Lung Development In Children Research Articles

Determinants of lung function development from birth to age 5 years: an interrupted time series analysis of a South African birth cohort

Early life is a key period that determines long-term health. Lung development in childhood predicts lung function attained in adulthood and morbidity and mortality across the life course. We aimed to assess the effect of early-life lower respiratory tract infection (LRTI) and associated risk factors on lung development from birth to school age in a South African birth cohort. We prospectively followed children enrolled in a population-based cohort from birth (between March 5, 2012 and March 31, 2015) to age 5 years with annual lung function assessment. Data on multiple early-life exposures, including LRTI, were collected. The effect of early-life risk factors on lung function development from birth to age 5 years was assessed using the Generalised Additive Models for Location, Scale and Shape and Interrupted Time Series approach. 966 children (475 [49·2%] female, 491 [50·8%] male) had lung function measured with oscillometry, tidal flow volume loops, and multiple breath washout. LRTI occurred in 484 (50·1%) children, with a median of 2·0 LRTI episodes (IQR 1·0-3·0) per child. LRTI was independently associated with altered lung function, as evidenced by lower compliance (0·959 [95% CI 0·941-0·978]), higher resistance (1·028 [1·016-1·041]), and higher respiratory rate (1·018 [1·063-1·029]) over 5 years. Additional impact on lung function parameters occurred with each subsequent LRTI. Respiratory syncytial virus (RSV) LRTI was associated with lower expiratory flow ratio (0·97 [0·95-0·99]) compared with non-RSV LRTI. Maternal factors including allergy, smoking, and HIV infection were also associated with altered lung development, as was preterm birth, low birthweight, female sex, and coming from a less wealthy household. Public health interventions targeting LRTI prevention, with RSV a priority, are vital, particularly in low-income and middle-income settings. UK Medical Research Council Grant, The Wellcome Trust, The Bill & Melinda Gates Foundation, US National Institutes of Health Human Heredity and Health in Africa, South African Medical Research Council, Hungarian Scientific Research Fund, and European Respiratory Society.

Effects of spinal deformities on lung development in children: a review

Scoliosis before the age of 5 years is referred to as early-onset scoliosis (EOS). While causes may vary, EOS can potentially affect respiratory function and lung development as children grow. Moreover, scoliosis can lead to thoracic insufficiency syndrome when aggravated or left untreated. Therefore, spinal thoracic deformities often require intervention in early childhood, and solving these problems requires new methods that include the means for both deformity correction and growth maintenance. Therapeutic strategies for preserving the growing spine and thorax include growth rods, vertically expandable titanium artificial ribs, MAGEC rods, braces and casts. The goals of any growth-promoting surgical strategy are to alter the natural history of cardiorespiratory development, limit the progression of underlying spondylarthrosis deformities and minimize negative changes in spondylothorax biomechanics due to the instrumental action of the implant. This review further elucidates EOS in terms of its aetiology, pathogenesis, pathology and treatment.

Application of computational fluid dynamics (CFD) and fluid-structure interaction (FSI)in biofluids simulation to solve actual surgery tasks

Computational fluid dynamics (CFD) is a dynamically developing tool in me-chanical engineering and interdisciplinary research. Medicine is one of the areas, where the application of current computational methods is extremely necessary. This study presents the results of using computational fluid dy-namics methods to solve actual problems of surgery (modeling of blood flow in the patient-specific aorta of a child with congenital heart disease during bypass surgery; modeling of the flow of bile in the biliary system to predict cholecystectomy outcome; modeling of the chime flow in the colon). Simu-lation of blood flow in the aorta during shunting. Cardiovascular diseases are most common in the population and cause the prevailing part of premature mortality and disability in both adults and children. Blalock-Taussig shunt-ing is mainly used to eliminate pathological changes in children. However, this procedure is carried out empirically: surgeons use their own experience. FSI enabled to numerically evaluate the shunt parameters and its location for proper lung development in children with congenital heart disease after shunt installation. Biomechanical analysis of the bile flow in healthy state, pathology, and after cholecystectomy. Cholecystectomy (removal of the sur-gical gallbladder) is usually taken to treat patients suffering from gallbladder disease and gallbladder pain. However, it should be noted that the results of the operation are not always successful. The biomechanical patient-specif-ic model was created to assess the cholecystectomy outcome. Study of the chyme flow features in the colon. The large intestine is a long hollow muscle tube of complex shape, which digests and absorbs nutrients and water from food (which is commonly called chyme in medicine). The goal is to create a patient-specific model of the chyme and feces flow in the colon in the healthy state and pathology. Clinical applications of this model can be ex-pressed in the description and understanding of the causes of the disorders as well as drug efficiency assessment to reduce the number of patients.

