Search

Study Objective: To compare the expression of plasminogen activators (PA) and plasminogen activator inhibitors (PAI) in normal lung mucosa and lung carcinomas., Design: Immunohistochemical localization of urokinase-type PA (uPA), tissue-type PA (tPA), type 1 PAI (PAI-1), and type 2 PAI (PAI-2) in four normal lung biopsy specimens and in four adenocarcinomas (AC), four squamous carcinomas (SC), two large-cell carcinomas (LCC), and ten small-cell carcinomas (SCC) biopsy specimens. Qualitative immunostaining scoring system., Results: tPA and uPA immunostaining scores from all specimens were statistically similar. The cellular staining for uPA and tPA was generally constant (normal epithelial layers, AC cells, SC cells) except for LCC cells (inconstant uPA staining, p < 10(-3). Both PAIs were detected in cells of the normal epithelial layer. The four carcinoma cell types stained for PAI in a statistically different pattern (p < 10(-3)). Cells of the peripheral cords of SCC were inconstantly PAI-1 and PAI-2 positive (p < 10(-3)). LCC were PAI-2 negative and inconstantly stained for PAI-1. SCC cells were PAI-1 and PAI-2 negative., Conclusion: Lung carcinomas of worst clinical prognosis no longer express PAI reactivity. The imbalance of the plasminogen activation pathway may favor the spreading of the more invasive histologic types of bronchogenic carcinomas.

We report two cases of pneumothorax detected by echographic examination immediately after ultrasonically guided aspiration biopsy and confirmed by chest x-ray film. The pneumothorax was characterized by the disappearance of the lung tumor. In the real-time image, the respiratory excursions of the visceral pleura also disappeared.

Ground level ozone is a potent respiratory toxicant with decades of accumulated data demonstrating respiratory harms to children. Despite the ubiquity of ozone in the United States, impacting both urban and rural communities, the associated harms of exposure to this important air pollutant are often infrequently or inadequately covered during medical training including pulmonary specialization. Thus, many providers caring for childrens respiratory health may have limited knowledge of the harms which may result in reduced discussion of ozone pollution during clinical encounters. Further, the current US air quality standard for ozone does not adequately protect children. In this nonsystematic review, we present basic background information for healthcare providers caring for childrens respiratory health, review the US process for setting air quality standards, discuss the respiratory harms of ozone for healthy children and those with underlying respiratory disease, highlight the urgent need for a more protective ozone standard to adequately protect childrens respiratory health, review impacts of climate change on ozone levels, and provide information for discussion in clinical encounters.

BackgroundEvidence in the literature suggests that air pollution exposures experienced prenatally and early in life can be detrimental to normal lung development, however the specific timing of critical windows during development is not fully understood.ObjectivesWe evaluated air pollution exposures during the prenatal and early-life period in association with lung function at ages 6-9, in an effort to identify potentially influential windows of exposure for lung development.MethodsOur study population consisted of 222 children aged 6-9 from the Fresno-Clovis metro area in California with spirometry data collected between May 2015 and May 2017. We used distributed-lag non-linear models to flexibly model the exposure-lag-response for monthly average exposure to fine particulate matter (PM2.5) and ozone (O3) during the prenatal months and first three years of life in association with forced vital capacity (FVC), and forced expiratory volume in the first second (FEV1), adjusted for covariates.ResultsPM2.5 exposure during the prenatal period and the first 3-years of life was associated with lower FVC and FEV1 assessed at ages 6-9. Specifically, an increase from the 5th percentile of the observed monthly average exposure (7.55 μg/m3) to the median observed exposure (12.69 μg/m3) for the duration of the window was associated with 0.42 L lower FVC (95% confidence interval (CI): -0.82, -0.03) and 0.38 L lower FEV1 (95% CI: -0.75, -0.02). The shape of the lag-response indicated that the second half of pregnancy may be a particularly influential window of exposure. Associations for ozone were not as strong and typically CIs included the null.ConclusionsOur findings indicate that prenatal and early-life exposures to PM2.5 are associated with decreased lung function later in childhood. Exposures during the latter months of pregnancy may be especially influential.

