Hydrochlorothiazide induced pulmonary oedema and alveolar epithelial ion transport

Abstract

Solar et al. reported on a case of hydrochlorothiazide induce pulmonary oedema [1]. In the discussion, like authors of previous case reports [2], they speculated about immunological factors involved in its pathogenesis without explaining how they could induce pulmonary oedema. A much more obvious mechanism of pulmonary oedema induction by this drug not taken into account in previous discussions is its direct effect on pulmonary epithelial ion and associated fluid transport. Over the last decade it has emerged that in non-cardiogenic pulmonary oedema a disturbance of pulmonary epithelial sodium and chloride transport is a very important aetiological factor [3]. We have recently established that a systemic reduction of epithelial sodium and chloride transport is strongly associated with pulmonary oedema in meningococcal septicaemia [4]. Hydrochlorothiazide is an inhibitor of the Na–K–2Cl cotransporter, which transports sodium and chloride across the basolateral membrane of airway epithelial cells [5,6]. In spheres of human airway epithelial cells hydrochlorothiazide reduced amiloride insensitive fluid absorption significantly [7]. It was found to inhibit amiloride insensitive sodium absorption in airway epithelial cells in another experiment [8]. These experiments have shown that hydrochlorothiazide affects respiratory epithelial ion and fluid transport directly without a requirement for immunological mechanisms. Future research needs to investigate why