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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Variations in the pathophysiology of respiratory syncytial virus infection depend on the age at onset
Tsunehisa Nagamori1, Youichiro Yoshida1, Emi Ishibazawa1
1Department of Pediatrics, Asahikawa Medical University, Asahikawa-City, Hokkaido, Japan.
Insights
Respiratory syncytial virus lower respiratory tract infections show age-dependent pathophysiology. Older children may exhibit hyperinflammation, unlike infants, impacting treatment strategies for severe RSV illness.
Area of Science:
- Pediatric Infectious Diseases
- Respiratory Medicine
- Immunology
Background:
- Respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) are a significant cause of infant and child morbidity and mortality.
- Understanding the precise pathophysiology of severe RSV LRTIs is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the differences in pathophysiology of RSV LRTIs based on patient age.
- To evaluate clinical parameters and serum cytokine levels in relation to disease severity and age groups.
Main Methods:
- Retrospective review of medical records for 189 hospitalized patients with RSV LRTI.
- Patients categorized into groups based on treatment (no oxygen, oxygen, or nasal high-flow cannula) and age (<6 months vs. ≥6 months).
- Analysis of clinical data and serum concentrations of high-mobility group box-1 and key cytokines (IL-6, sTNFR-1/2, IL-18, IFI6).
Main Results:
- Infants (<6 months) presented with lower pH, higher pCO2, HCO3-, and base excess.
- Older children (≥6 months) showed lower pH, higher pCO2, decreased total protein and albumin, and elevated AST, ALT, LDH, ferritin, and CRP.
- In older children, higher levels of IL-6, sTNFR-1/2, and HMGB1 were observed in groups receiving oxygen support.
Conclusions:
- The pathophysiology of severe RSV LRTIs differs significantly between infants and older children.
- A subset of older children with RSV LRTI may experience a hyperinflammatory state, indicated by elevated inflammatory markers and cytokines.
Background:
Lower respiratory tract infections due to respiratory syncytial virus are associated with morbidity and mortality in infants and children. Thus precise elucidation of respiratory syncytial virus lower respiratory tract infection pathophysiology is important.
Methods:
Medical records of hospitalized patients were reviewed. Patients were divided into three groups. Group I: patients who improved without oxygen supply. Group II: patients who received oxygen supply, but not nasal high-flow cannula therapy. Group III: patients who received nasal high-flow cannula. Patients were also divided by age group into the <6 months and ≥6 months groups. Parameters for differentiating the severity among groups were then evaluated. Further, serum concentration of high-mobility group box-1 and several cytokines (Inerleukin-6, soluble tumor necrosis factor receptor-1/2, Interleukin-18, Interferon-gamma responsive protein-100) were evaluated.
Results:
One hundred eighty-nine were enrolled. An analysis of variance for those <6 months showed overall differences including younger age, lower pH, and increased partial pressure of carbon dioxide (pCO2), bicarbonate (HCO3-), and base excess at the time of admission. On the other hand, analysis of variance for ≥6 months revealed that, in addition to a lower pH and increased pCO2, patients showed differences including decreased serum total protein and albumin, and increased aspartate aminotransferase (AST), alanin aminotransferase (ALT), lactate dehydrogenase (LDH), Ferritin and C-reactive protein (CRP) levels. Further, evaluation of serum cytokines showed that IL-6, s tumor necrotizing factor receptor-1/2, and high-mobility group box-1 were higher in Group II/III among the ≥6 months age group, but not for those in the <6 months group.
Conclusions:
The pathophysiology of severe respiratory syncytial virus lower respiratory tract infection varies according to the age at onset. In late infancy and childhood, a certain proportion of patients show a hyperinflammatory status.
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