BackgroundExposure to ozone (O3) is associated with increased risk of exacerbations of asthma, but the underlying mechanisms are not well studied.ObjectiveWe sought to determine whether O3 exposure would enhance airway inflammatory responses to allergen and the GSTM1-null genotype would modulate this enhancement.MethodsIn a crossover design, 10 asthmatic participants (5 with GSTM1-null genotype) who had specific sensitization to Dermatophagoides pteronyssinus (DP) were exposed to 160 ppb O3 or filtered air (FA) control for 4 hours on 2 separate days at least 3 weeks apart. At 20 hours after exposure, endobronchial challenge with DP allergen, and sham normal saline (NS) instillation, were performed in separate bronchi. Six hours later, a second bronchoscopy was performed to collect bronchoalveolar lavage (BAL) from the DP- and NS-challenged segments for analyses of inflammatory biomarkers. Linear regression compared cell and cytokine responses across the 4 exposure groups (FA-NS, O3-NS, FA-DP, O3-DP). Effect modification by GSTM1 genotype was assessed in stratified regressions.ResultsBAL eosinophil counts were increased in segments challenged with DP compared to sham-challenged segments (P < .01). DP challenge compared to sham also caused a significant increase in BAL concentrations of the TH2 cytokines IL-4, IL-5, IL-10, and IL-13 (P < .03 for all comparisons). O3 exposure did not significantly affect BAL cells or cytokine after DP challenge. Compared to GSTM1-present participants, GSTM1-null participants had significantly lower eosinophil (P < .041) and IL-4 (P < .014) responses to DP challenge after O3 exposure.ConclusionsWhile O3 did not cause a clear differential effect on airway inflammatory responses to allergen challenge, those responses did appear to be modulated by the antioxidant enzyme, GSTM1.

Previous studies have reported associations between air pollution and COVID-19 morbidity and mortality, but most have limited their exposure assessment to a large area, have not used individual-level variables, nor studied infections. We examined 3.1 million SARS-CoV-2 infections and 49,691 COVID-19 deaths that occurred in California from February 2020 to February 2021 to evaluate risks associated with long-term neighborhood concentrations of particulate matter less than 2.5 μm in diameter (PM2.5). We obtained individual address data on SARS-CoV-2 infections and COVID-19 deaths and assigned 2000-2018 1km-1km gridded PM2.5 surfaces to census block groups. We included individual covariate data on age and sex, and census block data on race/ethnicity, air basin, Area Deprivation Index, and relevant comorbidities. Our analyses were based on generalized linear mixed models utilizing a Poisson distribution. Those living in the highest quintile of long-term PM2.5 exposure had risks of SARS-CoV-2 infections 20% higher and risks of COVID-19 mortality 51% higher, compared to those living in the lowest quintile of long-term PM2.5 exposure. Those living in the areas of highest long-term PM2.5 exposure were more likely to be Hispanic and more vulnerable, based on the Area Deprivation Index. The increased risks for SARS-CoV-2 Infections and COVID-19 mortality associated with highest long-term PM2.5 concentrations at the neighborhood-level in California were consistent with a growing body of literature from studies worldwide, and further highlight the importance of reducing levels of air pollution to protect public health.

BackgroundPrevious research has revealed links between air pollution exposure and metabolic syndrome in adults; however, these associations are less explored in children.ObjectiveThis study aims to investigate the association between traffic-related air pollutants (TRAP) and biomarkers of metabolic dysregulation, oxidative stress, and lung epithelial damage in children.MethodsWe conducted cross-sectional analyses in a sample of predominantly Latinx, low-income children (n = 218) to examine associations between air pollutants (nitrogen dioxide (NO2), nitrogen oxides (NOx), elemental carbon, polycyclic aromatic hydrocarbons, carbon monoxide (CO), fine particulates (PM2.5)) and biomarkers of metabolic function (high-density lipoprotein (HDL), hemoglobin A1c (HbA1c), oxidative stress (8-isoprostane), and lung epithelial damage (club cell protein 16 (CC16)).ResultsHDL cholesterol showed an inverse association with NO2 and NOx, with the strongest relationship between HDL and 3-month exposure to NO2 (-15.4 mg/dL per IQR increase in 3-month NO2, 95% CI = -27.4, -3.4). 8-isoprostane showed a consistent pattern of increasing values with 1-day and 1-week exposure across all pollutants. Non-significant increases in % HbA1c were found during 1-month time frames and decreasing CC16 in 3-month exposure time frames.ConclusionOur results suggest that TRAP is significantly associated with decreased HDL cholesterol in longer-term time frames and elevated 8-isoprostane in shorter-term time frames. TRAP could have the potential to influence lifelong metabolic patterns, through metabolic effects in childhood.

