Tezepelumab is a humanized monoclonal antibody that blocks the activity of thymic stromal lymphopoietin (TSLP), an epithelial cytokine implicated in asthma pathogenesis. This post hoc analysis describes the incidence of infection-related adverse events (AEs) in patients treated with tezepelumab, using pooled data from the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies. PATHWAY and NAVIGATOR were multicenter, randomized, double-blind, placebo-controlled studies. Patients with severe, uncontrolled asthma received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Reported AEs in the infections and infestations Medical Dictionary for Regulatory Activities system organ class (SOC) were analyzed by treatment group. The safety analysis set comprised 1334 patients (tezepelumab, n=665; placebo, n=669). On-treatment AEs (event rate per 100 patient-years) were reported for 55.5% (57.4) and 57.7% (60.5) of patients receiving tezepelumab and placebo, respectively. Nasopharyngitis was the most frequently reported AE (19.5% [tezepelumab] vs 19.1% [placebo]). Other AEs reported by ≥3.0% of patients in at least one treatment group included upper respiratory tract infection (9.3% vs 13.3%), bronchitis (4.4% vs 5.4%), bacterial bronchitis (3.8% vs 2.5%), urinary tract infection (3.6% vs 3.4%), sinusitis (3.5% vs 6.3%), pharyngitis (3.0% vs 2.5%), and viral upper respiratory tract infection (3.0% vs 2.1%). Serious AEs were reported by 2.0% (tezepelumab) and 2.2% (placebo) of patients. The incidence of infection-related AEs was similar between the tezepelumab and placebo groups. Tezepelumab treatment did not lead to an increased risk of infection.

Objective: To review the worldwide safety data for budesonide inhalation suspension (Pulmicort Respules) to provide a budesonide inhalation suspension pediatric tolerability profile.Data Sources: Clinical study data were obtained from AstraZeneca safety databases used by the US Food and Drug Administration to support the approval of budesonide inhalation suspension and from postmarketing surveillance reports (January 1, 1990, through June 30, 2002).Study Selection: Completed parallel-group studies of patients with asthma 18 years and younger.Results: Safety data for budesonide inhalation suspension were pooled from 3 US, 12-week, randomized, double-blind, placebo-controlled studies (n = 1,018); data from their open-label extensions (n = 670) were pooled with data from a fourth US open-label study (n = 335). Data for 333 patients 18 years and younger enrolled in 5 non-US studies also were analyzed. No posterior subcapsular cataracts were reported in any study, and the frequencies of oropharyngeal events and infection with budesonide inhalation suspension were comparable with those of reference treatments. No increased risk of varicella or upper respiratory tract infection was apparent, and budesonide inhalation suspension did not cause significant adrenal suppression in studies assessing this variable. There were small differences in short-term growth velocity between children who received budesonide inhalation suspension and those who received reference treatment in 2 of 5 trials that evaluated this variable. No increased risk of adverse events was apparent from postmarketing reports.Conclusions: Short- and long-term treatment with budesonide inhalation suspension, using a wide range of doses, is safe and well tolerated in children with asthma.