Prenatal exposure to metal mixtures and lung function in children from the New Hampshire Birth Cohort Study

BACKGROUND AND AIM: Prenatal environmental exposure to metals and metalloids (referred to as “metals”) has been associated with childhood lung development, but limited data exist on metal mixtures. We aimed to investigate the association between gestational exposure to metal mixtures and childhood lung function among 267 maternal-child dyads from the New Hampshire Birth Cohort Study. METHODS: Maternal ~24-28-week gestational urinary arsenic speciation, aluminum, cadmium, cobalt, chromium, copper, iron, mercury, manganese, molybdenum, nickel, tin, lead, antimony, selenium, thallium, uranium, vanadium and zinc concentration were assessed using inductively coupled plasma mass spectroscopy (ICP-MS). Forced vital capacity (FVC), forced expiratory volume in the first second of exhalation (FEV1), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) standardized z-scores were obtained at a median age of 7.4 years. We used quantile g-computation for each outcome and urinary metals adjusted for maternal smoking status, children’s age, sex and height. RESULTS:Urinary concentrations of cobalt, lead, nickel, cadmium, and chromium were inversely associated with lung function z-scores. Arsenic concentrations were inverse associated specifically with FVC and FEV1 z-scores. In contrast, lung function z-scores increased with vanadium, molybdenum, and thallium urine concentrations. CONCLUSIONS:Our findings suggest that prenatal exposure to metal mixtures impact lung function, with varying direction and magnitudes of effects. KEYWORDS: mixture, heavy metals, children’s environmental health, respiratory outcomes, biomarkers of exposure

Association between prenatal and early life household air pollution exposure and child lung function in rural Ghana

BACKGROUND AND AIM: Impaired lung development in early childhood increases risk for future pulmonary disease. Millions of people worldwide are exposed to household air pollution (HAP), however the impact of early life HAP on childhood lung development is poorly described. Leveraging the Ghana Randomized Air Pollution and Health Study (GRAPHS) birth cohort, we examined associations between prenatal and early life HAP exposure, as indexed by carbon monoxide (CO), and age four lung function. METHODS: GRAPHS enrolled pregnant women prior to 24 weeks gestation. We quantified HAP exposure by repeated personal prenatal (maternal) and early life (child) carbon monoxide (CO) assessments. Mother-child dyads were followed prospectively and children performed impulse oscillometry (IOS) at age four years. For analyses, IOS lung function variables were converted to z-scores adjusting for age, sex, ethnicity, height and weight. We then employed multivariable generalized linear regression models to examine associations between prenatal and early childhood CO and IOS variables. Sex-specific effects were explored. RESULTS:Of the 699 study children, 612 (88%) performed acceptable IOS. Children were aged 4.1 years (0.35 SD) on average at the time of IOS and 52% (N=315) were female. In adjusted models, increased prenatal CO exposure was associated with increased R5 (R5 z-score β=0.17 (95% CI 0.00, 0.34) and R20 (β = 0.20 (95% CI 0.03, 0.37), indicative of increased total and large airway resistance, respectively. Exploratory analyses suggested that boys were more vulnerable to the effects of prenatal CO exposure on both R5 and R20. CONCLUSIONS:Higher prenatal HAP exposure, as indexed by CO, is associated with impaired lung function at age four years and boys may be more vulnerable. These findings add to the growing literature of the adverse health effects of early life HAP exposure on child health. KEYWORDS: household air pollution exposure, carbon monoxide, child lung function, sex-specific effects

Impact of Air Pollution on Lung Function among Preadolescent Children in Two Cities in Poland.

