TY - GEN
T1 - Early diagnosis of Community-Acquired Pneumonia in the Emergency Department: Imaging and Biomarkers
AU - Heltborg, Anne
PY - 2024/9/2
Y1 - 2024/9/2
N2 - BackgroundThis thesis addresses the early diagnosis of community-acquired pneumonia in emergency departments. The background is an increasing prevalence of
antibiotic-resistant bacteria, which pose a significant global health threat. There
is a need to rationalise antibiotic consumption in hospitals in order to support
efforts to combat antibiotic resistance.Community-acquired pneumonia is the most common infection requiring
hospitalisation. However, correct identification of patients with pneumonia can be
challenging because symptoms and findings are non-specific and can be atypical.
Chest X-rays are the most commonly used diagnostic imaging tool to confirm the
disease; however, chest X-rays have low sensitivity for pneumonia, and the imaging quality is poor in supine patients. More rational antibiotic consumption requires more accurate diagnostics.Ultralow-dose CT of the thorax is a safe and more precise alternative to
chest X-rays and has the potential to improve the radiological diagnosis of community-acquired pneumonia. However, the interpretation of CT scans requires
expertise in radiology, which is not always available in the emergency department.Blood markers for systemic inflammation are not considered central in
pneumonia diagnostics but are often used as guidance. C-reactive protein (CRP)
is most commonly used, but its utility is limited by low specificity and a delayed
response time. No tissue-specific blood biomarkers to reflect acute lung injury are
in use.This thesis describes three clinical studies with the following aims:
1) To evaluate the diagnostic accuracy of emergency department physicians’ interpretations of ultralow-dose CTs of the chest for pneumonic
changes.
2) To evaluate the diagnostic accuracy of the lung injury markers SP-D,
KL-6, and CC16 in distinguishing between pneumonia and non-pneumonia in patients suspected of having community-acquired pneumonia.
3) To evaluate the diagnostic accuracy of the inflammatory biomarkers
CRP, PCT, IL-6, suPAR, and YKL-40, and to develop a diagnostic model
based on these biomarkers and symptom duration for patients suspected of having community-acquired pneumonia. Methods
All studies were designed as diagnostic cross-sectional studies. Patients
with an initial clinical suspicion of community-acquired pneumonia were included
in the emergency departments of three Danish hospitals. The participants underwent ultra-low-dose CT of the thorax and had additional blood samples taken to
investigate the study biomarkers. Ten doctors from the emergency departments assessed 128 ultra-low-dose
CT scans after completing a focused, interactive course on identifying changes
compatible with pneumonia on ultralow-dose CT. The reference standard was a
radiologist's assessment of the same scans.The biomarker values were compared with the patients' final diagnoses,
which were assigned by two medical experts through a medical chart review.The primary outcome measures were diagnostic accuracy estimates in the
form of sensitivity, specificity, positive/negative predictive values (PPV/NPV), and
area under the curve (AUC). For the inflammatory markers, we investigated their
combined diagnostic value by developing a classification tree. Results
We included 411 patients suspected of community-acquired pneumonia,
which was the final diagnosis in 58% of the cases.The physicians’ overall accuracy in assessing ultralow-dose CT for pneumonia was: sensitivity=83%, specificity=70%, PPV=80%, NPV=78%. The lung injury markers revealed no ability to distinguish between patients
with and without pneumonia, with AUC’s ranging from 0.50 to 0.55.None of the investigated inflammatory biomarkers were effective in diagnosing CAP. The diagnostic performance of the classification tree did not differ
from the performance of IL-6 and CRP alone, and they were effective at differentiating patients without and without infection (AUC=0.86 and 0.88, respectively). Conclusions
The results indicate that emergency department physicians with limited
training can assess ultralow-dose CT for pneumonic changes with good accuracy. None of the investigated biomarkers can be used to diagnose pneumonia
with satisfactory accuracy. IL-6 and CRP have the potential to support the diagnosis of patients suspected of pneumonia by differentiating between infected and
non-infected patients. Further studies are needed to assess the impact of ultralow-dose CT, CRP, and IL-6 on antibiotic prescriptions in emergency departments.