OBJECTIVE To compare the effects of 2 nebulizable controller asthma medications on caregiver and pediatric quality of life. METHODS In this 52-week, randomized trial, children aged 2 to 6 years with mild to moderate persistent asthma received budesonide inhalation suspension 0.5 mg (total daily dose) once or twice daily (n = 168) or cromolyn sodium nebulizer solution 20 mg 4 times daily (n = 167) for 8 weeks, with dosage adjustment thereafter at the investigators' discretion. The Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ), Compliance/Caregiver Satisfaction Questionnaire (CCSQ), Modified Child Health Questionnaire-Parent Form 50 (CHQ-PF50), and Functional Status-II(R) (FS-II[R]) Questionnaire were administered at baseline and weeks 8, 28, and 52. Global assessments of ease of asthma management and child health status were obtained from caregivers and physicians at the end of the study. RESULTS Improvements from baseline in domain-specific (activities and emotional function) and total PACQLQ scores were greater at each time point (weeks 8, 28, and 52) for caregivers of patients treated with budesonide compared with caregivers of patients receiving cromolyn sodium. Only the budesonide group met the criterion for a clinically important improvement (>or=0.5 unit change) in all PACQLQ domains by week 8, which was maintained at weeks 28 and 52. Moreover, improvements surpassed the criterion for moderate clinical importance (1.0 unit change) in all PACQLQ domains for the budesonide group, but this level of improvement was only achieved in the activities domain (at week 28) for the cromolyn sodium group. Based on the CCSQ, budesonide resulted in greater caregiver satisfaction, treatment convenience, ease of use, and compliance compared with cromolyn sodium. Thus, 90.7% of caregivers in the budesonide group were "completely or very satisfied" compared with 53.4% in the cromolyn sodium group. Over half (54.6%) of caregivers in the budesonide group rated budesonide "highly or very convenient" compared with 23% for cromolyn sodium; 77% rated budesonide "extremely or very easy" to use compared with 47% for cromolyn. Adherence with daily medication regimens was reported for 76% of children in the budesonide group compared with 57% in the cromolyn sodium group. Child health status, as indicated by mean FS-II(R) scores, showed improvements from baseline in both groups at weeks 8, 28, and 52. There was a trend for these improvements to be superior in the budesonide group. Additionally, budesonide was superior to cromolyn sodium in caregiver and physician global assessments. At the end of the study, 76% of caregivers of children receiving budesonide reported asthma management to be "a great deal easier" compared with the start of the study, and 74% rated the overall health status of their child as "much better now than 1 year ago." In contrast, only 29% and 37% of caregivers whose children received cromolyn sodium provided these respective ratings. CONCLUSIONS Budesonide inhalation suspension improved the quality of life for caregivers of children with asthma. Caregivers of children treated with budesonide had significantly fewer limitations in daily activities and emotional functioning compared with caregivers of children treated with cromolyn sodium nebulizer solution. The improvements in caregiver quality of life occurred earlier with budesonide compared with cromolyn sodium. Only caregivers in the budesonide group had a clinically important mean change from baseline in all PACQLQ domains by week 8. These benefits were maintained at week 52. Children treated with budesonide inhalation suspension and cromolyn sodium experienced improvements in health status, assessed using the FS-II(R). The greatest differences between treatments were seen in the disease-specific portion of the FS-II(R), which relates impairments in functional status to the child's illness. Caregiver and physician global assessment indicated significantly better overall child health after 1 year of treatment with budesonide, supporting an improvement in health status. Clinical trials in children 4 to 16 years of age with asthma have demonstrated greater effectiveness of inhaled corticosteroids versus cromolyn sodium on several clinical measures of efficacy. Measures of asthma control in this study, reported in detail elsewhere [Leflein et al. Pediatrics 2002;109:866-872], also have shown greater improvements with budesonide therapy. Treatment with budesonide inhalation suspension resulted in a significantly lower mean rate of asthma exacerbations, significantly longer times to first asthma exacerbation, significantly longer times to first additional use of chronic asthma therapy, and significant improvements in asthma symptom scores and breakthrough medication use compared with cromolyn sodium therapy. Additionally, children receiving budesonide inhalation suspension experienced more symptom-free days and episode-free days compared with children receiving cromolyn sodium. Safety profiles were similar between the 2 treatment groups. Budesonide inhalation suspension was associated with significantly greater caregiver satisfaction, convenience, ease of use, and compliance compared with cromolyn sodium nebulizer solution. This greater caregiver satisfaction and quality of life may be related to the greater asthma control achieved in children treated with budesonide therapy compared with cromolyn sodium. In addition, the convenience of once- or twice-daily dosing with budesonide inhalation suspension, compared with 3- or 4-times-daily dosing of cromolyn sodium, may decrease caregiver burden and enhance the willingness of caregivers to adhere to treatment regimens prescribed for their young children with asthma. This effect on caregiver adherence could further improve treatment effectiveness. This is the first clinical trial comparing the effects of a nebulized corticosteroid with that of an alternative nebulized therapy on quality of life in young children with asthma and their families. Compared with nebulized cromolyn sodium, budesonide inhalation suspension not only provides better overall child health status and asthma management, but greater caregiver quality of life and greater caregiver satisfaction, convenience, ease of use, and compliance.