Ambient air pollution impairs lung development in children, particularly in industrialized areas. The air quality in Zabrze, a city located in the Upper Silesian Industrial Region of Poland, is among the worst in Europe. We compared lung function and the frequency of respiratory or allergic symptoms between children living in Zabrze and those living in Gdynia, a city on the Baltic coast, which has the best long-term air quality in Poland. We enrolled children aged 9–15 years from both cities who were able to perform a spirometry. The following spirometry variables were measured for all participants: forced vital capacity (FVC), forced expiratory volume during the first second of expiration (FEV1), FEV1/FVC index, and peak expiratory flow (PEF). The frequencies of respiratory or allergic symptoms were taken from a survey completed by the participants’ parents. In total, 258 children from Gdynia and 512 children from Zabrze were examined. The mean values of FVC, FEV1, and PEF were significantly greater among children in Gdynia than those reported in Zabrze (p ≤ 0.032), and the frequencies of seasonal rhinorrhea (p = 0.015) or coughing episodes (p = 0.022) were significantly higher in Zabrze than in Gdynia. In conclusion, lung function was significantly impaired in children living in Zabrze, an area which is associated with poor air quality. Strategies to improve air quality in the Silesia region are urgently needed.

Impact of prenatal and postnatal household air pollution exposure on lung function of 2-year old Nigerian children by oscillometry

RationaleLung function is adversely affected by exposure to household air pollution (HAP). Studies investigating the impact of prenatal and postnatal HAP exposure on early childhood lung development are limited, especially from Sub-Saharan Africa. ObjectiveWe used oscillometry to investigate the impact on lung function of prenatal and postnatal HAP exposure of children born to Nigerian women who participated in a randomized controlled cookstove intervention trial. MethodsWe performed oscillometric measurements (R: airway resistance; X: airway reactance; Fres: resonant frequency; AX: reactance area) in 223 children starting at age of 2 years (ethanol stove, n = 113; firewood/kerosene, n = 110). Personal exposure monitoring assessed mothers' prenatal exposure to particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5). Postnatal HAP exposure was measured by determining household PM2.5 levels. We employed linear regression analysis to examine the association of prenatal and postnatal HAP exposures with children's lung function. Models were adjusted for age, gender, weight, height, group (intervention or control), birthweight and gestational age. ResultsMean age of the children was 2.9 years (standard deviation = 0.3); 120 were boys (53.8%) and 103 were girls (46.2%). Higher postnatal PM2.5 exposures were significantly associated with higher airway reactance at 5 Hz (X5 Hz; p = 0.04) in adjusted models. There were no significant associations between prenatal or postnatal PM2.5 exposure levels and other oscillometry parameters in adjusted regression analysis. ConclusionsThis is the first study to use oscillometry to explore the relationship between HAP exposure and lung function in children as young as 2 years. The findings provide some evidence that increased postnatal HAP exposure may result in poorer lung function in children, although larger studies are needed to confirm observed results. This study indicates that oscillometry is a low-cost and effective method to determine lung function in early childhood.

Effects of indoor environment and lifestyle on respiratory health of children in Chongqing, China

