Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life

Can Circulating Biomarkers Identify Different FEV <sub>1</sub> Trajectories of COPD Patients?

Association between very to moderate preterm births, lung function deficits, and COPD at age 53 years: analysis of a prospective cohort study

COPD—more than just tobacco smoke

Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study

Early-life origins of respiratory diseases: a key to prevention

Chronic obstructive pulmonary disease (COPD) results from a complex interaction between genes and the environment, and occupational exposures are an underappreciated risk factor. Until now, little research attention has been paid to the potential impact of occupational risk factor exposure on the COPD in China. The aim of this retrospective study was to analyze the role of occupational risk factor exposure on the severity and progression of COPD for exploring new prevention strategies for this disease. This study adopted a random cluster-sampling method. Five grade-A tertiary hospitals that met the inclusion criteria were selected as the survey sites, and patients with COPD hospitalized in these hospitals from January 1, 2019, to December 31, 2019, were selected as the research subjects. Data of the patients diagnosed with COPD met the Global Initiative for Chronic Obstructive Lung Disease (2019) criteria and were collected from the computerized medical record databases. Among 4082 investigated COPD patients, 1063 (26%) were found to have occupational risk factor exposure history. The top 3 industries with a large COPD case number and a history of occupational risk factor exposure ranked in the order of agriculture (including farming, forestry, animal husbandry, and fishery), manufacturing, and mining. Further multivariate logistic regression analysis indicated that when setting a low exposure level as a reference, medium and high exposure levels were correlated with the severity of COPD (odds ratio values were 2.837 and 6.201, respectively, P < .05). Linear regression analysis showed that cumulative exposure to occupational risk factors was negatively correlated with the forced expiratory volume in 1-second percentage of COPD patients, with a correlation coefficient of 0.68. Our results indicated that occupational risk factor exposure levels were related to the severity of COPD significantly. The incubation period of COPD in the exposure group was significantly shorter than that in the non-exposure group. To prevent worked-related COPD, special attention and control efforts should be taken to reduce the level of occupational risk factors such as organic dust, irritating chemicals, etc in the work environments, especially in the industries of agriculture, forestry, animal husbandry and fishery, manufacturing, and mining.

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death worldwide, is traditionally considered a disease of smoking. However, <20% of people who smoke develop COPD, indicating the disease is complex, resulting from the interplay of genetic and environmental factors. Emerging evidence highlights the importance of exposure in early life to environmental irritants that impair fetal lung development and subsequent lung function trajectories, increasing risk for future COPD. Specifically, childhood asthma, preterm birth, and surfactant deficiency have been associated with lung function impairments and an increased COPD risk later in life. Furthermore, prenatal exposure to cigarettes influences sensitivity of individuals to smoking in their later life. A mounting body of evidence now indicates that diabetes exposure during pregnancy increases the risk for several childhood conditions linked to COPD risk, suggesting that maternal diabetes may be an unexplored risk factor for COPD. This article reviews the current literature on the influence of maternal diabetes on known early-life COPD risk factors (asthma and preterm birth), and identifies knowledge gaps that need to be addressed to pindown a potential association with COPD. Specifically, whether exposure to maternal diabetes influences offspring risk for COPD through already identified risk modifiers, or directly by altering lung function trajectories or sensitivity to cigarettes. Maternal diabetes rates are rising worldwide, with type 2 diabetes mellitus (T2DM) during pregnancy and gestational diabetes mellitus (GDM) nearly doubling over the last 15 years. Understanding how prenatal diabetes influences COPD risk is imperative to establishing whether intervening early can prevent COPD in this population.

Lifetime Risk Factors for Post Bronchodilator Lung Function Decline: A Population-Based Study from 1st to 6th Decade

