Effect of Nedocromil Sodium on Aspecific Bronchial Hyper-Reactivity in Asthmatic Children A group comparative study of the safety and efficacy of nedocromil sodium (Tilade) in reversible airways disease: a preliminary report. Association of body mass with pulmonary function in the Childhood Asthma Management Program (CAMP) Association of Hypothalamic-Pituitary-Adrenal Axis Function with Neuropsychological Performance in Children with Mild/Moderate Asthma Predictors of protocol adherence in a pediatric asthma clinical trial. A double-blind comparative trial of nedocromil sodium and placebo in the management of bronchial asthma in patients routinely using oral bronchodilators. [The effect of nedocromil sodium on levels of IL-4 and IgE in serum of children with bronchial asthma]. Family-based association analysis of beta2-adrenergic receptor polymorphisms in the childhood asthma management program. The prevalence of environmental exposure to perceived asthma triggers in children with mild-to-moderate asthma: data from the Childhood Asthma Management Program (CAMP). Recruitment of participants in the childhood Asthma Management Program (CAMP). I. Description of methods: Childhood Asthma Management Program Research Group. Dissociation in the effect of nedocromil on mannitol-induced cough or bronchoconstriction in asthmatic subjects. Nedocromil sodium vs. sodium cromoglycate pressurized aerosol in the prevention of bronchoconstriction induced by ultrasonic nebulized distilled water in asthmatic children. Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma. Treatment of nocturnal asthma with nedocromil sodium. The CONSORT Statement: Revised Recommendations for Improving the Quality of Reports of Parallel-Group Randomized Trials [Study of the protective action of nedocromil sodium with bronchial cold-air provocation in children with bronchial asthma]. The effect of nedocromil sodium on the bronchoconstrictor effect of neurokinin A in subjects with asthma. Long-term effect of budesonide on hypothalamic-pituitary-adrenal axis function in children with mild to moderate asthma. Effects of ambient air pollution on symptom severity and medication use in children with asthma. Paternal history of asthma and airway responsiveness in children with asthma. Effect of nedocromil sodium on bronchial hyperreactivity in children with nonatopic asthma. Progression of asthma measured by lung function in the childhood asthma management program. Double‐blind, randomized, placebo‐controlled trial of effect of nedocromil sodium on clinical and inflammatory parameters of asthma in children allergic to dust mite Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial Long-term effects of budesonide or nedocromil in children with asthma. Relationship between disease and psychological adaptation in children in the Childhood Asthma Management Program and their families. CAMP Research Group. Predicting children's quality of life in an asthma clinical trial: what do children's reports tell us? The effect of nedocromil sodium on childhood asthma during the viral season. A double‐blind, placebo‐controlled study to assess the efficacy of nedocromil sodium in the management of childhood grass‐pollen asthma A placebo-controlled, blind comparison of nedocromil sodium and beclomethasone dipropionate in bronchial asthma. The efficacy of nedocromil sodium (Tilade) in asthma. Safety and application of induced sputum analysis in childhood asthma. A trial comparing nedocromil sodium (Tilade®) and placebo in the management of bronchial asthma Minimizing attrition in a long-term clinical trial of pediatric asthma. Comparison of two different dose regimens of nedocromil sodium with placebo in the management of childhood asthma. Nocturnal awakening caused by asthma in children with mild-to-moderate asthma in the childhood asthma management program. A placebo-controlled blinded comparison of nedocromil sodium and beclomethasone dipropionate in bronchial asthma Prevention of fog-induced bronchoconstriction in asthmatic children by nedocromil sodium nebulizer solutions. Double blind, placebo controlled study of nedocromil sodium in asthma. [Nedocromil sodium therapy in asthma patients. Therapeutic effect in addition to treatment with oral theophylline and inhaled bronchodilator agents]. Withdrawal of inhaled corticosteroid under cover of nedocromil sodium. Effects of nedocromil sodium in steroid-resistant asthma: a randomized controlled trial. Relationships between duration of asthma and asthma severity among children in the Childhood Asthma Management Program (CAMP) Comparison of nedocromil sodium at two dosage frequencies with placebo in the management of chronic asthma. The Childhood Asthma Management Program (CAMP): design, rationale, and methods. Childhood Asthma Management Program Research Group. Early use of inhaled nedocromil sodium in children following an acute episode of asthma The use of twice daily nedocromil sodium in the treatment of asthma. Effect of inhaled nedocromil sodium therapy on blood gas changes in children challenged with ultrasonically nebulized distilled water. A comparison of 8 mg versus 16 mg daily dose. The effect of nedocromil sodium on histamine responsiveness in clinically stable asthmatic children. Effect of nedocromil sodium on the immediate response to antigen challenge in asthmatic patients Neurocognitive functioning in children with mild and moderate asthma in the childhood asthma management program. The Childhood Asthma Management Program (CAMP) Research Group. A double-blind study of the efficacy of nedocromil sodium in the management of asthma in patients using high doses of bronchodilators. The long-term effects of nedocromil sodium and beclomethasone dipropionate on bronchial responsiveness to methacholine in nonatopic asthmatic subjects. Bronchodilation and bronchoconstriction: predictors of future lung function in childhood asthma. A 3-month evaluation of the efficacy of nedocromil sodium in asthma: a randomized, double-blind, placebo-controlled trial of nedocromil sodium conducted by a Canadian multicenter study group. Effectiveness of nedocromil sodium versus placebo as additions to routine asthma maintenance therapy: a multicentre, double-blind, group comparative trial.
The purpose of this study was to evaluate whether nedocromil sodium benefits urban asthmatic children showing seasonal bronchial hyper-reactivity to ultrasonic nebulization of distilled water ( UNDW ) . A prospect i ve , r and omized , placebo-controlled , parallel-group , double-blind study was carried out at the outpatient pulmonology service at a tertiary-care teaching hospital . Twelve children living in Milan , who were 7–17 years of age , who were SPT and RAST-negative to perennial allergens , who were suffering from episodic asthma , and showing seasonal bronchial hyper-reactivity to UNDW during winter , participated in this study . All the children received either placebo or nedocromil sodium , 4 mg every 6 h for 6 weeks . Spirometry and UNDW challenge were done at the following times : day−7 ; day 0 ; day 1 ; day 7 ; day 14 ; day 28 ; day 42 . No differences were found in the basal spirometric parameters , which were normal in both nedocromil and placebo groups . Bronchial reactivity to UNDW was found to be significantly decreased in the group treated with nedocromtl starting from day 7 . It is therefore concluded that nedocromil sodium can reverse bronchial hyper-reactivity caused by seasonal factors such as cold , viral infections and atmospheric pollutants in children suffering from asthma Nedocromil sodium in a dose of 4 mg b.i.d . or q.i.d . by inhalation was used to treat asthmatic patients in a double-blind , placebo-controlled , r and omized , parallel study . 80 patients ( 39 active drug and 41 placebo ) received q.i.d . dosage and 87 patients ( 45 active drug and 42 placebo )  received b.i.d .  dosage . The patients selected were not on oral or inhaled steroids but required oral sustained-release theophylline with or without an inhaled beta-agonist aerosol . There was a significant reduction in daytime asthma symptoms ( p = 0.04 ) and asthma severity ( p less than 0.01 ) 6 weeks after the onset of therapy in the nedocromil sodium q.i.d . treated group as compared with placebo . In the nedocromil sodium b.i.d . treated group , the following variables showed statistically significant improvements compared with placebo : daytime and night-time asthma ( p = 0.002 in both instances ) , wheezing assessed by auscultation ( p = 0.03 ) and overall asthma severity ( p less than 0.01 ) . All these variables showed improvements within 2 weeks of the onset of therapy and became statistically significant at 6 weeks . Side-effects were minor and occurred only in a small number of patients . It can be concluded from this study that nedocromil sodium is a safe and effective drug in the management of asthma Background : While increases in body mass index ( BMI ) have been associated with the incidence and prevalence of asthma , the mechanisms behind this association are unclear . Methods : We hypothesised that BMI would be independently associated with measures of asthma severity in a population of children with mild to moderate asthma enrolled in the Childhood Asthma Management Program ( CAMP ) . A multivariable baseline cross sectional analysis of BMI with our outcomes of interest was performed . Results : BMI was generally not associated with symptoms , nor was it associated with atopy . While BMI was positively associated with the methacholine concentration that causes a 20 % fall in forced expiratory volume in 1 second ( PC20FEV1 ) , this association did not persist after adjustment for FEV1 . Increasing BMI was associated with increasing FEV1 ( β = 0.006 l , 95 % CI ( 0.001 to 0.01 ) ) and forced vital capacity ( FVC ) ( β = 0.012 l , 95 % CI ( 0.007 to 0.017 ) ) . However , decrements in the FEV1/FVC ratio were noted with increasing BMI ( β = −0.242 , 95 % CI ( −0.118 to −0.366 ) ) . Thus , an increase in BMI of 5 units was associated with a decrease in FEV1/FVC of over 1 % . Conclusions : Although the association of FEV1 and FVC with BMI did not support our initial hypothesis , the decrease noted in the FEV1/FVC ratio has potential relevance in the relationship between BMI and asthma severity The present study examines the relationship between hypothalamic-pituitary-adrenal ( HPA ) axis function and child psychological/neuropsychological function in a group of children with mild to moderate asthma . The goal of the study was to determine whether child neuropsychological functioning and psychological functioning were associated with cortisol production in response to adrenocorticotropic hormone(ACTH ) stimulation when assessed as area under the curve . Data for this study were gathered from 63 children who participated in an ancillary study within the Childhood Asthma Management Program ( CAMP ) during the pre-r and omization phase of the CAMP trial . At 2 of the 8 CAMP clinical centers participants completed an ACTH stimulation test after an overnight stay in the General Clinical Research Center . Gender differences on baseline cortisol and change in cortisol 30 minutes after infusion of ACTH were present . Results further indicated significant associations between cortisol production and measures of child neuropsychological function . Stepwise multiple regression analysis revealed that cortisol change could be predicted by measures of gender , working memory , and arousal maintenance , providing support for the hypothesis that cortisol plays a modest role in the neuropsychological function of children with mild and moderate asthma . In contrast , cortisol production was not associated with child reports of psychological functioning . Limitations to the methods employed in this study are discussed BACKGROUND Declining protocol adherence can threaten the validity of a clinical trial . OBJECTIVE We sought to explore patient and family factors important for protocol adherence in the 133 patients followed at one of the 8 Childhood Asthma Management Program ( CAMP ) clinical centers . Difficulties with timely return of diary cards (  diary card  problem ) , with keeping or frequently rescheduling appointments ( appointment problem ) , and with commitment to all aspects of the trial ( commitment problem ) were tracked prospect ively during the treatment phase of CAMP , which ranged from 20 to 40 months at the time of the