Confirming C pneumoniae infection by bronchoscopy before beginning treatment has been recommended20 but might be impractical; also, diagnostic testing for C pneumoniae is limited in availability and has potentially low sensitivity for diagnosing chronic deep lung infection.
So should you test for C pneumoniae biomarkers (or for biomarkers of Mycoplasma pneumoniae, another atypical infection implicated in the pathogenesis of asthma21) before initiating treatment? Azithromycin has antimicrobial, immunomodulatory, and potential antiviral properties.3 The body of evidence reviewed here indicates that the effects of macrolides on asthma might be, at least in part, antimicrobial. However, there is no direct evidence that the benefit of azithromycin in asthma is limited to patients who have positive infection biomarkers.22 Therefore, infection biomarker testing as a decision aid cannot be recommended at this time (although future research might alter this recommendation).
Acute bronchitis and asthma-onset associated with an acute lower respiratory tract infection have been statistically associated with biomarkers of C pneumoniae infection.23 However, C pneumoniae biomarkers are also prevalent in patients who have asthma that is not associated with an infectious onset.23 Several other matters are worth noting:
C pneumoniae-specific IgA23 and IgE24 are promising biomarkers that deserve further investigation.
M pneumoniae infection has also been associated with asthma and a response to antibiotic therapy.21,25
Noneosinophilic severe asthma is another potential predictive characteristic.26 The applicability of this biomarker to primary care practice is limited, however, by the invasive nature of bronchoscopy and by the uncertain validity of the diagnostic concept: There is no guarantee that dynamic inflammatory infiltrates remain stable over a lifetime. Furthermore, the AMAZES Trial7 reported that azithromycin benefit was comparable in eosinophilic and noneosinophilic asthma.
Potential for harm withlong-term macrolide use?
Controversies about the role of macrolides in asthma involve uncertainty about who might benefit from treatment and the potential harms of macrolides use (TABLE 127,28 and discussed below).29
Adverse effects. The newer macrolides azithromycin and clarithromycin offer favorable safety and tolerability profiles, compared with those of older agents.30 In clinical trials of azithromycin, gastrointestinal symptoms (nausea, vomiting, abdominal pain, and diarrhea) were usually mild or moderate and rarely (< 2% of subjects) required discontinuation of study medication.31,32Clostridium difficile diarrhea has not been reported in any of the large clinical trials, in which thousands of patients received azithromycin for 3 to 12 months.31,32 The major clinical “side effects” attributable to azithromycin are a significant reduction, compared to placebo, in acute respiratory illness, bronchitis, pneumonia, and sinusitis.31,32