Childhood risk factors for long-term lung health often coexist and their specific patterns may affect subsequent lung function differently. To identify childhood risk factor profiles and their influence on lung function and chronic obstructive pulmonary disease (COPD) in middle age, and potential pathways. Profiles of 11 childhood respiratory risk factors, documented at age 7, were identified in 8,352 participants from the Tasmanian Longitudinal Health Study using latent class analysis. We investigated associations between risk profiles and post-bronchodilator lung function and COPD at age 53, mediation by childhood lung function and adult asthma, and interaction with personal smoking. Six risk profiles were identified: 1) unexposed or least exposed (49%); 2) parental smoking (21.5%); 3) allergy (10%); 4) frequent asthma, bronchitis (8.7%); 5) infrequent asthma, bronchitis (8.3%); and 6) frequent asthma, bronchitis, allergy (2.6%). Profile 6 was most strongly associated with lower forced expiratory volume in 1 second (FEV1) (-261; 95% confidence interval, -373 to -148 ml); lower FEV1/forced vital capacity (FVC) (-3.4; -4.8 to -1.9%) and increased COPD risk (odds ratio, 4.9; 2.1 to 11.0) at age 53. The effect of profile 6 on COPD was largely mediated by adult active asthma (62.5%) and reduced childhood lung function (26.5%). Profiles 2 and 4 had smaller adverse effects than profile 6. Notably, the effects of profiles 2 and 6 were synergistically stronger for smokers. Profiles of childhood respiratory risk factors predict middle-age lung function levels and COPD risk. Specifically, children with frequent asthma attacks and allergies, especially if they also become adult smokers, are the most vulnerable group. Targeting active asthma in adulthood (i.e., a dominant mediator) and smoking (i.e., an effect modifier) may block causal pathways and lessen the effect of such established early-life exposures.

Susceptibility of the lungs to cigarette smoke is poorly understood. It is not known whether maternal smoking increases chronic obstructive pulmonary disease (COPD) risk. In 1998 we reported an inverse association between maternal smoking (prerecorded) and FEV(1) in adults. Because FEV(1) and FVC are strongly correlated, it is unclear whether the association in question reflects a link with lung volume, airflow limitation, or both. We extended our original analysis to investigate whether maternal and personal smoking synergize to increase airflow limitation. We estimated residual FEV(1) to express FEV(1) variation that was not associated with FVC. Maternal smoking was inversely associated with FVC and FEV(1) irrespective of personal smoking. It was inversely associated with FEV(1)/FVC, forced midexpiratory flow rates (FEF(25-75) [mean forced expiratory flow during the middle half of the FVC], FEF(25-75)/FVC), and residual FEV(1) in current smokers but not in never or former smokers (heterogeneity p = 0.016, 0.024, 0.021, and 0.016, respectively). We tested the clinical relevance of findings in ever smokers without asthma: 10 cigarettes/day maternal smoking increased prevalent COPD by 1.7 (95% confidence interval: 1.2-2.5) after adjustment for covariates. Maternal smoking impairs lung volume irrespective of personal smoking and appears to synergize with personal smoking to increase airflow limitation and COPD.

Trajectories of asthma and allergies from 7 years to 53 years and associations with lung function and extrapulmonary comorbidity profiles: a prospective cohort study

Management of chronic obstructive pulmonary disease: Moving beyond the asthma algorithm

BackgroundLung function trajectories in chronic obstructive pulmonary disease (COPD) vary among individuals. However, evidence on the clinical characteristics and prognosis of mild-to-moderate COPD developing from different lung function trajectories is limited. We aim to explore whether differences exist in the clinical features and prognosis of mild-to-moderate COPD developed through different lung function trajectories.MethodsIndividuals who participated in the Early COPD study (2019–2020) and who had available spirometry data from the China Epidemiological Survey of COPD (2012–2013) were included and categorized into three groups: (I) previously normal forced expiratory volume in one second (FEV1) trajectory group: participants had developed mild-to-moderate COPD in 2019–2020, with normal lung function in 2012–2013; (II) previously low FEV1 trajectory group: participants had developed mild-to-moderate COPD in 2019–2020, with subnormal lung function in 2012–2013; (III) non-COPD group: participants had not developed COPD in 2019–2020, with normal lung function in 2012–2013. Baseline assessments (2019–2020) included spirometry, impulse oscillometry (IOS), and chest computed tomography (CT). Lung function decline and exacerbation risk were analyzed over a 2-year follow-up (2021–2022).ResultsOverall, 96 participants were included in the previously normal FEV1 trajectory group, 32 in the previously low FEV1 trajectory group, and 118 in the non-COPD group. Compared with the previously normal FEV1 trajectory group, the previously low FEV1 trajectory group had poorer lung function, more severe dyspnea, and greater small-airway dysfunction and emphysema. During the 2-year follow-up, the previously normal FEV1 trajectory group had a faster annual rate of forced vital capacity (FVC) decline, and the previously low FEV1 trajectory group had a higher moderate-to-severe exacerbation risk than the non-COPD group.ConclusionsThere were significant differences in the clinical characteristics and longitudinal prognosis of mild-to-moderate COPD progressing from different pulmonary function trajectories, reflecting the need for individualized management.

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991–1993, 1999–2002 and 2010–2013. Disease status was classified in 2010–2013, when the subjects were aged 40–68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.

Associations between life-course FEV1/FVC trajectories and respiratory symptoms up to middle age: analysis of data from two prospective cohort studies