To the Editor: In the study of rescue use of beclomethasoneand albuterol in a single inhaler for mild asthma reported byPapi et al. (May 17 issue),1 the morning peak expiratory flowrate (based on peak-flow diaries) was the primary end point,although there is enough reason to doubt its clinical relevance,its validity, and its physiological meaning in a disease thatpredominantly affects smaller airways. The peak expiratory flowrate reflects mainly central-airway mechanics2 and is insensitivefor the monitoring of peripheral-airway patency. Only becauseno Bonferroni correction was used, the morning peak expiratoryflow rate — but not the evening peak expiratory flow rateor variability in peak expiratory flow rate — was marginallysignificantly different (P=0.04) between the as-needed combinationgroup and the as-needed albuterol group, whereas the secondaryend points of forced expiratory volume in 1 second and forcedvital capacity (percent of the predicted value) proved to bemuch more sensitive in detecting a treatment effect. A similarsituation was reported previously,3 and the study by Papi etal. once again illustrates that measures of peak expiratoryflow rate are insensitive and therefore, in my opinion, do notreflect the disease adequately.
Peter J.F.M. Merkus, M.D., Ph.D. Sophia Children's Hospital 3000CB Rotterdam, the Netherlands p.j.f.m.merkus{at}erasmusmc.nl
References
Papi A, Canonica GW, Maestrelli P, et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med 2007;356:2040-2052. [Free Full Text]
Pedersen OF, Brackel HJL, Bogaard JM, Kerrebijn KF. Wave-speed-determined flow limitation at peak flow in normal and asthmatic subjects. J Appl Physiol 1997;83:1721-1732. [Free Full Text]
Boushey HA, Sorkness CA, King TS, et al. Daily versus as-needed corticosteroids for mild persistent asthma. N Engl J Med 2005;352:1519-1528. [Free Full Text]
To the Editor: The conclusions by Papi and colleagues with respectto the effectiveness and medication-sparing capacity of inhaledbeclomethasone–albuterol as intermittent therapy for mildpersistent asthma are based on their study of adults. The applicationof this method to children requires proof of principle. Lunggrowth, which affects treatment outcomes over time in children,could obviously not be accounted for in their study.
Luigi Terracciano, M.D. Alessandro Fiocchi, M.D. Gabriel R. Bouygue, M.Sc. University of Milan Medical School 20129 Milan, Italy allerg{at}tin.it
The authors reply: Merkus is concerned that the use of the morningpeak expiratory flow rate, based on peak-flow diaries, may bemisleading because it is insensitive and may not reflect small-airwayabnormalities. Measurement of the peak expiratory flow rateis still recommended in international guidelines1 for monitoringasthma. It is incorrect to state that the peak expiratory flowrate did not differ significantly between the groups in ourstudy, since the morning peak expiratory flow rate was indeedsensitive enough to detect significant differences, in directcomparisons of the experimental treatment (as-needed use ofcombination albuterol–beclomethasone and regular use ofbeclomethasone) and the control treatment (as-needed use ofalbuterol). To the best of our knowledge, there is no singletest of airway function that reflects the prevalent site ofairflow obstruction in asthma, and there is no evidence fromclinical trials that physiological measures that are thoughtto reflect peripheral airways correlate better with respiratorysymptoms than other tests of airway function.2 We agree thatsince the objective of asthma treatment is to ensure clinicalcontrol, it would be of value to design trials that involvepatient-centered outcomes.3
We also agree with Terracciano and colleagues that treatmentsfor asthma should be tested in children with mild asthma. Arandomized clinical trial sponsored by the National Heart, Lung,and Blood Institute is currently under way to address this importantissue (the Childhood Asthma Research and Education [CARE] NetworkTrial — Treating Children to Prevent Exacerbations ofAsthma [TREXA]; ClinicalTrials.gov number, NCT00394329
[ClinicalTrials.gov]
).
Alberto Papi, M.D. University of Ferrara 44100 Ferrara, Italy
Leonardo M. Fabbri, M.D. University of Modena and Reggio Emilia 41100 Modena, Italy
References
Global Initiative for Asthma. Global strategy for asthma management and prevention: NHLBI/WHO workshop report. Bethesda, MD: National Heart, Lung, and Blood Institute, 2005. (Updated 2006.)
Boulet LP. Comparative improvement of asthma symptoms and expiratory flows after corticosteroid treatment: a method to assess the effect of corticosteroids on large vs. small airways? Respir Med 2006;100:496-502. [CrossRef][Web of Science][Medline]
Holgate ST, Bousquet J, Chung KF, et al. Summary of recommendations for the design of clinical trials and the registration of drugs used in the treatment of asthma. Respir Med 2004;98:479-487. [CrossRef][Web of Science][Medline]
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