RESUMO
The perinatal period and early infancy are considered critical periods for lung development. During this period, adversities such as environmental exposures, allergic sensitization, and asthma are believed to impact lung health in adulthood. Therefore, we hypothesized that concomitant exposure to allergic sensitization and urban-derived fine particulate matter (PM2.5) in the early postnatal period of mice would cause more profound alterations in lung alveolarization and growth and differently modulate lung inflammation and gene expression than either insult alone in adult life. BALB/c mice were sensitized with ovalbumin (OVA) and exposed to PM2.5 from the fifth day of life. Then, we assessed lung responsiveness, inflammation in BALF, lung tissue, and alveolarization by stereology. In addition, we performed a transcriptomic analysis of lung tissue on the 40th day of life. Our results showed that young adult mice submitted to allergic sensitization and exposure to ambient PM2.5 since early life presented decreased lung growth with impaired alveolarization, a mixed neutrophilic-eosinophilic pattern of lung inflammation, increased airway responsiveness, and increased expression of genes linked to neutrophil recruitment when compared to animals that were OVA-sensitized or PM2.5 exposed only. Both, early life allergic sensitization and PM2.5 exposure, induced inflammation and impaired lung growth, but concomitant exposure was associated with worsened inflammation parameters and caused alveolar enlargement. Our experimental data provide pathological support for the hypothesis that allergic or environmental insults in early life have permanent adverse consequences for lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice. Together with our data, current evidence points to the urgent need for healthier environments with fewer childhood disadvantage factors during the critical windows of lung development and growth.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar , Inflamação/induzido quimicamente , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Material Particulado/análise , Fenótipo , Pneumonia/induzido quimicamenteRESUMO
Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM2.5 (from São Paulo, Brazil; target dose 600⯵g/m3 for 1â¯h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse.
Assuntos
Poluição do Ar/efeitos adversos , Pulmão/fisiopatologia , Material Particulado/efeitos adversos , Material Particulado/análise , Alvéolos Pulmonares/patologia , Proteína 4 Semelhante a Angiopoietina/biossíntese , Animais , Brasil , Proteínas de Ciclo Celular/biossíntese , Dano ao DNA/efeitos dos fármacos , Elasticidade/fisiologia , Feminino , Proteínas Ligadas por GPI/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Pulmão/crescimento & desenvolvimento , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fatores de Transcrição SOXE/biossíntese , Fatores de TempoAssuntos
Displasia Broncopulmonar/patologia , Displasia Broncopulmonar/fisiopatologia , Hiperóxia/complicações , Recém-Nascido Prematuro , Respiração Artificial/efeitos adversos , Fatores Etários , Displasia Broncopulmonar/etiologia , Pré-Escolar , Compreensão , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/patologia , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/terapia , Masculino , Avaliação das Necessidades , Prognóstico , Respiração Artificial/métodos , Medição de Risco , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease of prematurity. The so-called new BPD has replaced the classic BPD described by Northway, as a result of maternal use of corticosteroids, early surfactant and less aggressive mechanical ventilation and the survival of younger premature, born during the canalicular stage and that completed their alveolization outside the uterus. The new BPD is a less severe disease, but lung function is impaired in the long-term. An update of the new BPD, focused on the management after discharge from neonatology, from a pediatric pulmonologist perspective is presented.
La Displasia Broncopulmonar (DBP) es la enfermedad pulmonar crónica más prevalente del prematuro. La denominada nueva DBP ha reemplazado a la DBP clásica descripta por Northway, como consecuencia del uso de corticoides maternos, surfactante precoz, ventilación mecánica menos agresiva y la sobrevivencia de prematuros más pequeños, que nacen en etapa canalicular de su desarrollo pulmonar y completan su alveolización fuera del útero. La nueva DBP es una patología menos severa, pero con compromiso funcional respiratorio a largo plazo. A continuación se describe una actualización de la nueva DBP, enfocada en el manejo realizado luego del alta de neonatología, desde el punto de vista del Neumólogo Pediatra.