Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children.

AIM: The fixed combination of beclomethasone (BDP) and formoterol pressurized metered dose inhaler (pMDI) (Foster®, Chiesi Farmaceutici) is being developed in the lower strength (BDP/formoterol: 50/6 µg) to provide an appropriate dosage for children with asthma. The aim of this work was to investigate the systemic bioavailability of beclomethasone-17-monoproprionate (B17MP, the active metabolite of BDP) and formoterol after single inhalation of Foster® pMDI 50/6 µg vs. the free combination of BDP and formoterol pMDIs in asthmatic children. METHODS: Children aged 5-11 years old inhaled BDP 200 µg and formoterol 24 µg as fixed vs. free combination in an open label, randomized, two way crossover single dose study. Blood was collected pre-dose up to 8 h post-dose for pharmacokinetic evaluation (AUC(0,t), AUC(0,∞), AUC(0,0.5 h, Cmax , tmax , t1/2 ). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow and adverse events were monitored. RESULTS: Twenty subjects were evaluable. The systemic exposure of B17MP and formoterol administered as fixed combination did not exceed the free combination: B17MP AUC(0,t) (pg ml(-1) h) ratio test : reference (90% CI), 0.81 (0.697, 0.948) and formoterol AUC(0,t) (pg ml(-1) h) ratio test : reference 0.97 (0.85, 1.10). All pharmacokinetic and pharmacodynamic end points showed non-superiority in favour of the test drug. One adverse event (vertigo) occurred but was not considered treatment-related. CONCLUSION: BDP and formoterol pharmacokinetic and pharmacodynamic effects are non-superior after administration of the two actives as fixed vs. the free combination in 5-11-year-old asthmatic children.

"To wheeze or not to wheeze": That is not the question.

BACKGROUND: The diagnosis of asthma in young children is difficult and based on clinical assessment of symptoms and results of physical examination. Respiratory wheeze has traditionally been used to define asthma in young children. OBJECTIVE: We sought to compare the qualitative diagnosis of wheeze with a quantitative global assessment of significant troublesome lung symptoms during the first 3 years of life as a predictor of asthma by age 7 years. METHODS: Children born to asthmatic mothers (n= 411) were followed prospectively to age 7 years. Parents were instructed to visit the research clinic during the first 3 years of life each time the child had significant troublesome lung symptoms for 3 days. At the clinic, a research physician performed a physical examination, including auscultation for wheeze and excluding differential diagnoses. We tested whether wheeze was independently associated with asthma at age 7 years after adjusting for the total number of episodes. RESULTS: Three hundred thirteen children had full follow-up by age 7 years. In a multivariable analysis the total number of acute clinic visits for asthma symptom was significantly associated with later asthma (P< .0001), whereas the presence of wheeze at these visits was not (P= .5). The total number of acute clinic visits for significant troublesome lung symptoms was also significantly associated with later asthma in children who had never presented with any wheeze (P= .03). CONCLUSION: A quantitative global assessment of significant troublesome lung symptoms in the first 3 years of life is a better predictor of asthma than assessment of wheeze. Doctor-diagnosed wheeze is not a prerequisite for the diagnosis of asthma, and relying on the symptom of wheeze will likely be an important cause of undertreatment.

Association of bacteria and viruses with wheezy episodes in young children: prospective birth cohort study.

OBJECTIVE: To study the association between wheezy symptoms in young children and the presence of bacteria in the airways. DESIGN: Birth cohort study. SETTING: Clinical research unit in Copenhagen. PARTICIPANTS: Children of asthmatic mothers, from age 4 weeks to 3 years, with planned visits and acute admissions to the research clinic. MAIN OUTCOME MEASURE: Frequency of bacteria and virus carriage in airway aspirates during wheezy episodes and at planned visits without respiratory symptoms. RESULTS: 984 samples (361 children) were analysed for bacteria, 844 (299 children) for viruses, and 696 (277 children) for both viruses and bacteria. Wheezy episodes were associated with both bacterial infection (odds ratio 2.9, 95% confidence interval 1.9 to 4.3; P<0.001) and virus infection (2.8, 1.7 to 4.4; P<0.001). The associations of bacteria and viruses were independent of each other. CONCLUSION: Acute wheezy episodes in young children were significantly associated with bacterial infections similar to but independent of the association with virus infections.