Inflammatory and microbiological associations with near-fatal asthma requiring extracorporeal membrane oxygenation

Patel, Sunil; Shah, Neeraj M.; Malhotra, Akanksha M.; Lockie, Christopher; Camporota, Luigi; Barrett, Nicholas; Kent, Brian D.; Jackson, David J.

These findings may suggest the possibility of complex inflammatory cascades that lead to lung injury, refractory hypercapnic respiratory failure and failure of mechanical ventilation. From review of the clinical notes, ECMO was indicated in all cases due to maximal mechanical ventilatory support being reached or deemed extremely detrimental to the individual (i.e. leading to ventilator-induced lung injury) rather than overwhelming infection. Despite this finding, all patients received empirical antibacterial and/or targeted anti-influenza treatment (if confirmed as positive or deemed high risk) on admission to hospital before antimicrobial regimes were rationalised based on positive isolates, a practice that is common when respiratory/ventilatory failure is unexplained or deteriorating. Single-site positive isolates of Candida species were not treated. There were no cases of fungaemia and antifungal therapy was only started in the presence of raised peripheral blood markers (i.e. β-D-glucan) or high index of suspicion of fungal infection. All patients with BAL isolates of Aspergillus species were treated. In addition, we did not collect data relating to prehospital use of antimicrobial therapy. Studies have shown that virally mediated inflammatory pathways (acute or quiescent) are implicated in near-fatal asthma and occur in as much as 50% of patients [3] . The association of fungal isolates with near-fatal asthma is a novel finding but consistent with the association of these organisms in acute asthma [4, 5] . This finding suggests the possibility of defective antifungal and/or antiviral immune pathways in these patients. Rhinovirus is well recognised as a trigger for acute asthma, and deficient antiviral type 1 and 3 interferons has been reported in asthma [6] [7] [8] .