analysis . METHODS We performed a cross-sectional analysis . RESULTS During the course of this investigation , no St Louis CAMP patients dropped out of the study , although signs of eroding participation were observed in 44 % of patients . For this cross-sectional analysis , the percentage of patients exhibiting protocol -adherence problems was greater the longer patients had been in the trial : 33.3 % at 20 to 25 months , 39.5 % at 26 to 30 months , 51.4 % at 31 to 35 months , and 69.2 % at 36 to 40 months ( P < .01 ) . The diary card problem was present in 22.2 % of the patients enrolled in the trial for 20 to 25 months compared with 66.7 % for patients enrolled for 36 to 40 months ( P < .005 ) . Appointment and commitment problems were present in smaller percentages of patients and did not change by time in the trial ( P = .41 and .22 , respectively ) . A logistic regression analysis of demographic characteristics indicated that age at r and omization and time in the trial were significant factors : for every 2-year increase in age , a child was twice as likely to have a commitment problem ( odds ratio [ OR ] , 1.96 ; 95 % CI , 1.50 - 2.57 ) , and for each additional 5 months of participation in the study , a child was twice as likely to have a diary card problem ( OR , 1.91 ; 95 % CI , 1.76 - 2.07 ) . There was no influence of family income , patient race , or patient sex on the occurrence of any of the 3 protocol -adherence problems . A similar analysis of psychologic characteristics of the child and family indicated ( 1 ) a 2-fold increase in the risk of a diary card problem with a 10 % increase in the percentage of total commissions on the attention scale of the Gordon Diagnostic Study ( OR , 2.18 ; 95 % CI , 2.02 - 2.35 ) , ( 2 ) a 2-fold decrease in the risk of an appointment problem with a 10-unit increase in the Child Manifest Anxiety Scale ( OR , 0.46 ; 95 % CI , 0.44 - 0.49 ) , ( 3 ) a 2-fold decrease in risk of an appointment problem with a 10-unit increase in the cohesion subscale of the Family Environment Scale ( OR , 0.58 ; 95 % CI , 0.55 - 0.60 ) , and ( 4 ) a 5-fold decrease in the risk of a commitment problem with a 10-unit increase in the Child Depression Index score ( OR , 0.21 ; 95 % CI , 0.18 - 0.24 ) . CONCLUSIONS Adherence and retention problems commonly occur in longer clinical trials . CAMP patients and families were selected in part on the basis of likelihood of being able to participate in the trial to enhance the conclusions of the trial . Despite this selection process , adherence problems were noted . Problems increased with duration of participation , increasing child age , and the presence of less family cohesion or attention problems in the child . In contrast , the presence of mild emotional distress ( anxiety and depression ) in the child was associated with fewer protocol -adherence problems . Incorporating procedures that help anticipate and identify adherence problems early might improve continued participation in all aspects of a trial and even retention in long-term clinical trials The efficacy and tolerability of nedocromil sodium , 4 mg four times daily , were investigated in a 4-week , r and omized , placebo-controlled , double-blind trial in 54 asthmatic patients . Significant improvements were seen in the nedocromil sodium treated patients with respect to asthma severity ( recorded by patients on diary cards ) ; lung function ( assessed by PEFR ) ; daytime and night-time asthma ( patients ' diary cards ) , and morning and evening peak flow rates ( measured by patients at home ) . Unusual symptoms were few and of a minor nature , differing little between active and placebo treatment . Nedocromil sodium , at the dosage used in this study , was well tolerated and provided a useful addition to asthma therapy Levels of pro-allergic cytokine IL-4 are increased in asthmatic airways , contributing to allergic inflammation . IL-4 and IL-13 are the most important factors in production of class E immunoglobulin , playing major role in childhood atopic asthma . The mechanism of effect of nedocromil , often prescribed in children , has been discussed . Our previous study on the effect of nedocromil on different inflammatory markers , showed decreased levels of IL-4 and IgE after monotherapy in 15 asthmatic children . The purpose of this study was to define the effect of treatment with nedocromil on serum level of IL-4 and IgE , clinical symptoms and bronchial hyperreactivity ( BHR ) in children with moderate atopic asthma . It was 8 week , placebo-controlled and r and omized , double blind trial of 81 children with moderate atopic asthma allergic to dust mite . Patients were r and omly allocated to receive nedocromil sodium two puffs four times daily ( 0.002 g/puff ) ( n = 34 ) or placebo ( n = 47 ) . 69 children completed the study . After treatment with nedocromil the levels of IL-4 and IgE in blood serum in study group significantly decreased , and all clinical parameters improved . Mean levels of IL-4 in serum before and after treatment with nedocromil were 0.13 pg/ml + /- 0.01 and 0.12 pg/ml + /- 0.02 respectively ( p < 0.01 ) . Mean serum levels of IgE before and after treatment with nedocromil were 556.83 IU/ml + /- 201.3 and 485 IU/ml + /- 200.5 respectively ( p < 0.02 ) . This study demonstrate that one possible way by which nedocromil contribute to inhibition of allergic inflammation is by decreasing IL-4 and IgE levels BACKGROUND Beta2-adrenergic receptor ( B2AR ) polymorphisms have been associated with a variety of asthma-related phenotypes , but association results have been inconsistent across different studies . OBJECTIVE We sought to apply family-based association methods to individual single nucleotide polymorphisms ( SNPs ) and haplotypes of SNPs in B2AR to define the relationship of these genetic variants to asthma-related phenotypes . METHODS DNA sample s were obtained from 707 Childhood Asthma Management Program participants , representing 650 sibships , as well as their parents .  Genotyping was performed at 8 B2AR SNPs . Qualitative asthma-related phenotypes were analyzed with single SNPs and haplotypes by using TRANSMIT ; quantitative asthma-related phenotypes were analyzed with the Family-Based Association Test . RESULTS Several SNPs , including SNP -654 and SNP + 46 , demonstrated significant associations ( P < .05 ) to postbronchodilator FEV1 as both a qualitative ( < 80 % of predicted value ) and quantitative phenotype . Quantitative phenotypic association analysis demonstrated significant evidence for association of SNP + 523 with bronchodilator responsiveness expressed as a percentage of baseline FEV1 ( P = .012 ) or a percentage of predicted FEV1 ( P = .008 ) . Similar evidence for association between the + 523 SNP and qualitative bronchodilator responsiveness phenotypes was also found . Analysis of haplotypes supported an association of B2AR variants with spirometric values and bronchodilator responsiveness . CONCLUSION B2AR variants are associated with spirometric values and bronchodilator responsiveness , but different regions of the gene provide evidence for association with these phenotypes BACKGROUND The Childhood Asthma Management Program , a 5-year r and omized clinical trial of treatments for childhood asthma , has enrolled and characterized a cohort of 1041 children with mild-to-moderate asthma . OBJECTIVE We sought to describe self-reported sensitivities and environmental exposures and investigate the relationships between self-report of these exposures as asthma triggers and their prevalence in the home . METHODS Self-reports of sensitivities and home exposures were obtained by interview with the child or parent .  Sensitivities were further assessed by using  allergy skin testing ( prick or puncture ) against a core battery of allergens . Home exposures were further assessed by using analysis of a home dust sample . RESULTS Environmental exposures were surprisingly common despite self-reported sensitivities to environmental factors . Of patients reporting that cigarette smoking frequently causes asthma symptoms , 26 % reported having at least one parent who smokes cigarettes . Thirty-nine percent of patients reporting that exposure to animals frequently causes asthma symptoms live with a furry pet in their home . We found a smaller proportion of homes with a high level of cat allergen ( P < .001 ) among the children who reported that animals frequently or always trigger asthma symptoms compared with those who reported that animals never or occasionally trigger asthma symptoms , suggesting modification of the home environment . No such results were seen for dog exposure . However , clinical symptoms did not reduce exposure to parental cigarette smoking ( P = .15 ) , house dust ( P = .31 ) , or damp and musty areas ( P = .51 ) . CONCLUSION These data suggest that children with mild-to-moderate asthma are frequently symptomatic and exposed to a wide variety of environmental exposures that are perceived to trigger symptoms by means of self-report . Although environmental modification of asthmatic homes may occur , many children remain exposed to agents that are known to trigger their asthma The Childhood Asthma Management Program ( CAMP ) , a multicenter clinical trial sponsored by the Division of Lung Diseases of the National Heart , Lung , and Blood Institute ( NHLBI ) , is the largest outcome study of mild to moderate asthma in children to be undertaken , with eight clinical centers in the United States and Canada participating . The initial recruitment goal was 960 children within an 18-month recruitment period . Recruitment was extended to 23 months , with 1041 children r and omized from late December , 1993 , to early September , 1995 . In this time interval each of the eight centers met the recruitment goal of 120 using a variety of self-selected recruitment strategies . The goal for minority recruiting was 33 % , or 320 of the planned 960 children to be recruited . CAMP achieved the overall goal for the number of minorities , with 330  patients . Three centers recruited at or above the expected rate from the beginning . The other five centers had significant delays in recruitment . Examination of the recruitment experiences of the centers with and without delays did not indicate any single recruitment strategy that was certain to be successful . The most commonly cited factors for success were a cohesive staff , endorsement of participation by the child 's primary care provider , and ability of the staff to be flexible and honest in assessing progress and the value of recruiting methods being used OBJECTIVE Inhaled mannitol induces both bronchoconstriction and cough .  