Thai pediatricians' current practice toward childhood asthma

Background: Childhood asthma is a substantial health burden in Thailand. Due to a lack of pediatric respiratory specialists (pediatric pulmonologists and allergists; RS), most Thai children are cared for by general pediatricians (pediatric primary care providers (PCP)). Objectives: We investigated whether current practices of Thai pediatricians complied with asthma guidelines and compared practices (diagnosis and treatments) provided by PCP and RS. Methods: A cross-sectional study was conducted using electronic surveys including four case scenarios of different asthma phenotypes distributed to Thai pediatricians. Asthma diagnosis and management were evaluated for compliance with standard guidelines. The practices of PCP and RS were compared. Results: From 800 surveys distributed, there were 405 respondents (51%). Most respondents (81%) were PCP, who preferred to use clinical diagnosis rather than laboratory investigations to diagnose asthma. For acute asthmatic attacks, 58% of the pediatricians prescribed a systemic corticosteroid. For uncontrolled asthma, 89% of the pediatricians prescribed at least one controller. For exercise-induced bronchospasm, 55% of the pediatricians chose an inhaled bronchodilator, while 38% chose a leukotriene receptor antagonist (LTRA). For virus-induced wheeze, 40% of the respondents chose an LTRA, while 15% chose inhaled corticosteroids (ICS). PCP prescribed more oral bronchodilators (31% vs. 18%, p = 0.02), antibiotics (20% vs. 6%, p < 0.001), and antihistamines (13% vs. 0%, p = 0.02) than RS for the management of an acute asthmatic attack. Conclusions: Most of the Thai pediatricians' practices toward diagnosis and treatment of acute asthmatic attack and uncontrolled asthma conform to the guidelines. PCP prescribed more oral bronchodilators, antibiotics, and antihistamines than RS.     

Management Preferences of Pediatricians in Moderate and Severe Acute Asthma

Objective. To assess and compare management preferences of physicians for moderate and severe acute asthma based on case scenarios and to determine the factors influencing their decisions.Methods. A questionnaire based on the Global Initiative on Asthma (GINA) guideline and comprising eight questions on management of acute asthma was delivered to participants of two national pediatric congresses. Management of moderate and severe acute asthma cases was evaluated by two clinical case scenarios for estimation of acute attack severity, initial treatment, treatment after 1h, and discharge recommendations. A uniform answer box comprising the possible choices was provided just below the questions, and respondents were requested to tick the answers they thought was appropriate. Results. Four-hundred and eighteen questionnaires were analyzed. All questions regarding moderate and severe acute asthma case scenarios were answered accurately by 15.8% and 17.0% of physicians, respectively. The initial treatment of moderate and severe cases was known by 100.0% and 78.2% of physicians, respectively. Knowledge of the appropriate plan for treatment after 1h was low both for moderate (45.0%) and severe attacks (35.4%). Discharge recommendations were adequate in 32.5% and 70.8% of physicians for moderate and severe attacks, respectively. Multiple logistic regression analysis revealed that working at a hospital with a continuing medical education program was the only significant predictor of a correct response to all questions regarding severe attacks (p = .04; 95%CI, 1.02–3.21). No predictors were found for information on moderate attacks. Conclusions. Pediatricians have difficulty in planning treatment after 1 hour both for moderate and severe asthma attacks. Postgraduate education programs that target physicians in hospitals without continuing medical education facilities may improve guideline adherence.     

Bronchial reactivity in asthma to inhaled histamine during treatment with ketotifen.

A 12-week open trial using varying dosages of ketotifen, an oral drug with a prophylactic anti-asthmatic effect, was carried out in 20 patients with stable chronic bronchial asthma (age 20--50 years, no steroid treatment) to determine whether the frequency of asthma attacks and bronchodilator consumption could be reduced, and whether pulmonary function would improve. The protective action of ketoifen against a histamine inhalation test was measured at the beginning of the trial and at regular intervals during the trial. The patients experienced a significant improvement in their asthma and a significant decrease in the number of asthma attacks during the trial. Concomitantly, the need for other anti-asthma agents was reduced. Pulmonary function tests improved before and following histamine inhalation after 4, 8 and 12 weeks of treatment. In some patients cromoglycate was successfully replaced by ketotifen. Efficacy was rated as very good or good in 17 patients and moderate in 3 patients. Tolerance was good in all patients, no serious side-effects were observed. Summing up, it may be stated that ketotifen is a compound which by virtue of its activity profile and route of administration offers a new approach to the prophylactic treatment of bronchial asthma.     