SETTING: Household air pollution (HAP) and chronic obstructive pulmonary disease (COPD) are both major public health problems, reported to cause around 4 million and 3 million deaths every year, respectively. The great majority of these deaths, as well as the burden of disease during life is felt by people in low- and middle-income countries (LMICs).OBJECTIVE and DESIGN: The extent to which HAP causes COPD is controversial; we therefore undertook this review to offer a viewpoint on this from the Global Initiative for COPD (GOLD).RESULTS: We find that while COPD is well-defined in many studies on COPD and HAP, there are major limitations to the definition and measurement of HAP. It is thus difficult to disentangle HAP from other features of poverty that are themselves associated with COPD. We identify other limitations to primary research studies, including the use of cross-sectional designs that limit causal inference.CONCLUSION: There is substantial preventable morbidity and mortality associated with HAP, COPD and poverty, separately and together. Although it may not be possible to define clear causal links between HAP and COPD, there is a clear urgency to reduce the avoidable burden of disease these inflict on the world´s poor.

Women and children in rural regions of low-income countries are exposed to high levels of household air pollution (HAP) as they traditionally tend to household chores such as cooking with biomass fuels. Early life exposure to air pollution is associated with aeroallergen sensitization and developing allergic diseases at older ages. This prospective cohort study assigned HAP-reducing chimney stoves to 557 households in rural Guatemala at different ages of the study children. The children's air pollution exposure was measured using personal CO diffusion tubes. Allergic outcomes at 4-5 years old were assessed using skin prick tests and International Study of Asthma and Allergies in Childhood (ISAAC)-based questionnaires. Children assigned to improved stoves before 6 months old had the lowest HAP exposure compared to the other groups. Longer exposure to the unimproved stoves was associated with higher risks of maternal-reported allergic asthma (OR = 2.42, 95% CI: 1.11-5.48) and rhinitis symptoms (OR = 2.01, 95% CI: 1.13-3.58). No significant association was found for sensitization to common allergens such as dust mites and cockroaches based on skin prick tests. Reducing HAP by improving biomass burning conditions might be beneficial in preventing allergic diseases among children in rural low-income populations.

BACKGROUND: The greatest burden of chronic respiratory disease is in low- and middle-income countries, with recent population-based studies reporting substantial levels of obstructive and restrictive lung function.OBJECTIVE: To characterise the common chronic respiratory diseases encountered in hospital outpatient clinics in three African countries.METHODS This was a cross-sectional study of consecutive adult patients with chronic respiratory symptoms (>8 weeks) attending hospital outpatient departments in Ethiopia, Kenya and Sudan. Patients were assessed using a respiratory questionnaire, spirometry and chest radiography. The diagnoses of the reviewing clinicians were ascertained.RESULT: A total of 519 patients (209 Kenya, 170 Ethiopia, 140 Sudan) participated; the mean age was 45.2 years (SD 16.2); 53% were women, 83% had never smoked. Reviewing clinicians considered that 36% (95% CI 32-40) of patients had asthma, 25% (95% CI 21-29) had chronic bronchitis, 8% (95% CI 6-11) chronic obstructive pulmonary disease (COPD), 5% (95% CI 4-8) bronchiectasis and 4% (95% CI 3-6) post-TB lung disease. Spirometry consistent with COPD was present in 35% (95% CI 30-39). Restriction was evident in 38% (95% CI 33-43). There was evidence of sub-optimal diagnosis of asthma and COPD.CONCLUSION: In Ethiopia, Kenya and Sudan, asthma, COPD and chronic bronchitis account for the majority of diagnoses in non-TB patients with chronic respiratory symptoms. The suboptimal diagnosis of these conditions will require the widespread use of spirometry.

