Asthma In Japan Research Articles

Surveys on the Prevalence of Pediatric Bronchial Asthma in Japan: A Comparison between the 1982, 1992, and 2002 Surveys Conducted in the Same Region Using the Same Methodology

We conducted and reported the first (1982; 55,388 subjects), and second (1992; 45,674 subjects), epidemiological surveys conducted on bronchial asthma in elementary students across 11 prefectures in western Japan. The 2 surveys were conducted in the same regions using the same methodology employing a modified Japanese version of the American Thoracic Society-Division of Lung Diseases (ATS-DLD) Epidemiology Questionnaire. We conducted the third survey in 2002, and compared the findings to those of previous studies. In the third survey, 37,036 students attending the same schools as in previous surveys (in 11 prefectures) were given the questionnaire. A total of 35,582 responses (96.1%) were collected. An ATS-DLD Epidemiology Questionnaire was also used in this study, and the findings were compared to those of previous studies. 1. The prevalence of bronchial asthma (BA) in boys, girls, and all students was 3.8%, 2.5%, and 3.2%, respectively, for the first survey; 5.6%, 3.5%, and 4.6% for the second survey; and 8.1%, 4.9%, and 6.5% for the third survey. 2. A decline in the BA prevalence in older subjects which could be seen in the first survey was absent in the second and third surveys. There were no regional differences in the third survey. 3. The boys-to-girls ratio in the first, second, and third surveys was 1.5, 1.6, and 1.6, respectively. 4. BA was more prevalent among subjects with a past history of respiratory disease in infancy and those with a family history of allergic disease. 5. The prevalence of asthma symptoms and wheezing in the first, second, and third surveys was 7.1%, 9.8%, and 11.8%, respectively. 6. A comparison of the prevalence of other allergic diseases between the second and third surveys revealed a decrease in atopic dermatitis and an increase in allergic rhinitis, allergic conjunctivitis, and cedar pollinosis. BA prevalence in the third survey increased 2.1 and 1.4 times respectively compared to the first survey and second survey, indicating an upward trend in all regions and age groups surveyed.

Mortality and variables associated with heart failure on admission in patients with acute myocardial infarction

compared those registries data with ADHERE, Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) and Euro Heart Failure Survey (EHFS) II database. Method: We analyzed characteristics and managements in 217 consecutive patients from hospital based ADHF registry database in a single National Cardiovascular Center in Japan. Results: In characteristics, age, serum BNP level and creatinine level were similar between four databases, but we had more patients with systolic dysfunction, hypotension and cardiomyopathy, and less frequently had COPD or asthma in Japan. There is considerable difference was seen in the use of inotrope and vasodilator. In the US, fewer patients were treated with inotropic agent or nitroglycerin as vasodilator than those in Japan or Europe. Especially in Japan, more than one third of patients were treated with human natriuretic peptide which has similar pharmacological effect as Nesiritide.

Inhaled Corticosteroid Use and Asthma Hospitalization Rates in Japan

This epidemiological study assessed whether the use of anti-inflammatory drugs, in particular inhaled corticosteroids, affected hospitalization rates for asthma in Japan between 1990 and 2002. Asthma hospitalization rates were calculated from the number of asthma in-patients recorded in governmental surveys. Information concerning use of anti-inflammatory drugs was extracted from the IMS prescription database. Patients were stratified into four age groups: < or = 4 years, 5 - 19 years, 20 - 39 years and 40 - 64 years. Over the study period, the number of prescriptions for inhaled corticosteroids per year increased dramatically and hospitalizations for asthma decreased in all groups except those < or = 4 years of age. Increased use of leukotriene receptor antagonists was also noted in all age groups. The use of anti-inflammatory drugs may have contributed to the observed decrease in asthma hospitalizations. Increased use of inhaled corticosteroids in infants and very young children may help prevent hospitalization in this age group.

