MicroRNA Levels in Exhaled Breath Condensate of Patients with Esophageal Atresia.

MicroRNAs (miRNAs) are noncoding RNAs that play an important role in the regulation of inflammation and have not been evaluated in exhaled breath condensates (EBC) of patients with esophageal atresia and tracheoesophageal fistula (EA-TEF). It is aimed to evaluate the levels of miRNA-21 and miRNA-24 in EBC of patients with EA-TEF. Patients who received surgery for EA-TEF (EA) were assessed for age, sex, types of anomaly, surgical treatments, and respiratory problems. A 500-1000 mL of EBC was obtained from each participant with EcoScreen. The levels of miRNA-21 and miRNA-24 in the EBC were analyzed by real-time polymerase chain reaction and compared between the EA group and the control group consisting of healthy children with no history of respiratory problems (n = 17). The levels of miRNAs in relation to respiratory problems and gastroesophageal reflux (GER) were also assessed. A total of 19 patients were enrolled in the EA group with a mean age of 7.8 ± 3.2 years and a male-to-female ratio of 10:9 EA cases had significantly lower levels of miRNA-21 (P < 0.05) compared to that in control group. The miRNA-24 levels did not differ between groups (P > 0.05). EA patients with positive pH testing for GER (n = 6) and fundoplication (n = 6) had higher levels of miRNA-21 than those with normal pH testing and without fundoplication, respectively (n = 13, P < 0.05). The levels of miRNA-21 and miRNA-24 did not differ between patients with and without proton pump inhibitor treatment (P > 0.05). The lower levels of miRNA-21 in the EBC of EA patients suggest a hyperreactive airway problem, which may be associated with GER and its surgical treatment.

Omalizumab treatment in adolescents with chronic spontaneous urticaria: Efficacy and safety.

BACKGROUND: Omalizumab is useful as an add-on treatment in patients unresponsive to high doses of second-generation antihistamines. This study aimed to evaluate the efficacy and safety of omalizumab treatment in adolescents with refractory chronic spontaneous urticaria (CSU). METHODS: CSU patients aged 12-18 years old with the diagnosis of symptomatic CSU and unresponsive to classical treatment were included in the study. All patients had an urticaria-activity-score (UAS7) of ≥16 or and were treated with 300mg omalizumab every four weeks. The degree of response was classified into complete, partial and non-responders due to UAS7. RESULTS: A total of 29 patients were evaluated. The median age and symptom onset age of the patients was 15.2 (IQR, 12.8-16.5) years and 14.0 (IQR, 11.8-15.9) years, respectively. The median duration of urticaria was eight (IQR, 4-24) months at admission. Eleven (37.9%) patients had angioedema and ten (34.5%) patients had concomitant allergic diseases. The median age at the beginning of treatment with omalizumab was 15.4 (IQR, 12.9-16.9) years. The median symptom duration was 12 (IQR, 6.5-27.5) months before the omalizumab treatment. Twenty-eight (96.5%) of the patients (89.6% complete, 6.9% partial) achieved response; however, one patient was a non-responder (3.5%). The adverse effect was observed in one (3.4%) patient as angioedema after the third dose. Twenty-three patients were followed up for a median of 18 (IQR, 13-27) months. Relapse was observed in three (13%) patients. CONCLUSIONS: Omalizumab is considered as an effective and safe treatment for CSU in adolescents. Relapses mostly occur within the first year after the cessation of treatment.

Physicians prescribe adrenaline autoinjectors, do parents use them when needed?

BACKGROUND: Anaphylaxis is a sudden, severe, and potentially life-threatening allergic reaction, affecting a portion of allergic patients. Adrenaline is the first-line medication for anaphylaxis and available in many parts of the world as adrenaline autoinjectors (AAIs). OBJECTIVE: Aim of this study was to determine attitudes and knowledge levels of patients/parents regarding the use of AAIs, frequency, and rate of appropriate AAI use and to give a standardized and better education by improving on mistakes during administration. METHOD: 190 patients aged 1-18 years who were prescribed AAIs for any reason between 2012 and 2017 in Hacettepe University Pediatric Allergy Unit. Demographic data were collected during face-to-face interview or by telephone. Parents completed a mini-survey regarding use, carriage, and storage of AAI. RESULTS: Some 190 patients (64.7% male) aged 7.83 (4.99-12.08) years, median (inter-quartile), were included in the study. The indications for AAI prescription were food allergy (78.9%); venom allergy (14.2%); idiopathic anaphylaxis (3.7%); mastocytosis (2.1%); and drug allergy (1.0%). One-fourth of AAI-prescribed patients experienced anaphylaxis requiring the use of AAI within the past five years. However, only 30% of the patients dared to use AAI; only three-quarters of whom had managed to use it correctly. CONCLUSION: After prescription of AAI and initial training, patients and parents' concerns and fears should be taken into consideration and necessary support should be provided. At every opportunity and each clinical visit, not only should training sessions be repeated but also the patients and parents should be psychologically supported.