Japanese guidelines for adult asthma 2020

Bronchial asthma is characterized by chronic airway inflammation, which manifests clinically as variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma may induce airway remodeling and become intractable. The prevalence of asthma has increased; however, the number of patients who die from it has decreased (1.3 per 100,000 patients in 2018). The goal of asthma treatment is to control symptoms and prevent future risks. A good partnership between physicians and patients is indispensable for effective treatment. Long-term management with therapeutic agents and the elimination of the triggers and risk factors of asthma are fundamental to its treatment. Asthma is managed by four steps of pharmacotherapy, ranging from mild to intensive treatments, depending on the severity of disease; each step includes an appropriate daily dose of an inhaled corticosteroid, which may vary from low to high. Long-acting β₂-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs, while anti-immunoglobulin E antibodies and other biologics, and oral steroids are reserved for very severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled β₂-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by selecting treatment steps for asthma based on the severity of the exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-exacerbated respiratory disease, and pregnancy are also important conditions to be considered in asthma therapy.     

Survey of asthma control in Thailand

OBJECTIVE: The aim of the study was to determine whether asthma management in Thailand is succeeding in achieving the levels of control, specified in national and international asthma guidelines. METHODOLOGY: Adults with asthma in Bangkok, Chiang Mai, Songkhla, and Khon Kaen were interviewed, and we have reported on their asthma severity, morbidity, control, perception of asthma, and healthcare use. RESULTS: A total of 466 asthma sufferers were interviewed. The burden of asthma was high, with 14.8% of respondents being hospitalized for their asthma in the past year. One-quarter of those surveyed had lost workdays as a result of their asthma, and most patients felt that their lifestyle was limited. The majority of respondents had intermittent asthma (62.9%), 10.5% had mild persistent asthma, 17.6% had moderate persistent asthma, and 9.0% had severe persistent asthma; increasing severity was significantly associated with increased emergency healthcare use (P < 0.00001). Asthma sufferers greatly underestimated the severity of their condition. Only 36.0% used reliever medication, and use of inhaled corticosteroids was low at 6.7%. Understanding of the inflammatory basis of asthma was poor. Few patients underwent lung function tests or took peak flow meter readings. CONCLUSIONS: The burden of asthma is high in Thailand, and guidelines are not being followed. Encouraging greater use of inhaled corticosteroids will be an important step towards improving asthma control.     

Intravenous magnesium sulfate in acute severe asthma

OBJECTIVE: Intravenous magnesium sulfate (MgSO4), as an adjunctive medication to the standard treatment of acute asthma, improves admission rate or severity score in acute severe asthma patients. METHODOLOGY: We conducted a randomized double-blind placebo controlled trial with subjects from the emergency room, Ramathibodi Hospital, Bangkok, Thailand. Patients, aged 15-65 years with acute severe asthma attack, whose severity scores were greater than 4 and who were willing to be enrolled in a study during March to November 1997 participated in the study. Randomly allocated patients received either 2 g intravenous MgSO4 or placebo, sterile water, as an adjunctive medication to standard therapy for acute asthma. The medication was diluted in 50 mL of 0.9% normal saline. MEASUREMENT: Severity scores were measured by two investigators using Fischl's indices. The times interval of measurements were at the initial (0), 60, 120, 180, and 240 min from receipt of treatment. Patients were hospitalized if the severity scores at 240 min exceeded 1. Risk ratio (RR) and 95% confidence interval (CI) of RR were applied to estimate the risk of admission. Analysis of variance with repeated measurement on time was used to determine the severity score between two groups. RESULTS: Thirty-four patients with acute severe asthma were enrolled in the present study. One patient from the placebo group was excluded because he did not consent to undergoing peak expiratory flow rate. Seventeen patients received MgSO4 and 16 patients received placebo. The general characteristics between the two groups were not significantly different, which reflected the quality of randomization. The admission rates of the placebo and MgSO4 group were 25.00% and 17.65%, respectively. Patients who received MgSO4 had preventive risk to be hospitalized 0.71 times relative to patients who received placebo. However, this preventive risk did not reach statistical significance (95% CI of RR = 0.19-2.67). The severity score at any time between the two groups was also not statistically significantly different (P = 0.366). CONCLUSION: With the present evidence, the hypothesis was not confirmed. Magnesium sulphate as an adjunct to standard therapy did not improve either admission rate or severity score in patients with acute severe asthma.     

