Acquired cystic fibrosis transmembrane conductance regulator dysfunction.

Rhinorrhoea associated with viral upper respiratory tract infections or reactions to aeroallergens affects all human beings and has been associated with loss of quality of life. Pulmonary fluid accumulation in acute lung injury is a leading cause of hospital admission and death from lower respiratory tract infection and sepsis. In this review, the evidence is presented supporting the hypothesis that both rhinorrhoea and inflammation-related pulmonary fluid accumulation are primarily due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). Novel concepts of the mechanisms involved are introduced. Upper airway as well as alveolar surface liquid volumes have been shown to be dependent on the function of the CFTR. Its function is regulated directly by cytokines and through increased hydrostatic tissue pressure secondary to vasodilatation in allergic inflammation and infection. Regulation of upper airway fluid secretion manifested in allergic inflammation and viral infections can be explained by CFTR activation through vasodilatation mediated by bradykinin and histamine, and CFTR upregulation by interleukin-4. Alveolar fluid accumulation is related to inactivation of CFTR through microRNA derived from genomic cytokine effects including interleukin-1, interleukin-8, transforming growth factor, and tumour necrosis factor. The role of concomitant sodium-potassium ATPase inhibition is explained. Therapeutic interventions including already known CFTR inhibitors for excessive fluid secretion in the upper respiratory tract and remedies for inflammation-induced fluid accumulation in the lower respiratory tract due to CFTR dysfunction using anti-inflammatory and CFTR activating agents are introduced.