Reducing the Effects of Air Pollution on Children With Cystic Fibrosis

Background:

Cystic fibrosis (CF) is the commonest hereditary life-shortening respiratory condition, resulting in premature death secondary to recurrent airway infections and inflammation, leading to irreversible lung damage. The screening programme in infancy has improved life expectancy but the lifespan of CF patients is still reduced by 20 years at present. Thus interventions to reduce inflammation, infection and lung damage in CF are still needed.

One potential intervention is to reduce exposure of CF children to air pollution. Particulate matter (PM) are microscopic soot particles from petrol and diesel engine emissions; PM is linked to adverse respiratory health effects in children. Children with cystic fibrosis are particularly vulnerable to PM but, to date, no exposure-reduction advice is available, and the mechanism underlying this vulnerability is unclear.

Personal exposure of CF children to PM is due to: i) locally-generated sources (relative to the proximity to busy roads) and ii) background concentrations (i.e. PM blown across the whole city from other areas). Although a link between air pollution and reduced lung function growth in healthy children is well established, the link with CF lung disease has only recently emerged. A recent study found that long-term exposure of CF children to PM increases risk of airway infection with Pseudomonas. Another study also found that short-term background pollution is associated with increased need for antibiotics in children and adults with CF. The need to reduce patients' personal exposure to PM has been recognised by Barts Health NHS Trust. Working with Global Action Plan, the Trust has developed tips on how to reduce adults' personal exposure to air pollution. These tips include traveling outside rush hours, taking low pollution routes (maps provided), and signing up to the airText air pollution warning App. Since travel outside rush hours is not feasible for school children, child-friendly tips are urgently needed.

Recent research in asthma patients suggests a putative mechanism of impaired removal of inhaled PM. In the healthy lung, inhaled PM is quickly removed (phagocytosed) by airway macrophages (AM). AM patrol the surface of epithelial cells lining the airways; after taking up PM, they move up and out of the lung. Thus AM with normal phagocytic function act to both reduce PM exposure of other airway cells - including epithelial cells, and to ensure that PM does not accumulate in the lung. The amount of carbon particles in AM was previously used to assess the effects of long-term effects of exposure of healthy children and adults. The amount of black carbon (BC) in AM reflects the intrinsic capacity of AM to remove PM (phagocytic capacity). AM carbon is significantly lower in conditions such as severe asthma, where AM phagocytic capacity is impaired. Furthermore, a role for prostaglandin E2 (PGE2) in mediating impaired phagocytic function in asthma has been identified. First, PGE2 suppresses AM phagocytosis of urban PM in vitro; and second, children with severe asthma had increased urinary PGE2 metabolites. Shift of inhaled PM away from AM to other cells has the potential to stimulate interleukin-8 (IL-8) release by epithelial cells - a phenomenon observed in mouse, where inhalation of non-inflammatory particles produces significant airway neutrophilia when AM phagocytic function is impaired.