Oral purified bacterial extracts in acute respiratory tract infections in childhood: a systematic quantitative review.

BACKGROUND: Recurrent acute respiratory tract infections (ARTI) are a common problem in childhood. Some evidence suggests a benefit regarding the prevention of ARTI in children treated with the immunomodulator OM-85 BV (Bronchovaxom). METHODS: We summarised the evidence on the effectiveness of the immunomodulator OM-85 BV in the prevention of ARTI in children. We searched randomised comparisons of oral purified bacterial extracts against inactive controls in children with respiratory tract diseases in nine electronic databases and reference lists of included studies. We extracted salient features of each study, calculated relative risks (RR) or weighted mean differences (WMD) and performed meta-analyses using random-effects models. RESULTS: Thirteen studies (2,721 patients) of low to moderate quality tested OM-85 BV. Patients and outcomes differed substantially, which impeded pooling results of more than two trials. Two studies (240 patients) reporting on the number of patients with less than three infections over 6 month of follow-up in children not in day care showed a trend for benefit RR 0.82 (95% CI, 0.65-1.02). One out of two studies examining the number of children not in day care without infections over 4-6 month reported a significant RR of 0.42 (95% CI, 0.21-0.82) whereas the smaller, second study did not [RR 0.92 (95% CI, 0.58-1.46)]. Two studies reporting the number of antibiotic courses indicated a benefit for the intervention arm [WMD 2.0 (95% CI, 1.7-2.3)]. Two out of the three studies showed a reduction of length of episodes of 4-6 days whereas a third study showed no difference between the two groups. CONCLUSION: Evidence in favour of OM-85 BV in the prevention of ARTI in children is weak. There is a trend for fewer and shorter infections and a reduction of antibiotic use.

In vitro determination of the optimal particle size for nebulized aerosol delivery to infants.

We investigated the in vitro influence of breathing patterns on lung dose (LD) and particle size distribution in an infant upper airway cast model in order to determine the optimal particle size for nebulized aerosol delivery to infants. Budesol (nebulizer solution of budesonide) delivery from a perforated vibrating membrane nebulizer (eFlow Baby functional prototype) through an upper airway cast of a nine month old infant (SAINT-model) was measured at a fixed respiratory rate (RR) of 30 breaths per minute (bpm) and a tidal volume (Vt) of 50, 100, and 200 mL, respectively, and at a fixed Vt of 100 mL and a RR of 30, 60, and 78 bpm, respectively. LD expressed as a percentage of the nominal dose (ND; range, 5.8-30.3%) decreased with increasing Vt (p < 0.001) and with increasing RR (p < 0.001). Median mass aerodynamic diameter (MMAD) after passage (range, 2.4-3.4 microm) through the upper airway cast showed a negative correlation with increasing Vt (p < 0.001) and with increasing RR (p = 0.015). Particles available as LD for all simulated breathing pattern showed a particle size distribution with a MMAD of 2.4 microm and a geometric standard deviation (GSD) of 1.56. From our in vitro study, we conclude that the optimal particle size for nebulized aerosols for inhalation therapy for infants should have a MMAD of <2.4 microm.

The effect of montelukast on exhaled nitric oxide and lung function in asthmatic children 2 to 5 years old.

OBJECTIVE: The study was undertaken to investigate the influence of once-daily treatment with montelukast (Singulair; MSD; Glattbrugg, Switzerland) on levels of exhaled nitric oxide (eNO) and lung function in preschool children with asthma. METHODS: A total of 30 children (19 girls), 2 to 5 years of age, in whom asthma had been newly diagnosed, who had a positive first-degree family history of asthma and a positive allergy test result, were allocated to undergo a 1-week run-in period of montelukast treatment. eNO and airway resistance were measured in all patients before (visit 1) and after the run-in period (visit 2), and after treatment with montelukast (4 mg once daily) for 4 weeks (visit 3). RESULTS: There were no significant differences in all parameters before and after the run-in period. However, the mean (SD) levels of eNO and the mean (SD) levels of airway resistance after treatment at visit 3 were 11.6 parts per billion (ppb) [9.5 ppb] and 1.15 kPa/L/s (0.26 kPa/L/s), respectively, and were significantly lower compared to values of 33.1 ppb (12.0 ppb) and 1.28 kPa/L/s (0.23 kPa/L/s), respectively, before treatment (p < 0.001) and at visit 2 (p = 0.01). There was no significant change in mean bronchodilator responsiveness between visit 3 (13.2%; SD, 6.8%) and visit 1/visit 2 (13.3%; SD, 7.0%; p = 0.47). CONCLUSION: We have shown that montelukast has a positive effect on lung function and airway inflammation as measured by nitric oxide level in preschool children with allergic asthma.

Correlation of nitrites in breath condensates and lung function in asthmatic children.

We aimed to evaluate the value of exhaled breath condensates in monitoring airway inflammation in childhood asthma before and after high altitude climate therapy. Forty-eight asthmatic children on regular anti-asthma treatment with a normal FEV1 and positive skin prick test for house dust mites were recruited. All children had been referred to an alpine clinic for high altitude climate therapy, because of persistent asthmatic symptoms despite use of daily anti-inflammatory treatment. Subjects were assessed on their arrival and before departure from the alpine clinic. Spirometry, bronchial provocation tests and measurements of nitrites in breath condensates were performed. Median levels of nitrites were significantly higher before than after high altitude climate therapy (1.27 vs. 0.93 microm; p = 0.008). In addition, MEF50 improved significantly (p < 0.0005). There was a significant correlation between nitrites in breath condensates and MEF50 (r = -0.63, p < 0.0001), symptoms (r = 0.47, p = 0.0007) and airway hyper-reactivity (AHR) (r = -0.41, p = 0.004). In summary, we found a reduction in nitrites in breath condensates after a high altitude climate therapy. Significant correlations were found between nitrites and MEF50, AHR and symptoms. We conclude that the measurement of nitrites may be feasible to objectively assess airway inflammation in asthmatic children in order to detect ongoing inflammation in children with normal FEV1 but persistent symptoms.