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This study found low tissue levels of the fatty acid docosahexaenoic acid (DA) and a raised ratio of arachidonic acid (AA) to DA in patients with cystic fibrosis (CF) compared with healthy controls in nasal and rectal biopsy specimens (p<0.001 and p = 0.009 for the ratios, respectively). In cells from nasal scrapings the AA:DA ratio was also significantly higher in subjects with CF than in controls (p<0.001), with CF carriers showing intermediate levels between the two (p<0.001). Intermediate levels similar to CF carriers were observed in patients with asthma or acute upper respiratory tract infections (UTRI), but lower levels were observed in those with inflammatory bowel disease. The findings in CF were independent of pancreatic sufficiency status. No difference between plasma levels of two essential amino acids, linoleic acid and eicosatrienoic acid, or AA were noted between CF patients, carriers, and healthy controls. The authors suggest that the imbalance may be a result of cystic fibrosis transmembrane conductance regulator gene expression in these tissues rather than a consequence of malabsorption, although “intermediate” levels in those with asthma or an URTI suggest that other factors are involved. Fatty acids such as DA can be converted into potent anti-inflammatory mediators and the low levels observed in this study may lead to the excessive inflammatory response observed in CF.
This study confirms a tissue abnormality of fatty acid metabolism in CF, previously only demonstrated in CF knockout mice. Correction of this imbalance could be a potential treatment target in CF.
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