March 30, 2022
Pneumonia remains one of the most significant public health problems, with even more prominence in the ongoing COVID-19 pandemic. Its impact on the health care system includes increased outpatient and emergency room visits, hospitalization rates, organ support, intensive care need, post-hospitalization risk, and mortality.
Outcomes have improved in recent decades due in part to the following innovations:
- Earlier antimicrobial treatment
- Improved organ support
- Prevention of iatrogenic lung injury from lung-injurious ventilator practices
However, the impact of pneumonia and acute respiratory distress syndrome (ARDS), a related severe complication, on patient outcomes remains substantial.
"Strategies to maximize the best outcomes are needed urgently," says Yewande E. Odeyemi, M.B.B.S., Pulmonary and Critical Care Medicine, at Mayo Clinic in Rochester, Minnesota.
Anti-inflammatory therapy
Dr. Odeyemi explains: "The use of adjunct anti-inflammatory therapy to potentially improve outcomes has been the most explored strategy. Inflammation is a hallmark pathologic feature of pneumonia regardless of the underlying infectious pathogen. The increased concentrations of pro-inflammatory mediators have been associated with increased need for respiratory support and mortality in patients with community-acquired pneumonia, including COVID-19 pneumonia.
"Unfortunately, early antimicrobial therapy alone, when available, falls short in curbing exaggerated local and systemic inflammation, leading to disease progression with multiorgan involvement and worse outcomes. This result has prompted multiple scientific investigations into the role of specific anti-inflammatory treatment strategies. Corticosteroids are by far the most often studied."
Adjunctive corticosteroid treatment
Dr. Odeyemi continues: "Despite multiple studies over the last three decades, the use of adjunctive corticosteroid treatment to curb excessive inflammation in pneumonia remains controversial and undefined, with four key knowledge gaps: optimal patient selection, optimal timing, optimal dosing regimen and duration.
"The decision to use adjunctive corticosteroid treatment in clinical practice is based on either the clinician's decision or the presence of coexisting conditions such as chronic obstructive pulmonary disease and shock, and more recently a 'one-size-fits-all' recommendation for patients with COVID-19. Corticosteroid use has been variable in both clinical practice and trials, with arbitrary dosing regimens irrespective of individual patient characteristics and degree of inflammation.
"Past randomized clinical trials with significant heterogeneity have suggested possible beneficial effects of corticosteroid use on the need for mechanical ventilation, hospital stay and progression to ARDS. In those past trials, reduction in mortality was most pronounced in patients with severe pneumonia, as defined by multiple criteria, including the pneumonia severity index, CURB -65, the Infectious Diseases Society of America and American Thoracic Society criteria without consideration for markers of inflammation. A study using C-reactive protein (CRP) alone as an enrichment strategy, published in JAMA in 2015, did observe decreased treatment failure rates in the corticosteroid arm.
"More recently, corticosteroid use in pneumonia has been associated with improved clinical outcomes, including decreased mortality in patients with SARS-CoV-2 infection and acute hypoxemic respiratory failure, specifically when given early (within 48 hours) and in a subset of patients with elevated inflammatory markers. This research was published in the Journal of Hospital Medicine in 2020.
"These beneficial effects of corticosteroids are likely mediated by their anti-inflammatory effects, but inflammatory markers are not routinely used to guide initiation, dosing and duration of corticosteroids. Rather, severity of hypoxemia is used as a surrogate for inflammation in lieu of any measurement of an individual's inflammatory response. This approach introduces substantial imprecision from patient to patient, with some patients receiving a greater than necessary corticosteroid dose or duration and others potentially receiving inadequate therapy.
"This imprecision presents an opportunity to see how corticosteroid administration in pneumonia can be optimized and tailored to patient-specific characteristics, leading to an efficient use of corticosteroids with a higher likelihood of clinical success and decreased steroid adverse effects."
Biomarker-guided dosing
To address these knowledge gaps, an individualized, biomarker-guided corticosteroid dosing approach using C-reactive protein (CRP) was recently evaluated in hospitalized patients with COVID-19 pneumonia and acute hypoxemic respiratory failure in a pilot randomized controlled trial at Mayo Clinic in Minnesota. Study results were published in Critical Care in 2022.
"This novel approach of corticosteroid dosing was found to be feasible, safe and with potential clinical benefits, including lower cumulative corticosteroid exposure and shorter duration of oxygen supplementation and hospital length of stay, compared with usual care that included a fixed dose of corticosteroid," says Dr. Odeyemi. "CRP was the preferred biomarker as it is relatively inexpensive, is readily available and has a quick turnaround time for results compared with other molecular inflammatory markers."
Dr. Odeyemi and fellow researchers hope to inform future clinical trials evaluating corticosteroid use in community-acquired pneumonia, regardless of the infectious pathogen, by identifying the following:
- Patients at high risk of clinical deterioration (prognostic enrichment)
- Steroid responsive phenotypes (predictive enrichment)
"These novel strategies that consider patient-specific variables, including markers of inflammation, will potentially result in an individualized approach to corticosteroid use in community-acquired pneumonia," Dr. Odeyemi concludes.
For more information
Torres A, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA. 2015;313:677.
Keller MJ, et al. Effect of systemic glucocorticoids on mortality or mechanical ventilation in patients with COVID-19. Journal of Hospital Medicine. 2020;15:489.
Odeyemi YE, et al. Early, biomarker-guided steroid dosing in COVID-19 pneumonia: A pilot randomized controlled trial. Critical Care. 2022;26:9.
Refer a patient to Mayo Clinic.