BackgroundOzone effects on lung function are particularly important to understand in the context of the air pollution-health outcomes epidemiologic literature, given the complex relationships between ozone and other air pollutants with known lung function effects.Research questionWhat has been learned about the association between ozone exposures and lung function from epidemiology studies published from 2013 through 2020?Study design and methodsOn March 18, 2018, and September 8, 2020, PubMed was searched using the terms health AND ozone, filtering to articles in English and about humans, from 2013 or later. An additional focused review searching for ozone AND (lung function OR FEV1OR FVC) was performed June 26, 2021. Articles were selected for this review if they reported a specific relationship between a lung function outcome and ozone exposure.ResultsOf 3,271 articles screened, 53 ultimately met criteria for inclusion. A systematic review with assessment of potential for bias was conducted, but a meta-analysis was not carried out because of differences in exposure duration and outcome quantification. Consistent evidence exists of small decreases in children's lung function, even associated with very low levels of short-term ozone exposure. The effects on adult lung function from exposure to low-level, short-term ozone are less clear, although ozone-associated decrements may occur in the elderly. Finally, long-term ozone exposure decreases both lung function and lung function growth in children, although few new studies have examined long-term ozone and lung function in adults.InterpretationMuch of this literature involves concentrations below the current US Environmental Protection Agency's National Ambient Air Quality Standard of 70 parts per billion over an 8-h averaging time, suggesting that this current standard may not protect children adequately from ozone-related decrements in lung function.

Rationale: The Southeast Asian tuberculosis burden is high, and it remains unclear if urban indoor air pollution in this setting is exacerbating the epidemic. Objectives: To determine the associations of latent tuberculosis with common urban indoor air pollution sources (secondhand smoke, indoor motorcycle emissions, and cooking) in Southeast Asia. Methods: We enrolled child household contacts of patients with microbiologically confirmed active tuberculosis in Vietnam, from July 2017 to December 2019. We tested children for latent tuberculosis and evaluated air pollution exposures with questionnaires and personal aerosol sampling. We tested hypotheses using generalized estimating equations. Measurements and Main Results: We enrolled 72 patients with tuberculosis (27% with cavitary disease) and 109 of their child household contacts. Latent tuberculosis was diagnosed in 58 (53%) household contacts at baseline visit. Children experienced a 2.56-fold increased odds of latent tuberculosis for each additional household member who smoked (95% confidence interval, 1.27-5.16). Odds were highest among children exposed to indoor smokers and children

BackgroundIn Sub-Saharan Africa cross-sectional studies report a high prevalence of abnormal lung function indicative of chronic respiratory disease. The natural history and health impact of this abnormal lung function in low-and middle-income countries is largely unknown.MethodsA cohort of 1481 adults representative of rural Chikwawa in Malawi were recruited in 2014 and followed-up in 2019. Respiratory symptoms and health-related quality of life (HRQoL) were quantified. Lung function was measured by spirometry.Findings1232 (83%) adults participated; spirometry was available for 1082 (73%). Mean (SD) age 49.5 (17.0) years, 278(23%) had ever smoked, and 724 (59%) were women. Forced expiratory volume in one second (FEV1) declined by 53.4 ml/year (95% CI: 49.0, 57.8) and forced vital capacity (FVC) by 45.2 ml/year (95% CI: 39.2, 50.5) . Chronic airflow obstruction increased from 9.5% (7.6, 11.6%) in 2014 to 17.5% (15.3, 19.9%) in 2019. There was no change in diagnosed asthma or in spirometry consistent with asthma or restriction. Rate of FEV1 decline was not associated with diagnosed Chronic obstructive pulmonary disease (COPD), asthma, or spirometry consistent with asthma, COPD, or restriction. HRQoL was adversely associated with respiratory symptoms (dyspnoea, wheeze, cough), previous tuberculosis, declining FEV1 and spirometry consistent with asthma or restriction. These differences exceeded the minimally important difference.InterpretationIn this cohort, the increasing prevalence of COPD is associated with the high rate of FEV1 decline and lung function deficits present before recruitment. Respiratory symptoms and sub-optimal lung function are independently associated with reduced HRQoL.

Wildland fires are diminishing air quality on a seasonal and regional basis, raising concerns about respiratory health risks to the public and occupational groups. This American Thoracic Society (ATS) workshop was convened in 2019 to meet the growing health threat of wildland fire smoke. The workshop brought together a multidisciplinary group of 19 experts, including wildland fire managers, public health officials, epidemiologists, toxicologists, and pediatric and adult pulmonologists. The workshop examined the following four major topics: 1) the science of wildland fire incidence and fire management, 2) the respiratory and cardiovascular health effects of wildland fire smoke exposure, 3) communication strategies to address these health risks, and 4) actions to address wildland fire health impacts. Through formal presentations followed by group discussion, workshop participants identified top priorities for fire management, research, communication, and public policy to address health risks of wildland fires. The workshop concluded that short-term exposure to wildland smoke causes acute respiratory health effects, especially among those with asthma and chronic obstructive pulmonary disease. Research is needed to understand long-term health effects of repeated smoke exposures across fire seasons for children, adults, and highly exposed occupational groups (especially firefighters). Other research priorities include fire data collection and modeling, toxicology of different fire fuel sources, and the efficacy of health protective measures to prevent respiratory effects of smoke exposure. The workshop committee recommends a unified federal response to the growing problem of wildland fires, including investment in fire behavior and smoke air quality modeling, research on the health impacts of smoke, and development of robust clinical and public health communication tools.

