Abstract
IntroductionTIMP3 expression in the lung increases with age and in ILD. TIMP3 binds extracellular matrix (ECM) where it influences cellular behaviour both via inhibition of MMPs and unique functions including...
Highlights
Most inflammatory diseases demonstrate diurnal variation in severity, for example, chronic obstructive pulmonary disease (COPD) and asthma
For the first time we reveal that the inflammatory response is dependent on clock phase, exemplified by altered IL-6 LPS
The analysis revealed a novel mechanism of action, reverse cholesterol transport, previously implicated in pulmonary inflammation
Summary
About a third of all children wheeze (Martinez, NEJM 1995), yet only half will develop asthma (Morgan, AJRCCM 2005). We know that increased reticular basement membrane (RBM) thickness, a feature of airway remodelling in older children with asthma, develops at 2e3 years of age in preschool severe recurrent wheezers (Saglani, AJRCCM 2007) but unlike older children (Regamey, AJRCCM 2008) nothing is known about any changes in airway smooth muscle (ASM) at pre-school age. Hypothesis There is increased ASM and ASM infiltration by mast cells in preschool children. A subgroup of children (n1⁄433) had sections stained for mast cell tryptase. Conclusion Severe preschool wheezers have evidence of increased RBM thickness, but not increased ASM compared to age-matched non-wheezing controls.
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