TY - JOUR
T1 - Neonatal chlamydial pneumonia induces altered respiratory structure and function lasting into adult life
AU - Jupelli, Madhulika
AU - Murthy, Ashlesh K.
AU - Chaganty, Bharat K.R.
AU - Guentzel, M. Neal
AU - Selby, Dale M.
AU - Vasquez, Margarita M.
AU - Mustafa, Shamimunisa B.
AU - Henson, Barbara M.
AU - Seidner, Steven R.
AU - Zhong, Guangming
AU - Arulanandam, Bernard P.
N1 - Funding Information:
This work is supported by the National Institutes of Health Grant 1 RO1 AI074860.
PY - 2011/10
Y1 - 2011/10
N2 - Respiratory dysfunction in adults has been correlated with neonatal Chlamydia trachomatis pneumonia in several studies, but a causal association has not been clearly demonstrated. In this study, we examined radial alveolar counts (RACs) by microscopy, and airway and parenchymal lung function using a small animal ventilator in juvenile (5 weeks age) and adult (8 weeks age) BALB/c mice challenged as neonates with Chlamydia muridarum (C. mur) on day 1 or day 7 after birth, representing saccular (human pre-term neonates) and alveolar (human term neonates) stages of lung development, respectively. Pups challenged with C. mur on either day 1 or 7 after birth demonstrated significantly enhanced airway hyperreactivity and lung compliance, both as juveniles (5 weeks age) and adults (8 weeks age), compared with mock-challenged mice. Moreover, mice challenged neonatally with Chlamydia displayed significantly reduced RACs, suggesting emphysematous changes. Antimicrobial treatment during the neonatal infection induced early bacterial clearance and partially ameliorated the Chlamydia-induced lung dysfunction as adults. These results suggest that neonatal chlamydial pneumonia, especially in pre-term neonates, is a cause of respiratory dysfunction continuing into adulthood, and that antimicrobial administration may be partially effective in preventing the adverse respiratory sequelae in adulthood. The results of our studies also emphasize the importance of prenatal screening and treatment of pregnant women for C. trachomatis in order to prevent the infection of neonates.
AB - Respiratory dysfunction in adults has been correlated with neonatal Chlamydia trachomatis pneumonia in several studies, but a causal association has not been clearly demonstrated. In this study, we examined radial alveolar counts (RACs) by microscopy, and airway and parenchymal lung function using a small animal ventilator in juvenile (5 weeks age) and adult (8 weeks age) BALB/c mice challenged as neonates with Chlamydia muridarum (C. mur) on day 1 or day 7 after birth, representing saccular (human pre-term neonates) and alveolar (human term neonates) stages of lung development, respectively. Pups challenged with C. mur on either day 1 or 7 after birth demonstrated significantly enhanced airway hyperreactivity and lung compliance, both as juveniles (5 weeks age) and adults (8 weeks age), compared with mock-challenged mice. Moreover, mice challenged neonatally with Chlamydia displayed significantly reduced RACs, suggesting emphysematous changes. Antimicrobial treatment during the neonatal infection induced early bacterial clearance and partially ameliorated the Chlamydia-induced lung dysfunction as adults. These results suggest that neonatal chlamydial pneumonia, especially in pre-term neonates, is a cause of respiratory dysfunction continuing into adulthood, and that antimicrobial administration may be partially effective in preventing the adverse respiratory sequelae in adulthood. The results of our studies also emphasize the importance of prenatal screening and treatment of pregnant women for C. trachomatis in order to prevent the infection of neonates.
KW - airway hyperreactivity
KW - antimicrobial treatment
KW - infection during saccular and alveolar lung development
KW - lung parenchymal changes
KW - neonatal pulmonary chlamydial infection
KW - respiratory sequelae in juvenile and adult life
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U2 - 10.1038/labinvest.2011.103
DO - 10.1038/labinvest.2011.103
M3 - Article
C2 - 21769086
AN - SCOPUS:80053372954
SN - 0023-6837
VL - 91
SP - 1530
EP - 1539
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 10
ER -