Throughout the United States, wildland firefighters respond to wildfires, performing arduous work in remote locations. Wildfire incidents can be an ideal environment for the transmission of infectious diseases, particularly for wildland firefighters who congregate in work and living settings. In this review, we examine how exposure to wildfire smoke can contribute to an increased likelihood of SARS-CoV-2 infection and severity of coronavirus disease (COVID-19). Human exposure to particulate matter (PM), a component of wildfire smoke, has been associated with oxidative stress and inflammatory responses; increasing the likelihood for adverse respiratory symptomology and pathology. In multiple epidemiological studies, wildfire smoke exposure has been associated with acute lower respiratory infections, such as bronchitis and pneumonia. Co-occurrence of SARS-CoV-2 infection and wildfire smoke inhalation may present an increased risk for COVID-19 illness in wildland firefighters due to PM based transport of SARS CoV-2 virus and up-regulation of angiotensin-converting enzyme II (ACE-2) (i.e. ACE-2 functions as a trans-membrane receptor, allowing the SARS-CoV-2 virus to gain entry into the epithelial cell). Wildfire smoke exposure may also increase risk for more severe COVID-19 illness such as cytokine release syndrome, hypotension, and acute respiratory distress syndrome (ARDS). Current infection control measures, including social distancing, wearing cloth masks, frequent cleaning and disinfecting of surfaces, frequent hand washing, and daily screening for COVID-19 symptoms are very important measures to reduce infections and severe health outcomes. Exposure to wildfire smoke may introduce additive or even multiplicative risk for SARS-CoV-2 infection and severity of disease in wildland firefighters. Thus, additional mitigative measures may be needed to prevent the co-occurrence of wildfire smoke exposure and SARS-CoV-2 infection.

We review the interaction between coronavirus disease (COVID-19) and coccidioidomycosis, a respiratory infection caused by inhalation of Coccidioides fungal spores in dust. We examine risk for co-infection among construction and agricultural workers, incarcerated persons, Black and Latino populations, and persons living in high dust areas. We further identify common risk factors for co-infection, including older age, diabetes, immunosuppression, racial or ethnic minority status, and smoking. Because these diseases cause similar symptoms, the COVID-19 pandemic might exacerbate delays in coccidioidomycosis diagnosis, potentially interfering with prompt administration of antifungal therapies. Finally, we examine the clinical implications of co-infection, including severe COVID-19 and reactivation of latent coccidioidomycosis. Physicians should consider coccidioidomycosis as a possible diagnosis when treating patients with respiratory symptoms. Preventive measures such as wearing face masks might mitigate exposure to dust and severe acute respiratory syndrome coronavirus 2, thereby protecting against both infections.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the pediatric pulmonary medicine core, including pediatric hypoxemic respiratory failure; modalities in noninvasive management of chronic respiratory failure in childhood; surgical and nonsurgical management of congenital lung malformations; an update on smoke inhalation lung injury; an update on vaporizers, e-cigarettes, and other electronic delivery systems; pulmonary complications of sarcoidosis; pulmonary complications of congenital heart disease; and updates on the management of congenital diaphragmatic hernia.

BackgroundAmbient environmental pollutants have been shown to adversely affect respiratory health in susceptible populations. However, the role of simultaneous exposure to multiple diverse environmental pollutants is poorly understood.ObjectiveWe applied a multidomain, multipollutant approach to assess the association between pediatric lung function measures and selected ambient air pollutants and pesticides.MethodsUsing data from the US EPA and California Pesticide Use Registry, we reconstructed three months prior exposure to ambient air pollutants ((ozone (O3), nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter

