S. Ranganathan

Pulmonary infection and inflammation in infancy is associated with reduced spirometry at school-age in children with cystic fibrosis (CF)

Background : The current guidelines for acceptable levels of ambient PM ( Methods : The PM fraction was extracted from surface soil samples from 4 communities across Western Australia. BALB/c 10 mice were intranasally exposed to 100 µg of PM . Control mice received 100 µg of polystyrene beads (2.5 µm) or vehicle 10 alone. Mice were assessed for inflammation (cellular influx, MIP-2, IL-6 and IL-1β), lung volume (plethysmography) and lung mechanics (forced oscillation technique) 6, 24 or 168 hours post-exposure. The physical and chemical characteristics of the particles were assessed by cascade impactor and ICP-MS/OES respectively. Principal component analysis of the outcome measures were used to construct lung impairment scores. Multivariate linear regression models were then used to identify the characteristics of the particles driving the lung responses. Results : Exposure to geogenic particles caused an acute inflammatory response (6 hours post-exposure), an acute impairment in lung mechanics (24 hours post-exposure) and a long term deficit in lung volume (168 hours post-exposure). Both the inflammatory response and long term deficits in lung volume were associated with the concentration of Fe and variability in particle size (GSD) while the impairment in lung mechanics was associated with Fe and particle size (MMAD). Conclusions : Despite the complex physico-chemical characteristics of geogenic dusts we were able to identify the concentration of Fe and physical dimensions of the particles as the key drivers of lung responses. Using these data we may be able to predict which communities are at greatest risk of adverse respiratory health due to high geogenic particle loads.

Pulmonary infection in infants with cystic fibrosis (CF) leads to progressive ventilation inhomogenities

Background : The current guidelines for acceptable levels of ambient PM ( Methods : The PM fraction was extracted from surface soil samples from 4 communities across Western Australia. BALB/c 10 mice were intranasally exposed to 100 µg of PM . Control mice received 100 µg of polystyrene beads (2.5 µm) or vehicle 10 alone. Mice were assessed for inflammation (cellular influx, MIP-2, IL-6 and IL-1β), lung volume (plethysmography) and lung mechanics (forced oscillation technique) 6, 24 or 168 hours post-exposure. The physical and chemical characteristics of the particles were assessed by cascade impactor and ICP-MS/OES respectively. Principal component analysis of the outcome measures were used to construct lung impairment scores. Multivariate linear regression models were then used to identify the characteristics of the particles driving the lung responses. Results : Exposure to geogenic particles caused an acute inflammatory response (6 hours post-exposure), an acute impairment in lung mechanics (24 hours post-exposure) and a long term deficit in lung volume (168 hours post-exposure). Both the inflammatory response and long term deficits in lung volume were associated with the concentration of Fe and variability in particle size (GSD) while the impairment in lung mechanics was associated with Fe and particle size (MMAD). Conclusions : Despite the complex physico-chemical characteristics of geogenic dusts we were able to identify the concentration of Fe and physical dimensions of the particles as the key drivers of lung responses. Using these data we may be able to predict which communities are at greatest risk of adverse respiratory health due to high geogenic particle loads.

Optimal lung function tests for monitoring cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheezing in children less than 6 years of age

Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.