There has been a fall globally in pneumonia-related fatality in children during the Millennium Development and early Sustainable Development Goal era.

However, pneumonia remains the single largest contributor to mortality with issues including antibiotic resistance, pollution, a change in infective epidemiology, equipoise over effects of adjunctive treatments and identification of sick, decompensating children. 

This thesis examines 4 of these controversies as original research.

Theme 1; two papers, 1 and 2: The first discusses the background motivation. The second a large randomized, non-inferiority controlled trial undertaken (‘RETAPP’) in a suburban slum area of Karachi, Pakistan. Oral amoxicillin treatment was compared with placebo, in the treatment of WHO-defined, uncomplicated, fast breathing pneumonia.

Theme 2 (paper 3) The role of indoor air pollution and poverty in recurrent fast breathing pneumonia: a nested case control study.

Theme 3 (paper 4). The role of adjunctive use of zinc to standard treatment in children with severe pneumonia: a systematic review and meta-analysis of randomised controlled trials.

Theme 4 (paper 5). Recognition of the child with severe respiratory illness using the Clinical Respiratory Score in the emergency department 

Results: In the RETAPP study, 4,002 randomised children were enrolled. There was a significant difference in treatment failure rates in the amoxicillin and placebo groups (2.6 % vs 4.9 %). The number needed to treat was high at 44, and mortality very low and similar in both groups, discussion points for policy makers.

There does not appear to be an enhanced risk with Indoor Air Pollution in recurrence of pneumonia. The only predictor was household poverty: external pollution could be a factor.

Adjunctive zinc confers no additional advantage to children with severe pneumonia.

The clinical respiratory score is a highly sensitive, but non-specific marker for severe illness.

Conclusions: The small, though significant, differences in treatment failure rates in fast breathing pneumonia are likely to have implications for setting of management.

The role of environmental predictors needs to turn to poverty and external pollution.

Zinc has no role as an adjunctive treatment. The clinical respiratory score has excellent predictive value for severe illness.