Practice patterns for oral corticosteroid burst therapy in the outpatient management of acute asthma exacerbations

The use of a short course of oral corticosteroids (OCS), or "steroid burst," is standard practice in the outpatient management of acute severe exacerbations of asthma. Despite published guidelines, the actual practice patterns are unknown. A Web-based survey about typical patterns of OCS administration and total steroid burst dose was administered to pulmonologists (n = 150), allergists (n = 150), primary care physicians (n = 153), and pediatricians (n = 150). No predominant dosing regimen was observed, although a fixed single daily dose was the most commonly prescribed regimen (59%). The majority of physicians treating patients ≥12 years of age prescribed a total burst dose of ≤200 mg and essentially all (99.7%) prescribed ≤600 mg. Among physicians treating younger children, approximately one-quarter prescribed ≤1 mg/kg per day for 3 days (27.8% for children aged 5-11 years of age and 28.1% for children aged <5 years, respectively) and essentially all prescribed ≤2 mg/kg per day for 10 days (99.8% for children aged 5-11 years and 100% for children aged <5 years of age). When prescribing OCS burst therapy for asthma exacerbations, physicians tend to prescribe less than the upper dose recommended in the guidelines; with many physicians prescribing a total steroid burst dose below the lower end of the recommended dose range. Additional study is needed to determine the optimal dose and duration for treating exacerbations of asthma with OCS to minimize both side effects and time to reestablishing asthma control.     

Treatment understanding and compliance in asthma of children. Results of a prospective survey]

Compliance with treatment is a crucial factor in the management of asthmatic children which depends on the understanding of the disease and its treatment. The understanding of, and compliance with treatment were evaluated by means of a questionnaire in 50 parents of asthmatic children. 50% of these parents used anti-histamines as maintenance treatment and 30% also used these drugs during attacks. Half the parents knew about the bronchodilator effects of theophylline and B2-agonists. 42% and 30% respectively of the parents thought that the side-effects of theophylline or corticosteroids were few or inexistent; 86% claimed regular attendance to out-patient clinics, but 30% confessed that they had forgotten such drugs as theophylline and antihistamines. 50% took the appropriate therapeutic measures when confronted with a moderate or severe attack of asthma. Each child received 2.3 drugs on average for his or her asthma. This study shows that parents have an insufficient knowledge of asthma treatments, and this may partially explain the poor compliance with therapy as well as the morbidity and mortality associated with childhood asthma.     

Efficacy and safety of intravenous theophylline administration for treatment of mild acute exacerbation of bronchial asthma

OBJECTIVE: The present study was designed to evaluate the efficacy and safety of intravenously administered theophylline (IAT) for the treatment of an acute exacerbation of bronchial asthma. The theophylline was solubilized and not combined with ethylenediamine. METHODOLOGY: The subjects were 22 asthmatic patients with mild acute exacerbation of bronchial asthma. All patients had been taking oral sustained-release theophylline and their serum concentrations of theophylline were measured. The 16 patients whose serum theophylline concentrations were <13 microg/mL were randomly selected and treated with IAT (200 mg theophylline in 200 mL saline) for 2 h. Six patients were randomly selected as controls and received 200 mL of saline. Pulmonary function and asthma severity (Borg scale) before and after treatment were measured. RESULTS: After IAT, both PEF (before IAT, 313+/-79 L/min; after IAT, 335+/-107; P<0.05) and FEV(1) (before IAT, 1.66+/-0.47 L; after IAT, 1.83+/-0.44; P<0.05) increased significantly. Furthermore, their severity of asthma as assessed by the Borg scale (before IAT, 2.5+/-1.2; after IAT, 1.3+/-1.0; P<0.05) improved significantly. In contrast, neither FEV(1), PEF, severity of asthma or Borg scale changed significantly in the group who only received saline. None of the patients treated in this study had any adverse effects. CONCLUSION: These results suggest that IAT is useful for patients with mild acute exacerbation of bronchial asthma and is safe if serum theophylline concentrations are measured.     