BackgroundThe prevalence of certain respiratory diseases of children in China appears to be on the rise in recent decades. This study aims to explore residential environmental factors that may affect respiratory diseases and lung function of children and to assess the effects of lifestyle (diet and exercise) on lung function.MethodsThe study was conducted in Chongqing, southwest of China in June, 2017. Information on respiratory diseases was obtained from 2,126 primary school children through a family questionnaire by purposive sampling. In addition, a random sample of 771 children participating in the family-questionnaire was selected for physical measurements and lung function test as well as lifestyle questionnaire survey. Chi-square test and multivariate logistic regressions were used to analyze the relationship between indoor environment and children’s respiratory diseases. The effects of indoor environment and lifestyle on lung function indices were analyzed by t-test, variance analysis, and univariate and multivariate linear regression methods.ResultsAmong residential environmental factors, indoor ventilation and air circulation were significant associated with children’s respiratory health outcomes. The use of air conditioning for more than 8 h/day in summer was a risk factor for asthma with an adjusted odds ratio (AOR) of 1.99, bronchitis (AOR =1.62), and allergic rhinitis (AOR =1.51). Ventilation for less than 12 h per day during summer increased the risk for allergic rhinitis (AOR =1.40). Children living in homes with an opened kitchen had the risk of developing allergic rhinitis 1.51 times higher than children living in homes with a closed kitchen. Indoor dampness and mold were significantly associated with increased risks for childhood asthma (AOR =2.16), bronchitis (AOR =1.55) and allergic rhinitis (AOR =1.55). The frequent use of hygienic incense and mosquito coils also increased the risk for asthma (AOR =2.58) and bronchitis (AOR =1.42) in children. The multiple linear regression results showed that frequent use of air fresheners reduced children’s peak expiratory flow (PEF) and small airway function (FEF25–75) after potential influencing factors were adjusted for. Analyses of lifestyle variables showed that increased lung function (FVC, FEV1, FEV3) was associated with increasing consumption of vegetable and fruit as well as increasing time of physical exercise.ConclusionsThis study identified the following residential risk factors for children’s respiratory diseases in Chongqing: poor indoor ventilation, home dampness and mold presence, and frequent use of hygienic incense and mosquito coils. Frequent use of air fresheners is associated with reduced lung function in children. High frequency consumption of vegetables, fruits and dairy products as well as daily exercise for more than 1 hour have positive effects on children’s lung development.

Prenatal smoke exposure dysregulates lung epithelial cell differentiation in mouse offspring: role for AREG-induced EGFR signaling.

Prenatal smoke exposure is a risk factor for impaired lung development in children. Recent studies have indicated that amphiregulin (AREG), which is a ligand of the epidermal growth factor receptor (EGFR), has a regulatory role in airway epithelial cell differentiation. In this study, we investigated the effect of prenatal smoke exposure on lung epithelial cell differentiation and linked this with AREG-EGFR signaling in 1-day-old mouse offspring. Bronchial and alveolar epithelial cell differentiations were assessed by immunohistochemistry. Areg, epidermal growth factor (Egf), and mRNA expressions of specific markers for bronchial and alveolar epithelial cells were assessed by RT-qPCR. The results in neonatal lungs were validated in an AREG-treated three-dimensional mouse lung organoid model. We found that prenatal smoke exposure reduced the number of ciliated cells and the expression of the cilia-related transcription factor Foxj1, whereas it resulted in higher expression of mucus-related transcription factors Spdef and Foxm1 in the lung. Moreover, prenatally smoke-exposed offspring had higher numbers of alveolar epithelial type II cells (AECII) and lower expression of the AECI-related Pdpn and Gramd2 markers. This was accompanied by higher expression of Areg and lower expression of Egf in prenatally smoke-exposed offspring. In bronchial organoids, AREG treatment resulted in fewer ciliated cells and more basal cells when compared with non-treated bronchiolar organoids. In alveolar organoids, AREG treatment led to more AECII cells than non-treated AECII cells. Taken together, the observed impaired bronchial and alveolar cell development in prenatally smoke-exposed neonatal offspring may be induced by increased AREG-EGFR signaling.

The Potential Effects of Policy-driven Air Pollution Interventions on Childhood Lung Development.

Rationale: Although elevated air pollution exposure impairs lung-function development in childhood, it remains a challenge to use this information to estimate the potential public health benefits of air pollution interventions in exposed populations.Objectives: Apply G-computation to estimate hypothetical effects of several realistic scenarios for future air pollution reductions on lung growth.Methods: Mixed-effects linear regression was used to estimate FEV1 and FVC from age 11 to 15 years in 2,120 adolescents across 3 cohorts (1993-2001, 1997-2004, and 2007-2011). Models included regional pollutants (nitrogen dioxide [NO2] or particulate matter with an aerodynamic diameter ≤2.5 μm [PM2.5]) and other important covariates. Using G-computation, a causal inference-based method, we then estimated changes in mean lung growth in our population for hypothetical interventions on either NO2 or PM2.5. Confidence intervals (CIs) were computed by bootstrapping (N = 1,000).Measurements and Main Results: Compared with the effects of exposure from observed NO2 concentrations during the study period, had communities remained at 1994 to 1997 NO2 levels, FEV1 and FVC growth were estimated to have been reduced by 2.7% (95% CI, -3.6 to -1.8) and 4.2% (95% CI, -5.2 to -3.4), respectively. If NO2 concentrations had been reduced by 30%, we estimated a 4.4% increase in FEV1 growth (95% CI, 2.8-5.9) and a 7.1% increase in FVC growth (95% CI, 5.7-8.6). Comparable results were observed for PM2.5 interventions.Conclusions: We estimated that substantial increases in lung function would occur as a result of interventions that reduce NO2 or PM2.5 concentrations. These findings provide a quantification of potential health benefits of air quality improvement.

