A Link Between Chronic Asthma and Chronic Infection

There is considerable interest in the role that respiratory infections may have on asthma. In infants, respiratory syncytial virus and parainfluenza infections are major causes of wheezing . In susceptible individuals, these infections in early life may lead to recurrent episodes of wheezing and, possibly, the development of asthma . Therefore, respiratory infections may be important in inception of asthma. In patients with existing viral respiratory infections, rhinoviruses are the major cause of asthma exacerbations  Martin and colleagues extend our interest in the link between respiratory infections and asthma by evaluating the frequency of Mycoplasma and Chlamydia pneumoniae in airway tissues from patients with chronic asthma. Although it was not the intent of this study, a possible interpretation of their findings is that these particular infections may be a cause of persistent symptoms of asthma in some patients. Since bacterial organisms are sensitive to treatment with antimicrobials, these further findings suggest a new therapeutic approach for some individuals with persistent asthma.

The relationship of a chronic respiratory infection and persistent asthma has been of interest for years . The study by Martin and co-workers is an important new contribution to this area of research. First, 66 subjects were recruited to the study, and all had evidence of asthma, i.e., reversible airflow obstruction, bronchial hyperresponsiveness, and, in some cases, ongoing treatment. Second, all subjects had a bronchial biopsy, and the existence of infection was assessed by culture, serology, and PCR. Third, Mycoplasma was detected by PCR in 25 of the 55 asthmatic subjects evaluated and Chlamydia in 6 of the 55 subjects. In contrast, only 1 of the 11 normals had evidence for Mycoplasma. Wu and colleagues  had found similar associations with Chlamydia in bronchial biopsy of asthma subjects. The work by Martin et al. extends current findings by suggesting, at least in this population, that Mycoplasma is a more frequently found organism in chronic asthma than Chlamydia.

Martin et al. used bronchial biopsies to evaluate the histopathological findings in association with these infections. Interestingly, PCR-positive/PCR-negative subjects had a similar pattern of cellular inflammation in their lavage-fluid analysis. In addition, immunohistochemical assessment was also similar in the two groups except for a higher frequency of mast cells in the PCR-positive group. The relevance of an increase in mast cells to the consequences of a persistent infection is, however, not clear at present. In addition, inhaled corticosteroids were used in 23% of the PCR-positive group, whereas 48% of the PCR-negative subjects had used inhaled corticosteroids. From this small sample, the authors speculate that inhaled corticosteroids may reduce the inflammatory process associated with the infection, whereas the bacterial load is antibiotic sensitive. This is an intriguing observation that will require additional study for verification and clinical relevance.

The significance of these findings is multiple. First, these findings are further evidence that some respiratory organisms, Mycoplasma and Chlamydia, may lead to persistent infections in asthma. Second, by association, the studies raise the possibility that these respiratory infections may be important in the pathogenesis of persistent asthma. Third, the obvious therapeutic extension of this study is a need to evaluate antimicrobial in patients with organism-positive, persistent asthma. Finally, this study carries forth this new area of research and indicates the frequency of the problem in a representative sample of subjects. The next areas of investigation are obvious and important, i.e., what are the inflammatory mediators, who are the "at-risk" individuals, and what is the best therapeutic approach for these patients? Like heliobacter in ulcer disease and Chlamydia in atherosclerotic disease, this study follows the possible paradigm that some chronic diseases, particularly where an inflammatory response is present, may have a causal linkage to infections. These studies also extend the paradigm that infections in asthma may be important from inception to exacerbation to persistence of disease.

William W. Busse, M.D.
University of Wisconsin
Madison, Wisconsin

References

1. Folkerts G, Busse WW, Nikander K, Sorkness R, Gern JE. Virus-induced Airway Hyperresponsiveness and Asthma. Am J Respir Cell Mol Biol 1998; 157:1708-20.

2. Renzi PM, Turgeon JP, Marcotte JE, Drblik SP, Berube D, Gagnon MF, Spier S. Reduced interferon-gamma production in infants with bronchiolitis and asthma. Am J Respir Crit Care Med 1999; 159:1417-22.

3. Renzi PM, Turgeon JP, Yang JP, Drblik SP, Marcotte JE, Pedneault L, Spier S. Cellular immunity is activated and a TH-2 response is associated with early wheezing in infants after bronchiolitis. J Pediatr 1997; 130:584-93.

4. Rakes GP, Arruda E, Ingram JM, Hoover GE, Zambrano JC, Hayden FG, Platts-Mills TA, Heymann PW. Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses. Am J Respir Crit Care Med 1999; 159:785-90.

5. Johnston SL, Pattemore PK, Sanderson G, Smith S, Lampe F, Josephs L, Symington P, O'Toole S, Myint SH, Tyrrell DAJ, Holgate ST. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children. B Med J 1995; 310:1225-8.

6. Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. BMJ 1993; 307:982-6.

7. Wu L, Skinner SJ, Lambie N, Vuletic JC, Blasi F, Black PN. Immunohistochemical staining for Chlamydia pneumoniae is increased in lung tissue from subjects with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 162:1148-51.

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Ellen Epstein, M.D.
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Dr. Epstein is a Board Certified Allergist affiliated with Long Island Jewish Medical Center, South Nassau Communities Hospital and Franklin Hospital Medical Center

 

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