Actual drug allergy during childhood: Five years' experience at a tertiary referral centre.

BACKGROUND: Drug hypersensitivity reactions (DHR) are common in the paediatric population, representing a public health problem. Recent studies have confirmed that the frequency of drug allergy is overestimated by both parents and physicians. The aim of this study is to determine the prevalence and risk factors of actual drug allergies in children admitted to a tertiary referral allergy centre. METHODS: Medical records covering the period of 2005-2010 of children with a history of DHR were reviewed. Demographic features of the patients and results of skin and drug provocation tests were noted. The European Network for Drug Allergy (ENDA) questionnaire was filled by using medical records and making phone calls with parents. RESULTS: Ninety-six patients with 140 DHRs were evaluated. Seventeen children had confirmed drug allergy by positive skin tests (n=11) and drug provocation tests (n=5). One patient underwent severe anaphylaxis and subsequent cardiac arrest during infusion of the drug, and therefore diagnostic tests were not performed. Actual drug allergy was more frequent in children with chronic diseases (58.8% vs. 26.5%, p=0.018) and histories of anaphylaxis during DHR (58.8% vs. 24%, p=0.001). The patients' history of anaphylaxis [OR: 5.789, 95%CI: 1.880-17.554, p=0.002], sweating [OR: 7.8, 95%CI: 1.041-58.443, p=0.046] and dyspnoea [OR: 5.230, 95%CI: 1.836-14.894, p=0.002] during suspicious DHRs increased the risk for actual drug allergy. CONCLUSION: Actual drug allergy was determined in 17.7% of the patients with a suspicious DHR. Having a history of anaphylaxis during suspected drug reactions as well as symptoms of sweating and dyspnoea increased the risk for actual drug allergy.

Baseline management of asthma control.

Asthma is a complex, chronic inflammatory disease of the lower airways affecting people of all ages. Approximately 300 million individuals are currently suffering from asthma worldwide. The prevalence of asthma is estimated to range from 3% to 38% in children and from 2% to 12% in adults. The disease causes lost school and work days, limitations in daily activities, and sleep disturbances. Lung function impairment also occurs, resulting in decreased quality of life unless disease control is achieved and a high annual financial burden is incurred. Achievement and maintenance of control through assessment of clinical manifestations and future risk has become the aim of treatment over the years. Unfortunately, the desired level of asthma control has not been achieved in a considerable number of regions throughout the world, and the level of control is overestimated by both patients and their parents. This review examines the mortality and morbidity rates for asthma, emphasizes the challenges inherent to control management, and provides data on the tools used to measure control level.

Importance of serum basal tryptase levels in children with insect venom allergy.

BACKGROUND: The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of venom-allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR). METHODS: Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings. RESULTS: A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex-matched control subjects) with a median age of 8.9 years (range 3.2-17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) [4.2 µg/l (3.6-4.9)] was significantly higher than in children with LLRs [3.1 µg/l (2.5-4.0)] and healthy control subjects [2.9 µg/l (2.3-3.4)] (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 µg/l as a significant risk factor for severe SR (5.7 [1.5-21.4]; P = 0.01) in children with venom allergy. CONCLUSIONS: Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy.

Similar prevalence, different spectrum: IgE-mediated food allergy among Turkish adolescents.

