF PATIENTS
A triple-combination drug has been shown to be effective in markedly improving
lung function for the majority of patients with cystic fibrosis. The new triple therapy
should provide therapeutic benefits for 90% of all patients with the genetic
disease.
In findings published in the New England Journal of Medicine, UAB Medicine
researchers report that the medication – which combines an experimental
compound known as VX-659 with two existing medications, tezacaftor and
ivacaftor – improved lung function by more than 12% compared to placebo.
“Ivacaftor was the first medication to treat the underlying cause of CF, and it was
a major breakthrough for that small group of patients when it was introduced
in 2012,” says Steven Rowe, MD, director of the Gregory Fleming James Cystic
Fibrosis Center and a professor in the UAB Medicine Division of Pulmonary,
Allergy, and Critical Care Medicine. “However, it only worked for a small number of
patients.”
Last year’s announcement of the combination therapy of ivacaftor and tezacaftor
was another major step. New findings of the triple combination’s effectiveness
indicate that we are now “even closer to having meaningful therapy for the vast
majority of individuals with cystic fibrosis,” Dr. Rowe adds.
Tezacaftor and VX-659 are known as CF correctors. They help mutant CFTR
proteins fold properly. Ivacaftor is a potentiator, serving to activate CFTR to help
keep the ion channel open. In combination, the three work to improve overall lung
function by restoring proper operation of the CFTR ion channel.
“When we presented our findings last year that ivacaftor and tezacaftor worked
well in combination, we were extremely excited, as we knew that these next-
generation medications — VX-659 and VX-445 — were in development and
depended upon that success,” Dr. Rowe says. “The current discoveries represent
a tremendous step toward creating a treatment strategy that could provide highly
effective CFTR modulation therapy for the vast majority of patients with CF.”
METFORMIN REVERSES ESTABLISHED LUNG FIBROSIS
UAB Medicine pulmonary researchers have shown that established lung fibrosis
can be reversed using a drug treatment. A team led by Jaroslaw Zmijewski, PhD,
and Victor Thannickal, MD, showed the reversal of lung fibrosis and the underlying
cellular mechanisms affected by the drug treatment. The drug that accelerated
lung fibrosis reversal is metformin, a safe and widely used agent for non-insulin-
dependent diabetes.
The research focused on AMP-activated protein kinase (AMPK), an enzyme that
senses energy state in the cell. Using a mouse model for lung fibrosis elicited by
the anti-cancer drug bleomycin, the research team found metformin treatment
accelerated the resolution of well-established fibrosis. Such resolution was not
apparent in AMPK-knockout mice, showing that the effect of metformin was
AMPK-dependent.
HIGHLIGHTS/NEWS BRIEFS
USING BAG-MASK VENTILATION DURING
INTUBATION IMPROVES PATIENT OUTCOMES
To learn more, please visit uabmedicine.org/referpulm
ALPHA-1 ANTITRYPSIN DEFICIENCY
TESTING & TREATMENT
New research published in the New
England Journal of Medicine shows
that using bag-mask ventilation during
intubation improves outcomes and
potentially could change the standard
of care.
Intubation is a dangerous but necessary
procedure for many critically ill patients,
Derek Russell, MD
and thousands of Americans die each
year during the process. More than 1.5
million patients undergo tracheal intubation each year in the
United States.
Up to 40% of tracheal intubations in the intensive care unit are
complicated by hypoxemia, which may cause damage to the
brain and heart, and 2% of people suffer cardiac arrest, a sudden
failure of heart function that is frequently fatal.
Some doctors are hesitant to use bag-mask ventilation during
tracheal intubation due to fears of causing aspiration. However,
co-author and UAB Medicine Division of Pulmonary, Allergy,
and Critical Care Medicine Assistant Professor Derek Russell,
MD, says that, through the Preventing Hypoxemia with Manual
Ventilation During Endotracheal Intubation (PreVent) trial, he
and his colleagues found bag-mask ventilation to be effective
in preventing low oxygen levels without any evidence that it
increases aspiration risk.
In this multicenter randomized controlled trial, conducted in
seven intensive care units across the United States, randomly
assigned adults undergoing tracheal intubation received either
ventilation with a bag-mask device at the time of induction or no
ventilation until oxygen levels fell.
Among the 401 patients enrolled, including 113 at UAB, the
lowest median oxygen saturation was 96% in the bag-mask
ventilation group, as compared to 93% in the no-ventilation
group. A total of 21 patients in the bag-mask ventilation group
had severely low oxygen levels, as compared with 45 patients in
the no-ventilation group.
“Our findings have changed my practice,” Dr. Russell says.
“These findings will change the way we train people to perform
this procedure given the solid evidence provided by this
randomized clinical trial.”
Dr. Russell says his colleagues in the division also have taken
notice of these findings and have begun changing their standard
of care.
Speaking of the role that he and UAB Medicine play in this study
and others like it, “It is very rewarding to be a part of something
that can have a profound impact on medicine,” Dr. Russell says.
Michael Wells, MD
Alpha-1 antitrypsin deficiency,
one of the most common genetic
causes of COPD and emphysema,
is characterized by an abnormal
production of the alpha-1 antitrypsin
protein. For patients with this
condition, this protein is not folded
normally, which can cause it to
accumulate in the liver and not be
released into circulation.
“The protein misfolding and accumulation in the liver can
cause liver damage and cirrhosis,” says Michael Wells,
MD, assistant professor and the driving force behind UAB
Medicine’s Alpha-1 Clinical Resource Center. “The lack of
overall circulating alpha-1 antitrypsin leads to critically low
levels of alpha-1 protein in the lungs, which in turn leads to
excess pulmonary inflammation and development of lung
disease, including emphysema in non-smokers.”
The condition is under-diagnosed and is more common than
once thought to be.
“We should be actively screening for this in patients with
chronic asthma or COPD and in patients with family members
who have a known diagnosis of alpha-1 antitrypsin deficiency,”
Dr. Wells says.
UAB Medicine is designated as an Alpha-1 Clinical Resource
Center by the Alpha-1 Foundation, so Dr. Wells and other clinic
staff members are able to test and counsel patients suspected
of having the condition. Testing usually can be done with a
blood draw or a finger prick dried blood spot test. A genetic
screening test that uses oral swabs is expected this fall.
“For those diagnosed with alpha-1 antitrypsin deficiency,
we offer comprehensive evaluations, medical testing, and
therapies,” Dr. Wells says. “We collaborate closely with our
hepatology group, so if there are signs of liver injury or liver
damage, we make sure that we are addressing any needs. We
also offer genetic counseling for people who have questions
or are considering things such as insurance and family
planning.”
Dr. Wells says this is an exciting time for alpha-1 research.
“There are many new and exciting treatments on the horizon,
including oral neutrophil elastase inhibitors, gene therapies,
and new strategies using augmentation therapy,” he says.
“The UAB Alpha-1 CRC and the UAB Lung Health Center are
actively involved in these trials and encourage providers to
refer alpha-1 patients and family members of alphas who may
be interested in participating.”