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Communications to the Editor |

Chlamydia pneumoniae, Clarithromycin, and Severe AsthmaChlamydia pneumoniae, Clarithromycin, and Severe Asthma FREE TO VIEW

Claus Kroegel, MD, PhD, FCCP; Jürgen Rödel, PhD; Bettina Mock, MD
Author and Funding Information

Affiliations: Friedrich-Schiller-University Jena, Germany,  University of Illinois at Chicago Chicago, IL

Correspondence to: Claus Kroegel, MD, PhD, FCCP, Department of Pneumology and Allergy/Immunology, Friedrich-Schiller-University, Erlanger Allee 101, D-07740 Jena, Germany



Chest. 2001;120(3):1035-1036. doi:10.1378/chest.120.3.1035
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Published online

We read with interest the recent article by Garey et al (December 2000),1 which notes a prednisone-sparing effect of long-term treatment with the oral macrolide antibiotic clarithromycin. The authors discuss their observations with respect to the possible anti-inflammatory action of the macrolides, which has been shown to be distinct from the antimicrobial activity. However, the data support the view that chronic bacterial infection may play a role in severe chronic asthma and suggest that the improvement observed might be due to the antimicrobial effect of clarithromycin on atypical bacteria.

Several reports suggest a relationship between asthma and chronic Chlamydia infection of the airways. For instance, a high titer of antibodies to Chlamydia pneumoniae is associated with bronchial hyperreactivity, duration, and severity of asthma.23 In addition, infection with C pneumoniae elicits a local immunologic response potentially relevant to asthma, which includes the production of proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, and IL-6), neutrophil chemotaxis,4 and inhibition of cellular apoptosis.5Moreover, C pneumoniae not only infects airway epithelial and mononuclear cells, but also smooth-muscle cells, which results in the secretion of significant amounts of both IL-6 and basic fibroblast growth factor.6 Collectively, the data suggest that Chlamydia may interact with and perpetuate airway inflammation, leading to increased symptoms and severity of asthma.

C pneumoniae is an obligate intracellular respiratory pathogen that has developed mechanisms of escaping the intracellular bactericidal activity of human host cells, thus ensuing a chronic infection. In addition, Chlamydia has been shown to withstand standard antimicrobial therapy providing one source for sustained airways inflammation. Thus, the observations by Garey et al may also be explained by the antimicrobial effect of clarithromycin administered for an extended period of time.

Figure Jump LinkFigure 1. Potential role of atypical bacteria in the pathogenesis of asthma.Grahic Jump Location
Garey, KW, Rubinstein, I, Gotfried, MH, et al (2000) Long-term clarithromycin decreases prednisone requirements in elderly patients with prednisone-dependent asthma.Chest118,1826-1827. [PubMed] [CrossRef]
 
von Hertzen, L, Toyryla, M, Gimishanov, A, et al Asthma, atopy andChlamydia pneumoniaeantibodies in adults.Clin Exp Allergy1999;29,522-528. [PubMed]
 
Black, PN, Scicchitano, R, Jenkins, CR, et al Serological evidence of infection withChlamydia pneumoniaeis related to the severity of asthma.Eur Respir J2000;15,254-259. [PubMed]
 
Wyrick, PB, Knight, ST, Paul, TR, et al Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis.J Infect Dis1999;179,954-966. [PubMed]
 
Geng, Y, Shane, RB, Berencsi, K, et al Chlamydia pneumoniaeinhibits apoptosis in human peripheral blood mononuclear cells through induction of IL-10.J Immunol2000;164,5522-5529. [PubMed]
 
Rödel, J, Woytas, M, Groh, A, et al Production of basic fibroblast growth factor and interleukin-6 by human smooth muscle cells following infection withChlamydia pneumoniae.Infect Immun2000;68,3635-3641. [PubMed]
 

Chlamydia pneumoniae, Clarithromycin, and Severe Asthma

To the Editor:

We would like to thank Dr. Kroegel and his colleagues for their comments on our recent case series concerning the use of long-term clarithromycin treatment in elderly patients with prednisone-dependent asthma. We are well aware of the literature regarding the role of atypical bacteria in the pathogenesis of asthma.1 However, our patients had chronic asthma, in which the likelihood of finding live bacteria is remote. Nonetheless, bacterial products may persist in the airway mucosa, thereby precipitating chronic inflammation characteristic of asthma. If this is the case, long-term macrolide therapy would be efficacious through its anti-inflammatory properties. A schema of our hypothesis is presented in Figure 1 .

