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Eur Respir J 2004; 24:709-710
Copyright ©ERS Journals Ltd 2004

Methacholine and macrolides

G.P. Currie1 and D.K.C. Lee2

1 Dept of Respiratory Medicine, Aberdeen Royal Infirmary, Aberdeen, and 2 Dept of Respiratory Medicine, Ipswich Hospital, Ipswich, UK.

To the Editor:

The paper by Kostadima et al. 1 provides a valuable insight into the effects of clarithromycin upon nonspecific airway hyperresponsiveness (AHR) to methacholine in asthmatics.

It is important to point out that AHR to methacholine is only very loosely related to the degree of underlying inflammation, whereas the use of an indirect bronchoconstrictor stimulus in the Kostadima et al. 1 study would have provided more convincing evidence of anti-inflammatory activity 2. Bronchoprovocation with indirect stimuli, such as adenosine monophosphate (AMP), is considered to be particularly relevant to real life situations, since cold air, exercise and allergens also act in a similar fashion, in terms of the release of inflammatory mediators from primed mast cells. Indeed, shifts in the AMP threshold are more closely related to underlying airway eosinophilic inflammation and associated with symptoms of atopic asthma than direct stimuli, such as methacholine 3, 4. Furthermore, it has been shown that in asthmatics treated with budesonide in a dose-escalation study, AMP was more sensitive than methacholine in detecting differences in AHR by approximately one doubling dilution 5.

Despite improvements in airway hyperresponsiveness, clarithromycin conferred no worthwhile improvement upon lung function. Therefore, the study by Kostadima et al. 1 provides a timely reminder that monitoring the effects of asthma pharmacotherapy based solely on lung function can miss potentially beneficial effects upon airway hyperresponsiveness and underlying inflammation 6. Further long-term studies are needed to assess whether effects upon airway hyperresponsiveness with clarithromycin translate into clinically meaningful reductions in exacerbations. Moreover, whether macrolides confer benefit upon inflammatory biomarkers, such as airway hyperresponsiveness to adenosine monophosphate and sputum eosinophilia, requires investigation.

References

  1. Kostadima E, Tsiodras S, Alexopoulos EI, et al. Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma. Eur Respir J 2004;23:714–717.[Abstract/Free Full Text]
  2. Cockcroft DW. How best to measure airway responsiveness. Am J Respir Crit Care Med 2001;163:1514–1515.[Free Full Text]
  3. Van Den Berge M, Meijer RJ, Kerstjens HA, et al. PC(20) adenosine 5'-monophosphate is more closely associated with airway inflammation in asthma than PC(20) methacholine. Am J Respir Crit Care Med 2001;163:1546–1550.[Abstract/Free Full Text]
  4. De Meer G, Heederik D, Postma DS. Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV(1). Am J Respir Crit Care Med 2002;165:327–331.[Abstract/Free Full Text]
  5. Wilson AM, Lipworth BJ. Dose-response evaluation of thetherapeutic index for inhaled budesonide in patients withmild-to-moderate asthma. Am J Med 2000;108:269–275.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  6. Currie GP, Lee DKC, Haggart K, Bates CE, Lipworth BJ. Effects of montelukast on surrogate inflammatory markers in corticosteroid treated patients with asthma. Am J Respir Crit Care Med 2003;167:1232–1238.[Abstract/Free Full Text]




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