KL2 Profile: Developing a More Precise Approach for Pneumonia
Pneumonia is the leading cause of adult hospitalization in the United States — an estimated one million people are admitted each year — and the debilitating lower respiratory tract infection represents one of the greatest lethal challenges in global health. Both community-acquired pneumonia (CAP) and hospital/ventilator-acquired pneumonia (HAP/VAP) are associated with high morbidity, healthcare expenditures, and subsequent mental and physical impairments.
Despite this notable prevalence, pneumonia is difficult to diagnose, and finding the infectious cause of pneumonia is even harder.
KL2 scholar Chiagozie Pickens, MD, MSc, has focused her research on this topic. As an assistant professor of Medicine in the Division of Pulmonary and Critical Care, Pickens is committed to the implementation of diagnostic excellence in the move toward a precision medicine approach for pneumonia. She presented her findings at a recent Department of Medicine Medical Grand Rounds event.
If the diagnostic process is not helping us manage the patient better, if it’s not informing goals of care discussions, then our efforts should be put elsewhere.”
Diagnostic excellence is achieved through the acquisition of a precise and accurate patient diagnosis. Pickens is optimistic this approach will improve the current diagnostic routine, which streamlines identification with a chest X-ray, antibiotic treatment, and general monitoring across patients. This current clinical diagnosis has garnered poor interrater reliability as the lung is particularly challenging to evaluate.
The refined case-by-case approach Pickens is exploring will instead personalize early detection and treatment with the goal of decreasing mortality. It is believed diagnostic excellence will improve care; therefore, Pickens maintains patient personalization is a process all clinicians should strive to optimize.
“If the diagnostic process is not helping us manage the patient better, if it’s not informing goals of care discussions, then our efforts should be put elsewhere. Diagnostic excellence should be efficient, timely, safe, equitable, effective, and patient centered,” Pickens says.
“The critical care community is focused on precision medicine, meaning they want to identify physiological or biological mechanisms of the patient that make it more likely for them to respond to an intervention. The goal of precision medicine is to identify unique characteristics of the patient that we can address to improve their outcome.”
Based at Northwestern, the NIH-funded Successful Clinical Response in Pneumonia Therapy (SCRIPT) team led by principal investigator Richard Wunderink aims to maximize precision medication through clinical adjudication, a standardized process for assessment of safety and efficacy of pharmacologic therapies in clinical trials.
“We adjudicate every case of pneumonia for every patient enrolled in SCRIPT and we do that by having two physicians independently review every case and take into account the clinical picture, microbiology, radiology, etc. to decide if a patient truly has pneumonia or not.”
SCRIPT has enrolled more than 700 ICU patients with a clinical suspicion of pneumonia. The systems science approach takes into account the dynamic interplay of various internal characteristics that can vary from patient-to-patient.
“We acknowledge the complex interactions between the host and the pathogens that can’t be appreciated or understood by studying the host by itself, the pathogen by itself, or the microbiome by itself. They all need to come together.”
In addition, Pickens credits culture-independent diagnostics, specifically multiplex PCR, as an avenue toward precision medication. A multiplex PCR is a pathogen identification technique where PCR is used to augment several distinct DNA sequences simultaneously; it is a high-sensitivity, fully automated approach to pneumonia detection: “The PCR panel detects bacteria viruses that are very commonly implicated in CAP. They also detect methicillin-resistant staphylococcus aureus (MRSA). Pretty consistently, PCR results led to antibiotic de-escalation in both CAP and VAP.”
The cellular analysis of bronchoalveolar lavage (BAL) fluid is a crucial biomarker leveraged to determine signs of infection. The lungs’ alveolar space generally has a greater count of BAL neutrophil in patients who were diagnosed with bacterial pneumonia.
When pneumonia is evaluated in terms of signs, symptoms, and chest X-rays fused with clinical adjudication, multiplex PCR, and analysis of the alveolar space, Pickens is confident in the medical community’s ability to determine precisely defined groups of pneumonia than can be further examined to establish mechanisms of disease and clinical trajectories.
"The diagnosis of pneumonia is challenging. However, culture-independent diagnostics, the biomarker analysis, and clinical adjudication can all improve precision when we think about diagnosing patients with pneumonia."
Written by Alex Miranda