Objective. The availability of antiinflammatory asthma medications for infants and young children has been limited. The objective of this study was to compare effects of nebulized budesonide inhalation suspension and cromolyn sodium nebulizer solution on asthma-related health outcomes in young children with asthma.Methods. We conducted a randomized, parallel-group, 52-week, open-label study in 36 US clinical sites. Patients included 335 children who were 2 to 6 years of age and had persistent asthma that had been treated with at least 1 long-term control medication; 287 children (86%) completed the study. Patients received budesonide inhalation suspension, 0.5 mg daily (n = 168), or cromolyn sodium nebulizer solution, 20 mg 4 times daily (n = 167), for 8 weeks, followed by dose titration at the investigator's discretion. The main outcome measure was the rate of asthma exacerbations over 52 weeks. Secondary measures included times to first asthma exacerbation and first use of additional asthma therapy, asthma symptom scores, rescue medication use, and health care resource use.Results. The budesonide group had a mean (median) asthma exacerbation rate of 1.23 (0.99) per year compared with 2.41 (1.85) for the cromolyn group, significantly longer times to first exacerbation and first use of additional long-term asthma medication, greater improvements in asthma symptom scores, reduced use of rescue medication, and fewer urgent care visits. Both treatments were well tolerated.Conclusions. Budesonide inhalation suspension was more effective than nebulized cromolyn sodium in young children with persistent asthma. Both treatments were well tolerated with similar adverse event profiles.

Background: The initial 12-week, double-blind phases of three studies demonstrated that budesonide inhalation suspension (BIS) is effective and well tolerated in infants and young children (6 months to 8 years of age) with persistent asthma.Objective: Open-label, 52-week extensions to these studies were conducted to evaluate long-term safety of BIS, including effects of treatment with the lowest effective dose of BIS on hypothalamic-pituitary-adrenal (HPA)-axis function, as compared with conventional asthma therapy (CAT). Complete results of the earlier phases of the studies and of long-term safety are reported elsewhere; only results pertaining to HPA-axis function are summarized here.Methods: Patients eligible for the open-label phases of the three trials were randomized to treatment with nebulized BIS (n = 447) or CAT (n = 223). CAT included short-acting oral or inhaled beta(2)-agonists, methylxanthines, or cromolyn sodium; in two of the studies, CAT could have included other inhaled corticosteroids. HPA-axis function, which had been evaluated during the 12-week double-blind studies, was again evaluated at the beginning and end of the 52-week study period using basal plasma cortisol concentrations and response to stimulation with a 250-mug dose of adrenocorticotropic hormone.Results: There was no evidence of altered HPA-axis function attributable to BIS treatment. No clinically or statistically significant differences in basal or adrenocorticotropic hormone-stimulated plasma cortisol concentrations were observed between BIS and CAT in either the 12-week, double-blind or 52-week, open-label phases of the three studies.Conclusions: The results indicate that treatment with BIS does not result in clinically significant suppression of HPA-axis function in infants and young children.

