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Eur Respir J 2007; 29:1284-1285
Copyright ©ERS Journals Ltd 2007

From the authors

F. Tahan

Paediatric Allergy, Erciyes University School of Medicine, Kayseri, Turkey.

We would like to thank M. Korppi for his comments regarding our recently published study on the use of clarithromycin in the treatment of respiratory syncytial virus (RSV) bronchiolitis 1.

RSV is the most common cause of upper and subsequent lower respiratory tract infection in children and it is most severe in children aged 8–30 weeks 2. Despite many attempts to find effective treatments for patients with RSV bronchiolitis, no consistently effective therapy has yet been described. Since RSV infection initiates an immune inflammatory response that may produce long-lasting harmful effects, in our study we hypothesised that we could modify the course of the disease and prevent wheezing after bronchiolitis by administering macrolides (due to their anti-inflammatory effect) to infants during an acute episode of RSV bronchiolitis. Despite the small number of children in each group, the results of the study were exciting for us. This is important, as, to date, there has been no effective therapy for RSV bronchiolitis. Our results should encourage the undertaking of further studies to confirm the use of clarithromycin in RSV bronchiolitis, especially in infants aged <6 months who present with severe disease.

In our study, Bordetella pertusis was not investigated since all subjects tested positive for RSV and presented normal leukocyte counts, with leukocytosis (15,000–100,000 cells·mm–3) being characteristic of B. pertusis infection 3.

We did not investigate Simcania negevensis or Chlamydia trachomatis. Although in some populations the involvement of S. negevensis seemed to be common in association with RSV bronchiolitis 4, 5, results of one study 6 did not reveal any significant difference in the prevalence of S. negevensis infection between children with bronchiolitis and control subjects. In that study of 188 patients and 110 healthy control subjects, S. negevensis serological assays were positive in 18% of patients compared with 29% of control subjects 6.

We did not investigate C. trachomatis but we know that pneumonia due to C. trachomatis develops in 10–20% of infants born to females with chlamydial infection. C. trachomatis pneumonia of infancy has a very characteristic presentation and auscultation reveals rales while wheezing is uncommon. A distinctive laboratory finding is the presence of peripheral eosinophilia (>400 cells·mm–3) 7. In our study group, only one child had eosinophilia.

The use of bronchodilator agents continues to be controversial. The results of the meta-analysis indicated that some children treated with bronchodilators might have a transient improvement in clinical score 8. Although there is no evidence from randomised controlled trials to justify the routine use of bronchodilators, clinical experience suggests that, in selected infants, there is an improvement in the clinical condition after bronchodilator administration 912. In our study, the infants received ß2-agonist treatment based on clinical parameters, including the presence of wheezing on auscultation of the chest or respiratory distress with retractions. Wheeze and chest tightness has traditionally been associated with enhanced bronchial responsiveness. Airway hyperresponsiveness appears to be one manifestation of the airway inflammation induced by RSV. It has been shown that a correlation exists between airway inflammation and the degree of airway hyperresponsiveness (as discussed in our paper). Following this, duration of the need for ß2-agonist treatment (even for minimal improvement in clinical condition) may provide some indication as to the degree of airway inflammation.

In the process of re-analysis of the data for readmission, we realised that there was a data entry error. Unfortunately, this changes the statistical significance in the readmission rate. In our study, five patients were readmitted to hospital with wheezing within 6 months of discharge: four (44%) from the placebo group and one (8.3%) from the clarithromycin group. Although the values were higher in the placebo group, this difference did not reach significance, which may be attributed to the small number of children in each group.

REFERENCES

  1. Tahan F, Ozcan A, Koc N. Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial. Eur Respir J 2007;29:91–97.[Abstract/Free Full Text]
  2. Openshaw PJ, Tregoning JS. Immune responses and disease enhancement during respiratory syncytial virus infection. Clin Microbiol Rev 2005;18:541–555.[Abstract/Free Full Text]
  3. Long SS. Pertusis (Bordetella pertusis and B. Parapertusis). In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 17th Edn. Philadelphia, Saunders, 2003; pp. 908–912
  4. Kahane S, Greenberg D, Friedman M, Haikin H, Dagan R. High prevalence of "Simkania Z", a novel Chlamydia-like bacterium, in infants with acute bronchiolitis. J Infect Dis 1998;177:1425–1429.[Web of Science][Medline] [Order article via Infotrieve]
  5. Greenberg D, Banerji A, Friedman MG, Chiu CH, Kahane S. High rate of Simcania negevensis among Canadian Inuit infants hospitalized with lower respiratory tract infections. Scand J Infect Dis 2003;35:506–508.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  6. Kumar S, Kohlhoff SA, Gelling M, et al. Infection with Simcania negevensis in Brooklyn, New York. Pediatr Infect Dis J 2005;24:989–992.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  7. Hammerschlag MR. Chlamydial Infections. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 17th Edn. Philadelphia, Saunders, 2003; pp. 994–999
  8. American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics 2006;118:1774–1793.[Abstract/Free Full Text]
  9. Klassen TP, Rowe PC, Sutcliffe T, Ropp LJ, McDowell IW, Li MM. Randomized trial of salbutamol in acute bonchiolitis. J Pediatr 1991;118:807–811.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  10. Schweich PJ, Hurt TL, Walkley EI, Mullen N, Archibald LF. The use of nebulized albuterol in wheezing infants. Pediatr Emerg Care 1992;8:184–188.[Web of Science][Medline] [Order article via Infotrieve]
  11. Schuh S, Canny G, Reisman JJ, et al. Nebulized albuterol in acute bronchiolitis. J Pediatr 1990;117:633–637.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  12. Menon K, Sutcliffe T, Klassen TP. A randomized trial comparing the efficacy of epinephrine with salbutamol in the treatment of acute bronchiolitis. J Pediatr 1995;126:1004–1007.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]




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