Published January 30, 2014
Conventional wisdom has held that even though bacteria persist in the lungs of patients with chronic obstructive pulmonary disease (COPD), their presence, referred to as “colonization,” is innocuous so long as the patient isn’t having a flare-up, or exacerbation, of respiratory symptoms.
Now, a new study by researchers in the School of Medicine and Biomedical Sciences, in cooperation with the U.S. Department of Veterans Affairs, shows that COPD patients do experience more respiratory symptoms when their lungs are colonized by bacteria, even in the absence of an acute exacerbation.
The paper was published online this month as an article in press in the Annals of the American Thoracic Society.
COPD, which is most commonly caused by smoking and includes chronic bronchitis and emphysema, compromises the lungs’ innate defense against bacteria, allowing bacteria to persist.
In previous work, these UB researchers illustrated that having bacteria in the lungs in COPD is associated with increased inflammation. This study takes the next step by proving that such bacterial colonization is sufficient to trigger clinically significant increases in shortness of breath, cough and sputum in COPD patients.
Several unique features of this study helped investigators make this important observation: It is the first longitudinal study of symptoms in COPD during bacterial colonization with a well-validated tool for assessing symptoms and it also controlled for variables, such as local air pollution levels and weather-related factors like humidity, that can affect daily symptoms in these patients.
“These findings demonstrate that it’s time for a paradigm shift in how we treat patients with stable COPD,” says Sanjay Sethi, senior author and UB professor of medicine and division chief of pulmonary, critical care and sleep medicine.
“The lungs are constantly being exposed to microbes ‘with every breath you take’ as well as from aspiration of small amounts of secretions from the throat, especially during sleep,” says Sethi, who also is director of the COPD Study Clinic and staff physician at the Veterans Affairs Western New York Healthcare System (Buffalo VA).
“If the persistence of these bacteria contributes to increased symptoms and inflammation in the lungs in stable COPD, we should regard this as a chronic infection, not innocuous colonization. For that reason, more must be done to reduce chronic infections in COPD.”
However, because of the risk of developing resistance, he says, long-term antibiotics are not the answer.
“Instead, we need to go beyond traditional approaches of bronchodilation and anti-inflammatory agents to reduce symptoms,” Sethi says. “We need to put more emphasis on developing therapies that can decrease bacterial colonization in COPD.”
He explains that clinicians have known that most patients with stable COPD experience daily fluctuations in respiratory symptoms, but why this is so is not well understood. Furthermore, he says, even though these fluctuations often qualify as exacerbations in terms of intensity and duration, only a third of them are reported.
“Bad days and unreported exacerbations are at least partially explained by bacteria causing inflammation in the lower airways in COPD,” he says. “The role of infection in COPD is not fully documented and this finding helps add to our understanding of how it affects patients on a daily basis.”
The study focused on four common pathogens encountered in COPD: Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Pseudomonas aeruginosa. Researchers used sensitive molecular detection methods, as well as conventional laboratory cultures, to detect these bacterial pathogens.
The longitudinal study was conducted from October 2005 to January 2009 with 41 elderly male veterans with smoking-related COPD in the COPD Study Clinic at the Buffalo VA.
Patients used electronic diaries to record daily symptoms of breathlessness, cough and sputum. They were seen in the clinic each month, in addition to whenever they had exacerbations, providing sputum and blood samples in addition to clinical information. Sputum samples also were obtained every two weeks in the patients’ homes.
Sethi notes that research support from the Buffalo VA and participation of patients was absolutely critical. “We can model inflammation and other effects of smoking using animals, but documenting respiratory symptoms can only be done with human subjects,” he says. “We could not have done this study without the generous participation of our patients.”
Healthy people and patients can sign up online to participate in UB clinical trials at ResearchMatch.org.
Co-authors on the study are Timothy F Murphy, SUNY Distinguished Professor and senior associate dean; Himanshu Desai, previously a UB fellow in pulmonary and critical care medicine; Aarti Aggarwal, previously a UB fellow in infectious disease; Karen Eschberger of the Buffalo VA; G. Iyer Parameswaran, UB research assistant professor of medicine and infectious diseases physician at the Buffalo VA; Catherine Wrona and Lori Grove, UB research technicians; Brydon Grant, UB professor of medicine and now pulmonologist at the Fayetteville VA Medical Center; and Jingjing Yin, UB student in biostatistics.
The study was funded by the U.S. Department of Veterans Affairs.
I have emphysema with 30 percent lung function. Even being on oxygen 24/7, I still have days when I feel worse than others. It's something others don't understand. My husband says, "Of course you don't feel good, you have COPD." It's hard to explain to someone that even though you do have a disease, some days are worse than others and you can also feel a worsening of your disease, even though you have not had a bacterial infection, flu, pneumonia, etc.
What about people who have never smoked or maybe smoked over 20 years ago? My husband has sarcoidosis, which has caused scarring on the lungs and in the airways, and he was diagnosed with COPD (bronchitis) nearly 4 years ago. He has mucoclear to help produce mucus and dispose of it, but has constant throat irritation and his breathing definitely changes with the weather. He is 62 and has sarc for nearly 23 years.
I was diagnosed with emphysema and sarcoidosis after contacting pneumonia six years ago and have been attending the chest clinic ever since. At my last appointment about three months ago, a registrar decided to send me for a bronchoscopy the following Monday. The bronchoscopy resulted in a "lot of purulent matter" being siphoned from my lungs. As I don't cough or bring up mucus at all I have to assume that this matter has been lying in my lungs for some time. To date, I have not had the results of the bronchoscopy but have been given oxygen for 15 hours per day. My lung function has rapidly decreased from 50 percent to 23 percent. I have days where I can function almost normally compared to days when I am so breathless I can only do the most basic of tasks.
This article makes so much sense to me. I was habitually sick with bronchitis, given an antibiotic, then after feeling better I knew it was going to gradually become another exacerbation as the symptoms equaled another infection. The COPD medications were working well for me when there was no infection.
My doctor was concerned, as she knew I was further damaging my lungs and the antibiotics would be ineffective in the long term use. She decided to put me on Daliresp, a newly approved drug in the U.S. in 2011, and in early 2012, I was taking a medication for severe COPD. My COPD numbers were moderate. The Daliresp controlled the excess mucus and in the span of two years I have been sick one time with an infection. That is a the difference between every 2-3 months and once in two years. Thank you for this article, it makes sense!
Research makes the world a better place! Communicating research articles .. awesome!