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Abstract

Dutch investigators identified patients with difficult-to-treat asthma and followed them for 5 to 6 years to identify risk factors for accelerated decline in FEV1 (IH van Veen. Eur Respir J 2008;32:344-8). Patients who at baseline had a high fractional exhaled nitric oxide were at risk for increased loss of lung function, particularly if they had normal pulmonary function at baseline. This suggested that those patients with difficult-to-treat asthma who have greater airway inflammation are most likely to experience accelerated decline in lung function.“High FeNO increased loss of lung function” “High FeNO increased loss of lung function” Three different genetic mutations associated with children that have invasive pyogenic bacterial disease were identified by von Bernuth and colleagues in a report in Science (2008;321:691-6). Previous reports had associated invasive pneumococcal disease in children with a lack of IL-1 receptor-associated kinase 4 (IRAK-4). The authors analyzed 9 clinical cases of children with invasive pyogenic bacterial disease who did not have IRAK-4 deficiency. These children had normal resistance to other microbial infections. The results from genetic analyses turned up 3 different mutations of the MYD88 gene: 1 deletion, 1 heterozygous missense, and 1 homozygous missense mutation. The mutations caused the children to express MyD88, a required protein for Toll-like receptor (TLR) signaling, but the protein was functionally compromised. The authors concluded that MyD88-dependent immunity provided protection from a limited number of pyogenic bacteria.We asked Dr Jean-Laurent Casanova, senior author on the paper, to comment on these findings: “I think this paper is an encouragement both to decipher the human genetic basis of pediatric infectious diseases and also to reconsider immunological theories in the light of the human model.”“MyD88 mutations cause recurrent bacterial infections” “MyD88 mutations cause recurrent bacterial infections” A new innate immune defense mechanism associated with eosinophils has been described by Yousefi et al (Nat Med 2008; Aug 10 [epub ahead of print]). The authors demonstrated that eosinophils are capable of propelled release of mitochondrial DNA and granule proteins in response to inflammatory challenge and suggested that this acted as a secondary physical barrier when the mucosal barrier is disrupted by microbial infection. This effect was observed to be reactive oxygen species–dependent and occurred in the absence of eosinophil death.We asked Dr Hans-Uwe Simon, coauthor on the paper, to comment on these findings: “Interestingly, the released mitochondrial DNA serves to bind eosinophil granule proteins in the extracellular space, and these structures exhibit antibacterial activities. Although we know that reactive oxygen species are absolutely required for DNA release and that everything happens in the absence of cell death, there are several open questions regarding the exact molecular mechanism. Moreover, it remains unclear how and which eosinophil granule proteins kill bacteria.”“Eosinophils defensively catapult their DNA” “Eosinophils defensively catapult their DNA” News items are written by Sherri Gabbert, PhD.