While we agree that atypical bacteria may play a role in the pathogenesis of asthma, ex vivo and in vitro evidence support an additional anti-inflammatory effect of macrolide antibiotics, independent from their anti-infective properties. Clinically, this effect was first noted2in Japanese patients with diffuse panbronchiolitis (DPB), a chronic, noninfectious inflammatory disease of the airways. Since the initiation of low-dose macrolide therapy, the 10-year survival for patients with DPB has increased from < 10% to > 90%.3Laboratory and animal models45 also support these clinical observations of anti-inflammatory effects of macrolides independent from their anti-infective properties. Macrolides have been shown45 to decrease neutrophil oxidant burst capacity, neutrophil chemotaxis, proinflammatory cytokine concentrations, reactive oxygen species, and mucus secretion.

Overall, an increasing amount of literature has commented on the benefits of antibiotic therapy for the treatment of asthma. Whether this effect is due to an antibacterial effect on atypical organisms, the nonantibacterial, immunomodulatory effects of these antibiotics, or a combination of the two remains to be determined. Future randomized, placebo-controlled trials will help to answer these questions.

References
Hahn, DL Chlamydia pneumoniae, asthma, and COPD: what is the evidence?Ann Allergy Asthma Immunol1999;83,271-288,291. [PubMed] [CrossRef]
 
Epler, GR Bronchiolar disorders with airflow obstruction.Curr Opin Pulm Med1996;2,134-140. [PubMed]
 
Kudoh, S Erythromycin treatment in diffuse panbronchiolitis.Curr Opin Pulm Med1998;4,116-121. [PubMed]
 
Avila, PC, Boushey, HA Macrolides, asthma, inflammation, and infection.Ann Allergy Asthma Immunol2000;84,565-568. [PubMed]
 
Labro, MT Antibacterial agents–phagocytes: new concepts for old in immunomodulation.Int J Antimicrob Agents1998;10,11-21. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Potential role of atypical bacteria in the pathogenesis of asthma.Grahic Jump Location

Tables

References

Garey, KW, Rubinstein, I, Gotfried, MH, et al (2000) Long-term clarithromycin decreases prednisone requirements in elderly patients with prednisone-dependent asthma.Chest118,1826-1827. [PubMed] [CrossRef]
 
von Hertzen, L, Toyryla, M, Gimishanov, A, et al Asthma, atopy andChlamydia pneumoniaeantibodies in adults.Clin Exp Allergy1999;29,522-528. [PubMed]
 
Black, PN, Scicchitano, R, Jenkins, CR, et al Serological evidence of infection withChlamydia pneumoniaeis related to the severity of asthma.Eur Respir J2000;15,254-259. [PubMed]
 
Wyrick, PB, Knight, ST, Paul, TR, et al Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis.J Infect Dis1999;179,954-966. [PubMed]
 
Geng, Y, Shane, RB, Berencsi, K, et al Chlamydia pneumoniaeinhibits apoptosis in human peripheral blood mononuclear cells through induction of IL-10.J Immunol2000;164,5522-5529. [PubMed]
 
Rödel, J, Woytas, M, Groh, A, et al Production of basic fibroblast growth factor and interleukin-6 by human smooth muscle cells following infection withChlamydia pneumoniae.Infect Immun2000;68,3635-3641. [PubMed]
 
Hahn, DL Chlamydia pneumoniae, asthma, and COPD: what is the evidence?Ann Allergy Asthma Immunol1999;83,271-288,291. [PubMed] [CrossRef]
 
Epler, GR Bronchiolar disorders with airflow obstruction.Curr Opin Pulm Med1996;2,134-140. [PubMed]
 
Kudoh, S Erythromycin treatment in diffuse panbronchiolitis.Curr Opin Pulm Med1998;4,116-121. [PubMed]
 
Avila, PC, Boushey, HA Macrolides, asthma, inflammation, and infection.Ann Allergy Asthma Immunol2000;84,565-568. [PubMed]
 
Labro, MT Antibacterial agents–phagocytes: new concepts for old in immunomodulation.Int J Antimicrob Agents1998;10,11-21. [PubMed]
 
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