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Long-Term Pulmonary Dysfunction by Hyperoxia Exposure during Severe Viral Lower Respiratory Tract Infection in Mice
Thijs A Lilien1,2, Miša Gunjak2,3,4, Despoina Myti2,3,4
1Pediatric Intensive Care Unit, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Insights
Hyperoxia during viral lower respiratory tract infection (LRTI) in young mice worsened long-term lung function, increasing airway resistance. This suggests oxygen therapy might negatively impact recovery from severe infant LRTI.
Area of Science:
- Pediatric Pulmonology
- Respiratory Medicine
- Developmental Biology
Background:
- Viral lower respiratory tract infections (LRTI), particularly RSV, pose significant health risks to young children.
- Severe LRTI often requires oxygen therapy, raising concerns about potential long-term pulmonary complications.
- The impact of hyperoxia during acute viral LRTI on subsequent lung health remains unclear.
Purpose of the Study:
- To investigate the effect of hyperoxia exposure during the acute phase of viral LRTI on long-term pulmonary outcomes in a mouse model.
- To determine if concurrent oxygen therapy exacerbates respiratory dysfunction after severe infant viral infections.
Main Methods:
- Used a mouse model (C57Bl/6J) infected with pneumonia virus of mice (PVM) at post-natal day 7.
- Exposed infected mice to hyperoxia (85% O2) or normoxia (21% O2) from post-natal day 10 to 17.
- Assessed lung function and structure at post-natal day 28 (3 weeks post-inoculation).
Main Results:
- Hyperoxia exposure led to transient growth arrest without catch-up growth in PVM-infected mice.
- A significant long-term increase in airway resistance was observed in hyperoxia-exposed mice.
- No significant developmental changes in airway or lung structure were found despite functional deficits.
Conclusions:
- Concurrent hyperoxia during acute viral LRTI in early life may worsen long-term pulmonary sequelae.
- Hyperoxia appears to alter pulmonary function without affecting lung structure development.
- Further research is necessary to elucidate the mechanisms behind hyperoxia-induced pulmonary dysfunction.
Abstract:
Viral-induced lower respiratory tract infection (LRTI), mainly by respiratory syncytial virus (RSV), causes a major health burden among young children and has been associated with long-term respiratory dysfunction. Children with severe viral LRTI are frequently treated with oxygen therapy, hypothetically posing an additional risk factor for pulmonary sequelae. The main goal of this study was to determine the effect of concurrent hyperoxia exposure during the acute phase of viral LRTI on long-term pulmonary outcome. As an experimental model for severe RSV LRTI in infants, C57Bl/6J mice received an intranasal inoculation with the pneumonia virus of mice J3666 strain at post-natal day 7, and were subsequently exposed to hyperoxia (85% O2) or normoxia (21% O2) from post-natal day 10 to 17 during the acute phase of disease. Long-term outcomes, including lung function and structural development, were assessed 3 weeks post-inoculation at post-natal day 28. Compared to normoxic conditions, hyperoxia exposure in PVM-inoculated mice induced a transient growth arrest without subsequent catchup growth, as well as a long-term increase in airway resistance. This hyperoxia-induced pulmonary dysfunction was not associated with developmental changes to the airway or lung structure. These findings suggest that hyperoxia exposure during viral LRTI at young age may aggravate subsequent long-term pulmonary sequelae. Further research is needed to investigate the specific mechanisms underlying this alteration to pulmonary function.
