Journal CHEST®
Predicting Clinical Response to Benralizumab Using CT Imaging
By Arnaud Bourdin, MD, PhD
Could lung or sinus CT scan characteristics help predict a patient’s response to an asthma biologic? The prospective, two-center, open-label BenraliScan study explored a novel set of potential biomarkers for biologic selection: pretreatment chest and sinus CT scan findings. Investigators followed 47 patients with severe eosinophilic asthma for 52 weeks after starting benralizumab. Baseline spirometrically gated chest CT scan and sinus CT scan measures were evaluated against treatment response.
Most participants (42 of 47) achieved at least a 50% reduction in exacerbations, leaving too few nonresponders to identify predictors of that outcome alone. However, baseline parametric response mapping of small-airways disease (PRM-SAD) and Lund-Mackay sinus scores predicted a broader composite response better than blood eosinophil counts. Composite responders met at least two of three criteria: a 50% reduction in exacerbations, an FEV₁ increase greater than 300 mL, and an ACQ-5 improvement greater than 0.5 points. Responders generally had less CT-defined small-airways disease but greater sinus involvement.
Spirometrically gated CT scan and advanced CT-derived metrics are not yet widely available in clinical practice, and these findings require validation in larger cohorts. Still, this study offers an intriguing glimpse of a more precise approach to biologic selection informed by objective, noninvasive measures of disease across both the upper and lower airways, rather than expert opinion alone.
Commentary by Megan Conroy, MD, MAEd, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Critical Care
A Clinically Actionable Risk Score for Ventilator-Associated Pneumonia Using Interpretable Machine Learning
By Yeleen Fromage, PharmD, and colleagues
This machine learning study used data from a cohort of more than 3,500 European adult patients who were intubated and mechanically ventilated. Authors developed a ventilator-associated pneumonia (VAP) risk score that stratified patients; those with the highest risk had a positive predictive value for VAP of up to 61.5%. The diagnosis of VAP can be difficult in critically ill patients who are intubated, and the work represents a step forward in leveraging machine learning strategies as diagnostic aids.
As with all nonclinician-driven diagnostic tools, this approach still requires clinical validation, particularly regarding its impact on appropriate antibiotic utilization, duration of mechanical ventilation, and ICU length of stay.
Commentary by Yuri Matusov, MD, FCCP, Member of the CHEST Physician Editorial Board
CHEST® Pulmonary
Clinical Evaluation of Omadacycline for Pulmonary Mycobacterium abscessus Complex Infections
By Mohammed Al Musawa, PharmD, MPH, and colleagues
Treatment options for Mycobacterium abscessus complex (MABC), the second most common pathogenic driver of nontuberculous mycobacteria-related pulmonary disease, remain limited by intrinsic antimicrobial resistance and a paucity of validating studies supporting newer therapies. To evaluate the safety and efficacy of omadacycline (OMC), a tetracycline-class antibiotic, Musawa and colleagues conducted a multicenter retrospective study of 35 adults treated with OMC for confirmed MABC pulmonary disease.
Clinical success—defined as the absence of microbiologic recurrence, clinical improvement, continued OMC therapy, and survival—was observed in 71.4% (25 of 35) of participants at three months, 89.7% (26 of 29) of participants at six months, and 90.9% (20 of 22) of participants at 12 months. Adverse drug reactions led to treatment discontinuation in 22.9% (8 of 35) of participants. These results provide encouraging early evidence supporting OMC as a potential treatment option for MABC pulmonary disease; however, larger prospective trials are needed to better define its safety and long-term efficacy.
Commentary by Michael Marll, MD, Member of the CHEST Physician Editorial Board