Japanese guidelines for adult asthma 2017

Adult bronchial asthma is characterized by chronic airway inflammation, and presents clinically with variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma induces airway remodeling, leading to intractable asthma. The number of patients with asthma has increased; however, the number of patients who die of asthma has decreased (1.2 per 100,000 patients in 2015). The goal of asthma treatment is to enable patients with asthma to attain normal pulmonary function and lead a normal life, without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management by therapeutic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high levels. Long-acting β₂-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonist are recommended as add-on drugs, while anti-immunoglobulin E antibody and oral steroids are considered for the most severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled β₂-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by choosing treatment steps for asthma in accordance with the severity of exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-induced asthma, and pregnancy are also important issues that need to be considered in asthma therapy.     

Evaluation of a structured treatment and teaching programme on asthma

The objective of this study was to evaluate a structured treatment and teaching programme for adult patients with moderate to severe asthma. The design consisted of a prospective, before-after trial: the same consecutive patients were studied before and after intervention with observation periods 1 year before and 1 year after intervention. The investigation took place within a tertiary care centre (university hospital). A total of 142 consecutive patients were referred for in-patient treatment of their asthma, of whom 132 (93%) patients participated in the follow-up examination. The intervention consisted of a structured 5-d in-patient treatment and teaching programme presented by a specialized nurse educator. The aim of the programme was for the patient to assume greater responsibility for disease management, including self-monitoring of peak expiratory flow and qualified self-adaptation of drug therapy. The main outcome measures were the frequency of severe asthma attacks, hospitalization, and absenteeism from work (data provided by health insurance companies), patients' compliance and management skills. During the year before and the year after the intervention 71% and 36%, respectively of patients had one or more severe asthma attacks (mean difference 35%, 95% CI: 25-45%, P less than 0.0001). The percentage of patients who were hospitalized because of asthma decreased from 39% to 22% (mean difference 17%, 95% CI: 7-27%, P less than 0.002). The percentage of employed patients (n = 67) who were absent from work because of asthma decreased from 60% to 43% (mean difference 17%, 95% CI: 4-30%, P less than 0.04). The patients' adherence to maintenance drug therapy and their management skills improved significantly. It was concluded that the participation of patients with moderate to severe asthma in a structured treatment and teaching programme resulted in a substantial reduction in asthma morbidity in the year following the intervention.     

Asthma control in adults in Asia-Pacific

OBJECTIVE: The Asthma Insights and Reality in Asia-Pacific (AIRIAP) survey collected detailed information on asthma severity and management in the urban centres of eight areas of the Asia-Pacific region. This study compared asthma morbidity and management practices in these areas. METHODOLOGY: Following recruitment, face-to-face interviews were completed with 2323 adults with diagnosed asthma, who had current symptoms or were using asthma medication. Comparisons between areas were made for asthma severity, asthma burden and management practices. RESULTS Asthma severity varied significantly between areas (P < 0.01), with Vietnam and mainland China reporting the most cases with severe, persistent symptoms. Severity of asthma was significantly associated with advancing age and a lower level of education in a multivariate analysis (P < 0.001). The total use of acute healthcare for asthma was significantly associated with increased asthma severity. Work absence due to asthma was highest in the Philippines (46.6%) and lowest in South Korea (7.5%). The use of inhaled corticosteroids was associated with age in a non-linear manner. There was significant variation among countries in usage of inhaled corticosteroids, from 1.3% in South Korea to 29.0% in Taiwan (P < 0.00001). A peak flow meter was owned by a total of 7.7% of respondents, and overall, 17.9% of adults had a written action plan for asthma management. CONCLUSIONS: Within the Asia-Pacific region, asthma in adults differs significantly in disease severity, management and treatment according to area of residence. International recommendations on the management of asthma are generally not being followed.     