potent than MF (EC50 -_-10 -I°M versus 4 x 10 -1°M), particularly at the highest concentrations, with a maximum of 40-fold inductions of reporter activity for FP as compared to 27-fold inductions for ME However, there is no difference in the transactivating effects of FP and MF at concentrations reached in the plasma (peak ~ 10 -10M).Thus, there should be no difference in their ability to trigger systemic side effects.There are little differences in transrepression assays, FP being slightly more potent than MF at inhibiting NF-vd3 (IC50 ~ 10 -13M versus 2.5 x 10 -13M) and MF being slightly more potent than FP at inhibiting AP-1 (IC50 ~ 4 x 10 -llM versus 5 x 10 -llM) in reporter gene assays.Nevertheless, in immunoassays, both drugs inhibited TNF-c~ induced RANTES release by 78% at 10 -6M, with an IC50 ~ 10 -10M.Thus, it seems that the differences between the transcriptional potencies of FP and MF, detected by reporter gene assays, are too small to be biologically and clinically relevant.

Three open-label extension trials evaluated the safety of budesonide inhalation suspension (BIS; Pulmicort Respules) in 670 children (8 months-9 years of age) with mild-to-severe persistent asthma. Patients were randomized to receive either BIS or conventional asthma therapy (CAT) for 52 weeks. The percentage of patients who discontinued because of clinical adverse events was low and similar among the CAT (0.4%) and BIS (0.7%) groups. After adjusting for length of time in the studies, there were no clinically relevant differences between the BIS and CAT groups in the type, incidence, or intensity of adverse events; vital signs or physical examination outcomes; or changes in clinical laboratory evaluations or oral fungal cultures.

A retrospective analysis, based on a randomized, placebo-controlled, 12-week study in children 6 months to 8 years of age with persistent asthma, was performed to compare the efficacy and safety of budesonide inhalation suspension 0.25 mg and 0.5 mg twice daily vs. placebo in children <4 and ≥4 years of age. Both age groups demonstrated significant (p ≤ 0.050) improvement in nighttime and daytime asthma symptom scores and decreased bronchodilator use compared with placebo. In addition, the safety profile of twice-daily budesonide inhalation suspension was favorable in both age groups.

It is believed that there are many high school age athletes that have undiagnosed asthma including EIA.The screening of high school athletes for exercise induced asthma (EIA) would allow for safer and more competitive sports.In several suburban Pennsylvania schools, a project to screen athletes for asthma or EIA using several tools, which included a peak flow meter (PEFR), a questioner, and a free running test as part of their sports participation physical.This project was also considered a possible first step in screening for asthma in schools.OBJECTIVES:(1) Obtain reliable PEFR measurements from high school age.(2) To administer questionnaires so as to obtain a symptomatic history for assessing their asthma risk.(3) To identify athletes who would be at high risk for EIA by a free run challenge test.(4) Evaluate if an athlete's present asthma medications for effectiveness.(5) Evaluate these tools for their value as screening tools for asthma or EIA.METHOD: Eight hundred and one student athletes suburban Pittsburgh were screened for EIA as part of their pre participation sports physicals.The screening included athletes from all sports.The athletes were given a brief questionnaire and then had peak expiratory flow rate measured.All athletes then participated in a free running exercise challenge.RESULTS:Forty-six athletes identified themselves as having asthma or EIA, Leaving the results of 755 athletes to be analyzed for EIA.Forty-nine athletes that were previously undiagnosed with asthma or EIA were identilied by having a positive free running test.The incidence of EIA for all participants was 12 % Eighty -five percent (39/46) of the known asthmatic athletes still had a greater than a fifteen percent drop of their PEFR with the free running test despite taking their recommended medication.CONCLUSION:The asthmatic high school athlete needs on going attention to assure that the therapies that are prescribe are effective.The free running test is a good test for identifying the athlete with EIA.The peak flow meter alone is not a good tool for screening the high school athlete for EIA.A questionnaire maybe a good negative screening tool, but further development is needed to increase its positive predictive value before it can be used for wide spread screening.

