title: Neonatal viral bronchiolitis and pneumonia induces bronchiolar hypoplasia and alveolar dysplasia in rats.
abstract: The objective of this research was to determine the effects of viral bronchiolitis and pneumonia on postnatal bronchiolar and alveolar growth. Neonatal (5-day-old) and weanling (25-day-old) outbred rats were infected with parainfluenza type 1 (Sendai) virus and were studied from 0 to 110 days after inoculation by scanning and transmission electron microscopy, by light microscopic morphometry, and by analysis of airway corrosion casts. Viral infection induced necrotizing bronchiolitis and interstitial pneumonia in both age groups of rats. Viral infection had a much more marked effect on neonatal rats in the proliferative stage of lung growth than on weanlings in the equilibrated stage of lung growth. Viral infection in neonatal rats resulted in delayed or impaired growth of secondary septa into alveolar saccules. The impaired septal ingrowth was multifocal and predominantly centriacinar in distribution and was associated with alveolar enlargement and significant decreases (14 to 26%, p less than 0.01) in alveolar surface density. Total alveolar surface area in rats inoculated with virus as neonates was 22% lower (p less than 0.05) that that in control animals by 110 days after inoculation. Alveolar septa in these rats inoculated as neonates had enlarged interalveolar pores and defects compatible with mild alveolar emphysema. Airway corrosion casts prepared at 30 and 90 days after neonatal viral inoculation had terminal bronchioles that were 11 and 20% smaller in diameter (p less than 0.02), respectively, than those from age-matched control rats. The density of attachments of alveolar septa to bronchiolar walls in viral-inoculated rats at these times was significantly decreased (p less than 0.001). Viral-infected rats had elevated respiratory resistance (p less than 0.005) and decreased dynamic compliance (p less than 0.02) at 39 days after inoculation. The results indicate that viral bronchiolitis and pneumonia during early life in rats induces abnormal alveolar development and bronchiolar hypoplasia that are associated with abnormalities in pulmonary function. Continued postnatal lung growth does not compensate for early virus-induced abnormalities in alveolar and bronchiolar growth.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison.
authors.forename: W L
authors.initials: WL
authors.lastname: Castleman
authors.forename: R L
authors.initials: RL
authors.lastname: Sorkness
authors.forename: R F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: G
authors.initials: G
authors.lastname: Grasee
authors.forename: M M
authors.initials: MM
authors.lastname: Suyemoto
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001980:Bronchi / Q000473:pathology*; D001990:Bronchiolitis, Viral / Q000473:pathology* / Q000503:physiopathology; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D008855:Microscopy, Electron, Scanning; D011024:Pneumonia, Viral / Q000473:pathology* / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000473:pathology*; D051381:Rats; D013997:Time Factors; D014886:Weaning