Author:
Gao Jing,Um-Bergström Petra,Pourbazargan Melvin,Berggren-Broström Eva,Li ChuanXing,Merikallio Heta,Kaarteenaho Riitta,Reinke Nichole Stacey,Wheelock Craig E,Melén Erik,Anders Lindén,Wheelock Åsa M,Rassidakis Georgios,Ortiz-Villalon Cristian,Sköld Magnus Carl
Abstract
Abstract
Background
Bronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction later in life. The distribution of T cell subtypes in the large airways is largely unknown.
Objective
To characterize cellular and T cell profiles in the large airways of young adults with a history of BPD.
Methods
Forty-three young adults born prematurely (preterm (n = 20), BPD (n = 23)) and 45 full-term-born (asthma (n = 23), healthy (n = 22)) underwent lung function measurements, and bronchoscopy with large airway bronchial wash (BW). T-cells subsets in BW were analyzed by immunocytochemistry.
Results
The proportions of both lymphocytes and CD8 + T cells in BW were significantly higher in BPD (median, 6.6%, and 78.0%) when compared with asthma (3.4% and 67.8%, p = 0.002 and p = 0.040) and healthy (3.8% and 40%, p < 0.001 and p < 0.001). In all adults born prematurely (preterm and BPD), lymphocyte proportion correlated negatively with forced vital capacity (r= -0.324, p = 0.036) and CD8 + T cells correlated with forced expiratory volume in one second, FEV1 (r=-0.448, p = 0.048). Correlation-based network analysis revealed that lung function cluster and BPD-birth cluster were associated with lymphocytes and/or CD4 + and CD8 + T cells. Multivariate regression analysis showed that lymphocyte proportions and BPD severity qualified as independent factors associated with FEV1.
Conclusions
The increased cytotoxic T cells in the large airways in young adults with former BPD, suggest a similar T-cell subset pattern as in the small airways, resembling features of COPD. Our findings strengthen the hypothesis that mechanisms involving adaptive and innate immune responses are involved in the development of airway disease due to preterm birth.
Publisher
Springer Science and Business Media LLC
Reference51 articles.
1. Brostrom EB, Akre O, Katz-Salamon M, Jaraj D, Kaijser M. Obstructive pulmonary disease in old age among individuals born preterm. Eur J Epidemiol. 2013;28:79–85.
2. Martin RJ, Fanaroff AA. The preterm lung and airway: past, present, and future. Pediatr Neonatol. 2013;54:228–34.
3. Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB, Kinney M, Lawn J. Born too soon Preterm Birth Action G: born too soon: the global epidemiology of 15 million preterm births. Reprod Health. 2013;10(Suppl 1):2.
4. SWEDEN OSO CS-H. : Pregnancies, Deliveries and Newborn Infants The Swedish Medical Birth Register 1973–2013 Assisted Reproduction, treatment 1991–2014. www.socialstyrelsen.se.2014.
5. Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med. 2007;357:1946–55.