Asthma: What we learn from each other's problems? The present state of asthma in Japan and Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGTMA)

Asthma in children is defined as ‘‘A disease involving recurrent symptoms of airway narrowing, including episode of dyspnea, wheezing, and cough. Usually, the patient’s medical history is positive for airway hyperresponsiveness associated with chronic allergic inflammation from environmental allergens’’. Diagnosis of asthma is not difficult. But, It is difficult in infant, because asthma infants can not complain of dyspnea by themselves, and symptoms can be observed objectively. We use ‘‘Asthograph’’ to measure bronchial hyperresponsiveness for the diagnosis of infantile asthma. Sixty percents of childhood asthmatics develop their symptoms before the age 3years. As the saying goes, not all wheezes is asthma, however almost all that wheezes is asthma. Asthma in infancy can be confused with a variety of airway diseases, all of which produce similar signs, symptoms, and physiological changes. The names of diagnosis are wheezy bronchitis, pseudoasthma, asthmatoid bronchitis, spastic bronchitis, etc. But considering the definition of asthma, asthma is asthma. Assessment of the degree of attack is essential for the determination of adequate treatment, management.

Tulobuterol, aβ2-agonist, Attenuates Eosinophil Adhesion to Endothelial Cells

Transdermal patches containing tulobuterol, slow-releasing β2-agonist patches, are now widely used in the treatment of asthma in Japan. Unlike inhalational β2-agonists, tulobuterol patches act systemically and may modify the functional status of inflammatory cells in the peripheral circulation. The objective of this study is to examine the effect of tulobuterol on the adhesive interaction between blood eosinophils and endothelial cells. Peripheral blood eosinophils and human umbilical vein endothelial cells (HUVEC) were pretreated with either tulobuterol or a control medium, and adhesion of eosinophils to HUVEC was examined using an eosinophil peroxidase assay. Spontaneous adhesion of eosinophils to resting HUVEC was not modified by tulobuterol. On the other hand, eosinophil adhesion to IL-4 + TNFα-stimulated-HUVEC was inhibited minimally but significantly by tulobuterol. Furthermore, both IL-5- and FMLP-activated adhesions of eosinophils to HUVEc were partially but significantly inhibited by tulobuterol. Tulobuterol can decrease adhesion of blood eosinophils to endothelial cells. This finding sug gests that tulobuterol patches have anti-inflammatory properties, and may therefore contribute to the treatment of airway inflammation in asthma.

Economic Evaluation of an Asthma Therapy: Effect of Salmeterol on Loss of Labor Productivity in Japan

Asthma can have a negative impact on the productivity of paid and unpaid individuals. In this study, we aimed to investigate the impact of salmeterol, which, in recent years, has become available for the treatment of asthma in Japan, on the productivity of patients with asthma. Relevant data were extracted from the medical records of 54 patients aged ≥ 15 years with moderate or severe asthma. Loss of productivity was estimated via the human capital approach in the year before and the year after introduction of salmeterol. Lost productivity was significantly reduced ( p < 0.001) after salmeterol's introduction compared to the period before its introduction in both paid labors and unpaid ones. Reduced loss of productivity avoided loss of approximately 800,000 yen in the paid ones and 61.3 days in unpaid ones. It was estimated that loss of about 105.4 billion yen in the paid group and 64.5 billion yen in the unpaid group could be avoided if this result was expanded to the wider society. In paid labors, productivity loss was avoided when symptoms were absent during the day, irrespective of the presence or absence of symptoms during the night, whereas, in the unpaid group, the loss was avoided when symptoms were absent during the day or night. It was considered that improvement of clinical symptoms, which occurred in association with the introduction of salmeterol, resulted in avoidance of losses in productivity that had previously occurred in patients with asthma.

Autumn exacerbations of pediatric asthma in Japan is strongly associated with rhinovirus (RV) infection

Rationale Since more than 40% of admission cases due to childhood asthma exacerbations in our department occurs from September to November, we examined the association between viral infection and asthma exacerbations in our department. Methods In the past two years (2001-2002), two different kinds of studies were performed from October to November. In 2001, total 50 inpatients (mean age: 3.2 y) due to asthma exacerbations were examined about viral infections by using culture method. Based on the data obtained 2001 study, we then focused on RS virus and RV in 2002 study. Total 71 inpatients (mean age: 3.9y) due to asthma exacerbations were recruited to the study. Paired serum and diagnosis kit were used against proof of RS virus infection, and RT-PCR was used against detection of RV infection. Results Four cases of RS infections and three cases of RV infections were detected by culture method in 2001 study. In 2002 study, RV infections were identified in 57 cases out of 71 patients (80%). RS infections were identified in 6 cases out of 71 subjects. Overlapped infection of RS virus and RV were seen in 2 cases. Conclusions These studies indicate strong association between RV infection and pediatric asthma exacerbations in autumn in Japanese children. It is of interest to clarify the mechanisms of these links.

