Successful cooperation of three networks.
Improving the clinical management of CAP and its complications
Community-acquired pneumonia (CAP) can have a highly variable course. About 80 % of patients develop without complications. However, more severe infections can progress to septic shock. Predicting the individual course of the disease can be nearly impossible. This could change through the identification of new biomarkers, which, according to the researchers’ opinion, could enable more targeted diagnostics and therapy. The research network PROGRESS focuses precisely on this question – with success, as numerous publicationsPROGRESS Publications show. Through the targeted use of biomarkers and signatures, it should become easier for physicians to prescribe therapy tailored to the patient’s individual risk. PROGRESS-KOMORB now also considers patients with comorbidities and immunosuppression.
PROGRESS is a research project born of the collaborative activity of three networks which were funded by the German Federal Ministry of Education and Research (BMBF). A crucial contribution comes from CAPNETZ study data. CAPNETZ is closely associated with PROGRESS in its goals, supported by the Competence Network Sepsis and the NGFN (National Genome Research Network Infection and Inflammation). PROGRESS was also funded by the BMBF as part of the “Health Research: Research for People” program.
Search for typical signatures and markers of the transition
The goals of PROGRESS are clearly defined: transcriptome- and proteome-based “signatures” as well as biomarkers and genetic polymorphisms associated with pneumonia, whether acquired in an outpatient or inpatient setting, are to be identified. Of particular interest are markers of the transition from uncomplicated pneumonia to severe pneumonia and ultimately to pneumonia with an increased risk of sepsis. PROGRESS links well-defined clinical phenotypes with data on DNA, RNA, and proteins obtained from peripheral blood using high-throughput methods. This allows molecular disease characteristics to be related to clinical aspects of the infection, enabling the identification of typical signatures, so-called “fingerprints.”
“The PROGRESS consortium aims to identify clinical, genetic, and other molecular markers and combinations that can predict a severe course of CAP in the hospital. Such predictors will support decisions regarding more intensive monitoring or earlier transfer of patients to the intensive care unit,” says study leader Professor Dr. Norbert Suttorp, Charité University Medicine. This is being done in the PROGRESS-CAP cohort, which includes more than 2,000 CAP patients.
Pathophysiological processes of pneumonia
The cross-sectional analysis of such signatures in patients with and without disease progression should enable the development of risk factor models for predicting a severe disease course. The analysis of changes in molecular markers also expands the urgently needed knowledge about the pathophysiology of different forms of pneumonia. Ultimately, the patient also benefits from improved diagnostics, risk stratification, therapy, and therefore a more favourable prognosis. Decision-making is optimised, leading to better care for often severely ill patients.
Practical relevance: Consideration of severe pre-existing conditions
The risk of complications, septic shock, ARDS, or mortality for each individual CAP patient depends on various factors, including the pathogenicity of the pathogen, individual immunity, immunosenescence, and comorbidities. Cardiovascular comorbidities such as CAD (chronic atherosclerotic disease), CHF (chronic heart failure), or renal insufficiency are relevant in this context. More detailed information will now be provided by PROGRESS-KOMORB (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis). This is a prospective, longitudinal, multicentre case-cohort study that includes CAP patients with severe pre-existing conditions and immunosuppression, with at least 300 evaluable patients so far. Only on the basis of such results is clinical applicability possible. “Only then can the results of the PROGRESS-CAP study be implemented in clinical practice,” says Prof Suttorp.
The inclusion criteria are strict:
- Hospital admission with CAP
- Age ≥ 18 years
- Valid informed consent available
At the time of inclusion, the definition of CAP must meet the following four points:
- Clinical diagnosis of CAP by the enrolling physician
- No other hospital admission within the last 28 days before hospitalization with CAP
- Clinical findings for CAP (At least 2 of the following 5 criteria must be met):
- Purulent secretion from the lower respiratory tract
- Auscultatory findings (crackles and/or other signs of pulmonary infiltration (dullness to percussion, bronchial breathing))
- Shortness of breath or the need for ventilation (Shortness of breath: newly onset dyspnea, tachypnea, or hypoxemia)
- Fever (≥ 38.3°C rectal, intravesical, or intravascular OR ≥ 37.8°C oral or auricular/tympanic)
- Pulmonary infiltrate on imaging
In addition, at least one of the following criteria must be met before hospitalization:
- HIV positive
- Tumor disease with therapy within the last 6 months
- Steroid therapy (≥ 20 mg prednisolone equivalent/day for more than 14 days before inclusion)
- Non-steroidal immunosuppressive therapy within the last 6 months
- Cytostatic therapy in the last 6 months
- Radiation therapy in the last 6 months
- Bone marrow transplantation
- Home mechanical ventilation via tracheostomy
- Cystic fibrosis
- Heart failure NYHA-IV or HFrEF (defined as left ventricular ejection fraction <40%)
- Liver failure Child-C
- Diabetes mellitus with HbA1c ≥ 8.5%
- Terminal kidney failure requiring dialysis
- Pulmonary hypertension (all classes) with mPAP > 20 mm Hg (right heart catheter)