ASTHMA ASSOCIATED WITH BACTERIAL INFECTION
microbes appear to be involved in the etiology of some cases
of asthma. In addition to previous findings indicating that
viral infection may exacerbate acute asthma, emerging evidence
now implicates bacterial infection as a cause of chronic
asthma. Richard Martin, MD, and colleagues report detecting
infection with Mycoplasma pneumoniae or Chlamydia
pneumoniae in 31 of 55 asthma patients using a combination
of polymerase chain reaction (PCR), serology, and culture.
By contrast, PCR revealed mycoplasma infection in only one
of 11 normal controls.
that we detected infection in 56% of asthma patients
[vs one in 11 control subjects], there may indeed be a link
between bacteria in the airways and asthma in some patients,
said Dr. Martin, head of the Pulmonary Division and Vice
Chair of the Department of Medicine at National Jewish Medical
and Research Center (NJMRC) in Denver. The researchers did
not, however, find an association between chronic stable
asthma and viral infection.
were surprised to find these bacteria in the lower airways
of a subset of stable asthmatics, said coauthor Monica
Kraft, MD, Associate Professor in the Department of Medicine
and Division of Pulmonary Medicine at NJMRC. The association
raises an interesting chicken versus egg issuedid
the asthma allow microorganisms to set up shop,
or do the microorganisms actually cause chronic asthma?
Dr. Kraft told RESPIRATORY REVIEWS.
If the latter is true, then antibiotics would be expected
to help some patients with asthma.
LONG-TERM ANTIBIOTIC THERAPY?
The authors have garnered support for this idea from both clinical experience and research. Using an empirical approach, weve tried clarithromycin with some of our clinical patients. Anecdotally speaking, we have steroid-dependent asthmatics who improved with clarithromycin, said Dr. Kraft. Initially, we tried a six-week course, but we found that respiratory function continued to improve in many patients [if the antibiotic was administered] over three to six months.
Dr. Martin explained the reason for the lengthy course: Unfortunately, mycoplasma is difficult to eradicate from the airways. In true pneumonias, even after chest X-rays show that mycoplasma infection is largely cleared from the lungs, some residual infection lingers.
Dr. Martin and colleagues also back up their clinical experience with experimental evidence. Were submitting a manuscript shortly, describing a study demonstrating that asthmatics who are PCR-positive for chlamydia or mycoplasma infection show a 12% to 13% improvement in airway function following clarithromycin treatment, he reported. Said Dr. Kraft, Most antibiotics do have some anti-inflammatory quality, so its not clear how this works. Hopefully, animal studies will answer this question.
While the researchers are encouraged by clinical and experimental success with antibiotic therapy in a subset of asthma patients, Dr. Kraft recognizes that long-term antibiotic treatment for asthma may be controversial. In light of concerns regarding general overuse of antibiotics and need to justify long-term administration under managed health care, this approach might be questioned. However, in the absence of a practical means of establishing the diagnosis, she said, We havent found any other way.
Despite the experimental evidence
for an association between lower airway infection and chronic
asthma, testing patients for such infections in the clinical
setting is problematic. In the present study, all subjects
were seronegative for Mycoplasma pneumoniae, and
only three of seven subjects PCR-positive for chlamydia
were seropositive. Seropositivity is not a great marker
for mycoplasmalpha- or chlamydialpha-induced asthma. Mycoplasma
infection frequently can be shown by PCR to be very active
in the airways of seronegative individuals, explained
Dr. Martin. It seems to be triggering inflammation
but may not be potent enough to trigger an immune response,
said Dr. Kraft. On the other hand, she pointed out, Chlamydia
serology tends to give false positives.
PCR: FUTURE DIAGNOSTIC?
As demonstrated by the present study, PCR remains the only reliable way of demonstrating chronic infection. But PCR requires collecting relevant samples. The lower airway samples we need for diagnosis require invasive bronchoscopy, said Dr. Kraft.
told RESPIRATORY REVIEWS,
Were trying to work out procedures on cells
from induced sputum, which right now is not as sensitive
as PCR from samples obtained by bronchoscopy. For
now, PCR testing for lower airway chronic infections may
be impractical in the clinical setting.
finding was that, among the asthma patients tested, users
of inhaled corticosteroids were less likely to test positive
for the microbes by PCR. Dr. Martin cited evidence for one
explanation: In animal airway studies with another
species of Mycoplasma, steroids were equally efficacious
with antibiotics in reducing bacterial load and reducing
inflammatory processes. Were developing a mouse model
to look at how steroids might work to reduce infection with
Mycoplasma pneumoniae. Dr. Martin is hopeful
that animal work will reveal whether corticosteroids have
a direct action on the microbes or simply impede infection
by blocking inflammation.
Dr. Martin noted another interesting finding: In patients positive for mycoplasma, especially among those with allergic asthma, there were increased numbers of mast cells in the lungs. It looks like there could be a connection between infection and allergic sensitization. Yet immunoglobulin E elevation in these individuals was not significant. While this finding is intriguing, the study was not designed to reveal whether infection precedes sensitization or vice versa.
ONE OF MANY TYPES
In the past few decades, a lot of chronic inflammatory diseases have been shown to have infectious causesstable asthma may be another, said Dr. Kraft. Our work connecting chronic infection with asthma may change how we look at asthma in general. What were finding is that asthma is probably not one diseasehistorically, a lot of phenotypes have been lumped together, but theres a lot of heterogeneity in phenotype as well as etiology. Separating out the various types of asthma and their causes may be the first step toward finding more effective treatments and preventative strategies.
Mimi Zucker, PhD
1. Martin RJ, Kraft M, Chu HW, et al. A link between chronic
asthma and chronic infection. J Allergy Clin Immunol.