Chest
Volume 121, Issue 6, June 2002, Pages 1782-1788
Journal home page for Chest

Clinical Investigations
Infection
Mycoplasma pneumoniae and Chlamydia pneumoniae in Asthma: Effect of Clarithromycin

https://doi.org/10.1378/chest.121.6.1782Get rights and content

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-α 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.

Section snippets

Subjects

Fifty-five subjects were recruited via newspaper and radio advertisements from the general Denver, CO, community. The asthmatics fulfilled criteria for asthma,29 exhibiting a provocative concentration of methacholine causing a 20% decline in FEV1 of < 8 mg/mL, and reversibility of lung function by at least 12% with bronchodilator. Exclusion criteria included inpatient status; upper or lower respiratory tract infection within 3 months of study; use of macrolides, tetracyclines, or quinolones

Results

Of fifty-five subjects recruited, 52 subjects were randomized to receive clarithromycin or placebo. Three subjects underwent analysis for mycoplasma and chlamydia, but were excluded from the treatment analysis due to scheduling difficulties (n = 1) and noncompliance (n = 2). On entry into the study, no chest radiographs revealed infiltrates. The mean clarithromycin level in the treatment group was 2.78 ± 0.31 μg/mL.

Discussion

This study illustrates that M pneumoniae or C pneumoniae are present in the airways by PCR in > 55% of the patients with chronic, stable asthma studied. In addition, treatment with clarithromycin improved the FEV1 and reduced airway tissue expression of IL-5, but only in the PCR-positive subjects. There was no change in degree of sinus disease with clarithromycin.

The role of infectious agents in asthma has been shown in exacerbations, and there are now data suggesting a role in pathogenesis.1,2,

ACKNOWLEDGMENT

We gratefully acknowledge the technical assistance of L. Duffy, G. Gambil, J. Glass, and E. Keyser at the University of Alabama at Birmingham; C. Gaydos at Johns Hopkins University; B. Marmion at the Institute of Medical and Veterinary Science, University of Adelaide, Australia; J. Pak and J. Henson at the National Jewish Medical and Research Center, Denver, CO; and the General Clinical Research Center at National Jewish Medical and Research Center and the University of Colorado Health Sciences

References (46)

  • T Yano et al.

    Association of Mycoplasma pneumoniae antigen with initial onset of bronchial asthma

    Am J Respir Crit Care Med

    (1994)
  • M Kraft et al.

    Detection of Mycoplasma pneumoniae in the airways of adults with chronic asthma

    Am J Respir Crit Care Med

    (1998)
  • H Melbye et al.

    Reversible airflow limitation in adults with respiratory infection

    Eur Respir J

    (1994)
  • DL Hahn et al.

    Association of Chlamydia pneumoniae(strain TWAR) infection with wheezing, asthmatic bronchitis, and adult-onset asthma

    JAMA

    (1991)
  • DL Hahn et al.

    Asthma and chlamydial infection: a case series

    J Fam Pract

    (1994)
  • DL Hahn

    Treatment of Chlamydia pneumoniae infection in adult asthma: a before-after trial

    J Fam Pract

    (1995)
  • PJ Cook et al.

    Chlamydia pneumoniae and asthma

    Thorax

    (1998)
  • L Von Hertzen et al.

    Asthma, atopy and Chlamydia pneumoniae antibodies in adults

    Clin Exp Allergy

    (1998)
  • U Emre et al.

    The association of Chlamydia pneumoniae infection and reactive airway disease in children

    Arch Pediatr Adolesc Med

    (1994)
  • U Emre et al.

    Detection of anti-chlamydia pneumoniae IgE in children with reactive airway disease

    J Infect Dis

    (1995)
  • JS Seggev et al.

    Mycoplasma pneumoniae is a frequent cause of exacerbation of bronchial asthma in adults

    Ann Allergy

    (1986)
  • S Berkovich et al.

    The association of viral and mycoplasma infections with recurrence of wheezing in the asthmatic child

    Ann Allergy

    (1970)
  • JS Gil et al.

    Isolation of Mycoplasma pneumoniae from asthmatic patients

    Ann Allergy

    (1993)
  • Cited by (341)

    • Proteomic and mechanistic study of Qingxuan Tongluo formula and curcumin in the treatment of Mycoplasma pneumoniae pneumonia

      2021, Biomedicine and Pharmacotherapy
      Citation Excerpt :

      There was no clinical specificity for MPP [19]. The same primordia can also induce different clinical symptoms, and its initial symptoms can manifest only as fever, coughing and other nonspecific clinical symptoms, easily leading to an incorrect clinical diagnosis [20,21]. In the past, MPP was generally mild and had a good prognosis.

    View all citing articles on Scopus

    Supported by the American Lung Association Asthma Research Center Grant and Abbott Laboratories.

    View full text