Questionnaire-based analysis of the current level of asthma control and management in Niigata Prefecture, Japan: Changes from 1998 to 2000

It is very important to use antiinflammatory agents, including inhaled corticosteroids, in the management of asthma because bronchial inflammation is a fundamental component of bronchial asthma. Although management according to this strategy is recommended in several countries, the actual situation of asthmatic patients in Japan is poorly understood. To clarify the actual management of asthma in Japan, the present study was undertaken. In 1998, for 8 weeks from September through to October, questionnaires on asthma control and satisfaction in daily life were given to asthmatic patients. In addition, questionnaires regarding patient profiles and medication were given to the patients' physicians. The same questionnaires were repeated in 1999 and 2000. The information obtained from the same patients and their physicians who responded in each of the three years was used for analysis. We analyzed 840 cases. During this period, over 80% of patients used oral theophylline, although the percentage of patients using inhaled steroids and leukotriene receptor antagonists increased from 67.0 and 29.8% in 1998 to 75.1 and 34.2%, respectively, in 2000. Asthma control (including the presence of attacks and self-evaluation by each patient), asthma- related symptoms and sleep disturbance improved significantly. However, there was no improvement in satisfaction in daily life of asthmatic patients surveyed. Multiple-regression analysis revealed that self-evaluation of asthma control by each patient was significantly related to improvement in satisfaction in daily life. These results indicate that antiinflammatory agents, including inhaled corticosteroids and leukotriene receptor antagonists, contributed to improved asthma control, whereas oral theophylline is characteristically used in Niigata Prefecture, Japan. However, not all asthma-related problems, such as satisfaction in daily life, improved and self-evaluation of asthma control by patients may play a key role in improving their satisfaction in daily life.

Trends in asthma morbidity and mortality in Japan between 1984 and 1996.

To determine whether the increased prevalence of asthma in Japan has influenced its mortality. A descriptive study was conducted by the data obtained from Patient Survey and Vital Statistics of Japan between 1984 and 1996. Asthma fatalities were expressed as the number of deaths from asthma per 100,000 asthmatic patients receiving medical treatment on the day when the survey was conducted. Mortality, prevalence and asthma fatalities showed different changing patterns among several age groups. Asthma mortality for the 10-24 and 25-44 year-old groups increased during the study period, while for other age groups, it decreased. The prevalence increased for all groups classified by age and sex. Asthma fatalities peaked in 1987 among the 10-24, 25-44 and 45-64 year-old groups, and decreased for others throughout the study period. There is a possibility that an age-specific phenomenon is at work here because asthma mortality increased only in the 10-24 and 25-44 year-old groups, although the prevalence of asthma increased in all groups, whether classified by age or sex. The asthma fatality of the 10-24, 25-44 and 45-64 year-old groups peaked in 1987: it is conceivable that this was influenced by the particular drug therapy used. The increase in asthma mortality in the 10-24 and 25-44 year-olds might be influenced by the increased prevalence.

Trends in Asthma Mortality in Japan

Asthma mortality has been increasing in many developed countries in recent years, so we have described the epidemiological features of asthma in Japan. Data on all certified asthma deaths from 1950 to 1997 were obtained from The National Vital Statistics, published annually by the Ministry of Health and Welfare. Trends in crude and age-adjusted asthma mortality rates, as well as age-specific mortality rates, were analyzed. Age and birth cohort effects on mortality rates were also examined using multiplicative models. Between 1950 and 1980, crude asthma mortality rates steadily decreased in both sexes and began to level off thereafter. Age-adjusted mortality rates have also decreased since 1950, and showed a persistent downward trend in both sexes even in recent years. Asthma mortality rates were higher in males than in females during the entire study period. When analysis was restricted to those aged 5 to 34 years, an upward trend since 1980 was observed. The multiplicative model showed a rapidly decreasing cohort effect on mortality among those born after 1860. However, the slope increased in the cohorts born after 1950 in both sexes. The age effect increased linearly with advancing age after 50 years in both sexes. Overall asthma mortality rates have been decreasing during the past five decades in Japan, but the mortality rate has increased among the 5–34-year-old age group since 1980. The high fatality rate stemming from the overuse of beta 2-agonists may account for the mortality increase.