Nedocromil sodium greatly attenuates mannitol-induced bronchoconstriction . Knowledge about the effect of nedocromil on mannitol-provoked cough might , therefore , clarify the mechanisms of this response . METHODOLOGY Inhalation challenges with mannitol powder were performed after inhalation of 8 mg of nedocromil or its placebo in 24 subjects with asthma . The study was double-blind , r and omised , and placebo-controlled . The mannitol-provoked coughs were manually recorded and the mannitol-induced bronchoconstriction was measured with a spirometer . RESULTS The cumulative dose of  mannitol  that provoked at least two coughs tended to be higher on the nedocromil day than on the placebo day ( 34 ( 22 - -53 ) mg vs 26 ( 18 - -37 ) mg , P=0.051 ) . The cumulative number of coughs per dose of mannitol was slightly , but significantly , lower on the nedocromil than on the placebo day ( 4.2 ( 2.8 - -6.3 ) coughs/100 mg vs 6.1 ( 4.0 - -9.4 ) coughs/100 mg , P=0.037 ) . However , when analysed on a constant-dose basis , nedocromil provided no protection for coughing ( -1 % protection ) , whereas the protection for bronchoconstriction was clear ( 55 % protection ) . CONCLUSIONS Nedocromil strongly attenuates mannitol-induced bronchoconstriction but has a negligible effect on mannitol-provoked cough . Therefore , these responses seem to have different pathways in asthma . Recording of both provoked coughs and induced bronchoconstriction during mannitol challenge may provide supplementary information about a patient 's disease To compare the effectiveness of nedocromil sodium ( NS ) and sodium cromoglycate ( SCG ) , administered by metered dose inhaler ( MDI ) with a 700 mL holding chamber ( Fisonair Fisons UK ) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water ( UNDW ) , 12 asthmatic children were studied in a r and omized , double-blind , placebo-controlled , intrapatient study . Following a baseline challenge with UNDW , the protective effect of NS , SCG , or placebo was evaluated in each subject . Cumulative doses of delivered nebulized water producing a 20 % fall in forced expiratory volume in 1 sec ( PD20 UNDW ) was measured . Mean ( + /- SD ) PD20 UNDW was 4.83 ( + /- 4.84 ) , 10.16 ( + /- 7.05 ) , 1.58 ( + /- 0.5 ) , and 15.93 ( + /- 0.23 ) respectively , for baseline , and placebo , SCG , and NS-treated groups . A significant ( P < 0.05 ) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo , while no such effect was evident when the children were treated with SCG OBJECTIVE Exhaled nitric oxide ( FE(NO ) ) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide , nedocromil , or albuterol  as needed . STUDY DESIGN FE(NO ) , spirometry , total eosinophil count , and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout . RESULTS Budesonide-treated patients had significantly lower median ( 1st , 3rd quartile ) FE(NO ) ( 21.5 [ 13.2 , 84.4 ] vs 62.5 [ 26.2 , 115.0 ] ppb , P < .01 ) and eosinophil cationic protein levels ( 17.4 [ 10.1 , 24.3 ] vs 24.0 [ 15.4 , 33.9 ] mg/dL , P = .05 ) compared with placebo , whereas no differences were noted between nedocromil and placebo groups . After washout , FE(NO ) levels were similar between the three treatments . FE(NO ) levels significantly correlated with degree of bronchial hyperresponsiveness , bronchodilator reversibility , allergen skin prick tests , serum IgE , and total eosinophil count . FE(NO ) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly . CONCLUSIONS Budesonide therapy was more effective than nedocromil in reducing FE(NO ) . Unfortunately , the effects of long-term budesonide were not sustained after its discontinuation . FE(NO ) may be a complementary tool to current practice guidelines in assessing asthma control and medication response BACKGROUND --The association of nocturnal asthma symptoms with a diurnal increase in inflammatory activity suggests a role for anti-inflammatory therapy in nocturnal asthma . METHODS --Fifty patients with asthma with nocturnal symptoms entered a r and omised , double blind , placebo controlled , crossover study . After a two week baseline period patients received nedocromil sodium ( 4 mg ) or placebo four times daily . After eight weeks of treatment patients crossed to the alternative treatment for a further eight weeks . Symptom severity was recorded on a scale of 0 - 4 and inhaled bronchodilator use and peak flow ( PEFR ) were also recorded daily by the patients . Asthma severity , pulmonary function ( FEV1 , PEFR , FVC ) , and adverse events were recorded at clinic visits ( baseline and after four and eight weeks of treatment ) . Global effectiveness was rated by clinician and patient , and treatment preference was recorded . RESULTS --Efficacy was assessed from data from 28 patients .  Night-time asthma ( mean ( SE ) difference between nedocromil sodium and placebo : -0.52 ( 0.13 ) ) , total nocturnal symptom severity defined as night-time asthma plus morning tightness ( -0.72 ( 0.20 ) ) , and night-time bronchodilator use ( -0.62 ( 0.23 ) ) were reduced with nedocromil sodium compared with placebo treatment during the primary efficacy period ( weeks 5 - 8 ) and during weeks 1 - 4 ( -0.36 ( 0.12 ) , -0.63 ( 0.20 ) , and -0.55 ( 0.28 ) , respectively ) . Morning and evening PEFR values improved slightly -- but not significantly -- compared with placebo . Patient and clinician opinions favoured nedocromil sodium treatment . Daytime asthma , daytime cough , and clinic assessment of asthma severity ( secondary efficacy variables ) were improved with nedocromil sodium treatment ; day-time bronchodilator use and clinic pulmonary function were not . CONCLUSIONS --Nedocromil sodium was more effective than placebo in reducing nocturnal symptoms of asthma and bronchodilator use in this group of patients A report of a r and omized , controlled trial ( RCT ) should convey to the reader , in a transparent manner , why the study was undertaken and how it was conducted and analyzed . For example , a lack of adequately reported r and omization has been associated with bias in estimating the effectiveness of interventions ( 1 , 2 ) . To assess the strengths and limitations of an RCT , readers need and deserve to know the quality of its methods . Despite several decades of educational efforts , RCTs still are not being reported adequately ( 3 - 6 ) . For example , a review of 122 recently published RCTs that evaluated the effectiveness of selective serotonin-reuptake inhibitors as first-line management strategy for depression found that only 1 ( 0.8 % ) paper described r and omization adequately ( 5 ) . Inadequate reporting makes the interpretation of RCT results difficult if not impossible . Moreover , inadequate reporting borders on unethical practice when biased results receive false credibility . History of CONSORT In the mid-1990s , two independent initiatives to improve the quality of reports of RCTs led to the publication of the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement ( 7 ) , which was developed by an international group of clinical trialists , statisticians , epidemiologists , and biomedical editors . CONSORT has been supported by a growing number of medical and health care journals ( 8 - 11 ) and editorial groups , including the International Committee of Medical Journal Editors ( ICMJE , also known as the Vancouver Group ) ( 12 ) , the Council of Science Editors ( CSE ) , and the World Association of Medical Editors ( WAME ) . CONSORT is also published in Dutch , English , French , German , Japanese , and Spanish . It can be accessed on the Internet , along with other information about the CONSORT group ( 13 ) . The CONSORT statement comprises a checklist and flow diagram for reporting an RCT . For convenience , the checklist and diagram together are called simply CONSORT . They are primarily intended for use in writing , review ing , or evaluating reports of simple two-group , parallel RCTs . Preliminary data indicate that the use of CONSORT does indeed help to improve the quality of reports of RCTs ( 14 , 15 ) . In an evaluation ( 14 ) of 71 RCTs published in three journals in 1994 , allocation concealment was not clearly reported in 43 ( 61 % ) of the RCTs . Four years later , after these three journals required that authors reporting an RCT use CONSORT , the proportion of papers in which allocation concealment was not clearly reported had dropped to 39 % ( 30 of 77 ; mean difference , 22 % [ 95 % CI of the difference , 38 % to 6 % ] ) . The usefulness of CONSORT is enhanced by continuous monitoring of the biomedical literature ; this monitoring allows CONSORT to be modified depending on the merits of maintaining or dropping current items and including new items . For example , when Meinert ( 16 ) observed that the flow diagram did not provide important information about the number of participants who entered each phase of an RCT ( enrollment , treatment allocation , follow-up , and data analysis ) , the diagram could be modified to accommo date the information . The checklist is similarly flexible . This iterative process makes the CONSORT statement a continually evolving instrument . While participants in the CONSORT group and their degree of involvement vary over time , members meet regularly to review the need to refine CONSORT . At the 1999 meeting , the participants decided to revise the original statement . This report reflects changes determined by consensus of the CONSORT group , partly in response to emerging evidence on the importance of various elements of RCTs . Revision of the CONSORT Statement Thirteen members of the CONSORT group met in May 1999 with the primary objective of revising the original CONSORT checklist and flow diagram , as needed . The group discussed the merits of including each item in the light of current evidence . As in developing the original CONSORT statement , our intention was to keep only those items deemed fundamental to reporting st and ards for an RCT . Some items not considered essential may well be highly desirable and should still be included in an RCT report even though they are not included in CONSORT . Such items include approval of an institutional ethical review board , sources of funding for the trial , and a trial registry number ( as , for example , the International St and ard R and omized Controlled Trial Number [ IS RCT N ] used to register an RCT at its inception [ 17 ] ) . Shortly after the meeting , a revised version of the checklist was circulated to the group for additional comments and feedback . Revisions to the flow diagram were similarly made . All these changes were discussed when CONSORT participants met in May 2000 , and the revised statement was finalized shortly afterward . The revised CONSORT statement includes a 22-item checklist ( Table ) and a flow diagram ( Figure ) . Its primary aim is to help authors improve the quality of reports of simple two-group , parallel RCTs . However , the basic philosophy underlying the development of the statement can be applied to any design . In this regard , additional statements for other design s will be forthcoming from the group ( 13 ) . CONSORT can also be used by peer review ers and editors to identify reports with inadequate description of trials and those with potentially biased results ( 1 , 2 ) . Table . Checklist of Items To Include When Reporting a R and omized Trial Figure . Flow diagram of the progress through the phases of a r and omized trial ( enrollment , intervention allocation , follow-up , and data analysis ) . During the 1999 meeting , the group also discussed the benefits of developing an explanatory document to enhance the use and dissemination of CONSORT . The document is patterned on reporting of statistical aspects of clinical research ( 18 ) , which was developed to help facilitate the recommendations of the ICMJE 's Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals . Three members of the CONSORT group , with assistance from members on some checklist items , drafted an explanation and elaboration document . That document ( 19 ) was circulated to the group for additions and revisions and was last revised after review at the latest CONSORT group meeting . Changes to CONSORT 1 . In the revised checklist , a new column for Paper Section and Topic integrates information from the Subheading column that was contained in the original statement . 2 . The Was It Reported ? column has been integrated into a Reported on Page Number column , as requested by some journals . 3 . Each item of the checklist is now numbered , and the syntax and order have been revised to improve the flow of information . 4 . Title and Abstract are now combined in the first item . 5 . While the content of the revised checklist is similar to that of the original one , some items that previously were combined are now separate . For example , authors had been asked to describe primary and secondary outcome ( s ) measure(s ) and the minimum important difference(s ) , and indicate how the target sample size was projected . In the new version , issues pertaining to outcomes ( item 6 ) and sample size ( item 7 ) are separate , enabling authors to be more explicit about each . Moreover , some items request additional information . For example , for outcomes ( item 6 ) authors are asked to report any methods used to enhance the quality of measurements , such as multiple observations . 6 . The item asking for the unit of r and omization ( for example , cluster ) has been dropped because specific checklists have been developed for reporting cluster RCTs ( 20 ) and other design types ( 13 ) since publication of the original checklist . 7 . Whenever possible , new evidence is incorporated into the revised checklist . For example , authors are asked to be explicit about whether the analysis reported is by intention to treat ( item 16 ) . This request is based in part on the observations ( 21 ) that authors do not adequately describe and apply intention-to-treat analysis and that reports not providing this information are less likely to provide other relevant information , such as losses to follow-up ( 22 ) . 8 . