Is There a Role for Antibiotics in the Treatment of Asthma ? Involvement of Atypical Organisms

Emerging evidence suggests an association between some asthma and pulmonary infection by the atypical organisms Cl~laniydiu prleutrlotliae and Mycoplasrno prleunloniae, but a causal role for infection remains unproven and controversial. Most acute exacerbations of asthma are triggered by acute infections that are due to viral respiratory pathogens. not to bacteria or atypical organisms. Administration of antibiotics for acute exacerbations of asthma has been shown to be ineffective. Most evidence linking atypical infections to asthma is consistent with a promoting role for chronic infection in producing persistent asthma symptoms. Preliminary studies suggest that prolonged (26 weeks) administration of doxycycline or macrolides may eradicate C. pneutnoniuc from respiratory secretions and improve long term, not acute, asthma symptoms. Randomised, controlled trials are currently under way to investigate the effectiveness of these prolonged courses of macrolides and azalides iroxithrornycin, clarithrornycin and azithromycin) in adults with stable persistent asthma. Traditional courses (7 to I0 days) of any antibiotic are incapable of eradicating chronic C. p~zeutnot~iue or M. pnew rnoniue infection; furthermore. p-lactam and sulphonamide-based antibiotics that are commonly prescribed in acute respiratory syndromes are ineffective against these atypical organisms. Unless the goal is to treat documented sinusitis associated with asthma. it is inappropriate to prescribe traditional courses of any antibiotic for acute asthma exacerbations; whether longer courses of antibiotics should be prescribed to eradicate chronic atypical infections and decrease persistent asthma severity remains to be established. In 1991 colleagues and I [ ' ] first reported that wheezing. asthmatic bronchitis and adult-onset asthma were associated with serological evidence for Clllamydia pne~rn~otliae infection. Although acute infections were found to exacerbate and possibly even to initiate asthma in some cases. the preponderance of evidence from our study suggested that reinfection or chronic infection might have a causal association with asthma. This suggestion, that some asthma could be caused by infection, was widely reported at the time. Subsequent investigations. based mainly on serological associations. have supported the possibility that C. prleun~oniue could be related to asthma.1'1 Recently, M ~ ~ c ~ ~ p l u s m u pneunzoniur has also been added to the list of pathogens possibly contributing to asthma symptoms.1" That persistent infection with these organisms could produce chronic inflammation responsible for asthma symptoms is biologically plausible (table I). However, conclusive proof for such a causal association is not established and there is no scientific basis currently for widespread recommendations regarding antibiotic treatment for asthma. Nevertheless, I am aware that antibiotics are being prescribed in acute exacerbations of asthma. The purpose of this article is to explain why antibiotics are not indicated for acute exacerbations of asthma even if a causal association is eventually proven. 1 . Infection and Asthma: Potential Causal Relationships At least 3 different causal pathways exist whereby infection could cause or affect asthma: initiation, exacerbation and promotion. Initiation refers to the ability of an environmental inl-luence (in this case an infection) to produce asthma symptoms in a previously asymptomatic person. Exacerbation denotes that an infection temporarily intensifies already established asthma. Promotion indicates the ability of a chronic infection to persistently worsen asthma symptoms over a long period of time. In lay terms. persistent lung infection as a promoting agent may be thought of as a 'hidden allergen', exposure to which the patient is entirely unaware. Initiation of asthma can be expected to occur in about 1 adult patient per 1000 per year. [4. '] Little is known about asthma initiation because the event is transient and hard to capture in scientific studies. Exacerbation is most widely thought of when speculating on what 'causes' asthma. It is now clear that the majority of asthma exacerbations in both children and adults are related to acute respiratory viral infections16. '1 and that conventional courses of antibiotics are ineffective in asthma e x a c e r b a t i o n ~ . ~ ~ l Examples of proposed promoting agents include persistent exposure to dust mite antigen and to atypical respiratory pathogens such as C. pneurnoniue and M. pileutnoniur. Identification (and removal) of asthma promoting agents offers perhaps the greatest current potential for lessening the disease burden due to asthma. What role(s) might atypical infection play in asthma causation? Table I1 summarises current knowledge regarding C. pneuinoniue and M. pneunzoniue in the initiation, exacerbation and promoTable I. Atypical Infection and asthma: epidemiology and biological plausibility Chlamydia pneumoniae Mycoplasma pneumoniae