A Study of 456 cases of death from asthma (1993-1997) from an investigation by the Tokyo Medical Examiner’s Office

Mortality from asthma in Japan still remains at a higher level than in Europe and America and how to decrease that mortality rate is an important issue. For the prevention of death from asthma, it is essential to study the risk factors. However, there has been almost no such study performed in Japan and, for this reason, we performed the present study to elucidate the background of the recent cases of death from asthma. This study was performed on cases of death from asthma at the Tokyo Medical Examiner’s Office over a period of 5 years (1993-1997). There were 456 cases under study, with the age at death ranging from 4 to 96 years (average age 58.5 years). The male to female ratio was 1.8:1 and there was a tendency for a marked increase in the number of cases of death from asthma in women aged 60 years and older. The annual number of deaths was lowest in 1997, being 67 cases. The monthly number of deaths was higher in December and February and was lower in the months of June, July and September. Among the cases investigated, 60.2% died within 3 h after the onset of an asthmatic attack. In the cases of patients living alone, the chance of receiving emergency medical care was significantly lower compared with cases where patients lived with other people. Of the cases of death from asthma, 36.6% of patients were in the habit of drinking and 27.7% smoked. In an investigation of the 247 deaths that occurred during the 3 year period from 1995 to 1997, there were 140 cases (56.7%) for which emergency medical care was offered to treat the asthmatic attack. In 126 cases (90.0%), cardiopulmonary arrest was observed on arrival at hospital. Of these cases, a heart beat was restored in 27 patients (21.4%). In 133 of 456 deaths (29.2%), patients had used a metered dose inhaler (MDI). Among these cases, 80 patients (60.2%) seemed to have been using a MDI up to the time immediately before death. Those living alone have a significantly lower likelihood of receiving emergency medical care immediately before death compared with those living with other people. The cases of acute death within 3 h after the onset of the asthma attack accounted for 60.2% of all cases and this seems to be important for future studies of the medical care of deaths due to asthma.

Effect of thromboxane A 2 (TXA 2) synthase inhibitor and TXA 2 receptor antagonist alone and in combination on antigen-induced bronchoconstriction in guinea pigs

Thromboxane A 2 (TXA 2) causes bronchoconstriction and bronchial hyperresponsiveness. Two types of TXA 2 modifiers, one synthase inhibitor and one receptor antagonist, are widely used for the treatment of asthma in Japan. Although the target of TXA 2 modifiers is to inhibit bioactivity of TXA 2, the pharmacological properties are somewhat different between these drugs. We studied the inhibitory effects of the TXA 2 synthase inhibitor CS-518 and the TXA 2 receptor antagonist S-1452 alone and in combination on antigen-induced bronchoconstriction in passively sensitized guinea pigs treated with diphenhydramine. Both CS-518 and S-1452 inhibited the antigen-induced bronchoconstriction dose-dependently with the plateau. The combination of these drugs at the maximal inhibitory doses did not have any more effect compared with each single dosing. The combination at the submaximal doses tended to show an additive effect, but the effect was not significant. These findings suggest that other prostanoids such as PGE 2, PGI 2, PGD 2 and PGF 2α may not take an important role in the antiasthmatic effects of TXA 2 modifiers.

Identification of a Novel Cat Allergen – Cystatin

Background: Cat allergen is an important cause of sensitization among children with asthma in Japan. Although there is good evidence that cats produce other allergens, only one major allergen, Fel d 1, has been studied in detail. Aims: To identify and define the molecular structure of the other potential cat allergens. Methods: A cat skin cDNA library was screened using IgE antibodies to cat dander and selected clones were sequenced and expressed. Results: One cDNA clone contained an open reading frame encoding a 98-amino acid residue protein. Sequence homology searches revealed a high degree of identity with bovine and human cystatin A, 79 and 75%, respectively. This cat cystatin clone contained the conserved cysteine protease motif and two of three lipocalin motifs. By plaque immunoassay, 60–90% of cat allergic sera had IgE Ab to cat cystatin. This cysteine protease inhibitor motif was partially conserved in dog allergens, Can f 1 and Can f 2, which are lipocalins. Recombinant cystatin was produced in Escherichia coli cells and purified as an 11-kD protein, corresponding to the predicted MW of cystatin. The structure of cat cystatin was modeled on human cystatin B using the SWISS-MODEL. Conclusion: A newly identified allergen, cystatin, has been cloned from cat skin and is a member of the cysteine protease inhibitor family.

