Table 4.

Research Priorities for Community-acquired Pneumonia

	Summary of Research Priorities	Illustrative Examples
Before pneumonia (prevention)	• Evaluate systemic and pulmonary markers of host susceptibility to pneumonia	• Use imaging and biospecimens to define and differentiate mechanistic signals in “protected” individuals (e.g., young healthy humans and animal models with relevant exposures establishing lung protection) versus more “susceptible” individuals (e.g., humans at high risk for pneumonia and animal models with relevant risk factors); test if those signals calibrate pneumonia risk when measured in human populations or shift pneumonia risk when manipulated in animal models
	• Examine mechanisms that defend the lung against pneumonia, including the ability to eliminate microbes (immune resistance) and the ability to withstand injury from infection and inflammation (tissue resilience)
	• Develop and test interventions that reverse or slow the progression of increasing pneumonia susceptibility
	• Examine the effects of antecedent respiratory infections on innate immunity in the lung (e.g., alveolar macrophage phenotypes) and local immunological memory in the lung (e.g., resident memory T cells)
During pneumonia (treatment)	• Advance cross-disciplinary evaluation of host–pathogen interactions	• Identify candidate pharmacologic agents that phenocopy signaling pathways tied to protection or reverse signaling pathways tied to injury and test lead candidates in experimental systems for abilities to bolster immune killing of microbes or resilience of lung and extrapulmonary tissues
	• Collect pulmonary and nonpulmonary biospecimens in observational and interventional studies to identify biological pathways (endotypes) underlying clinical presentations of pneumonia to target interventions at mechanisms rather than clinical syndromes
	• Examine factors that influence the transition from localized infection (pneumonia) to inflammatory responses elsewhere in the lung (ARDS) or systemically (sepsis)
	• Develop and test interventions that 1) help the host to more efficiently kill microbes, 2) diminish the anatomical and physiological damage from infection and inflammation, and 3) interrupt pneumonia’s nonpulmonary sequelae (e.g., muscle wasting)
	• Leverage new technology for rapid, comprehensive pathogen identification to ensure that evaluation of pneumonia treatments occurs in the context of early and appropriate antibiotic therapy
	• Elucidate the transition from infection and inflammation to resolution and repair (e.g., the role of specialized proresolving mediators) and the implications for immunomodulatory therapy
After pneumonia (facilitating resolution and recovery)	• Examine the mechanisms linking pneumonia to long-term pulmonary sequalae (e.g., accelerated chronic respiratory disease) and nonpulmonary sequelae (e.g., cardiac and cerebrovascular events and impaired cognition)	• Identify discrete molecular, physiological, or clinical signals that discriminate patients with pneumonia who developed adverse long-term outcomes from others who did not; test those signals for prognostic value in human patients and causation in animal models
	• Incorporate noninfectious outcomes (e.g., cardiovascular events) into long-term outcomes in pneumonia research
	• Define trajectories of recovery after pneumonia, as well as the biological, clinical, and social factors that influence these trajectories

Definition of abbreviation: ARDS = acute respiratory distress syndrome.