BACKGROUND: Scarcity of reliable data on food allergy prevalence exists in Turkey. We aimed to assess reported and confirmed IgE-mediated food allergy prevalence, and define the spectrum of allergenic food. METHODS: We prospectively evaluated the ISAAC Phase II study population for food allergy. Participants that reported experiencing food allergy symptom in the last year and/or were skin prick test positive for a predefined list of food allergens, were interviewed via telephone, and those considered as having food allergy were invited to undergo clinical investigation, including challenge tests. RESULTS: A total of 6963 questionnaires were available. Parental reported food allergy prevalence and skin prick sensitisation rate were 20.2 ± 0.9% and 5.9 ± 0.6%. According to the above-defined criteria, 1162 children (symptom positive n=909, skin prick test positive n=301, both positive n=48) were selected and 813 (70.0%) were interviewed via telephone. Out of 152 adolescents reporting a current complaint, 87 accepted clinical investigation. There were 12 food allergies diagnosed in nine adolescents, with food allergy prevalence of 0.16 ± 0.11%. The most common foods involved in allergic reactions were walnut (n=3) and beef meat (n=2), followed by hen's egg (n=1), peanut (n=1), spinach (n=1), kiwi (n=1), cheese (n=1), hazelnut (n=1) and peach (n=1). CONCLUSIONS: While parental reported food allergy prevalence was within the range reported previously, confirmed IgE-mediated food allergy prevalence among adolescents was at least 0.16%, and the spectrum of foods involved in allergy differed from Western countries, implying environmental factors may play a role.

The reliability and validity of Turkish version of Childhood Asthma Control Test.

INTRODUCTION: The reliability and validity of Turkish version of Childhood Asthma Control Test (C-ACT). PURPOSE: The management of asthma is an important as well as difficult issue of physician's daily practice particularly in busy clinical settings. C-ACT was created to identify asthma control levels in children aged 4-11 years. Our aim was to evaluate the reliability, validity and responsiveness of C-ACT in a Turkish sample of children with asthma. METHOD: In this multicenter study, 368 children were enrolled. C-ACT was completed every month by parents and patients who were evaluated in 3 visits within 2 month intervals. At each visit, physicians interpret the control level and decided for the treatment step as established in GINA guidelines. RESULTS: The internal consistency reliability of the Turkish version of C-ACT (C-ACT1 to C-ACT5) was found to be 0.82, 0.83, 0.82, 0.82 and 0.80, respectively (reliability statistics, Cronbach's alpha). Test-retest reliability was 0.71. There was significant correlation between C-ACT and physician's assessment of asthma control at visit 1 (r = 0.65, P < 0.001). CONCLUSIONS: Turkish version of C-ACT is an accurate and reliable tool to evaluate asthma control in children aged 4-11 years. Its widespread use may facilitate appropriate assessment of asthma control and may lead to decrease the number of uncontrolled patients.

Prevalence, burden, and risk factors of atopic eczema in schoolchildren aged 10-11 years: a national multicenter study.

BACKGROUND: Little is known about the epidemiology of atopic eczema (AE), and studies from the Mediterranean region and the Middle East are limited. OBJECTIVE: We investigated the frequency, burden, and risk factors of AE in a developing country. METHODS: The International Study of Asthma and Allergies in Childhood Phase II questionnaire was used to survey a representative sample of 10 to 11-year-old children in Turkey. Children were examined by allergists, and parents completed standardized questionnaires. RESULTS: Among 6755 children, the prevalence of having eczema during one's lifetime or currently was 17.1% and 8.1%, respectively. The prevalence of visits to the doctor, nocturnal awakening, school absenteeism, and drug usage was 36.3%, 56%, 9.7%, and 28.7%, respectively. Associated factors were current rhinoconjunctivitis (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.99-3.21), current wheezing (OR, 2.10; 95% CI, 1.58-2.79), family history of allergic disease (OR, 1.62; 95% CI, 1.21-2.18), low birth weight (OR, 1.79; 95% CI, 1.08-2.94), and exposure to animals in the first year of life (OR, 1.47; 95% CI, 1.06-2.03). CONCLUSIONS: In a developing Mediterranean country, the prevalence of AE is comparable to that of developed countries in the same region and lower than that observed in developed countries elsewhere. The course of the disease and risk factors of AE probably differ in developing countries.

Extent and burden of allergic diseases in elementary schoolchildren: a national multicenter study.