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow-up , and analysis ) . The revised diagram explicitly includes the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers lets the reader know whether the authors have performed an intention-to-treat analysis ( 21 - 23 ) . Because some of the information may not always be known and to accommo date other information , the structure of the flow diagram may need to be modified for a particular trial . Inclusion of the participant flow diagram in the report is strongly recommended but may be unnecessary for simple trials , such as those without any participant withdrawals or dropouts . Discussion Specifically developed to guide authors about how to improve the quality of reporting of simple two-group , parallel RCTs , CONSORT encourages transparency with reporting of the methods and results so that reports of RCTs can be interpreted both readily and accurately . However , CONSORT does not address other facets of reporting that also require attention , such as scientific content and readability of RCT reports . Some authors , in their enthusiasm to use CONSORT , have modified the checklist ( 24 ) . We recommend against such modifications because they may be based on a different process than the one used by the CONSORT group . The use of CONSORT seems to reduce ( if not eliminate ) inadequate reporting of RCTs ( 14 , 15 ) . Potentially , the use of CONSORT should positively influence the manner in which RCTs are conducted . Granting agencies have noted this potential relationship and , in at least in one case ( 25 ) , have encouraged grantees to consider in their application how they have dealt with the CONSORT items . The evidence -based approach used to develop CONSORT has also been used 12 children with known bronchial hyperreactivity and asthma had isocapnic cold air hyperventilation challenges of their bronchial airways . In a double-blind cross-over study they inhaled either placebo or nedocromil sodium ( 2 puffs à 2 mg ) from a MDI before challenge . 2 subjects were found to be non-responders during the two days of the study . The remainder all reacted on the placebo days , while 5 subjects were completely protected on the nedocromil-days and 5 subjects were partially protected .  Nedocromil  is a potent agent for the suppression of bronchial hyperresponsiveness We have previously demonstrated that the neuropeptide , neurokinin A ( NKA ) ( substance K ) , causes bronchoconstriction in subjects with asthma . In a double-blind , crossover study we investigated the effect of nedocromil sodium on NKA-induced bronchoconstriction in subjects with asthma . Twelve patients with mild asthma ( mean FEV1 percent predicted + /- SE , 87.3 + /- 3.4 ) inhaled on 2 separate days either nedocromil sodium , 4 mg , or placebo , as two puffs from a metered-dose aerosol , 30 minutes before challenge with NKA . NKA was inhaled at three concentrations ( 10(-7 ) , 3.10(-7 ) , and 10(-6 ) mol/ml ) . The specific airway conductance ( SGaw ) and FEV1 were measured before and 5 and 15 minutes after each concentration step . On the placebo-treatment day , NKA caused a concentration-dependent decrease in SGaw and FEV1 ( mean log for the provocative concentration of NKA causing a 35 % fall in SGaw [ 10(-7 ) mol/ml ] , 0.49 ; mean log for the provocative concentration of NKA causing a 15 % fall in SGaw [ 10(-7 ) mol/ml ] , 0.90 ) . The inhalation of 4 mg of nedocromil sodium reduced the decrease in both SGaw and FEV1 . The maximal percentage decrease in SGaw on the nedocromil sodium-treatment day was 27 + /- 5.2 ( versus placebo , 53.3 + /- 5.4 ; p less than 0.05 ) , and the maximal percentage decrease in FEV1 was 5.5 + /- 1.4 ( versus placebo , 12.4 + /- 2.3 ; p less than 0.05 ) . The dose-response curves for NKA after nedocromil sodium treatment were significantly shifted to the right compared to the curve after placebo-treatment . We conclude that nedocromil sodium protects against NKA-induced bronchoconstriction in subjects with asthma OBJECTIVE To determine the safety of long-term ( 36 months ) administration of an inhaled corticosteroid ( budesonide ) on hypothalamic-pituitary-adrenal ( HPA ) axis function in children with mild to moderate asthma . METHODS This was an ancillary study of the Childhood Asthma Management Program ( CAMP ) . Sixty-three children who had mild to moderate asthma and were enrolled in CAMP underwent evaluation of HPA axis function before and 12 and 36 months after receiving continuous therapy with either an inhaled anti-inflammatory agent ( budesonide 400 microg/day or nedocromil 16 mg/day ) or placebo .  HPA axis function was assessed by serum cortisol levels 30 and 60 minutes after 0.25 mg of adrenocorticotrophic hormone ( ACTH ) and 24-hour urinary free cortisol excretion . RESULTS There were no differences in serum cortisol levels after ACTH stimulation between treatment groups , regardless of time after ACTH administration or months of follow-up . Urinary cortisol excretion per body surface area was similar in both treatment groups at 36 months , after adjusting for age at r and omization , race , gender , and clinic . Cumulative inhaled corticosteroid exposure did not influence serum cortisol response to ACTH or urinary free cortisol excretion at 36 months . CONCLUSIONS We found no effects of chronic budesonide treatment at a dose of 400 micro g/day on HPA axis function in children with mild to moderate asthma and demonstrated the absence of a cumulative effect on HPA axis function over a 3-year period BACKGROUND Exposure to air pollutants has been investigated as a possible cause of asthma attacks in children . OBJECTIVE To investigate the short-term effects of air pollutants on a panel of 133 children with asthma who enrolled in the Childhood Asthma Management Program . METHODS During screening , the children completed daily diary cards for an average of 58 days to indicate their medication use and asthma severity . We used ordinal logistic regression to compare the odds of a more serious relative to a less serious asthma attack , and we used a Poisson model to analyze medication use . In both analyses we accommo date dependence in the data and different periods of observation for study subjects . RESULTS Our results indicate that a 10-microg/m3 increase in particulate matter less than or equal to 2.5 microm ( PM2.5 ) lagged 1 day was associated with a 1.20 times increased odds of having a more serious asthma attack [ 95 % confidence interval ( CI ) , 1.05 to 1.37 ] and a 1.08-fold increase in medication use ( 95 % CI , 1.01 to 1.15 ) . A 10-microg/m3 increase in particulate matter less than or equal to 10 microm ( PM10 ) increased the odds of a more serious asthma attack ( odds ratio = 1.12 ; 95 % CI , 1.04 to 1.22 ) and also increased medication use ( relative risk = 1.05 ; 95 % CI , 1.00 to 1.09 ) . CONCLUSIONS Increases in PM2.5 and PM10 are significantly associated with an increased risk of more severe asthma attacks and medication use in Seattle area children with asthma . We also found associations with carbon monoxide , but we believe that carbon monoxide is a marker for exposure to combustion byproducts RATIONALE Little is known regarding the relationship between parental history of asthma and subsequent airway hyperresponsiveness ( AHR ) in children with asthma . OBJECTIVES We evaluated this relationship in 1,041 children with asthma participating in a r and omized trial of antiinflammatory medications ( the Childhood Asthma Management Program [ CAMP ] ) . METHODS Methacholine challenge testing was performed before treatment r and omization and once per year over an average of 4.5 years postr and omization . Cross-sectional and longitudinal repeated measures analyses were performed to model the relationship between PC20 ( the methacholine concentration causing a 20 % fall in FEV1 ) with maternal , paternal , and joint parental histories of asthma . Models were adjusted for potential confounders . MEASUREMENTS AND MAIN RESULTS At baseline , AHR was strongly associated with a paternal history of asthma . Children with a paternal history of asthma demonstrated significantly greater AHR than those without such history ( median log(e)PC20 , 0.84 vs. 1.13 ; p = 0.006 ) . Although maternal history of asthma was not associated with AHR , children with two parents with asthma had greater AHR than those with no parents with asthma ( median log(e)PC20 , 0.52 vs. 1.17 ; p = 0.0008 ) . Longitudinal multivariate analysis of the relation between paternal history of asthma and AHR using repeated PC20 measurements over 44 months postr and omization confirmed a significant association between paternal history of asthma and AHR among children in CAMP . CONCLUSIONS Our findings suggest that the genetic contribution of the father is associated with AHR , an important determinant of disease severity among children with asthma BACKGROUND AND OBJECTIVES Although cromones inhibit immediate bronchial responses to both allergen and nonspecific challenge , their effectiveness in treating nonatopic childhood asthma is unknown . We therefore investigated a possible effect of nedocromil sodium on bronchial hyperreactivity and asthmatic symptoms in a group of children receiving this drug for nonatopic asthma . STUDY DESIGN AND METHODS A double-blind , placebo-controlled , r and omized trial of two parallel groups was carried out in our pediatric respiratory disease clinic . Twenty children with mild , nonatopic asthma hyperreactive to fog-induced challenge were treated with inhaled nedocromil sodium 16 mg each day for 6 weeks ( group N ) or with a placebo ( group P ) . Five girls and five boys ( 7 to 13 years of age ) were r and omly assigned to group N , and three girls and seven boys ( aged 6 to 16 years ) to group P. Symptoms and bronchodilator use were reported on diary cards . Ultrasonic nebulized distilled water PD10 was measured administering increasing doses of nebulized distilled water ( 2.5 , 5 , 10 , 20 , and 40 L ) . RESULTS Symptom scores were significantly affected by the active treatment . Baseline lung function was normal and remained unaltered after treatment with nedocromil sodium . Nonspecific reactivity was significantly reduced over time only in the active treatment group . CONCLUSIONS Nedocromil sodium can reduce the severity of asthmatic symptoms and nonspecific bronchial hyperreactivity at fog-induced challenge in children with stable , nonatopic asthma From the Childhood Asthma Management Program cohort , which was r and omly assigned to receive budesonide , nedocromil , or placebo for 4 - 6 years , we determined the prevalence of and factors associated with at least 1 % per year loss in postbronchodilator FEV(1)% predicted . Participants who had a significant reduction in postbronchodilator FEV(1)% predicted ( SRP )  , comprised 25.7 % of the cohort ( n = 990 ) . Using logistic regression , predictors of SRP at baseline were younger age ( p = 0.0005 ) , male sex ( p < 0.0001 ) , clinic ( p = 0.02 ) , and higher postbronchodilator FEV(1)% predicted ( p = 0.02 ) . Examination of the SRPs indicated that the effect of baseline lung function was such that the higher the lung function , the less steep the reduction in postbronchodilator FEV(1)% predicted ( p < 0.0001 ) . A similar proportion of SRPs was found in each treatment group . Among the SRPs , the rate of reduction in postbronchodilator FEV(1)% predicted was similar in all treatment groups . At a single site where biomarker assessment was performed , SRPs also had more prominent eosinophilic inflammation during the washout period . The course and mechanisms of lung function reduction or slow lung growth velocity in children with asthma must be defined Background : The purpose of this study was to determine the clinical effect of nedocromil sodium and its relationship with serum levels of inflammatory mediators by monitoring lung function and noninvasive markers of airway inflammation , such as eosinophil blood counts ; serum ECP , sIL‐2R , IL‐4 and sICAM ; and total IgE. Anti‐inflammatory medications cause a reduction in the markers of airway inflammation , decrease the intensity of airway hyperresponsiveness , and improve clinical symptoms of asthma . Among the available choices is nedocromil sodium , which is favored in the treatment of asthmatic children due to its very mild side‐effects . It has been previously shown to improve the clinical parameters of asthma , but there are limited data on its effect on inflammatory mediators in the serum of asthmatic children BACKGROUND Although inhaled glucocorticosteroids are recommended for persistent asthma , their long-term effect on recent onset , mild , persistent asthma has yet to be established . METHODS We did a r and omised , double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide  in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids . Patients aged 5 - 66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications . The daily budesonide dose was 400 microg , or 200 microg for children younger than 11 years . The primary outcome was time to first severe asthma-related event , and analysis was by intention to treat . FINDINGS 198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation ; hazard ratio 0.56 ( 95 % CI 0.45 - 0.71 , p<0.0001 ) . Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo . Compared with placebo , budesonide increased postbronchodilator forced expiratory volume in 1 s ( FEV1 ) from baseline by 1.48 % ( p<0.0001 ) after 1 year and by 0.88 % ( p=0.0005 ) after 3 years ( expressed as percent of the predicted value ) . The corresponding increase in prebronchodilator FEV1 was 2.24 % after 1 year and 1.71 % after 3 years ( p<0.0001 at both timepoints ) . The effect of treatment on all outcome variables was independent of the baseline lung function ( prebronchodilator or postbronchodilator ) or baseline medication . In children younger than 11 years , 3-year growth was reduced in the budesonide group by 1.34 cm . The reduction was greatest in the first year of treatment ( 0.58 cm ) than years 2 and 3 ( 0.43 cm and 0.33 cm , respectively ) . INTERPRETATION Long-term , once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset BACKGROUND Antiinflammatory therapies , such as inhaled corticosteroids or nedocromil , are recommended for children with asthma , although there is limited information on their long-term use . METHODS We r and omly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide ( 311 children ) , 8 mg of nedocromil ( 312 children ) , or placebo ( 418 children ) twice daily . We treated the participants for four to six years . All children used albuterol for asthma symptoms . RESULTS There was no significant difference between either treatment and placebo in the primary outcome , the degree of change in the forced expiratory volume in one second ( FEV1 , expressed as a percentage of the predicted value ) after the administration of a bronchodilator . As compared with the children assigned to placebo , the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity ( FVC , expressed as a percentage ) before the administration of a bronchodilator ( decline in FEV1:FVC , 0.2 percent vs. 1.8 percent ) . The children given budesonide also had lower airway responsiveness to methacholine , fewer hospitalizations ( 2.5 vs. 4.4 per 100 person-years ) , fewer urgent visits to a caregiver ( 12 vs. 22 per 100 person-years ) , greater reduction in the need for albuterol for symptoms , fewer courses of prednisone , and a smaller percentage of days on which additional asthma medications were needed . As compared with placebo , nedocromil significantly reduced urgent care visits ( 16 vs. 22 per 100 person-years ) and courses of prednisone . The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group ( 22.7 vs. 23.8 cm , P=0.005 ) ; this difference was evident mostly within the first year . The height increase was similar in the nedocromil and placebo groups . CONCLUSIONS In children with mild-to-moderate asthma , neither budesonide nor nedocromil is better than placebo in terms of lung function , but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil . The side effects of budesonide are limited to a small , transient reduction in growth velocity OBJECTIVE To test the hypotheses that the burden of childhood asthma compromises psychological adaptation and that the degree of compromise increases with disease severity . DESIGN The Childhood Asthma Management Program ( CAMP ) is a multicenter r and omized clinical trial initiated and funded by the National Heart , Lung , and Blood Institute . SETTING Study sites were located in Albuquerque , NM , Baltimore , Md , Boston , Mass , Denver , Colo , St Louis , Mo , San Diego , Calif , Seattle , Wash , and Toronto , Ontario . PARTICIPANTS A total of 1,041 children aged 5 to 12 years were r and omized to the trial after confirming their mild to moderate asthma . MAIN OUTCOME MEASURES Psychological question naires administered at baseline to parents and participants assessed anxiety , depression , behavioral competence , social support , and family functioning . RESULTS Psychological difficulty was not increased in this group of asthmatic children and their families . Psychological adaptation in the children was associated with the psychological adaptation of the family but not with disease-related variables . Scores from the Impact on Family Scale , a measure of family quality of life related to the child 's illness , were associated more strongly with the overall psychological characteristics of the family and child and very little with disease characteristics or severity . CONCLUSIONS Mild to moderate asthma has imposed modest effects on the daily life but not the psychological health of this group of children . Variation in the psychological characteristics of these children was , as is the case for most children , traceable to the overall psychological adaptation of their families OBJECTIVE To define predictors of disease-specific quality of life ( QOL ) and the relationship between asthma symptoms and disease-specific QOL . STUDY DESIGN Three hundred thirty-nine children participated at 4 of 8 Childhood Asthma Management Program clinical centers . Included in the analyses were 2 weeks of asthma symptom data , child-reported health status , and QOL scores from the Pediatric Asthma Quality of Life Question naire . Data were obtained 12 months after r and omization into the Childhood Asthma Management Program . RESULTS Children were rated at baseline as having " moderate " asthma ( 63 % ) and " mild " asthma ( 37 % ) . QOL scores were correlated with the child-reported anxiety measures . Factor analysis of the QOL measure result ed in 2 factors . Stepwise multiple regression indicated that the strongest independent predictors of QOL were the child 's anxiety level , age , sex , and a measure of the child 's tendency to minimize or exaggerate symptoms . CONCLUSIONS Children had few asthma symptoms in the 2 weeks before their 12-month follow-up clinic visit and a generally positive QOL , suggesting that mild-to-moderate asthma does not significantly impair QOL . A child 's QOL was predicted primarily by their level of anxiety Viral-induced symptomatic respiratory infections ( SRI ) frequently cause exacerbations of asthma in children . This study investigated the protective effects of 0.5 % nedocromil sodium nebulizer solution given three times a day in preventing asthma exacerbations associated with SRI . Ninety-three mild-moderate asthmatic children ( 6 to 12 yr of age ) received either 0.5 % nedocromil sodium or placebo for 24 wk during the viral season . The nedocromil sodium group was symptom-free 58 % of the days , and the placebo-treated patients were symptom-free 45 % of the days ( p = 0.027 ) . During Weeks 1 - 12 , significant differences favored  nedocromil sodium for asthma summary score ( means : nedocromil sodium = 0.61 , placebo = 0.92 ; p = 0.026 ) , and daytime asthma ( nedocromil sodium = 0.78 , placebo = 1.22 ; p = 0.03 ) . Significant differences were noted during monthly intervals for cough ( Weeks 1 - 4 : nedocromil sodium = 0.61 , placebo = 0.92 , p = 0.027 ) and peak expiratory flow rate ( PEFR )  ( nedocromil sodium 262 , placebo = 254 L/min , p = 0.041 Weeks 9 - 12 ) . Patients in the active treatment group reduced their need for rescue inhaled beta 2-agonist by 10 % , whereas patients treated with placebo demonstrated a 24 % increase . There was a strong correlation between asthma symptoms and SRI symptoms ( r = 0.47 ; p < 0.001 ) . During SRIs , patients in the nedocromil sodium group demonstrated more rapid resolution of asthma symptoms immediately following infection ( p = 0.033 summary score , p = 0.039 sleep difficulty ) . No serious adverse events were noted . Nedocromil sodium did not prevent the infection or exacerbation of asthma symptoms during SRI . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this double‐blind placebo‐controlled trial was to assess the efficacy and tolerance of nedocromil sodium at a dose of 4 mg four times daily , in the management of children suffering from grass‐pollen asthma . Thirty‐one children suffering from seasonal asthma ( 24 boys and seven girls , aged 4–21 yr , mean 11 yr ) were enrolled in the study during the 1988 pollen season . Only one child was aged 4 yr , and she was a cooperative girl able to use the metered dose inhaler properly . In addition , in each group there was a patient aged 20 and 21 years , respectively , who had been followed up by us since childhood . Treatments were delivered by pressurized aerosol over a period of 4 weeks following a 1‐week baseline , during which patients were required to show active disease by obtaining a minimum symptom score ( almost 2 points of severity score on at least 3 days of the baseline period ) . The patients were r and omly assigned lo both treatment groups , all were taking inhaled or oral bronchodilators , when necessary . Twenty‐nine patients completed the trial , 16 in the nedocromil sodium treatment group and 13 in the placebo group . One child of each group was withdrawn due to treatment failure A multi-centre , r and omized , blind comparative group study was carried out in 202 adult patients , who had suffered from asthma for at least 2 years , to assess the effectiveness and tolerability of maintenance treatment with either  4 mg nedocromil sodium 4-times daily , 0.1 mg beclomethasone dipropionate 4-times daily or 2 puffs of placebo 4-times daily , given by inhalation . Lung function ( FEV1 and sRaw ) measurements were made at the beginning and end of a 2-week baseline period and then after 3 and 6 weeks of treatment : assessment were also made of asthma severity . Patients recorded daily on diary cards details of morning and evening PEFR , usage of inhaled bronchodilators , severity of dyspnoea , cough and morning tightness . The results showed that , compared with placebo , both nedocromil sodium and beclomethasone dipropionate-treated patients showed an improvement in FEV1 and a reduction in sRaw values : PEFR increased slightly in all three groups . There was an improvement in asthma severity , diminished rate of dyspnoea and cough , and reduced usage of inhaled bronchodilators in patients receiving active treatment but not in those on placebo . Overall assessment of treatment efficacy by both investigators and patients showed that opinions were significantly in favour of active treatment over placebo . Treatment was well tolerated and no serious side-effects were reported . It was concluded that at the dosages used nedocromil sodium was comparable with and equivalent to inhaled beclomethasone dipropionate in nearly all of the parameters assessed , and both drugs were superior to placebo in the maintenance treatment of asthma in adult patients Nedocromil sodium is a new antiasthmatic drug with properties similar to sodium cromoglycate . We examined the efficacy of nedocromil sodium compared to placebo in 71 asthmatic patients in a three-centre double-blind parallel group study over 12 weeks . During the study the patients ' maintenance inhaled corticosteroids were progressively withdrawn . Nedocromil sodium had an advantage over placebo in the number of withdrawals related to uncontrolled asthma , 14 and 24 respectively ( p = 0.03 ) . Changes in symptom scores , peak flow rates and bronchodilator use favoured nedocromil sodium occasionally during the study . The unusual taste of the active drug was reported frequently . Nedocromil sodium is more efficacious than placebo in asthma maintenance , but does not replace inhaled corticosteroids BACKGROUND The value of sputum induction in pediatric asthma lies in its potential to directly and noninvasively assess  airway inflammation in children , because bronchoscopy and biopsy carry some risk . The Childhood Asthma Management Program ( CAMP ) study was design ed to evaluate the long-term effects of budesonide and nedocromil compared with placebo in children