A host transcriptomic signature to identify patients with lower respiratory tract infection undergoing bronchoalveolar lavage – The PAX study

Introduction Pulmonary infections are escalating worldwide, and represent a significant proportion of total infections. Currently, there is no reliable reference standard to diagnose bacterial lower respiratory tract infection (LRTI), which poses an enormous challenge for clinical diagnosis and treatment. We prospectively explored the association between clinical presentation, microbiology and a blood-based 29 mRNA host-response test in patients with suspicion of LRTI.

Methods The PAX study is a prospective, single-centre observational study involving 600 cases with suspicion of LRTI who underwent bronchoscopy with bronchoalveolar lavage (BAL). This entails an interim analysis of 145 cases. A board of three specialists (pneumologists/infectious disease specialists) adjudicated each case by assessing a standardized, comprehensive data file including all clinical, laboratory, radiological and microbiological information. Blood and BAL fluid were analyzed for 29 mRNA host- response using InSep™ (Inflammatix, California, USA). Strict definitions for very likely, possible, unlikely and very unlikely bacterial and viral infections were provided to the adjudicators. BAL was analysed by both conventional and molecular microbiological methods. Follow-up extended for 30 days after bronchoscopy.

Results The average age of the subjects was 66±15 years with 52% immunocompromised (stem cell- and solid organ- transplantation). Clinical presentation but not microbiological methods was significantly differentiated across the categories assessing probability of bacterial infection using the mRNA signatures (p=0.036 and p=0.079). Not only clinical variables (CURB, CRP, previous antibiotic exposure) but also outcomes (length of hospital stay) differed between the categories very likely/possible and very unlikely/unlikely as assessed by both clinical presentation and mRNA. Except for CRP and WCC, neither clinical variables nor outcomes were differentiated by microbiology.

Conclusion/Discussion There is an association between clinical judgement and an inflammatory host-response test for bacterial infections. Clinical presentation, microbiology and mRNA host-response may be complementary aspects to inform about the likelihood of an infection. Peculiarities of the host (e. g. immunosuppression, colonization) may need to be considered when weighing the importance of each aspect. The analysis of the entire cohort will allow for robust inferences.

Publication History

Article published online:
17 February 2022