BACKGROUND: Scarcity of standardized, comparable data on allergic diseases in schoolchildren in Turkey requires further multicenter studies based on the use of objective tools in addition to parent-completed questionnaires to improve the validity and reliability of results. METHODS: Using International Study of Asthma and Allergies in Children (ISAAC) Phase II tools, elementary schoolchildren aged 9 to 11 years were surveyed in 5 city centers in different regions of Turkey. RESULTS: We surveyed 6963 children from 70 schools and found that 35% had had at least 1 symptom of allergic diseases in the past year. Based on parental reports, the overall prevalence rates for wheezing, rhinoconjunctivitis, and eczema in the past year were 15.8%, 23.5%, and 8.1%, respectively. The overall frequencies of atopy, flexural dermatitis, and bronchial hyperreactivity were 18.9%, 3.6%, and 24.2%, respectively. There were large variations in the prevalence of both symptoms and objective signs between study centers. Absence from school for at least 1 day was reported for 34.2% of children with a diagnosis of asthma or allergic rhinitis. CONCLUSIONS: Approximately one third of elementary schoolchildren reported symptoms compatible with allergic diseases in the past year. The interregional differences in both symptoms and objective test results are possibly due to differences in environmental conditions. Unfortunately, serious problems are still encountered in the timely and proper diagnosis and treatment of allergic diseases.

A multicenter survey of childhood asthma in Turkey. II: Utilization of asthma drugs, control levels and their determinants.

Many surveys worldwide have consistently demonstrated a low level of asthma control and under-utilization of preventive asthma drugs. However, these studies have been frequently criticized for using population-based samples, which include many patients with no or irregular follow-ups. Our aim, in this study, was to define the extent of asthma drug utilization, control levels, and their determinants among children with asthma attending to pediatric asthma centers in Turkey. Asthmatic children (age range: 6-18 yr) with at least 1-yr follow-up seen at 12 asthma outpatient clinics during a 1-month period with scheduled or unscheduled visits were included and were surveyed with a questionnaire-guided interview. Files from the previous year were evaluated retrospectively to document control levels and their determinants. From 618 children allocated, most were mild asthmatics (85.6%). Almost 30% and 15% of children reported current use of emergency service and hospitalization, respectively; and 51.4% and 53.1% of children with persistent and intermittent disease, respectively, were on daily preventive therapy, including inhaled corticosteroids. Disease severity [odds ratio: 12.6 (95% confidence intervals: 5.3-29.8)], hospitalization within the last year [3.4 (1.4-8.2)], no use of inhaled steroids [2.9 (1.1- 7.3)], and female gender [2.3 (1.1-5.4)] were major predictors of poor asthma control as defined by their physicians. In this national pediatric asthma study, we found a low level of disease control and discrepancies between preventive drug usage and disease severity, which shows that the expectations of guidelines have not been met even in facilitated centers, thus indicating the need to revise the severity-based approach of asthma guidelines. Efforts to implement the control-based approach of new guidelines (Global Initiative for Asthma 2006) would be worthwhile.

The effect of regular versus on-demand desloratadine treatment in children with allergic rhinitis.

OBJECTIVE: Desloratadine is a potent antihistamine. Whether regular or on-demand use of desloratadine influences its therapeutic efficacy in allergic rhinitis is unknown. The aim of the study was to compare the clinical efficacy and the anti-inflammatory activity of regularly administered desloratadine to its on-demand use in children with allergic rhinitis due to pollen allergy. METHODS: Thirty-seven patients with allergic rhinitis with or without mild intermittent asthma were enrolled in a prospective parallel group study. Patients were treated with desloratadine regularly or on-demand during pollen season. Rescue medications and symptom scores were recorded on a diary card. Nasal flow rate and inflammatory markers were recorded, and methacholine (Mch) challenge test was administered before and within the pollen season. RESULTS: Though symptoms were lower in the evening than in the morning (p<0.001), there was no difference between the two groups. There was no difference between the groups with respect to medication score except that the salbutamol use was lower in the regular treatment group during the fourth week (p=0.032) in the pollen season. Nasal flow rate and inflammatory markers failed to show any difference between the groups. A significant reduction in PC20 values (provocative concentration of Mch causing a 20% fall in FEV(1)) was observed in regular (p=0.016) and on-demand (p=0.005) treatment groups compared to the pre-season measurements. The number of children with a PC20 below 8 mg/ml increased significantly in the on-demand group. CONCLUSION: Our study demonstrates that on-demand use of desloratadine during the pollen season is clinically as effective as regular treatment. However, regular treatment may provide better control of lower airway symptoms and airway reactivity.