with mild to moderate asthma across 8 centers . OBJECTIVE At the Denver CAMP site , we sought to evaluate the safety of sputum induction , to determine differences in airway inflammation between treatment groups by using induced sputum analysis , and to examine correlations between other biomarkers and sputum eosinophils . METHODS Sputum induction was performed , and exhaled nitric oxide , circulating eosinophil counts , and serum eosinophil cationic protein were obtained at treatment discontinuation and after washout . Spirometry and a methacholine challenge were also performed according to the CAMP protocol . RESULTS Ninety of 117 children provided an adequate sputum sample for analysis . In 9 subjects ( 3 nedocromil and 6 placebo ) , sputum induction result ed in bronchospasm . These subjects had greater disease severity , as measured by a lower median prebronchodilator FEV 1 percentage predicted ( 85.0 % vs 96.0 % ; P = .024 ) and FEV 1 /FVC ratio ( 70.0 % vs 79.0 % ; P = .0008 ) ; greater bronchodilator reversibility ( 16.5 % vs 6.8 % ; P = .004 ) ; higher serum IgE ( 1390.0 vs 495.0 ng/mL ; P = .017 ) and circulating eosinophil count ( 757.0 vs 282.0/mm 3 ; P = .04 ) ; greater use of prednisone ( 1.9 vs 0.9 courses per 100 person-years ; P = .05 ) ; and greater supplemental inhaled steroid doses ( 85.3 vs 0 mg ; P = .016 ) . At treatment discontinuation , budesonide-treated patients had a lower median ( 1st , 3rd quartile ) sputum percentage eosinophil ( SPEos ) ( 0.2 % [ 0 % , 1.2 % ] vs 0.8 % [ 0.2 % , 4.6 % ] ; P = .03 ) compared with those treated with placebo ; no significant difference was noted between nedocromil- and placebo-treated patients . Higher SPEos at the time of treatment discontinuation was associated with asthma worsening that required rescue prednisone ( n = 23 ) during the washout period compared with patients who remained stable ( 3.6 % [ 0.4 % , 6.4 % ] vs 0.6 % [ 0.2 % , 3.2 % ] SPEos ; P = .023 ) . Finally , greater SPEos was associated with atopy , higher bronchodilator reversibility , lower FEV 1 /FVC ratio , higher exhaled nitric oxide levels , circulating eosinophils , sputum and serum eosinophil cationic protein , more prednisone courses during the treatment period , and greater asthma severity . CONCLUSIONS Sputum induction is a relatively noninvasive and safe procedure that can provide information on eosinophilic inflammation and treatment response and is also associated with several measures of asthma control . However , this procedure still remains a research tool in asthma because of its requirements for technical expertise Abstract . In a double‐blind group comparative trial nedocromil sodium ( Tilade ® ) at a dose of 4 mg four times daily was compared with placebo in the management of out‐ patients with bronchial asthma . Treatments were delivered by pressurized aerosol over a period of 28 days following a 2‐week base‐line during which patients continued on their usual therapy . Twenty‐one patients entered the nedocromil sodium group and twenty entered the placebo group . All were using beclomethasone dipropionate aerosol as maintenance steroid therapy plus intermittent use of a bronchodilator taken by inhalation . The dose of steroid was reduced for all patients after 2 weeks of treatment and again for approximately half the patients after 3 weeks trial treatment . Patients in the nedocromil sodium treatment group improved in respect of Diary Card symptom scores and peak expiratory flow rate ( PEFR ) , and in their requirements for inhaled bronchodilators . Patients in the placebo group were worse , particularly in respect of daytime asthma symptoms ( P < 0·01 ) , bronchodilator use ( P < 0·05 ) and morning PEFR during the third week of trial treatment ( P < 0·05 ) . More patients in the nedocromil sodium group than in the placebo group thought their treatment had been effective ( P < 0·05 ) .  Nedocromil was well tolerated . Despite the short duration of treatment imposed at this stage in the clinical evaluation of a new compound , our results were sufficiently encouraging to prompt further evaluation of nedocromil sodium over the longer period required ( 3–12 months ) for the clinical assessment of a new treatment for chronic asthma BACKGROUND Despite increased attention focused on the need to prevent patient attrition in long-term clinical trials , high dropout rates have threatened the success of numerous studies . OBJECTIVE To evaluate the disease , demographic , and psychological factors associated with missed visits and study dropout to help improve patient management in long-term clinical trials . METHODS Predictors of attrition were examined within the Childhood Asthma Management Program ( CAMP ) , a large , multicenter clinical trial that followed up 1,041 children with asthma for 4 to 6 years . RESULTS Eighty-two percent of patients attended all study visits . The tendency to miss visits was increased among older children with milder asthma , lower intellectual and social competence , and more symptoms of behavioral problems and emotional distress . Forty-two patients who missed 3 or more visits in a row and did not attend the final visit were considered study dropouts ; these patients at baseline had milder asthma ; lower cognitive , academic , and social competence skills ; and more family conflict and distress than found among participants who remained in the study . The 49 children who had erratic attendance but did not drop out also had lower intellectual and academic skills and less family social support . CONCLUSIONS The 4 % dropout rate in CAMP was lower than reported in any previous long-term asthma trial . The findings of milder disease , decreased psychological re sources , and increased distress in problem-attendance patients can assist in identifying patients who are at risk for missed visits or dropout during the trial either to block their entry into the trial or to focus efforts at maintaining their attendance once enrolled in the trial 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 , r and omized , 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 r and omly 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 r and omization 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 BACKGROUND Nocturnal symptoms of asthma are a cause of significant morbidity and are included as a central feature in the categorization of asthma severity . OBJECTIVES Data from the  Childhood Asthma Management Program  were used to estimate the prevalence of nocturnal awakenings in 1041 children with mild-to-moderate asthma and to investigate the relationships between awakenings and peak flows , severity of asthma , and allergen sensitivity and exposure . METHODS Daily diary care data were recorded during a 28-day interval in the Childhood Asthma Management Program screening process . The data on morning and evening peak flows , overall symptom codes , albuterol use for symptoms , and nocturnal awakenings for asthma symptoms were analyzed and compared with measures of personal characteristics , pulmonary function , and environmental characteristics of the patients . RESULTS Three hundred fifty-one ( 33.7 % ) children experienced 1 or more night awakenings caused by asthma during the 28-day screening period while not taking any maintenance medications . Greater risk of night awakening was associated with more severe asthma ( greater responsiveness to bronchodilator , airway reactivity to methacholine , peak flow variability , and use of albuterol for symptoms , all P < .0001 ) and atopy ( increased IgE and allergy skin test reactivity , both P = .0002 ) . Those with a positive skin test response to dog and a high level of dog allergen in the home had a greater risk of night awakening caused by asthma ( P = .01 ) , as did those with a positive skin test response to cat and a high level of cat allergen in the home ( P = .04 ) . Mean daily symptom code and use of albuterol for asthma symptoms increased in the 3 days immediately before a single awakening compared with in the 4 to 6 days before the awakening ( P = .02 and P = .01 , respectively ) ; however , both morning and evening peak flows as a percentage of personal best were similar in both intervals . Mean daily symptom code and daily use of albuterol  were greater in the 3 days after an awakening than in the 3 days before ( P < .0001 and P = .0002 , respectively ) . Mean evening peak flow percentage of personal best the day after an episode of awakening was lower when a second consecutive awakening occurred than when there was only a single awakening ( P = .01 ) . CONCLUSIONS Nocturnal awakening occurred in one third of the children with mild-to-moderate asthma during a month of relative stability and appears to be an indicator of asthma that is becoming increasingly severe Two hundred and two patients aged 12–78 with chiefly moderate to severe asthma took part in a multicenter r and omized blined group comparison of nedocromil sodium ( NS ) 4 mg four times daily , beclomethasone dipropionate ( BD ) 0.1 mg four times daily , and placebo . Patients were assessed at the start and end of a two week baseline and after three and six weeks of treatment . Compared with placebo , both NS and BD significantly improved day-time dyspnoea and day and nighttime cough , as assessed by diary card scores . Lung function ( FEV1 ) was significantly improved in the BD group . In the NS group there was also a significant reduction in concomitant use of inhaledβ2-agonists . Overall opinions of efficacy by clinicians and patients were significantly in favor of both active treatments over placebo . There were no significant differences between the three treatments for peak expiratory flow rates , morning tightness or nighttime dyspnoea . Comparison between the two active treatments showed no significant differences in any of the variables Nedocromi [ sodium is a new pyranoquinoline dicarboxylic acid derivative which is being studied extensively in adults with asthma . However , there are few publications which detail the use of nedocromil sodium in childhood asthma . One such study showed that nedocromil sodium administered by metered dose inhaler is able to protect against exercise-induced bronchoconstriction ( 1 ) . We report here on the findings of a study to determine whether nedocromil sodium nebulizer solutions block foginduced bronchoconstriction in asthmatic children After a two week baseline , 209 asthmatic children ( mean age 10 years , range 6 - 17 ) were r and omly allocated to receive 4 mg nedocromil sodium ( n = 110 ) or placebo ( n = 99 ) four times daily for 12 weeks in addition to their current treatment . The children completed daily diary cards and visited the clinic at four week intervals . Statistically significant differences in favour of nedocromil sodium were seen for clinician assessment of asthma severity and diary card symptom scores , pulmonary function and inhaled beta 2 bronchodilator use . Total symptom score decreased by 50 % from baseline in the nedocromil sodium group and by 9 % in the placebo group during the final four weeks . Nedocromil sodium was considered very or moderately effective by 78 % of children/parents ( placebo 59 % ) and 73 % of clinicians ( placebo 50 % ) . Nausea , headache and sleepiness , and dyspnoea led to withdrawal of one child from nedocromil sodium and placebo treatments , respectively . Reports of sore throat and headache were marginally greater with the nedocromil sodium treatment . It is concluded that nedocromil sodium was both effective and safe in the treatment of asthma in children 131 asthmatics aged 12 - 65 years , who still had symptoms despite inhaled or oral bronchodilators , were included in this double-blind group comparative study involving nedocromil sodium ( 2 puffs of 2 mg each twice daily ) and placebo ( 2 puffs twice daily ) . The study was carried out at 8 centers over six weeks . Under nedocromil sodium , cough , dyspnea and severity of attacks were reduced significantly . Overall patient assessment also clearly favoured the active substance . Nedocromil sodium was also superior to placebo in terms of the improvement of lung function ( FEV1 , FVC and PEFR ) .  26 patients complained of unusual symptoms ( 12 under nedocromil sodium , 14 under placebo ) .  