Early origins of lung disease: towards an interdisciplinary approach

Abstract

The prenatal and perinatal environments can have profound effects on the development of chronic inflammatory diseases. However, mechanistic insight into how the early-life microenvironment can impact upon development of the lung and immune system and consequent initiation and progression of respiratory diseases is still emerging. Recent studies investigating the developmental origins of lung diseases have started to delineate the effects of early-life changes in the lung, environmental exposures and immune maturation on the development of childhood and adult lung diseases. While the influencing factors have been described and studied in mostly animal models, it remains challenging to pinpoint exactly which factors and at which time point are detrimental in lung development leading to respiratory disease later in life. To advance our understanding of early origins of chronic lung disease and to allow for proper dissemination and application of this knowledge, we propose four major focus areas: 1) policy and education; 2) clinical assessment; 3) basic and translational research; and 4) infrastructure and tools, and discuss future directions for advancement. This review is a follow-up of the discussions at the European Respiratory Society Research Seminar "Early origins of lung disease: towards an interdisciplinary approach" (Lisbon, Portugal, November 2019).

FIGURE 1

Early-life exposures, immune maturation and priming of the developing lung for disease. The prenatal and perinatal environments can have profound effects on the development and progression of respiratory diseases. Different maternal exposures (diet, smoking, medication usage) and maternal inflammation can promote fetal immune programming. Moreover, early-life colonisation of the lungs is imperative for shaping of the immune response. Early-life changes in lung development, specific environmental exposures and alterations in lung immune maturation following such changes and exposures can lead to the development of childhood and adult respiratory diseases. Alterations in what is considered “healthy” lung development, caused by, for example, chorioamnionitis-associated bronchopulmonary dysplasia (BPD), or aberrant lung structure associated with preterm birth may prime the neonate, via changes in immune maturation or cellular mechanisms in the lung, for increased susceptibility to develop respiratory complications in later life. IL: interleukin; ST: suppression of tumorigenicity; ILC: innate lymphoid cell; Th: T-helper; PH: pulmonary hypertension.

FIGURE 2

Focus areas for future interdisciplinary research into early origins of chronic lung disease. To advance our understanding of the early origins of chronic lung disease four main focus areas and future directions for advancement within these areas have been identified: 1) policy; 2) clinical assessment; 3) research; and 4) infrastructure and tools. Central to these focus areas is education of researchers and clinicians, but also education of and communication to the general public. Clinical observations and research findings are required to inform policy making which consequently serves as a basis to inform, guide and educate the public. In order to facilitate proper clinical assessment and both basic and translational research, adequate infrastructure is needed in the form of databases and biobanks. Moreover, interdisciplinary training of professionals (clinicians, midwives, basic and translational researchers, and bioinformaticians and biostatisticians) working across the focus areas is required.