Almost 10% of patients with acute respiratory distress syndrome (ARDS) have no known ARDS risk factor at the time of diagnosis. To begin targeted treatment, the aetiology of ARDS must be identified as soon as possible. The goal of this study is to identify the most common uncommon causes of ARDS and offer doctors a practical diagnostic workup. Recent epidemiological data have suggested the identification of a subset of ARDS patients who have not been exposed to prevalent risk factors. These are classified as immune-mediated, drug-induced, malignant, or idiopathic illnesses. 

In most cases, a standardised diagnostic workup that includes chest imaging, objective assessment of left-heart filling pressures, bronchoalveolar lavage fluid microbiological investigations and cytologic analysis, immunologic tests, and a search for pneumotoxic drugs may allow for the identification of the cause of ARDS. In other situations, an open-lung biopsy should be explored.