Lung function trajectories from birth to school age in African children, and their early life determinants

肺病是全球健康状况不佳和过早死亡的主要原因，在非洲的负担尤其沉重。哮喘和慢性阻塞性肺疾病(COPD)非常常见，COPD是非洲的第三大杀手。与世界其他地区相比，非洲患者患上更严重的哮喘和慢性阻塞性肺病，而且年龄更小。青壮年肺功能低下是COPD发生的重要危险因素。此外，肺功能低下会增加早在生命的第三个十年就因各种原因过早死亡的可能性。来自高收入国家的研究表明，肺功能从上学到老年都有变化，儿童早期的肺功能是成年后慢性阻塞性肺疾病的重要决定因素。儿童哮喘和早期的下呼吸道感染会降低儿童时期的肺功能。与高收入国家相比，非洲的呼吸道感染和哮喘的负担和类型以及对肺功能发展产生不利影响的环境因素(如香烟烟雾、生物量暴露、过敏原或心理社会压力)明显不同。然而，尽管儿童哮喘的频率和严重性很高，呼吸道感染的发病率很高，以及许多有害的环境暴露，但到目前为止，还没有关于非洲与肺功能低下有关的早期生活因素及其发展轨迹的数据。我们已经表明，在儿童早期进行干预以改善肺功能，减少儿童肺功能低下的长期后果是有余地的。为了制定干预措施，降低非洲贫困人口低肺功能的风险，我们必须确定儿童肺功能轨迹，并发现他们早期生活的环境决定因素，这是世界这一地区特有的。这些信息对于在世界这一地区开发新的预防策略至关重要，这将对COPD和肺功能减退的其他不利后果产生影响。我们的总体目标是调查非洲儿童从出生到8岁的肺功能轨迹，并确定与低肺功能轨迹相关的早期生命危险因素。我们将重点关注儿童早期接触和呼吸结果，因为长期肺部健康的轨迹是在早期生活中建立的。为了实现这一目标，我们将在南非独特的1000对母婴出生队列的基础上，对怀孕和儿童期间的传染病和非传染性接触进行详细测量，对样本进行广泛的生物库，并对从出生到5岁的肺功能和呼吸系统疾病进行纵向测量。在这个项目的过程中，我们将测量肺功能和临床症状的进展或严重程度，直到8岁，并持续收集环境暴露。这将延长以相同方式测量临床症状和肺功能的时间点的数量，并为纵向分析奠定基础，从而创造出在低收入和中等收入国家无与伦比的独特资源。我们将汇集英国和南非的顶尖专家，调查南非儿童从出生到8岁的肺功能轨迹，并确定导致肺功能低下的早期生命暴露。我们将通过南非和英国专家组之间的合作和培训，建设非洲的研究能力。我们的总体愿景是为制定干预战略提供信息，以降低生长阶段低肺功能轨迹的风险，并防止非洲人口的多器官发病率和过早死亡，这是一个迫切需要的领域。

Lung diseases are a major cause of ill health and premature death globally, with a particularly large burden in Africa. Asthma and chronic obstructive pulmonary disease (COPD) are very common, and COPD is the third biggest killer in Africa. African patients develop more severe asthma and COPD, and at a younger age, compared to the rest of the world. Low level of lung function in young adult age is an important risk factor for the development of COPD. Furthermore, low lung function increases the likelihood of early death from all causes as early as the third decade of life. Studies from high-income countries have shown that lung function tracks from school age to old age, and that lung function in early childhood is an important determinant of COPD in adulthood. Childhood asthma and lower respiratory tract infections in early life reduce lung function through childhood. The burden and the type of respiratory infections and asthma, as well as environmental factors which adversely affect development of lung function (such as cigarette smoke, biomass exposure, allergens or psychosocial stressors), are markedly different in Africa compared to the high-income countries. However, despite the high frequency and severity of childhood asthma, high incidence of respiratory infections, and many harmful environmental exposures, to date there are no data on early-life factors associated with poor lung function and its trajectory in Africa.We have shown that there is a scope to intervene in early childhood to improve lung function, and reduce long-term consequences of low lung function in childhood. In order to develop interventions to reduce the risk of low lung function in the needy population in Africa, we have to identify childhood lung function trajectories, and discover their early life environmental determinants, which are specific to this part of the world. This information is crucial to develop novel preventative strategies in this part of the world, which will impact on COPD, and the other adverse consequences of diminished lung function. Our overall aim is to investigate lung function trajectories in African children from birth to 8 years of age, and to identify early-life risk factors associated with low lung function trajectory. We will focus on early-life exposures and respiratory outcomes during childhood, as the trajectory of long-term lung health is established in early life. To achieve this, we will build on the unique South African birth cohort of 1000 mother-child pairs, with detailed measures of infectious diseases and non-infectious exposures through pregnancy and childhood, extensive biobank of samples, and longitudinal measurements of lung function and respiratory diseases from birth to age 5 years. In the course of this project, we will measure lung function and the progression or severity of clinical symptoms through to age 8 years, with ongoing collection of environmental exposures. This will extend the number of time points at which clinical symptoms and lung function have been measured in an identical way, and lay foundations for longitudinal analyses, thereby creating a unique resource unparalleled anywhere in low-income and middle-income countries. We will bring together leading UK and South African experts, to investigate lung function trajectories in South African children from birth through age 8 years, and determine early life exposures which lead to the low lung function. We will build African research capacity through collaborations and training between South African and UK expert groups. Our overall vision is to inform the development of intervention strategies to reduce the risk of low lung function trajectories during the growth phase, and prevent multi-organ morbidity and premature death in African populations, an area of critical need.