Burden of rhinitis in children with asthma.

Although the clinical association of allergic rhinitis and asthma has been recognized for centuries, in recent years the association appears to be stronger than was reported previously. However, data for children are less clear, and some studies indicate that results observed in developing countries may differ from those observed in Western populations. We therefore intended to document the association of rhinitis with pediatric asthma in terms of caregivers' perception, physician practice, and file records. Asthmatic children aged 3-16 years with at least 1-year follow-up in an allergy-asthma outpatient clinic were invited to participate in the study during a 10-month interval. In addition to a face-to-face questionnaire-based interview, file records were evaluated retrospectively to obtain information relating to asthma and rhinitis. Of 396 patients included in the study, 369 with consistent replies were included in the analyses. The mean age of the study group was 10.6 +/- 0.2 (mean +/- SEM) years, and a greater proportion of the respondents were male (63.7%), atopic (78.3%), and mildly asthmatic (50.7%). House dust mite and grass pollens were the most commonly sensitized allergens (50.7% and 46.9%, respectively). Although only 5.4% of our study population regarded themselves as rhinitic and 23.8% had been diagnosed with allergic rhinitis according to the file records, almost 57.7% of patients had required medications for rhinitis within the last year, and 68.8% had findings consistent with allergic rhinitis. Furthermore, 41.2% and 58.8% reported that their rhinitis symptoms caused a significant burden in their daily life and exacerbated their asthma, respectively, and almost 50% felt that their rhinitis had not been given significant consideration by their physician. In conclusion, although we report a large discrepancy between caregivers' perception of rhinitis, documentation in file records, and treatments for rhinitis, the allergic rhinitis prevalence determined in the survey and the medication use for rhinitis appeared to be in agreement. We recommend a greater effort be made to identify, label, and educate children with rhinitis and their families in asthma outpatient clinics.

Prevalence of asthma symptoms in school children in Ankara, Turkey.

The aim of this study was to determine the prevalence of symptoms suggestive of asthma in children aged 7-14 years in Ankara, Turkey. For this purpose, the recently developed ISAAC (International Study for Asthma and Allergies in Childhood) questionnaire supplemented with six additional questions was issued to parents of 3154 primary school children from 12 schools. A separate page with questions regarding risk factors was also added to the questionnaire. The response rate was 88.3%. The cumulative and 12-month prevalence of wheezing were 14.4 and 4.7% respectively. The prevalence of physician-diagnosed asthma was 8.1%. A family history of atopy was found to be the strongest risk factor for having ever had wheezing (odds ratio (OR) = 2.89, 95% confidence interval (CI) = 2.32-3.60), wheezing in the past 12 months (OR = 3.21, CI = 2.21-4.67), and severe attack (OR = 2.41, CI = 1.36-4.25). Passive smoking was a risk only for having ever had wheezing (OR = 1.33, CI = 1.03-1.76). Increasing age was associated with a lower risk of current wheezing (OR = 0.85, CI = 0.81-0.90) and severe attack (OR = 0.77, CI = 0.67-0.88). Gender, socio-economic level and pet ownership did not appear to be risk factors for asthma-related symptoms. This study, the first epidemiological survey in Ankara, Turkey, using the ISAAC protocol, clearly shows that symptoms suggestive of asthma, albeit lower than in most European countries, are quite common and constitute a major health problem in Turkey.

The prevalence of self-reported asthma and respiratory symptoms in Ankara, Turkey.

The prevalence of self-reported asthma was studied in a group of Turkish adults using the European Community Respiratory Health Survey (ECRHS) questionnaire distributed during 1994 local elections in Ankara, Turkey. A total of 2020 questionnaires were issued and 1820(90%) were returned. The mean age of the subjects was 34.5 +/- 10.2 years. The prevalence of wheezing at any time in the past was 39.1% which is much higher than has been reported in the literature. However, only 21.7% of the study population had wheezing in the year preceding the survey and 2.9% of them had severe asthma attacks. The prevlaences of nocturnal wheeze, nocturnal cough and morning tightness were higher in females (P = 0.05 for each). The results of this study showed a high rate of reported symptoms but a low rate of diagnosis and treatment of asthma among the adult population in Ankara.