This study is a retrospective analysis comparing nebulized budesonide inhalation suspension (BIS; Pulmicort Respules™, AstraZeneca, Wilmington, DE) administered once daily by facemask or mouthpiece in 359 infants and young children with persistent asthma. The efficacy and safety of once-daily BIS (0.25, 0.5, and 1.0 mg) administered by facemask or mouthpiece were demonstrated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study reported by Kemp et al. (Ann Allergy Asthma Immunol 1999; 83:231–239). Three hundred fifty-nine children aged 6 months to 8 years with mild, persistent asthma received nebulized BIS 0.25, 0.5, or 1.0 mg once daily or placebo for 12 weeks via facemask or mouthpiece. Efficacy variables included nighttime and daytime asthma symptom scores, use of breakthrough bronchodilator medications, and pulmonary function tests (in children capable of consistently performing spirometry or peak flows). Changes in nighttime and daytime asthma symptom scores were not significantly different between children using facemasks and those using mouthpieces. Use of breakthrough medications and pulmonary function test results (in the subset of children able to perform them) also were not significantly different in facemask users and mouthpiece users. These results suggest that BIS is equally effective whether administered by facemask or mouthpiece and that young children who require the use of a facemask may be successfully treated.

Background: Budesonide inhalation suspension (Pulmicort Respules: Astra-Zeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma. Objective: To compare the efficacy and safety of once-daily budesonide inhalation suspension in children <4 years of age and in those greater than or equal to4 years of age with persistent asthma. Methods: A retrospective analysis stratified by age group was performed on data from two randomized, double-blind, placebo-controlled, parallel-group studies that evaluated the efficacy and safety of budesonide inhalation suspension 0.25 mg, 0.5 mg, or 1.0 mg once daily for 12 weeks in children 6 months to 8 years of age with persistent asthma. Clinical assessments included nighttime and daytime asthma symptoms, breakthrough medication use, adverse events, and hypothalamic-pituitary-adrenal-axis function. Results: In both randomized studies, budesonide inhalation suspension demonstrated statistically significant improvement in nighttime and daytime asthma symptom scores compared with placebo. In the retrospective analysis of pooled data from these studies, the efficacy of budesonide was maintained when children were stratified by age group. Clinical improvements from baseline in nighttime and daytime asthma symptom scores were observed in both age groups at all budesonide inhalation suspension dose levels. No significant differences were observed between age groups in breakthrough medication use in any of the treatment groups. No differences were observed in the incidence of adverse events between the two age groups, and significant (P < 0.01) effect on hypothalamic-pituitary-adrenal-axis function was apparent only in children <4 years of age at the 0.25-mg dose level. Conclusions: Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged <4 and greater than or equal to4 years of age.

A randomized, double-blind, placebo-controlled, parallel-group study including 481 children at 37 centers in the United States demonstrated the efficacy and safety of budesonide inhalation suspension in doses of 0.25 mg once daily, 0.25 mg twice daily, 0.5 mg twice daily, and 1.0 mg daily in infants and young children with persistent asthma. The retrospective analysis presented here compares the efficacy of treatment with the suspension administered through a face mask or mouthpiece. All patients receiving budesonide inhalation suspension via face mask or mouthpiece showed clinical improvements in nighttime and daytime asthma symptoms as compared with administration of a placebo. The improvements were of similar magnitude as those observed in an analysis of all patients treated. Improvements in nighttime asthma symptoms were statistically significant with budesonide at 0.25 mg daily (p = 0.040), 0.25 mg twice daily (p = 0.008), and 0.5 mg twice daily (p = 0.046) delivered by face mask. In patients using mouthpieces, nighttime asthma symptoms improved significantly in the 0.25-mg twice-daily (p = 0.005) and 1.0-mg daily (p = 0.035) groups. Patients receiving budesonide at 0.5 mg twice daily via a face mask improved significantly in daytime asthma symptoms (p = 0.009). The use of breakthrough medication was reduced in patients receiving budesonide via face masks or mouthpieces relative to placebo, and treatment was well tolerated in all study groups. This retrospective analysis suggests that nebulized budesonide inhalation suspension can be administered effectively by either face mask or mouthpiece to young children with persistent asthma.