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Objectives: To evaluate the blood levels, pharma-cokinetics and pharmacodynamic indices of pyrazinamide (PZA) in children suffering from tuberculosis, at doses administered under the weight band system of Revised National Tuberculosis Control Program of India (RNTCP) of India., Design: Prospective, open-label, non-randomized single-dose study., Setting: 20 children in the age group 5-12 years attending out-patient tuberculosis clinic of a tertiary hospital., Outcome Measures: Blood levels of pyrazinamide after single dose administration, as per the weight band system of RNTCP., Results: Group I (n=7) included children who received pyrazinamide within the recommended 30-35 mg/kg dose (mean 31.9 ± 0.8 mg/kg) and Group II (n=13) included those who received a dose lower than 30 -35 mg/kg (mean 28.1 ± 0.3 mg/kg). The Cmax (95% CI of difference 2.2, 13.2; P=0.008) and AUC (95% CI of difference 28.6, 208.1; P=0.01) were significantly lower in Group II. The duration of time for which the concentration was maintained above 25 ug ml-1 was 4-8 h in Group I and 3-5.5 h in Group II (95% CI of difference 0.1, 2.0; P=0.03). The half life, elimination rate constant, clearance and volume of distribution were comparable in the two groups. The ratios of Cmax and AUC to MIC (25 ug ml-1) in children were lower than that recommended for PZA in adults., Conclusions: Lower blood concentrations are being attained in children receiving PZA doses under the existing weight band system of RNTCP of India. The weight bands may need to be revised and dose recommendations be based on pharmacokinetic and efficacy data in children.

Objective: To compare the efficacy of a commercial spacer device versus an improvised spacer device in delivering aerosolized beta-2 agonist through metered dose inhaler in an acute exacerbation of bronchial asthma., Design: Randomized controlled trial., Setting: Urban tertiary care teaching hospital., Methods: 60 children between 1 to 12 years of age with acute asthma were prospectively enrolled and randomized into two groups. Detailed history, clinical evaluation and appropriate laboratory investigations were recorded on a pretested proforma. One group received inhaled salbutamol using metered dose inhaler via commercial spacer device (Group 1), while the other received it via improvised spacer device (Group II). The response was sequentially assessed after 20, 40 and 60 minutes of institution of therapy., Results: The two groups were comparable with respect to various parameters at presentation (p > 0.05). All the outcome parameters showed a significant improvement with time in both groups (p < 0.05). There was no statistical difference between the response in the two groups (p< 0.05)., Conclusion: Metered dose inhaler with improvised spacer device is equivalent in efficacy and a more cost effective alternative to metered dose inhaler with commercial spacer for administration of beta-2 agonist in acute asthma.

Objective: To compare the relative efficacy of jet nebulizer and metered dose inhaler (MDI) with spacer for the administration of aerosolized salbutamol in an acute exacerbation of bronchial asthma., Design: Randomized prospective study., Setting: Emergency Room., Methods: In 60 subjects with acute asthma aged between 1 to 12 years, clinical and laboratory assessment of severity at recruitment included heart rate, respiratory rate, pulsus paradoxus, arterial blood gas analysis (all cases) and peak expiratory flow rate (wherever possible). The subjects were randomized into two equal groups to receive aerosolized salbutamol either via nebulizer (Group I) or MDI-spacer (Group II) as per the Consensus Guidelines. The response to therapy was sequentially assessed after 20, 40 and 60 minutes of institution of therapy., Results: A significantly (p < 0.02) greater number of subjects in Group II presented with severe dyspnea and intercostal muscle retraction (subjective assessment). However, the objectively evaluable outcome parameters were comparable (p > 0.05) in both groups at presentation. All the outcome measures showed a significant (p < 0.05) improvement with time in both the groups. The recovery parameters were comparable (p > 0.05) at different time periods in the two groups., Conclusion: MDI-spacer is as effective as a nebulizer for the aerosolized administration of salbutamol in an acute exacerbation of asthma in children. However, for developing countries, distinct advantages (economic and power requirement) argue strongly for utilization of MDI-spacer in preference to nebulizer.

Objective: To identify the predictors of mortality due to acute lower respiratory tract infection (ALRI)., Design: Prospective cohort study., Setting: Urban tertiary care teaching hospital., Methods: 201 cases with ALRI between 2 weeks to 5 years of age were prospectively enrolled and followed up to determine outcome. Detailed history and clinical evaluation were recorded on a pretested proforma. Significant independent predictors of mortality were determined by comparison of dead subjects (n = 21) with surviving children (n = 180) in a multiple logistic analytic framework., Results: The case fatality rate (CFR) was 10.45%. Significant independent predictors of mortality were (OR, 95% CI) age less than 1 year (23.1, 2.7-197.5), inability to feed (6.2, 1.3-30.7), associated loose stools (5.1,1.2-27.3), weight for age Z score < -3 (3.9,1.01-9.7), short duration of fever (1.2,1.0-1.5) and bandemia (1.1,1.05-1.2). The WHO guidelines identified 91% of children diagnosed as ALRI by clinical and investigative criteria. The CFR was related to severity of WHO classification ("pneumonia"-0%, "severe pneumonia"-8.7% and "very severe pneumonia"-47.0%). However, 2 of the 18 subjects with a diagnosis of "no pneumonia" expired (CFR 11.1% and 10% of total mortality)., Conclusion: Even in settings of high case fatality, predictors of mortality can be identified in under five children suffering from ALRI. In this context, age below 1 year, inability to feed, presence of loose stools and severe malnutrition merit attention for interventional purposes.

The present study was undertaken to identify the clinical predictors of hospitalization in an acute attack of bronchial asthma in subjects aged 2-12 years. Seventy five children with an acute attack of bronchial asthma were evaluated. A detailed clinical history and examination was recorded and baseline investigations sent before starting therapy. All subjects were treated with injection adrenaline (two doses) and those who did not respond were hospitalized. Twenty subjects who were hospitalized were compared with 32 cases who were discharged and did not have a relapse on follow up. After multivariate analysis, the factors independently predictive of hospitalization were, pulsus paradoxus (> 10 mm Hg; OR = 1.02), younger age (below 5 years, OR = 0.98) and severe accessory muscle use (OR = 89.6). Presence of any 2 of these 3 clinical predictors has a high sensitivity (90%) and specificity (96%). The investigative variables significant after multivariate analysis were low pH (OR = 0.00) and polymorphonuclear leucocytosis (> 70%) on peripheral smear (OR = 1.12). The sensitivity of this model was similar (90%) but specificity was lower (90.6%). The addition of investigative variables to clinical model did not improve the predictability. It is concluded that it is possible to identify at presentation, children with acute bronchial asthma who require hospitalization and clinical variables are sufficient for this purpose.