Comparison of respiratory symptoms between schoolchildren in China and Japan

ABSTRACT Background Despite improvements in air pollution, the prevalence and incidence of bronchial asthma, which has attracted a great deal of attention in relation to air pollution, is tending to increase in Japan as well as worldwide. Severe air pollution conditions currently exist in China due to sulfur dioxide and particulate matter, resulting from coal burning and motor vehicle exhaust gases associated with the rapid increase in the number of vehicles. Methods Using the same questionnaire in China and Japan, we conducted a comparative study of the prevalence of various respiratory symptoms among schoolchildren in Anshan ( n = 4395), Taiyuan ( n = 3784 in 1997; n = 3995 in 1999) and Chengdu ( n = 7795 in 1991; n = 3000 in 1998) in China and in Yokohama ( n = 4161) in Japan. The pollution concentrations in the survey area of China resembled the concentrations observed in heavy industry areas in Japan in the 1970s. Results Comparisons between schoolchildren in Japan and China showed that the prevalence of persistent cough and persistent phlegm (persistent congestion and phlegm) was higher among schoolchildren in China (e.g. the prevalence of persistent cough in boys in China was 2.4-8.1%, whereas the rate was only 2.1% for boys in Yokohama), whereas the prevalence of wheezing and asthma-like symptoms was higher among schoolchildren in Japan (e.g. the prevalence of asthma-like symptoms was 0.2-1.8% for boys in China, whereas this rate was 9.6% in Yokohama, Japan). Conclusions If China follows the same path as Japan, that is, proceeds with conversion from coal to oil as its primary energy source, the popularization of motor vehicles and chemical contamination of food, housing and clothing, there is a risk that the prevalence of bronchial asthma in Chinese children will increase in the same way as it has in Japan. It is hoped that research will be conducted to determine the cause of the increases in bronchial asthma in Japan and that preventive measures will be established so that Chinese children do not repeat the experience of Japanese schoolchildren.

Interleukin 4 receptor alpha chain polymorphism Gln551Arg is associated with adult atopic dermatitis in Japan.

Localization of a locus for atopy to chromosome 16p12-p11 and reported associations of Ile50Val and Gln551Arg polymorphisms in interleukin-4 receptor alpha chain (IL 4R gene) with atopy prompted us to sequence the gene in 27 adult atopic dermatitis (AD) and 29 non-atopic (non-AD) subjects. Among six known polymorphisms, Gln551Arg was significantly associated with AD (P = 0.01). This polymorphism was found to be heterozygous in six of 27 patients with AD but none of the 28 non-AD controls. Ile50Val, which was previously reported to be associated with atopic asthma in Japan, showed no association with AD in our group. Glu375Ala and Cys406Arg also showed no association with AD. The IL 4R gene should thus be considered a compelling candidate gene for AD.

Survey of recognition and utilization of guidelines for the diagnosis and management of bronchial asthma in Japan.

In Japan in 1993, the Japanese Society of Allergology (JSA) developed guidelines for diagnosis and management of asthma (JGL), which were based on the concept that asthma is a chronic inflammatory disorder of the airway. This survey study was intended to investigate the recognition and utilization of JGL among physicians who had treated asthma. The survey comprised two methods: a quantitative mail survey and a qualitative door-to-door survey conducted by trained interviewers. In the mail survey, a total of 1028 physicians responded; 552 members of the JSA and 476 nonmembers. Ninety-four percent of JSA members were aware of adult asthma management guidelines, while 53% of nonmembers were aware of them. Although approximately half of the physicians, both members and nonmembers, found differences between the asthma management policies in JGL and their previous policies, most of them utilized JGL once they read it. In the qualitative door-to-door survey, 80-90% of physicians evaluated JGL as good after they read it. JGL was recognized and utilized by most JSA members, but only half of nonmember physicians were aware of JGL, although they utilized JGL after they read it. Further action to implement JGL among nonspecialist physicians is needed to improve management of asthma.

Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.

Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma.

Cost-effectiveness of budesonide Turbuhaler in the treatment of mild-to-moderate asthma in Japan

ABSTRACT Asthma therapy including inhaled corticosteroids (ICS) has been shown to be effective in many parts of the world, but its use is still limited in Japan. A 6-week, randomized, placebo-controlled, clinical trial was therefore undertaken to assess the efficacy of the ICS budesonide Turbuhaler (budesonide administered via the dry-powder inhaler Turbuhaler) in patients in Japan with mild-to-moderate asthma. Prior to, and during, the study, all concomitant medications, except corticosteroid preparations, were allowed (i.e. all pre-study medication was to be maintained throughout the study). In total, 218 patients randomized to receive budesonide Turbuhaler 200μg/day ( n = 53), 400μg/day ( n = 55), 800μg/day ( n = 57) or placebo ( n = 53) were included in the analysis. Due to the increased demand and interest for health economic data in Japan, this retrospective cost-effectiveness analysis reports on the economic impact of budesonide Turbuhaler compared with placebo (i.e. usual care), based on this clinical trial. At each dosage, budesonide Turbuhaler was significantly more effective than the placebo, according to the number of symptom-free and episode-free days. The number of emergency visits, days of lost production and days of hospitalization were all lower in the budesonide Turbuhaler groups, leading to significantly ( P

Saiboku-to, a Kampo herbal medicine, inhibits LTC4 release from eosinophils

Saiboku-to (TJ-96), a traditional Kampo herbal formation, has been used in the treatment of bronchial asthma in Japan as an anti-allergy herbal medicine. We investigated the effect of TJ-96 on leukotriene (LT)C4 release from eosinophils and basophils isolated from healthy volunteers. Pre-incubation of eosinophils with TJ-96 inhibited ionophore- or formyl-methionyl-leucyl-phenylalanine (FMLP)-induced LTC4 generation by eosinophils in a dose-dependent fashion. The TJ-96 was more potent in the release by ionophore (IC50 = 60 mg/mL) than the release induced by FMLP (IC50 = 300 mg/mL). Maximal inhibition was observed when eosinophils were pretreated with TJ-96 for 5 min. Although TJ-96 at high concentrations inhibited IgE-mediated histamine release from human basophils, inhibition of IgE-mediated LTC4 release was not statistically significant. The potent inhibitory activity was found in the extract of Glycyrrhiza root, one of the herbal components of TJ-96, but the inhibitory effects were not due to either glycyrrhizin or liquiritin, the main elements of the Glycyrrhiza root. These results raise the possibility that the clinical efficacy of TJ-96 is derived, at least in part, from its potent inhibitory effect on LTC4 release from eosinophils.

Increased use of inhaled corticosteroids and reduced hospitalizations in adult asthmatics: 11 years' experience in a Japanese hospital.

Until recently, inhaled corticosteroids have not been recognized as a first-line drug mainly because of the traditional polypharmaceutical approach to asthma in Japan. To examine the trend more precisely following the introduction of inhaled corticosteroids, we retrospectively analysed the relation between the number of prescriptions for anti-asthma drugs including inhaled corticosteroids and the number of hospitalizations due to asthma exacerbation, near fatal episodes and deaths from asthma for a period of 11 years from 1986 to 1996 at Kobe City General Hospital (KCGH). A marked decline in these actual indices in patients attending KCGH, which shows the improvement in asthma control, started coincidentally with the increased use of inhaled corticosteroid, which was followed by both a discontinuation of the trend for increased use of inhaled beta-agonists and the decreased use of oral anti-asthma agents. There was no significant difference in the mean duration of hospital stays between 1988 and 1996. Although the intensification of patient education is likely to play an important role in enhancing the protective effect of inhaled corticosteroids, we highly suspect that the major contributory factor in the great decline in hospitalizations is the increased use of inhaled corticosteroids.