Nedocromil sodium proved to be an effective , safe and well-tolerated drug in the antiinflammatory long-term treatment of reversible obstructive airways disease Patients satisfactorily controlled on both an inhaled corticosteroid and a regularly inhaled bronchodilator were r and omly allocated to 12 weeks of treatment with either nedocromil sodium ( 4 mg q.i.d . ) or matching placebo . After 3 weeks of treatment , inhaled steroids were abruptly withdrawn . Severity of asthma deteriorated in both groups but more rapidly in the placebo group ( p less than 0.05 ) . Lung function tests showed little between-group difference .  Nedocromil sodium  had greater efficacy than placebo in the control of asthma in patients requiring an inhaled corticosteroid but abrupt corticosteroid withdrawal is not recommended . However , there are some clinical suggestions of the benefits of the combined use of nedocromil sodium and an inhaled corticosteroid BACKGROUND Some patients with asthma respond poorly to corticosteroids and have persistent airway inflammation and daily clinical symptoms . The aim of this study was to investigate the effects of nedocromil sodium ( NS ) , a nonsteroidal antinflamatory drug , in the treatment of steroid-resistant asthma . METHODS Steroid-resistant asthma as diagnosed in any patient who demonstrated 20 % improvement in FEV1 after treatment with inhaled salbutamol with failure of FEV1 to improve by at least 15 % after a 2-week trial of prednisolone , 30 mg daily . In a double-blind placebo-controlled trial , the patients received either 4 mg of inhaled NS ( n = 13 ) or placebo ( n = 13 ) , 4 times daily for 3 months . RESULTS NS but not placebo result ed in a mean increase in FEV1 of 11.4 % after 12 weeks of therapy ( p = 0.05 ) and of 12.4 % ( p = 0.04 ) and 15 % ( 0.02 ) in morning peak expiratory flow after 8 and 12 weeks of treatment , respectively . Changes in FEV1 at 4 and 8 weeks and in peak expiratory flow at 4 weeks of NS therapy were not significant . NS was also effective in reducing variability of peak expiratory flow ( p = 0.02 ) and use of salbutamol ( p = 0.005 ) and in improving quality of life ( p = 0.007 ) by the trial end . Six of the 12 patients treated with NS who completed the treatment period showed a " good response , " defined by a reduction in salbutamol use of more than 50 % and an increase in morning peak expiratory flow of more than 20 % from baseline ; there were no clinical predictors of this response . Two patients were withdrawn from the study because of severe asthma exacerbation ( one from each treatment group ) . CONCLUSION Inhaled NS improved pulmonary function and decreased asthma severity in steroid-resistant asthma , but its effectiveness is not homogeneous and can not be predicted from baseline clinical data BACKGROUND Many factors , including heredity , atopic status , and environment , have been implicated in the determination of asthma severity . Relatively little is known about the degree to which asthma duration influences asthma severity . OBJECTIVE The  Childhood Asthma Management Program ( CAMP  ) , consisting of 1041 children ( age 8 . 9 + /- 2.1 years at enrollment ) with mild-to-moderate asthma , offers an opportunity to examine the relationship between asthma duration and asthma severity . METHODS By using the extensive CAMP baseline cross-sectional data on asthma duration , spirometry , bronchial responsiveness , symptomatology , and markers of atopy , univariate and multivariate regression models were used to evaluate whether asthma duration is associated with asthma severity . RESULTS Duration of asthma in the study cohort from time of diagnosis until r and omization into CAMP ranged from 0.3 to 12.1 years ( mean , 5.0 ; SD , 2.7 ; median , 4.8 ) . Asthma duration is associated in univariate analyses both with lower levels of several lung functions ( P < .001 ) , including methacholine bronchial reactivity ( natural log [ ln ] FEV1 PC20 , mg/mL ; r = -0.112 ) , prebronchodilator and postbronchodilator percent predicted FEV1 ( r = -0.176 and r = -0.130 , respectively ) , and prebronchodilator and postbronchodilator FEV1 /forced vital capacity ( FVC ) ( % ) ( r = -0.237 and r = -0.211 , respectively ) , as well as higher levels of symptoms ( symptom score : r = 0.147 , P < . 001 ) and borderline greater use of albuterol for symptoms ( r = 0.058 , P = .064 ) during a 28-day screening period before r and omization . Simple linear regression detected the following differences in lung functions per year of asthma duration : ln FEV1 PC20 , -0.050 mg/mL/y ; prebronchodilator FEV1 , -0.907 percent predicted/y ; and prebronchodilator FEV1 /FVC , -0.729 percent predicted/y . After controlling for potential explanatory variables ( atopy , inflammatory markers , household Der p 1 levels , anti-inflammatory medication use , and clinical center ) , regression models revealed that the duration of asthma remained significantly and independently associated with ln FEV1 PC20 ( P = .004 ) , prebronchodilator percent predicted FEV1 ( P = .043 ) , and prebronchodilator and postbronchodilator FEV1 /FVC ( % ) ( P < .001 ) , as well as being positively associated with mean daily symptom score ( P < .001 ) and albuterol use for symptoms ( P = .003 ) during a 28-day screening period . Duration was also found to be significantly associated with physician/nurse assessment of asthma severity and other historical measures of medication use . CONCLUSIONS These data demonstrate that asthma duration is associated with lower lung function , greater methacholine responsiveness , more asthma symptomatology , and greater use of as-needed albuterol , which are all measures of asthma severity . As such , early diagnosis and intervention may be necessary to ameliorate these adverse effects of persistent asthma Nedocromil sodium ( 4 mg b.d . or q.i.d . ) was added to the therapy of 76 chronic asthmatic patients in a four-centre , double-blind cross-over , placebo-controlled trial . Patients had troublesome symptoms uncontrolled by high doses of inhaled corticosteroids ( mean 1450 micrograms ) . In 54 patients who completed the study , nedocromil sodium was significantly more efficacious than placebo ( P < 0.01 ) in relieving morning chest-tightness and cough , in reducing total diary card score and nocturnal bronchodilator usage , and in increasing morning and evening peak flow . Asthma severity at clinic visits decreased significantly ( P = 0.001 ) following treatment with nedocromil sodium , which was globally rated more effective than placebo ( P < 0.01 ) . Treatment differences favored q.i.d . over b.d . dosage but without statistical significance . There were no serious adverse effects . Although the pulmonary function changes were small , these findings suggest that the addition of nedocromil sodium may benefit asthmatic patients who are inadequately controlled by high doses of inhaled corticosteroids The Childhood Asthma Management Program ( CAMP ) is a multicenter , r and omized , double-masked clinical trial design ed to determine the long-term effects of three inhaled treatments for mild to moderate childhood asthma : budesonide ( a glucocorticoid used daily ) and albuterol ( a short-acting beta-agonist bronchodilator used as needed ) ; nedocromil ( a nonsteroid anti-inflammatory agent used daily ) and albuterol ; and placebo and albuterol .  One thous and forty-one children ( 32 % from ethnic minority groups ) , aged 5 to 12 years at screening , are currently participating . The primary outcome measure is lung growth as indicated by postbronchodilator forced expiratory volume in 1 second ( FEV1 ) percent of predicted , observed over 5- to 6-year period . The trial also assesses differences between treatment groups with respect to airway responsiveness , morbidity , physical growth and development , and psychological growth and development . This report describes the design of the trial , the rationale for the design choices made , and the methods used to carry out the trial BACKGROUND Current guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator . The efficacy and safety of inhaled nedocromil sodium ( Tilade Mint aerosol ) administered using a Fisonair spacer at a dose of 4 mg three times daily was compared with placebo in the treatment of asthmatic children aged 6–12 years who are symptomatic and recovering from an acute exacerbation of asthma . METHODS A group comparative , double blind , placebo controlled trial was performed in children who were recovering from an acute episode of asthma following treatment in the emergency department of the hospital or in children referred from their general practitioner following a wheezing episode and documented evidence of at least two previous episodes of wheezing . A two week baseline period on existing bronchodilator treatment was followed by a 12 week treatment period on either nedocromil sodium ( 2 mg/puff ) or placebo . Both treatments were administered using a Fisonair spacer at a dose of two puffs three times daily . Changes from baseline values in daytime asthma and night time asthma symptom scores , usage of rescue bronchodilators , mean peak expiratory flow ( PEF ) recorded twice daily on diary cards , patients ’ opinion of treatment , and withdrawals due to treatment failure were measured during the primary treatment period ( last six weeks of treatment ) . RESULTS One hundred and forty two children aged 6–12 years entered the baseline period . Sixty three were withdrawn due to failure to meet the entry criteria ( 18 ) or the criteria for asthma symptom severity ( 15 ) or reversibility ( 9 ) , because they developed uncontrolled asthma ( 2 ) , because they took disallowed treatment ( 2 ) , or for other non-trial related reasons ( 17 ) . Seventy nine patients ( 46 boys ) of mean age 8.8 years entered the treatment period . There were significant differences in the changes from baseline values during the last six weeks of treatment in favour of nedocromil sodium compared with placebo in the primary variables of daytime asthma and night time asthma , morning and evening PEF , and the usage of rescue inhaled bronchodilators ; 53 % of patients reported nedocromil sodium to be very or moderately effective compared with 44 % placebo .  Improvement in asthma symptoms , PEF , and reduction in use of rescue bronchodilators did not reach statistical significance until after six weeks of treatment . Twenty two patients were withdrawn or dropped out during the treatment phase , 12 due to uncontrolled asthma or persistence of asthma symptoms , four due to suspected adverse drug reactions ( nedocromil sodium 3 ( headaches 2 , angio-oedema/urticaria 1 ) , placebo 1(persistent cough ) ) , and six due to non-treatment related reasons . Seventy one adverse events were reported by 27 patients in the nedocromil group and 75 by 30 patients in the placebo group . CONCLUSIONS Asthma symptoms , use of bronchodilators , and lung function can be improved significantly in children recovering from an acute exacerbation of asthma or wheeze and currently receiving treatment with bronchodilators alone by the addition of inhaled nedocromil sodium at a dose of 4 mg three times daily administered using a Fisonair holding chamber The efficacy and safety of nedocromil sodium inhalation aerosol ( 4 mg of Tilade administered by metered-dose inhaler ) given twice daily was compared with placebo in 112 patients with mild-to-moderate asthma who had been receiving maintenance therapy with oral or inhaled bronchodilators or both . After a 2-week run-in period and a subsequent 2-week baseline period , patients were r and omized to active treatment ( n = 56 ) or placebo ( n = 56 ) for 8 weeks . All maintenance bronchodilators were withdrawn before the baseline period , and patients entered the treatment period only after demonstrating a specified level of asthma symptoms . Twice daily administration of nedocromil sodium improved all asthma symptoms in these patients who had symptoms as a result of the withdrawal of their maintenance theophylline and /or oral and inhaled beta 2-agonist bronchodilators . During the primary time period ( treatment weeks 5 to 8) , statistically significant between-group differences favored nedocromil sodium for the asthma summary score ( primary variable , p = 0.001 ) , daytime asthma ( p = 0.001 ) , and sleep difficulty caused by asthma ( p = 0.006 ) . Furthermore , significant reductions in the use of as-needed rescue medications were reported in the nedocromil sodium group ( p = 0.003 ) compared with the placebo group . Final overall opinions of treatment effectiveness