• Aude Gibelin, Antoine Parrot, Muriel Fartoukh, and Nicolas de Prost.
• Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Réanimation médico-chirurgicale, Pôle Thorax Voies aériennes, Groupe hospitalier des Hôpitaux Universitaires de l'Est Parisien.
• Curr Opin Crit Care. 2019 Feb 1; 25 (1): 29-36.

Purpose Of ReviewA prompt identification of the cause of acute respiratory failure (ARF)/acute respiratory distress syndrome (ARDS) is required in order to initiate a targeted treatment. Yet, almost 10% of ARDS patients have no identified ARDS risk factor at ARDS diagnosis. Numerous rare causes of ARF have been reported in this setting. The purpose of this review is to delineate the main rare causes of ARF/ARDS and to provide clinicians with a pragmatic diagnostic work-up.Recent FindingsRecent epidemiological data have proposed the identification of a subgroup of ARDS patients lacking exposure to common risk factors. These can be categorized as having immune, drug-induced, malignant and idiopathic diseases. A standardized diagnostic work-up including chest imaging, the objective assessment of left heart filling pressures, bronchoalveolar lavage fluid microbiological investigations and cytological analysis, immunological tests and search for pneumotoxic drugs may allow for identifying the cause of ARF in most cases. Open lung biopsy should be considered in other cases.SummaryA prompt identification of the cause of ARF is required to initiate a targeted treatment. Patients with no identified ARDS risk factor should undergo a comprehensive and hierarchized diagnostic work-up.

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