Vocal cord dysfunction: more morbid than asthma if misdiagnosed.

Vocal cord dysfunction may lead to respiratory distress, which in turn may cause the misdiagnosis of asthma. We present two adolescents who were misdiagnosed as asthmatic and aggressively treated for asthma with resulting iatrogenic complications. Vocal cord dysfunction simulating or coexisting with asthma should be considered especially in patients with frequent emergency visits for episodic dyspnea despite aggressive treatment.

The effect of house dust mite specific immunotherapy on cysteinyl leukotriene production by blood leukocytes in subjects with perennial allergic rhinitis and asthma.

Specific immunotherapy has been successfully used in the treatment of allergic diseases for years. In this study, we examined the clinical efficacy of specific immunotherapy and its effect on cysteinyl leukotriene releasability by blood leukocytes in house dust mite allergic subjects with asthma and allergic rhinitis. In an open, parallel study, 13 subjects were treated with specific immunotherapy for 12 months and five patients served as the control group. Before specific immunotherapy treatment, and 1 and 12 months after, patients were evaluated with respect to total immunoglobulin (Ig) E levels, Dermatophagoides pteronyssinus specific IgE levels, symptom scores, usage of rescue medicines, lung function tests, nasal challenge scores, skin reactivity to D. pteronyssinus and cysteinyl leukotriene releasability by blood leukocytes. At the 12th month of specific immunotherapy, total asthma symptom scores, bronchodilator requirement, number of sneezes following nasal challenge and immediate skin reactivity to D. pteronyssinus was decreased, while FEV1 increased compared to the pretreatment values (p < 0.05 for each). These parameters remained unchanged in the control group. In vitro cysteinyl leukotriene releasability by blood leukocytes in response to D. pteronyssinus antigen and anti-IgE antibody remained unchanged both in the specific immunotherapy group and the control group. However, in the treated group, there were six patients who showed at least a 50% reduction in their symptoms after specific immunotherapy. In five of these, cysteinyl leukotriene release induced by both HACM buffer and D. pteronyssinus were decreased by more than 50% of the baseline values. The other patient demonstrated only a marked decrease (more than 50%) in background. Our results suggest that specific immunotherapy is effective in the treatment of allergic rhinitis and bronchial asthma due to house dust mite allergy and that the clinical response to specific immunotherapy may be associated with decreased cysteinyl leukotriene releasibility by blood leukocytes in some patients.

Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma.

According to the recent guidelines, persistent asthma requires daily antiinflammatory treatment with either nedocromil sodium, cromolyn sodium or inhaled corticosteroids. In choosing the most appropriate drug, it is wise to weigh the therapeutic advantages against possible side effects, particularly in patients at the milder end of disease spectrum and in children. Cromolyn sodium and nedocromil sodium both have strong safety profiles, and nedocromil sodium has been reported to have a broader spectrum of efficacy than cromolyn sodium. In an attempt to provide data for the efficacy of two different dose regimens of inhaled nedocromil sodium in childhood asthma, a placebo-controlled, randomized, double-blind, double-dummy, parallel group study was conducted in 38 subjects with mild to moderate persistent asthma. After a 2-week run-in period, patients were randomly allocated into one of the three study groups and treated with either placebo or with two times daily (4 mg b.i.d.) or four times daily (4 mg q.i.d.) regimens of inhaled nedocromil sodium for 8 weeks. Symptom scores, bronchodilator requirements, FEV1, daily PEFs and methacholine hyperreactivity were evaluated at study entry, before randomization and at weeks 4 and 8 of treatment. In the four times daily treatment group, slight but significant increases were observed in FEV1, peak expiratory flows and symptom scores (p < 0.05 for each). However, there was no significant change in methacholine hyperreactivity and bronchodilator requirement. In the two times dose regimen and placebo groups, there were no improvements in any of the variables. The compliance, measured as the reduced weight of the canisters, was low, but was not different between the two nedocromil sodium treatment groups. The four times daily regimen of nedocromil sodium was effective in improving control of mild to moderate persistent asthma in children, whereas the two times daily regimen failed.