Inhaled corticosteroids reduce the severity of bronchial hyperresponsiveness in asthma but oral theophylline does not

In a double-blind crossover study, we compared the relative effects of inhaled beclomethasone dipropionate (BDP) 800 micrograms per day and oral theophylline on the severity of bronchial hyperresponsiveness (BHR) to histamine. Daily doses of theophylline were sufficient to keep serum levels between 55 and 110 mumol/L. The subjects were 26 patients with severe asthma whose symptoms were inadequately controlled by regular treatment with inhaled salbutamol. The severity of BHR improved within 3 wk in the group treated with BDP, whereas no change occurred in the group treated with theophylline. There were no significant changes in FEV1 in either group during the study. When BDP was changed to theophylline there was a deterioration in BHR. Aerosol steroids, rather than theophylline, are the treatment of choice when reduction in the severity of BHR is the aim of treatment in patients with severe asthma.     

Association Between Traffic Volume and Health Care Use for Asthma Among Residents at a U.S.–Canadian Border Crossing Point

Our objective was to explore, in a predominantly Latino inner-city population, why caregivers bring their children with asthma to the ED (emergency department). We conducted bilingual parent surveys and medical chart abstractions of a consecutive ED sample consisting of 234 children with asthma (69% Latino; 54% Spanish-speaking) and their caregivers. Outcome measures included: the acute need for ED services based on objective physiological measures, the extent to which these children experienced barriers to quality primary care for asthma before the ED visit, and the relative importance caregivers assigned to worsening symptoms versus perceived barriers to non-ED care when deciding to bring their child to the ED. Most children had moderate or severe asthma attacks. In the prior month, only 33% went to a primary care provider, 83% had used a bronchodilator, and 63%, an age-appropriate spacer device. Seventy-five percent of caregivers cited perceived acute need, instead of barriers to primary care, as the most important reason for using the ED. This perception of acute need was associated with moderate or severe asthma attacks according to objective physiological measures, after controlling for health and sociodemographic characteristics. Children with asthma who use the ED encounter barriers to primary care, but caregivers' perception of acute need—validated by independent measures of attack severity—dominates caregivers' decision to use the ED. Ensuring continuity of care for children with asthma would involve not only improving various aspects of access to and quality of primary non-ED care—including parent education about early recognition and treatment of asthma attacks—but also providing families with practical low-cost alternatives for 24-hour care and assuring linkages between the ED and sources of primary care.     

Japanese guidelines for childhood asthma 2017

The Japanese Guideline for the Diagnosis and Treatment of Allergic Diseases 2017 (JAGL 2017) includes a minor revision of the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 (JPGL 2012) by the Japanese Society of Pediatric Allergy and Clinical Immunology. The section on child asthma in JAGL 2017 provides information on how to diagnose asthma between infancy and adolescence (0–15 years of age). It makes recommendations for best practices in the management of childhood asthma, including management of acute exacerbations and non-pharmacological and pharmacological management. This guideline will be of interest to non-specialist physicians involved in the care of children with asthma. JAGL differs from the Global Initiative for Asthma Guideline in that JAGL emphasizes diagnosis and early intervention of children with asthma at <2 years or 2–5 years of age. The first choice of treatment depends on the severity and frequency of symptoms. Pharmacological management, including step-up or step-down of drugs used for long-term management based on the status of asthma control levels, is easy to understand; thus, this guideline is suitable for the routine medical care of children with asthma. JAGL also recommends using a control test in children, so that the physician aims for complete control by avoiding exacerbating factors and appropriately using anti-inflammatory drugs (for example, inhaled corticosteroids and leukotriene receptor antagonists).     