expressed by physicians ( p = 0.016 ) and patients ( p = 0.002 ) strongly favored nedocromil sodium Changes in time course of blood partial pressures of oxygen ( PtcO2 ) and carbon dioxide ( PtcCO2 ) before , during and after challenge with ultrasonically nebulized distilled water ( UNDW ) were evaluated in 22 children with mild asthma in basal conditions , and after 8 weeks of therapy with inhaled nedocromil sodium at a daily dosage of 8 or 16 mg . PtcO2 and PtcCO2 were followed using transcutaneous O2 and CO2 monitoring system . All asthmatic subjects presented a significant decrease in PtcO2 and /or PtcCO2 ( > 20 % basal value ) during or after challenge . After therapy , the decrease in PtcO2 and PtcCO2 was normalized in the group treated with 16 mg/day , whereas only a partial yet significant reduction in the decrease of O2 and CO2 was observed in the group assuming 8 mg/-day . These data indicate that inhaled nedocromil is effective in treating  bronchial hyperresponsiveness in childhood and that the dose required to achieve this effect is of 16 mg/day A double-blind , r and omized , placebo-controlled , parallel-group study was undertaken in 120 clinical ly stable asthmatic children ( aged 6 - 19 years ) to determine the ability of 8 weeks of treatment with nedocromil sodium ( 4 mg , three times a day ) to reduce the level of histamine responsiveness . Despite the subjects being clinical ly stable and reporting few asthma symptoms , approximately one-third had abnormal pulmonary function on enrollment into the study . Statistically significant increases in pulmonary function were seen in the group treated with nedocromil sodium but not in the control group ( p = 0.01 ) . Furthermore , 52 % of the individuals with abnormal pulmonary function returned to normal following treatment with nedocromil sodium compared to 11 % of those with abnormal pulmonary function who received placebo . However , there were no differences in the level of histamine responsiveness between the two treatment groups at baseline or after 4 or 8 weeks of treatment with nedocromil sodium or placebo . These data suggest that the level of histamine responsiveness is not intimately related to the level of asthma control in children In this double‐blind placebo controlled crossover study the protective effect of nedocromil sodium against bronchial allergen challenge was evaluated in ten asthmatic patients . Single doses of 0.5 , 1.0 and 2.0 mg nedocromil sodium , administered as a pressurized aerosol 3 hr prior to challenge , were each significantly more effective than placebo in inhibiting allergen‐induced bronchoconstriction . The 1.0 and 2.0 mg doses of the active drug were significantly more effective than the 0.5 mg dose . No significant difference was demonstrated between the 1.0 and 2.0 mg doses . Duration of protection beyond 3 hr was not tested . The results suggest that nedocromil sodium may be a potentially useful therapeutic agent and is worthy of further evaluation for the treatment of reversible obstructive airways disease BACKGROUND The Childhood Asthma Management Program ( CAMP ) is a multicenter double-blind , r and omized , placebo-controlled , clinical trial of two anti-inflammatory agents and placebo in children with mild and moderate asthma . OBJECTIVE The interrelationship between asthma severity and neurocognitive functioning among 1041 children ( age range , 5 - 12 years ) enrolled in the CAMP trial was examined . METHODS Asthma severity was established at baseline with a clinical history of asthma symptomatology and measures of lung function ( spirometry and methacholine challenge ) . Diary cards were used in a screening to record nighttime awakenings and doctor contacts caused by asthma symptoms , symptom severity , and number of puffs from a rescue inhaler . All children received a comprehensive neurocognitive assessment at the end of the 28-day screening period ( before r and omization ) , including measures of intelligence , attention , memory , and academic achievement . RESULTS Significant differences were found between children with mild and moderate asthma on lung function and symptom outcome variables ( log(e)FEV(1)PC(20 ) , DeltaFEV(1 ) percent predicted , change in peak flow percent predicted , nighttime awakenings caused by asthma , average symptom severity score , and average daily number of puffs from a rescue inhaler ) but not on neurocognitive variables . Multiple regression analyses revealed that asthma outcomes could not be predicted by neurocognitive variables despite controlling for socioeconomic status . The prevalence of neurocognitive dysfunction , as indicated by the use of psychostimulant medication , was found to be consistent with that found in the existing literature . CONCLUSION Mild and moderate asthma symptoms are not related to neurocognitive functioning in the children enrolled in CAMP . Mean performance on neurocognitive variables was found to be similar to that of national normative data The effects of nedocromil sodium were assessed in 110 patients with asthma who experienced asthma symptoms despite the use of high doses of inhaled bronchodilators . During the baseline period , antiinflammatory agents were not permitted , and patients were treated with inhaled beta-agonists on an as-needed basis . Patients who required 12 or more puffs of albuterol and experienced continuing asthma symptoms for 7 of the 14 baseline days were r and omized to treatment groups . Subjects received either nedocromil sodium ( 4 mg ) or placebo four times a day for 10 weeks . Statistically significant ( p < 0.05 ) between-treatment differences ( weeks 3 to 10 ) , favoring nedocromil sodium , were determined for the asthma summary score , daytime asthma severity , asthmatic cough , morning peak flow rates , reduction of as-needed bronchodilator use , physician 's assessment of asthma severity , and patient and physician opinions of treatment effectiveness . By trial end ( week 10 ) , sleep difficulty caused by asthma decreased 29 % in the nedocromil sodium group and 4 % in the placebo group ( p = 0.006 ) . Nedocromil sodium was well tolerated and improved asthma control while reducing the inhaled bronchodilator load of these patients with moderately severe asthma We investigated the effects of long-term treatment with two anti-inflammatory drugs , nedocromil sodium and beclomethasone dipropionate , on airway hyperresponsiveness to methacholine ( PC20 ) , on baseline FEV1 and on the bronchodilating effect of a deep breath in 25 nonsteroid-dependent nonatopic asthmatic adults . In all subjects the pre study PC20 was less than 8 mg/ml , the postbronchodilator FEV1 was greater than 75 % predicted , and skin prick tests and RAST to 13 common allergens were negative . After 2 months run-in , the subjects were r and omly allocated into 3 parallel treatment groups to inhale double-blind either 4 mg nedocromil ( n = 9 ) or 100 micrograms beclomethasone ( n = 8) or placebo ( n = 8) 4 times daily for 4 months . PC20 was measured using the 2-min tidal breathing method . The effect of a deep breath was measured during methacholine-induced bronchoconstriction by st and ardized maximal and partial expiratory flow-volume curves and was expressed as a flow ratio ( M/P ratio ) . Pretreatment values of FEV1 , PC20 , and M/P ratio were not different between the 3 groups . PC20 did not change in the placebo group , but increased significantly by a factor of 3 after 8 wk of treatment with beclomethasone or nedocromil ( p less than 0.001 ) . FEV1 did not change after treatment with placebo or nedocromil ( p greater than 0.2 ) , but increased ( mean change 0.2 L , SD 0.2 ) after 4 wk of treatment with beclomethasone ( p less than 0.05 ) . Geometric mean M/P ratio increased from 1.98 to 2.66 after 4 wk of beclomethasone ( p less than 0.01 ) , but not after nedocromil or placebo . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Persistently low levels of lung function are associated with subsequent symptoms in patients with asthma as children . OBJECTIVES We hypothesized that objective measures of baseline pulmonary function would be independently associated with future lung function in the  Childhood Asthma Management Program and that these associations might vary with treatment . METHODS We evaluated the association of FEV1 , airway responsiveness , and bronchodilator response  at r and omization as predictors of longitudinal growth in FEV1 at the 48-month follow-up visit in the 1041 Childhood Asthma Management Program participants . RESULTS Baseline levels of airway responsiveness and bronchodilator response were significantly associated with baseline level of lung function . In multivariate models , higher bronchodilator response ( beta = 0.22 ; P < .0001 ) , log PC20 ( beta = 1.82 ; P < .0001 ) , and FEV1 ( beta = 0.58 ; P < .0001 ) at r and omization were each associated with higher levels of prebronchodilator FEV1 , as a percent of predicted , after 4 years . Similar associations were noted for prebronchodilator forced vital capacity and FEV1/forced vital capacity ratio . Baseline bronchodilator response was a particularly powerful predictor of lung function improvements while on inhaled corticosteroids , whereas airway responsiveness was a better predictor in subjects not r and omized to any controller medications . CONCLUSION We conclude that baseline bronchodilator response , airway responsiveness , and level of FEV1 are independent predictors of subsequent level of FEV1 in childhood asthma and may have treatment-specific prognostic significance for persistence of symptoms into early adulthood . CLINICAL IMPLICATION S In asthma , bronchodilator and bronchoconstrictor responses are independent predictors of future lung function and should not be used interchangeably ; bronchodilator response may indicate good response to inhaled corticosteroids Nedocromil sodium is a pyranoquinoline dicarboxylic acid derivative , formulated in a metered-dose inhaler . Because nedocromil sodium has in vitro and in vivo anti-inflammatory properties , it was evaluated in a group of steroid-dependent patients with asthma to observe how well it might be tolerated and for evidence of any beneficial effects . In a double-blind , group-comparative study , 127 patients received nedocromil sodium  and 61 received placebo  , administered as two puffs of 2 mg , four times per day , for 12 weeks . Ten patients developed adverse reactions , seven receiving active drug and three patients receiving placebo . Two patients of each group withdrew because of worsening asthma . Despite selecting patients whose asthma was stable , when they were receiving established therapeutic regimens that included steroids and bronchodilators , it was found that diary-card symptom scores , morning and evening peak expiratory flow rate values , and inhaled beta-agonist usage all demonstrated slight but significant benefit with addition of nedocromil sodium . It is concluded that the inhaled , anti-inflammatory agent , nedocromil sodium , may be added to asthma-treatment regimens with the reasonable expectation of further modest symptomatic benefit A total of 117 subjects took part in a double-blind , placebo-controlled trial of nedocromil sodium ( 4 x 4 mg daily by inhalation ) in the management of patients with moderately severe bronchial asthma . Treatment was r and omly allocated and was continued for 12 weeks following a 2-week baseline period on routine asthma therapy . Statistically significant differences for nedocromil sodium versus placebo were found for diary card asthma severity scores , morning and evening peak flow measurements and daily bronchodilator usage . The clinicians ' assessment s of asthma severity and global opinions of treatment efficacy were also significantly in favour of nedocromil sodium . Overall , the clinical status of these asthmatic patients was improved by adding nedocromil sodium onto their existing therapy
BACKGROUND Currently inhaled corticosteroids are the main stay in the maintenance treatment of chronic asthma in children .
Although inhaled corticosteroids play a crucial role in the management of childhood asthma , the long-term side effects of inhaled corticosteroids used in the management of chronic asthma in children are not clearly known .
OBJECTIVES The objective of this review is to compare the safety and efficacy of inhaled nedocromil sodium with placebo in the treatment of chronic asthma in children .