COPD Research Focuses On New Treatment Approach

For decades, bacterial infections in people suffering from COPD have been treated primarily with traditional antibiotics. While such drugs can be effective in treating acute infections, they have had little clinical effect on the patient population as a whole.

The disease remains the third most common cause of death in the U.S., and death rates have doubled since 1970.

Most commonly caused by smoking, COPD includes chronic bronchitis and emphysema; it compromises the lungs’ innate defense against bacteria, allowing bacteria to persist and causing respiratory symptoms, coughing and sputum production.

Current treatments include anti-inflammatory drugs, as well as frequent use of antibiotics.

Now, a Jacobs School team has received a five-year, $2.7 million National Institutes of Health (NIH) grant aimed at developing a much more precise method of treatment: the selective eradication of specific pathogens in the airways that affect quality of life and lead to the loss of lung function over time.

Highlights of the grant:

• The research includes the study of the pathogen Moraxella catarrhalis (Mcat) in addition to non-typeable Haemophilus influenzae (NTHi), which is the most common COPD pathogen. While Mcat is the second most common cause of bacterial infection in COPD, it is poorly understood and rarely studied; only a handful of labs in the world study Mcat.
• In addition to studying the DNA (the genomes) of the bacteria that cause infections, the researchers also will study the RNA that the DNA expresses (the transcriptomes) in order to understand which genes turn on or off during infection.
• Fresh sputum samples of newly enrolled patients will allow the researchers to study the key molecules present in patients’ airways.

This is the 33rd year of continuous NIH funding for the researchers, who are among the world’s top scientists studying COPD. 

Principal investigator Timothy F. Murphy, MD, SUNY Distinguished Professor of medicine and senior associate dean for clinical and translational research, and Sanjay Sethi, MD, professor of medicine and division chief of pulmonary, critical care and sleep medicine, have together conducted the longest prospective study of COPD in the world with monthly sampling.

The research has broken new ground in understanding how bacterial infections affect patients, and therefore, how best to treat them.

Sethi is also a division chief at UBMD Internal Medicine and a staff physician at the VA Western New York Healthcare System.

The presence of bacterial pathogens in the lower airways (bronchial passageways) reduces the quality of life for patients and accelerates the loss of lung function, Murphy explains.

“Long-term treatment with antibiotics is not a viable option,” he says, “since they are not effective, they cause adverse effects and lead to resistance. By contrast, the selective eradication or ‘disarming’ of pathogens in the lower airways has great potential as an intervention.”

Both of the pathogens under study, NTHi and Mcat, have evolved mechanisms that allow them to proliferate in the human respiratory tract.

“These are exclusively human pathogens,” Murphy says, “so inhibiting key molecules that cause them to persist will ‘tip the balance’ toward clearance.”

Murphy explains that selectively targeting these pathogens has the advantage of leaving undisturbed the respiratory tract microbiome — the bacteria that are present normally and that protect the airways.

“Traditional antibiotics wipe out the normal microbiome, leaving the patient more susceptible to infection and causing unpleasant side effects,” he notes. ”Selective eradication of pathogens is an entirely new approach to the problem.”

Murphy and Sethi work closely with Melinda Pettigrew, PhD, of the Yale School of Public Health, and Hervé Tettelin, PhD, of the Institute for Genome Sciences, University of Maryland School of Medicine.