Airway CD8(+) T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection.

Infants and young children are disproportionately susceptible to severe complications from respiratory viruses, although the underlying mechanisms remain unknown. Recent studies show that the T cell response in the lung is important for protective responses to respiratory infections, although details on the infant/pediatric respiratory immune response remain sparse. The objectives of the present study were to characterize the local versus systemic immune response in infants and young children with respiratory failure from viral respiratory tract infections and its association to disease severity. Daily airway secretions were sampled from infants and children 4 years of age and younger receiving mechanical ventilation owing to respiratory failure from viral infection or noninfectious causes. Samples were examined for immune cell composition and markers of T cell activation. These parameters were then correlated with clinical disease severity. Innate immune cells and total CD3(+) T cells were present in similar proportions in airway aspirates derived from infected and uninfected groups; however, the CD8:CD4 T cell ratio was markedly increased in the airways of patients with viral infection compared with uninfected patients, and specifically in infected infants with acute lung injury. T cells in the airways were phenotypically and functionally distinct from those in blood with activated/memory phenotypes and increased cytotoxic capacity. We identified a significant increase in airway cytotoxic CD8(+) T cells in infants with lung injury from viral respiratory tract infection that was distinct from the T cell profile in circulation and associated with increasing disease severity. Airway sampling could therefore be diagnostically informative for assessing immune responses and lung damage.

Pediatric acute respiratory distress syndrome associated with human metapneumovirus and respiratory syncytial virus.

OBJECTIVES: To study the incidence, risk factors, clinical course, and outcome of ARDS in children with HMP and RSV. WORKING HYPOTHESIS: We hypothesized that ARDS in children with HMP was similar in incidence, risk factors, clinical course, and outcomes to ARDS in children with RSV. STUDY DESIGN: Retrospective, observational study over 2 years. PATIENT-SUBJECT SELECTION: Patients included were <18 years old with HMP or RSV detected from nasopharyngeal specimens by commercial reverse transcriptase polymerase chain reaction assay admitted to a study site. METHODOLOGY: We described the incidence of ARDS within 1 week following the detection of HMP or RSV using recently developed Pediatric ARDS (PARDS) criteria. We also assessed risk factors, clinical course, and outcomes of children in the PICU with HMP or RSV and PARDS or non-PARDS. RESULTS: We identified 57 patients with HMP and 161 patients with RSV: the proportions of patients with either virus who developed PARDS (HMP: 23%, RSV: 20%) and severe PARDS (HMP: 9%, RSV: 7%) were similar, as were the proportions of patients with acute (or acute-on-chronic) respiratory failure who developed PARDS (HMP: 41%, RSV: 31%). In a logistic regression model, risk factors associated with PARDS included neurologic comorbidity and PIM 3 probability of mortality, but not virus type. The risk factors, clinical course, and outcomes were similar for patients with PARDS associated with HMP and RSV. CONCLUSIONS: About 1/3 of children with HMP or RSV and acute (or acute-on-chronic) respiratory failure developed PARDS. Children with either virus and a neurologic comorbidity or an increased PIM 3 probability of mortality were at increased risk for PARDS.