Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05701605 |
| Other study ID # |
Pneumonia biomarkers |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2023 |
| Est. completion date |
June 1, 2024 |
Study information
| Verified date |
January 2023 |
| Source |
Assiut University |
| Contact |
Nahla Sameh |
| Phone |
01096362551 |
| Email |
nahlasameh8115[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The current work aims to:
1. Measure the levels of Neutrophil CD64 Receptor, Monocyte Human Leukocyte Antigen-DR
(mHLA-DR), and Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) in children
suffering from pneumonia.
2. Compare these levels to their levels in healthy control children.
3. Analyze the cut-off point, sensitivity, specificity, and area under the ROC curve of
these biomarkers to test their abilities to early differentiate children with pneumonia
from healthy control children.
4. Conclude or reject their possible use as diagnostic and/or prognostic markers in
pediatric pneumonia.
Description:
Pneumonia is the world's leading infectious cause of mortality. It is one of the most common
lower respiratory tract infections, which contributes significantly to the burden of
antibiotic use. Because of the complexity of the pathophysiology, pneumonia is widely
recognized that the clinical diagnosis and prognosis are usually not enough to accurately
estimate the severity of the condition. The most difficult task for a doctor is above all the
value of risk in patients with community-acquired pneumonia. Early diagnosis is important to
reduce hospitalization and death.
There are widespread biomarkers, none of which looks perfect, and the demand for new
biomarkers that maximizes the severity and treatment response for pneumonia has increased.
Indirect methods are utilized to isolate the organism. These include polymerase chain
reaction of throat swab, gram stain, culture of nasopharyngeal aspirate, and blood cultures.
However, interpretation can be difficult as children are found to be asymptomatic carriers of
a range of organisms and a positive result on PCR may not be indicative of the cause of CAP.
C-reactive protein, and White blood cell count are often part of the diagnostic workup in an
inpatient setting. However, the changes observed are not specific to predict causative
pathogens. Instrumental diagnostics, such as a chest X-ray are not sensitive or specific and
are not recommended in the initial diagnosis of a suspected community acquired pneumonia.
Biomarkers in pneumonia may be the ones that indicate inflammation or may be released
specifically, after lung injury due to infection. The measured levels of biomarkers should be
interpreted cautiously and always be correlated with clinical findings as many confounding
factors should be taken into consideration for interpretation. Factors like age, antibiotic
pretreatment, chronic hepatic disease, corticosteroids, renal impairment, and viral
confection can critically affect some biomarker levels and thus their sensitivity and
specificity regarding treatment failure and clinical stability. Hence, results should be
interpreted in line with the clinical presentation, and they should never substitute clinical
judgment.
The importance of the classic biomarkers such as procalcitonin and C-reactive protein has
been declined. The limitations of PCT are being elevated in a variety of noninfectious
conditions, such as cirrhosis, pancreatitis, mesenteric infarction, burns, and aspiration
pneumonitis. Also, its diagnostic and predictive value declines in patients with severe
sepsis and in localized infections (e.g., endocarditis, empyema). Studies differ as to what
are the appropriate negative cut-off points for PCT. Criticism of the role of CRP in
diagnostics includes not only the delay in response to clinical stimulus but also its poor
specificity as it is elevated in a variety of pathologies, such as trauma, surgery, burns,
and immunological-mediated inflammatory diseases. Mendez et al. successfully demonstrated
that CRP is a significant independent predictor for the absence of severe complications in
CAP.
The establishment of new biomarkers in clinical practice would not only facilitate accurate
diagnosis but would also help to reduce the amount of antibiotics used. Burgos etal. [2016]
assess the usefulness of neutrophil CD64 expression to identify patients with
community-acquired pneumonia (CAP) at risk of a poor outcome. The sensitivity/specificity of
nCD64 in predicting poor outcome [defined as intensive care unit (ICU) admission and/or
clinical deterioration after arrival at the emergency department] was calculated. Although
nCD64 expression is associated with an increased risk of ICU admission or clinical
deterioration after admission, its accuracy in predicting these poor outcomes is modest and
does not significantly improve the predictive ability of severity scores. Qun and Mei-Yu
[2012], studied the clinical value of the expression of neutrophil surface CD64 in the
diagnosis of community-acquired pneumonia in children. They found that ROC curve analysis
showed that the threshold of CD64 and CRP was 2.8 and 8 mg/L respectively. Specificity of
CD64 index (90%) was much higher than CRP (74%). They stated that the determination of
peripheral blood neutrophil CD64 contributes to the early diagnosis of pulmonary bacterial
infection and the evaluation of the anti-infection effect.
Zhuang etal., [2015] study the level of monocyte-human leukocyte antigen-DR (mHLA-DR), an
immune function-related biomarker, at 24 h after admission, to predict the outcomes of
subjects with severe pneumonia. They found that mHLA-DR may be a reliable biomarker that can
predict the outcomes of patients with severe community-acquired pneumonia, and 27.2% may be
the cut-off value to predict the outcomes. They reported that non-survivors significantly
expressed reduced levels of mHLA-DR on their monocyte membranes. There is still not enough
evidence whether mHLA-DR could be a useful marker in CAP.
Triggering receptor expressed on myeloid cells 1 (TREM-1) is an inflammatory receptor that
causes inflammation after exposure to extracellular fungi and bacterial pathogens. Elevated
TREM-1 levels are a potential marker of lung disease. El Nady etal. [2019] found that TREM-1
level was significantly higher in ventilated children with pneumonia compared to the control
group (1). Grover et al. [2014] found that TREM-1 is a good predictor of
ventilator-associated pneumonia (VAP) ; however, Palazzo et al. 2012 claimed that TREM-1 can
be found elevated in the bronchoalveolar lavage (BAL) fluid of patients with and without
confirmed VAP. Therefore, further studies are required to fully determine the diagnostic
power of TREM-1 for VAP.