AB - BackgroundThis thesis addresses the early diagnosis of community-acquired pneumonia in emergency departments. The background is an increasing prevalence of
antibiotic-resistant bacteria, which pose a significant global health threat. There
is a need to rationalise antibiotic consumption in hospitals in order to support
efforts to combat antibiotic resistance.Community-acquired pneumonia is the most common infection requiring
hospitalisation. However, correct identification of patients with pneumonia can be
challenging because symptoms and findings are non-specific and can be atypical.
Chest X-rays are the most commonly used diagnostic imaging tool to confirm the
disease; however, chest X-rays have low sensitivity for pneumonia, and the imaging quality is poor in supine patients. More rational antibiotic consumption requires more accurate diagnostics.Ultralow-dose CT of the thorax is a safe and more precise alternative to
chest X-rays and has the potential to improve the radiological diagnosis of community-acquired pneumonia. However, the interpretation of CT scans requires
expertise in radiology, which is not always available in the emergency department.Blood markers for systemic inflammation are not considered central in
pneumonia diagnostics but are often used as guidance. C-reactive protein (CRP)
is most commonly used, but its utility is limited by low specificity and a delayed
response time. No tissue-specific blood biomarkers to reflect acute lung injury are
in use.This thesis describes three clinical studies with the following aims:
1) To evaluate the diagnostic accuracy of emergency department physicians’ interpretations of ultralow-dose CTs of the chest for pneumonic
changes.
2) To evaluate the diagnostic accuracy of the lung injury markers SP-D,
KL-6, and CC16 in distinguishing between pneumonia and non-pneumonia in patients suspected of having community-acquired pneumonia.
3) To evaluate the diagnostic accuracy of the inflammatory biomarkers
CRP, PCT, IL-6, suPAR, and YKL-40, and to develop a diagnostic model
based on these biomarkers and symptom duration for patients suspected of having community-acquired pneumonia. Methods
All studies were designed as diagnostic cross-sectional studies. Patients
with an initial clinical suspicion of community-acquired pneumonia were included
in the emergency departments of three Danish hospitals. The participants underwent ultra-low-dose CT of the thorax and had additional blood samples taken to
investigate the study biomarkers. Ten doctors from the emergency departments assessed 128 ultra-low-dose
CT scans after completing a focused, interactive course on identifying changes
compatible with pneumonia on ultralow-dose CT. The reference standard was a
radiologist's assessment of the same scans.The biomarker values were compared with the patients' final diagnoses,
which were assigned by two medical experts through a medical chart review.The primary outcome measures were diagnostic accuracy estimates in the
form of sensitivity, specificity, positive/negative predictive values (PPV/NPV), and
area under the curve (AUC). For the inflammatory markers, we investigated their
combined diagnostic value by developing a classification tree. Results
We included 411 patients suspected of community-acquired pneumonia,
which was the final diagnosis in 58% of the cases.The physicians’ overall accuracy in assessing ultralow-dose CT for pneumonia was: sensitivity=83%, specificity=70%, PPV=80%, NPV=78%. The lung injury markers revealed no ability to distinguish between patients
with and without pneumonia, with AUC’s ranging from 0.50 to 0.55.None of the investigated inflammatory biomarkers were effective in diagnosing CAP. The diagnostic performance of the classification tree did not differ
from the performance of IL-6 and CRP alone, and they were effective at differentiating patients without and without infection (AUC=0.86 and 0.88, respectively). Conclusions
The results indicate that emergency department physicians with limited
training can assess ultralow-dose CT for pneumonic changes with good accuracy. None of the investigated biomarkers can be used to diagnose pneumonia
with satisfactory accuracy. IL-6 and CRP have the potential to support the diagnosis of patients suspected of pneumonia by differentiating between infected and
non-infected patients. Further studies are needed to assess the impact of ultralow-dose CT, CRP, and IL-6 on antibiotic prescriptions in emergency departments.
KW - Community-acquired pneumonia
KW - Infection diagnosis
KW - Antibiotic stewardship
KW - Biomarkers
KW - Ultra-low-dose CT
KW - Emergency Medicine
U2 - 10.21996/qses-1s07
DO - 10.21996/qses-1s07
M3 - Ph.D. thesis
PB - Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet
ER -