Lung health and exposure to air pollution in Malawian children (CAPS): a cross-sectional study

BackgroundNon-communicable lung disease and exposure to air pollution are major problems in sub-Saharan Africa. A high burden of chronic respiratory symptoms, spirometric abnormalities and air pollution exposures has been found...

Long-Term Exposure to Air Pollution and the Incidence of Chronic Obstructive Pulmonary Disease (COPD) and Asthma: A Population-Based Cohort Study in Ontario, Canada

Background.Air pollution affects respiratory health, particularly children's lung development and exacerbation of chronic obstructive pulmonary disease (COPD). As the role of low air pollution levels in the development of COPD and adult-onset asthma remains uncertain, we examined their associations and characterized the shapes of concentration-response (CR) relationships in Ontario, Canada.Methods.We conducted a population-based cohort study of ~5.1 million adults, who were aged ≥35 years and free of asthma or COPD at baseline. From 2001 to 2015, we estimated 3-year average exposures of fine particles (PM2.5), nitrogen dioxide (NO2), and ozone (O3) from satellite-derived data, land-use regression models, and fusion-based methods, respectively, at residential postal codes. Oxidant capacity (Ox) was the redox-weighted average of NO2 and O3 (Ox). We used Cox proportional hazards models to estimate associations between air pollutants and outcomes, while controlling for individual and contextual covariates. We also conducted sensitivity analyses, such as further adjusting for deprivation. The shape of the CR relationship was examined using newly developed non-linear risk models based on optimal transformation of exposure concentrations.Results.340,733 and 218,005 individuals developed COPD and asthma, respectively. Each interquartile range increase of PM2.5 was associated with a 7% increase in the incidence of COPD (95% CI: 1.06-1.08). Similarly, NO2, O3, and Ox were significantly associated with 3-4% increased risk of COPD. We did not detect any strong evidence linking air pollution to asthma. Similar results were observed in most sensitivity analyses. When adjusting for deprivation, the association between PM2.5 and COPD attenuated slightly (HR 1.04; 1.03-1.05), whereas O3 and Ox attenuated to the null. The CR relationships for COPD showed sublinear associations.Conclusions.Exposure to air pollution was associated with increased COPD incidence, but not with asthma.

The London mayor's views on sustainability

Every year, thousands of Londoners lose their lives prematurely because of our city's filthy air. Toxic air hampers children's lung development and is linked to health problems such as cancer, dementia and heart disease. Health professionals know this better than anyone because they see the consequences of our filthy air first hand in many of their patients. I am one of those patients myself, having been diagnosed with asthma only a few years ago. Analysis from King's College found that most of London's NHS facilities, including hospitals and GP surgeries, are in areas where air pollution is well above legal limits. This harms patients and health workers alike. I refuse to stand idly by while Londoners’ health is threatened in this way. I have made air quality one of my top priorities, implementing the most ambitious clean-air strategy of any city in the world. My package of hard-hitting measures includes a new …

Impact of air pollution in respiratory allergic diseases

Allergic respiratory disease, which includes allergic rhinoconjunctivitis and asthma, is one of the most common diseases, with a major impact on a patient's quality of life. Air pollution is one of the main factors associated with the development of allergic respiratory disease, it has been shown to impair lung development in children and adolescents. The origins of particulate matter produced from various sources, including those issued by traffic and the burning of fuels such as coal, gasoline and diesel. Diesel emissions represent the majority of the particulate matter in urban air pollution. It has been found that the co-exposure of diesel emissions and airborne allergens increases allergen-specific IgE levels, severity of asthma, inflammation and airway hyper-responsiveness. In vivo and in vitro studies have reported the activation of anti-transcription and pro-inflammatory mediators. Polycyclic aromatic hydrocarbons, metal components or metabolites may increase due to the formation of oxygen reactive species that interact with DNA, producing different types of damage as oxidative damage.

