Identifying Bacterial Airways Infection in Stable Severe Asthma Using Oxford Nanopore Sequencing Technologies
Maisha Jabeen, Nicholas D. Sanderson, Dona Foster, Derrick W. Crook, Jennifer Cane, Catherine Borg, Clare Connolly, Samantha Thulborn, Ian Pavord, Paul Klenerman, Teresa L. Street, Timothy Hinks
Abstract
The human airways were once thought sterile in health. Now metagenomic techniques suggest bacteria may be present, but their role in asthma is not understood. Traditional culture lacks sensitivity and current sequencing techniques are limited by operational problems and limited ability to identify pathogens at species level. We optimized a new sequencing technique-Oxford Nanopore technologies (ONT)-for use on human sputum samples and compared it with existing methods. We found ONT was effective for rapidly analyzing samples and could identify bacteria at the species level. We used this to show Haemophilus influenzae was a dominant bacterium in the airways in people with severe asthma. The presence of Haemophilus was associated with a "neutrophilic" form of asthma - a subgroup for which we currently lack specific treatments. Therefore, this technique could be used to target chronic antibiotic therapy and in research to characterize the full breadth of bacteria in the airways.