BUFFALO, N.Y. – It can be almost painful to watch
individuals with chronic obstructive pulmonary disease (COPD)
breathe. When they’re not coughing, they’re fighting
for every breath. Approximately 24 million Americans struggle with
COPD — which typically worsens over time and is the third
most common cause of death.
A lung infection can be a life-threatening event for someone
Researchers now say that the bacterium, non-typeable
Haemophilus influenzae (NTHI), may be a key factor in the
hallmark signs of COPD: airway inflammation and impaired pulmonary
function. While NTHI frequently exists in healthy humans without
causing any problems, it seems to proliferate and flourish in the
lower respiratory airways of patients with COPD.
The University at Buffalo has recently been awarded a $2,287,587
five-year National Institutes of Health grant to study and detail
the mechanisms that allow NTHI to infect and survive in the airways
of adults with COPD. This understanding may lead to new drugs that
can effectively reduce NTHI infections and save lives.
This study represents the 28th year of a long running grant to
“In healthy people, H. influenzae is present in the
throat but not in the lower airways of the respiratory
tract,” said Timothy Murphy, MD, SUNY Distinguished Professor
and UB senior associate dean for clinical and translational
research in the UB School of Medicine and Biomedical Sciences and
the principal investigator on the grant.
“People with COPD, however, have diseased airways which
impairs the normal protective responses. Thus H. influenzae
is present in the lower airways of people with COPD. It is also the
most important bacterial cause of exacerbations or the worsening of
COPD symptoms, and can lead to serious complications.”
The three aims of the grant are to study how NTHI is able to
persist from months to years in airways; to assess potential
vaccine antigens that are under development; and to assess how NTHI
can survive repeated courses of antibiotic therapy.
The grant was first funded shortly after Murphy joined the UB
medical school. Every three to five years, the grant was renewed by
what’s called a competitive renewal where scientists write a
new grant that is reviewed and then competes with all other NIH
Sanjay Sethi, MD, professor of medicine and chief of the
Division of Pulmonary, Critical Care and Sleep Medicine, a
co-investigator on the study, also collaborated with Murphy on the
long-running study of adults with COPD.
The perfect score — a rare accomplishment – Murphy
says was most likely related to several factors:
- An 18 year prospective study with this level of rigorously
characterized bacterial strains is unique. No other set of strains
collected longitudinally and with this level of detailed clinical
data tied to each strain exists in the world.
- The application of state-of-the-art “next gen
sequencing” to this unique set of strains is compelling.
Sequencing technology is advancing so quickly that proposing such a
large amount of sequencing just a few years ago would simply not
have been feasible. Now this amount of sequencing can be performed
- The specific questions that have been proposed to study in the
grant’s three aims will advance the field significantly.
- Determining genome sequences on this large unique set of
well-characterized strains is likely to yield new and unexpected
results. This is the “exploratory” nature of this
In the study, how NTHI survives an onslaught of antibiotics will
be handled by using an innovative Hollow Fiber Infection Model
developed by Brian Tsuji, PharmD, UB associate professor of
pharmacy practice and co-investigator on the grant.
Tsuji’s model will expose NTHI to levels of antibiotics at
the exact levels that occurred in COPD patients. Murphy says they
will integrate these results with the results of genome analysis
for a better understanding of antibiotic resistance and
Michael Buck, PhD, assistant professor of biochemistry who
oversees the UB Next Gen Sequencing Core is also working as a
co-investigator and will be responsible for the genome
Murphy adds that the technicians who work in his lab are
essential to making all of this work possible. They are Charmaine
Kirkham, Aimee Brauer and Antoinette Johnson.
In the last 50 years, says Murphy, other than the development of
antibiotics, there has been little progress in developing new
treatments and prevention of infections in COPD.
“I am trying to understand the mechanisms by which H.
influenzae causes infection so that these observations can be
used to develop better treatments. This is an excellent example of