Long-term observations of the clinical course after step down of corticosteroid inhalation therapy in adult chronic asthmatics: correlation with serum levels of eosinophil cationic protein.
BACKGROUND
Symptoms often deteriorate in well-controlled asthmatics after a step down in inhaled beclomethasone dipropionate (iBDP) therapy if the serum concentration of eosinophil cationic protein (sECP) is high. This deterioration is significantly abrogated by pranlukast, a leukotriene receptor antagonist, or by seratrodast, a thromboxane A2 receptor antagonist. However, these results were based on short-term (less than 6 months) observations.


METHODS
We studied 35 well-controlled adult asthmatics. We assigned the patients into different groups according to their sECP levels before the step down: (i) group A, sECP < 25 microg/L; (ii) group B, sECP > or = 25 microg/L; and (iii) group C, sECP > or = 25 microg/L but patients treated with pranlukast or seratrodast. We began the study with a step down in iBDP therapy (initial step down), then followed the clinical course of the asthma for 2 years. During the study period, we decreased, increased or maintained the iBDP dose on the basis of the stepwise approach described in the National Institutes of Health guidelines. We monitored the time and frequency of exacerbation and evaluated the iBDP dose required to control the asthma symptoms.


RESULTS
The rates of exacerbation after the step down were high in groups A and B. In group A, the conditions were again qualified for the step down in all patients, but this was not the case for most group B patients. From 15 to 21 months after the initial step down, the average dose of iBDP required to control symptoms was significantly higher in group B than in group A patients (P = 0.0127-0.0373). The exacerbation rate in group C after 12 months tended to be lower than in the other two patient groups (P = 0.0743). In group C, the average dose of iBDP from 9 to 24 months after the initial step down was significantly lower than before the step down (P < 0.0001) and was not significantly different from the mean dose of iBDP in groups A or B.


CONCLUSIONS
High sECP in well-controlled asthma may indicate the necessity for a higher iBDP dose over a long period than when the sECP concentration is not high. Even if sECP is high, pranlukast or seratrodast help to prevent exacerbation of asthma and enable successful step down in iBDP therapy for at least 2 years thereafter.
Baba
Kenji
K
Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University, School of Medicine, Yazako, Nagakute, Aichi, Japan. baken@aichi-med-u.ac.jp
Sakakibara
Ayako
A
Yagi
Takeo
T
Niwa
Sayaka
S
Wakayama
Hideo
H
Takagi
Kenzo
K
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001249:Asthma / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage*; D016227:Benzoquinones / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism*; D002867:Chromones / Q000627:therapeutic use; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D047091:Eosinophil Granule Proteins; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011448:Prostaglandin Antagonists / Q000627:therapeutic use; D015656:Respiratory Mechanics / Q000187:drug effects; D012260:Ribonucleases; D018709:Statistics, Nonparametric
D016227:Benzoquinones; D001798:Blood Proteins; D002867:Chromones; D047091:Eosinophil Granule Proteins; D005938:Glucocorticoids; D006538:Heptanoic Acids; D020024:Leukotriene Antagonists; D011448:Prostaglandin Antagonists; C060230:seratrodast; D012260:Ribonucleases; D001507:Beclomethasone; C047681:pranlukast