on behalf of the American Thoracic Society/ European Respiratory Society Working Group on Infant and Young Children Pulmonary Function Testing This official statement of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) was approved by the ATS Board of Directors, September 2006, and the ERS Executive Committee, December 2006 6. Further multidisciplinary work is required to investigate the best combination of tests (e.g., structure, function, inflammation, atopy) and challenges (e.g., pharmaceutical vs. physical) to investigate specific clinical entities during early childhood.
long-term treatment instituted, without any objective diagnostic measurements ever being made. Is there any other chronic disease for which objective diagnostic tests are readily available of which this can be said? Although the Commissioners differed in their views on the strength of evidence for diagnosis and management guided by biomarkers, particularly in children, there was a consensus that the incorporation of biomarkers into the diagnosis could only enhance the capacity to diagnose asthma responsive to ICS and lead to a paradigm shift from the current approach to diagnose the umbrella term asthma, to the diagnosis of asthma phenotypes that respond to specific treatments. New drug development Until recently we have not seen the developments in new drug discovery enjoyed by other specialty areas (table 2) 19. This area perhaps exposes the limitations of our current view of 'asthma' and airway disease most obviously. New asthma treatments are largely variants on the old; a browner inhaler, with more potent topical effects, despite increasing concerns about topical immunosuppression 103. When new treatments become available, they are widely prescribed to all comers despite being largely ineffective (Sodium Cromoglycate, Ketotifen) or effective only in subgroups of patients (Omalizumab, Mepolizumab). There has been, until recently, no concept of targeted treatment. Progress in new drug discovery has been slow, with relatively few molecules progressing from the laboratory to the clinic and a depressingly high rate of failure at the later stages of clinical development (table 2) 19. Mepolizumab, a humanised monoclonal antibody that was developed to inhibit eosinophilic airway inflammation by blocking interleukin (IL)-5, is a good example. Mepolizumab was found to be safe and effective at blocking IL-5 and reducing eosinophilic airway inflammation when tested with in vitro systems and in vivo models 104,105. A subsequent clinical trial was designed based around incorporating Mepolizumab into a step-up guideline-based paradigm 106. Within this paradigm, Mepolizumab was investigated in patients who remained symptomatic on current ICS therapy and the clinical trial focused on lung function and asthma symptoms as traditional outcome measures. Despite adequate power, this trial was unexpectedly negative. This led to much soul-searching and the near-abandonment of the drug 107. Investigators who were experienced with non-invasive measures of airway inflammation identified two important problems with this initial clinical trial: first, the heterogeneity of airway inflammation in severe asthma meant that a significant number of the trial participants would not have had eosinophilic airway inflammation and therefore would not be expected to respond; and second, the
In the setting of a child suspected of having OSA, a positive nocturnal oximetry trend graph has at least a 97% positive predictive value. Oximetry could: 1) be the definitive diagnostic test for straightforward OSA attributable to adenotonsillar hypertrophy in children older than 12 months of age, or 2) quickly and inexpensively identify children with a history suggesting sleep-disordered breathing who would require PSG to elucidate the type and severity. A negative oximetry result cannot be used to rule out OSA.
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