Association of Improved Air Quality With Lung Development in Children

WJ Gauderman, R Urman, E Avol. N Engl J Med. 2015;372:905–913 To determine the effects of decreased air pollution in Southern California over 3 separate calendar periods from 1994 to 1998, 1997 to 2001, and 2007 to 2011. Children 11 to 15 years of age living in Southern California communities. There were 2120 children enrolled in 12 Southern California communities, and …

Lung development in children and its relationship to environmental pollution

Lung development in children and its relationship to environmental pollution

Attenuated Airway Epithelial Cell Interleukin-22R1 Expression in the Infant Nonhuman Primate Lung.

Respiratory tract infections are a leading cause of morbidity and mortality in children under 5 years of age. Increased susceptibility to infection is associated with deficiencies in immunity during early childhood. Airway epithelium represents the first line of mucosal defense against inhaled pathogens. However, little is known about epithelial immune mechanisms in the maturing lung. IL-22 and its receptor IL-22R1 are important in host defense and repair of epithelial barriers. The objective of this study was to determine whether a quantitative difference in IL-22R1 exists between infant and adult airways using the rhesus macaque monkey as a model of childhood lung development. Immunofluorescence staining of tracheal tissue revealed minimal expression of IL-22R1 in epithelium at 1 month of age, with a progressive increase in fluorescence-positive basal cells through 1 year of age. Western blot analysis of tracheal lysates confirmed significant age-dependent differences in IL-22R1 protein content. Further, primary tracheobronchial epithelial cell cultures established from infant and adult monkeys showed differential IL-22R1 mRNA and protein expression in vitro. To begin to assess the regulation of age-dependent IL-22R1 expression in airway epithelium, the effect of histone deacetylase and DNA methyltransferase inhibitors was evaluated. IL-22R1 mRNA in adult cultures was not altered by 5-aza-2'-deoxycytidine or trichostatin A. IL-22R1 mRNA in infant cultures showed no change with 5-aza-2'-deoxycytidine but was significantly increased after trichostatin A treatment; however, IL-22R1 protein did not increase concurrently. These data suggest that IL-22R1 in airway epithelium is regulated, in part, by epigenetic mechanisms that are dependent on chronologic age.

Cleaner Air Is Better for Kids' Lungs

Poor air quality has been associated with childhood asthma; however, the potential benefit of improved air quality on lung development in childhood is

Association of Improved Air Quality with Lung Development in Children

BackgroundAir-pollution levels have been trending downward progressively over the past several decades in southern California, as a result of the implementation of air quality–control policies. We assessed whether long-term reductions in pollution were associated with improvements in respiratory health among children.MethodsAs part of the Children’s Health Study, we measured lung function annually in 2120 children from three separate cohorts corresponding to three separate calendar periods: 1994–1998, 1997–2001, and 2007–2011. Mean ages of the children within each cohort were 11 years at the beginning of the period and 15 years at the end. Linear-regression models were used to examine the relationship between declining pollution levels over time and lung-function development from 11 to 15 years of age, measured as the increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) during that period (referred to as 4-year growth in FEV1 and FVC).ResultsOver the 13 years spanned by the three cohorts, improvements in 4-year growth of both FEV1 and FVC were associated with declining levels of nitrogen dioxide (P<0.001 for FEV1 and FVC) and of particulate matter with an aerodynamic diameter of less than 2.5 μm (P= 0.008 for FEV1 and P<0.001 for FVC) and less than 10 μm (P<0.001 for FEV1 and FVC). These associations persisted after adjustment for several potential confounders. Significant improvements in lung-function development were observed in both boys and girls and in children with asthma and children without asthma. The proportions of children with clinically low FEV1 (defined as <80% of the predicted value) at 15 years of age declined significantly, from 7.9% to 6.3% to 3.6% across the three periods, as the air quality improved (P=0.001).ConclusionsWe found that long-term improvements in air quality were associated with statistically and clinically significant positive effects on lung-function growth in children. (Funded by the Health Effects Institute and others.)

Demystifying the air quality health index.

Demystifying the air quality health index.