Mechanical ventilation in children with severe asthma

Hospital admissions for childhood asthma have increased during the past few decades. The aim of this study was to describe the need for mechanical ventilation for severe asthma exacerbation in children in Finland from 1976 to 1995. We reviewed medical records and collected data retrospectively from all 5 university hospitals in Finland, thus covering the entire population of about 5 million. The endpoints selected were the number of admissions and readmissions leading to mechanical ventilation, duration of stay in the hospital, and mortality. Moreover, asthma medications prescribed prior to admission and administered in the intensive care unit (ICU), as well as the etiology of the exacerbation associated with mechanical ventilation were examined. Mechanical ventilation was required in 66 ICU admissions (59 patients). This constituted approximately 10% of all 632 admissions for acute asthma to an ICU. The number of admissions decreased from 1976 to 1995: 41 admissions between 1976 and 1985 vs. 25 admissions during the next 10-year period. The mean age at admission to the ICU was 3.6 years, and 46% of the patients were boys. Prior to the index admission, 70% of the patients had used asthma medication such as oral bronchodilator (50%), inhaled bronchodilator (20%), theophylline (38%), inhaled glucocorticoid (18%), oral glucocorticoid (5%), and cromoglycate (7%). Respiratory infection was by far the most common cause of all the exacerbations (61%), followed by food allergy (8%) and gastroesophageal reflux (3%). In 28% of cases the cause of the severe asthma exacerbation could not be identified. In the mechanically ventilated patients readmissions occurred 38 times between 1976 and 1985 vs. 5 times between 1986 and 1995. Five of the patients who received mechanical ventilation died, and in 3 of these patients asthma was the event causing death. In conclusion, there has been decrease in the number of first and repeat ICU admission for asthma requiring mechanical ventilation between 1970 and 1995. This trend occurred despite a simultaneous 5% yearly increase in hospital admissions for childhood asthma during these 2 decades.     

A clinical trial to determine whether intravenous aminophylline is indispensable in the treatment of status asthmaticus

In Japan, intravenous aminophylline (AMP) is considered as the first treatment of choice for status asthmaticus, whereas inhaled beta 2-agonist is considered to be of no value for acute severe asthma. To determine the optimal therapy for acute asthma, the authors clinically investigated bronchodilating effects and the clinical role of aerosolized beta 2-agonist inhalation and intravenous AMP in 55 patients with status asthmaticus. Patients were classified into two groups treated without intubation and with artificial ventilation. Intravenous steroid (equivalent to 4 mg/kg of hydrocortisone) was administered in all cases. Further, all patients were randomly divided into two subgroups according to treatment regimen, i.e. repeated inhalation of aerosolized beta 2-agonists only, and combined with intravenous AMP. In all groups, the duration of treatment was significantly shorter in the subgroups treated with repeated aerosolized beta 2-agonist inhalation than those treated with intravenous AMP. The failure of intravenous AMP to effect more rapid or profound improvement both in objective and subjective parameters suggested that inhaled beta 2-agonist with intravenous steroid should be a rational choice in the initial treatment of acute asthma. Moreover, inhaled beta 2-agonist used optimally produces good bronchodilation several times greater than that produced by intravenous AMP. We concluded that repeated inhalation of aerosolized beta 2-agonists is the drug of choice combined with intravenous steroid regardless of the severity of attacks for short-term therapy of acute severe asthma, and that intravenous AMP may have only minor bronchodilating effects.     

Ketotifen in the prophylaxis of extrinsic bronchial asthma. A multicenter controlled double-blind study with a modified-release formulation

In a placebo controlled double-blind multicenter trial, 245 patients with bronchial asthma (131 male and 124 female patients) between 6 and 51 years of age were treated in two parallel groups. A slow-release oral formulation containing 2 mg of ketotifen or placebo was administered daily for a duration of 12 weeks. Over a period of four weeks before the study, 94 percent of the patients had asthmatic attacks. 78 percent had cough, and 62 percent had nasal symptoms. In the group treated with slow-release oral ketotifen, there were 3.9 asthmatic attacks (range, 0 to 20) per week, and in the placebo group, there were 2.9 (range, 0 to 12) (mean values during four weeks prior to start of treatment). At the end of treatment, asthmatic attacks were significantly reduced in the group treated with slow-release oral ketotifen compared with placebo. Significant reduction was also evident for cough and sputum production, as well as nasal discharge and obstruction; however, slow-release oral ketotifen did not significantly improve pulmonary function indices when compared to placebo. The use of concomitant medication (beta-sympathomimetic drugs) was also significantly reduced in the group receiving slow-release oral ketotifen. The overall efficacy assessed by the investigators was "very good" and "good" in 76 percent of the group receiving slow-release oral ketotifen and 30 percent in the group receiving placebo (p less than 0.001). Tolerability rated by the investigators was "very good" and "good" in 90 percent of the group with slow-release oral ketotifen and in 96 percent of the group with placebo (p less than 0.10). The most frequent side effects were "mild" and "moderate" sedation, sleepiness and drowsiness reported in 44 percent of the patients receiving slow-release oral ketotifen and in 26 percent of the patients receiving placebo. This difference was statistically significant (p less than 0.01).