Background Pneumonia is a major cause of mortality and morbidity, but the development of new antimicrobials is lacking. Radiological assessment of pneumonia severity may serve as an effective intermediate endpoint to reduce barriers to successful completion of antimicrobial trials. We sought to determine whether the Radiologic Severity Index (RSI) correlated with mortality and healthcare resource utilisation in patients with acute leukaemia undergoing induction chemotherapy.
Methods We measured RSI (range 0–72) on all chest radiographs performed within 33 days of induction chemotherapy in 165 haematological malignancy patients with pneumonia. Peak RSI was defined as the highest RSI score within 33 days of induction. We used extended Cox proportional hazards models to measure the association of time-varying RSI with all-cause mortality within the first 33 days after induction chemotherapy, and logistic regression or generalised models to measure the association of RSI with total daily cost and healthcare resource utilisation.
Results After adjustment for clinical variables, each one-point increase in RSI was associated with a 7% increase in all-cause 33-day mortality (HR 1.07, 95% CI 1.05 to 1.09, p<0.0001). Peak RSI values of 37.5 or higher were associated with 86% higher daily direct costs (p<0.0001), more days in intensive care unit (9.9 vs 4.8 days, p=0.001) and higher odds for mechanical ventilation (OR 12.1, p<0.0001).
Conclusions Greater radiological severity as measured by RSI was associated with increased mortality and morbidity in acute leukaemia patients with pneumonia. RSI is a promising intermediate marker of pneumonia severity and is well suited for use in antimicrobial trials.
- imaging/CT MRI etc
- respiratory infection
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Presented at This work was previously presented at the American Thoracic Society 2017 Conference.
Contributors AS, MG, SG, SEE, JB-G, RFC, BD and DO contributed to study planning and design. AS, MG, JJE, SEE, JB-G, BD and DO contributed to the conduct of the study. AS, MG, JJE, SG, AH and DO contributed to data acquisition and analysis. All authors contributed to writing the final draft of the manuscript.
Funding This study was funded by a sponsored research agreement with Pulmotect (Houston, Texas) and supported by a grant from the National Institute of Allergy and Infectious Diseases (K23 AI117024 to AS) and the National Cancer Institute (Cancer Center Support Grant, P30 CA016672, Biostatistics Resource Group) at the National Institutes of Health. The sponsor had no role in the conception, design, conduct or analysis of the study and in the preparation of the manuscript.
Competing interests SEE and BD are inventors of a technology to deliver aerosolised TLR ligands to induce resistance to microbial infection of the lungs; this technology has been licensed by MD Anderson Cancer Center to Pulmotect (Houston, Texas, USA), in which SEE and BD have ownership interests, and which has sponsored research in the laboratories of BD. RFC reports receiving research grants from Ansun Pharmaceuticals and Pulmotect.
Patient consent for publication Not required.
Ethics approval This study was approved by our Institutional Review Board with a waiver of informed consent (PA16-1091).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
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