Quantifying oxygen exposure as an area-under-the curve (OAUC) has been predictive of later respiratory symptoms among former low birth weight infants. Here, we test the hypothesis that quantifying OAUC in newborn mice can predict their risk for altered lung development and respiratory viral infections as adults. Newborn mice were exposed to room air or a FiO2 of 100% oxygen for 4 days, 60% oxygen for 8 days, or 40% oxygen for 16 days (same cumulative dose of excess oxygen). At 8 weeks of age, mice were infected intranasally with a non-lethal dose of influenza A virus. Adult mice exposed to 100% oxygen for 4 days or 60% oxygen for 8 days exhibited alveolar simplification and altered elastin deposition compared to siblings birthed into room air, as well as increased inflammation and fibrotic lung disease following viral infection. These changes were not observed in mice exposed to 40% oxygen Lapatinib concentration
for 16 days. Our findings in mice support the concept that quantifying OAUC over a currently unspecified threshold can predict human risk for respiratory morbidity later in life. Pediatr Pulmonol. ? 2014 Wiley Periodicals, Inc. ""The oral route has been considered superior to the nasal route for aerosol delivery S6 Kinase
to the lower respiratory tract (LRT) in adults and children. However, there are no data comparing aerosol delivery via the oral and nasal routes in infants. The aim of this study was to compare nasal and oral delivery of aerosol in anatomically correct replicas of infants' faces containing both nasal and oral upper selleck chemicals
airways. Three CT-derived upper respiratory tract (��URT��) replicas representing infants/toddlers aged 5, 14 and 20 months were studied and aerosol delivery to the ��lower respiratory tract�� (LRT) by either the oral or nasal route for each of the replicas was measured at the ��tracheal�� opening. A radio-labeled (99mDTPA) normal saline solution aerosol was generated by a soft-mist inhaler (SMIRespimat? Boehringer Ingelheim, Germany) and aerosol was delivered via a valved holding chamber (Respichamber? TMI, London, Canada) and an air-tight mask (Unomedical, Inc., McAllen, TX). A breath simulator was connected to the replicas and an absolute filter at the ��tracheal�� opening captured the aerosol representing ��LRT�� dose. Age-appropriate mask dimensions and breathing patterns were employed for each of the airway replicas. Two different tidal volumes (Vt) were used for comparing the nasal versus oral routes. Nasal delivery to the LRT exceeded that of oral delivery in the 5- and 14-month models and was equivalent in the 20-month model. Differences between nasal and oral delivery diminished with ��age��/size. Similar findings were observed with lower and higher tidal volumes (Vt). Nasal breathing for aerosol delivery to the ��LRT�� is similar to, or more efficient than, mouth breathing in infant/toddler models, contrary to what is observed in older children and adults.