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Letter

Reduction in airway epithelial chloride transport in septicaemia related pulmonary oedema reversible by beta agonist application

Michael Eisenhut

Author Affiliations

Paediatric Intensive Care Unit, Royal Liverpool Children's Hospital, Eaton Road, Liverpool L12 2AP, UK

Critical Care 2006, 10:412  doi:10.1186/cc4916


See related research by Manocha et al, http://ccforum.com/content/10/1/R12

Published: 15 May 2006

First paragraph (this article has no abstract)

Manocha and colleagues [1] found in a retrospective study on the association of beta-agonist use and lung injury a shorter duration and less severity of lung injury in patients on aerosolized beta-agonists. In their discussion of possible causes they and the investigators of the beta-agonist lung injury trial [2] did not comment on the effect of beta-agonist treatment on pulmonary chloride transport as an important independent determinant of pulmonary fluid clearance. It was first noted in experiments by Fang and colleagues [3] that mice with inhibited or defective cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels (delta F508 homozygous) have a reduced cAMP dependent and CFTR mediated pulmonary fluid clearance and more severe pulmonary oedema in the fluid overload pulmonary oedema model. This group then established that CFTR is present in alveolar epithelial cells and contributes independently to cAMP dependent fluid transport [4]. Other groups found that chloride channels in respiratory epithelial cells can be activated by beta agonists via an increase in intracellular cAMP [5]. We measured the nasal potential difference and the amiloride (ENaC blocker) response of the nasal respiratory epithelium, which both represent upper airway epithelial sodium transport, and the response of the nasal respiratory epithelium to a low chloride solution (CFTR stimulation), which represents chloride channel function in the upper airway of children with meningococcal septicaemia related pulmonary oedema [6]. We found that nasal potential difference and amiloride response were not different between children with and without meningococcal septicaemia related pulmonary oedema. Response of the upper airway epithelium to a low chloride solution was, however, absent in children with septicaemia related pulmonary oedema and this was significantly different to children ventilated for other forms of critical illness without pulmonary oedema. This indicated that the systemic reduction of epithelial chloride transport we found in the children with septicaemia induced pulmonary oedema, which was also reflected in increased sweat and saliva chloride levels, extended to the respiratory tract. The reduction in chloride transport seemed to be more closely related to pulmonary oedema and its severity than features of sodium transport. Topical stimulation of chloride channels in the nasal airway of the children with pulmonary oedema with the beta agonist isoprenaline resulted in activation of chloride transport. Future trials and laboratory research related to treatment of pulmonary oedema needs to take into account parameters reflecting pulmonary epithelial chloride transport as important additional explanatory outcomes.