Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: Effect of clarithromycin

Study objectives: To determine the effect of clarithromycin therapy in patients with asthma. Design: Randomized, double blind, placebo-controlled trial. Setting: A tertiary referral center. Patients or participants: Fifty-five subjects with chronic, stable asthma recruited from the general Denver, CO, community. Interventions: Patients underwent airway evaluation for Mycoplasma pneumoniae and Chlamydia pneumoniae by polymerase chain reaction (PCR) and culture, followed by treatment with clarithromycin, 500 bid, or placebo for 6 weeks. Measurements and results: Outcome variables were lung function, sinusitis as measured by CT, and the inflammatory mediators tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, and IL-12 messenger RNA (mRNA) measured via in situ hybridization, in airway biopsies, and BAL. Mycoplasma or chlamydia were detected by PCR in 31 of 55 asthmatics. Treatment resulted in a significant improvement in the FEV₁, but only in the PCR-positive subjects (2.50 ± 0.16 to 2.69 ± 0.19 L, mean ± SEM; p = 0.05). This was not appreciated in the PCR-negative subjects (2.59 ± 0.24 to 2.54 ± 0.18 L, p = 0.85) or the PCR-positive or PCR-negative subjects who received placebo. Sinus CTs revealed no change in sinusitis with clarithromycin treatment. In situ hybridization revealed no significant difference in baseline airway tissue or BAL-mediator expression between the PCR-positive and PCR-negative subjects. However, the PCR-positive subjects who received clarithromycin demonstrated a reduction in TNF-α (p = 0.006), IL-5 (p = 0.007), and IL-12 (p = 0.004) mRNA in BAL and TNF-3 mRNA in airway tissue (p = 0.0009). The PCR-negative subjects who received clarithromycin only demonstrated a reduction in TNF-α (p = 0.01) and IL-12 (p = 0.002) mRNA in BAL and TNF-α mRNA in airway tissue (p = 0.004). There were no significant differences in cytokine expression in those subjects who received placebo. Conclusions: These observations support the hypothesis that clarithromycin therapy improves lung function, but only in those subjects with positive PCR findings for M pneumoniae or C pneumoniae.