BackgroundExposure to household air pollution is associated with an increased risk of pneumonia in children in low- and middle-income countries; however, exposure-response data are limited, and there are uncertainties around the extent to which biomass-fueled cookstoves can reduce these exposures.Research questionWhat is the association between exposure to household air pollution and pneumonia in children under the age of 5 years in rural Malawi and what are the effects of a biomass-fueled cookstove intervention on personal exposure to household air pollution?Study design and methodsWe measured personal exposure to carbon monoxide (CO; 48 hours of continuous measurement and transcutaneous carboxyhemoglobin) every 6 months in children who participated in a cluster-randomized controlled trial of a cleaner burning biomass-fueled cookstove intervention to prevent pneumonia in children under the age of 5 years in rural Malawi (the Cooking And Pneumonia Study). Exposure-response and multivariable analyses were done.ResultsWe recruited 1805 (928 intervention; 877 control) children (mean age, 25.6 months; 50.6% female). We found no evidence of an association between exposure to CO (incident rate ratio, 1.0; 95% CI, 0.967 to 1.014; P = .53) or carboxyhemoglobin (incident rate ratio, 1.00; 95% CI, 0.993 to 1.003; P = .41) in children who experienced pneumonia vs those who did not. Median exposure to CO in the intervention and control groups was was 0.34 (interquartile range, 0.15 to 0.81) and 0.37 parts per million (interquartile range, 0.15 toa 0.97), respectively. The group difference in means was 0.46 (95% CI, -0.95 to 0.012; P = .06).InterpretationExposure to CO in our population was low with no association seen between exposure to CO and pneumonia incidence and no effect of the Cooking And Pneumonia Study intervention on these exposures. These findings suggest that CO may not be an appropriate measure of household air pollution exposure in settings such as rural Malawi and that there is a need to develop ways to measure particulate matter exposures directly in young children instead.Clinical trial registrationISRCTN59448623.

BackgroundChemicals found in personal care products and plastics have been associated with asthma, allergies, and lung function, but methods to address real life exposure to mixtures of these chemicals have not been applied to these associations.MethodsWe quantified urinary concentrations of eleven phthalate metabolites, four parabens, and five other phenols in mothers twice during pregnancy and assessed probable asthma, aeroallergies, and lung function in their age seven children. We implemented Bayesian Profile Regression (BPR) to cluster women by their exposures to these chemicals and tested the clusters for differences in outcome measurements. We used Bayesian Kernel Machine Regression (BKMR) to fit biomarkers into one model as joint independent variables.ResultsBPR clustered women into seven groups characterized by patterns of personal care product and plastic use, though there were no significant differences in outcomes across clusters. BKMR showed that monocarboxyisooctyl phthalate and 2,4-dichlorophenol were associated with probable asthma (predicted probability of probable asthma per IQR of biomarker z-score (standard deviation) = 0.08 (0.09) and 0.11 (0.12), respectively) and poorer lung function (predicted probability per IQR = -0.07 (0.05) and -0.07 (0.06), respectively), and that mono(3-carboxypropyl) phthalate and bisphenol A were associated with aeroallergies (predicted probability per IQR = 0.13 (0.09) and 0.11 (0.08), respectively). Several biomarkers demonstrated positive additive effects on other associations.ConclusionsBPR and BKMR are useful tools to evaluate associations of biomarker concentrations within a mixture of exposure and should supplement single-chemical regression models when data allow.

BackgroundWe previously reported chronic respiratory effects in children who were then 7-17 years of age in Matlab, Bangladesh. One group of children had been exposed to high concentrations of arsenic in drinking water in utero and early childhood (average 436 µg/L), and the other group of children were never known to have been exposed to >10 µg/L. The exposed children, both males and females, had marked increases in chronic respiratory symptoms.MethodsThe current study involves a further follow-up of these children now 14-26 years of age with 463 located and agreeing to participate. They were interviewed for respiratory symptoms and lung function was measured. Data were collected on smoking, body mass index (BMI), and number of rooms in the house as a measure of socioeconomic status.ResultsRespiratory effects were still present in males but not females. In the high exposure group (>400 µg/L in early life) the odds ratio (OR) among male participants for dry cough in the last 12 months was 2.36 (95% confidence interval [CI] = 1.21, 4.63, P = 0.006) and for asthma OR = 2.51 (95% CI = 1.19, 5.29, P = 0.008). Forced vital capacity (FVC) was reduced in males in the early life high-exposure group compared with those never exposed (-95ml, P = 0.04), but not in female participants.ConclusionsBy the age range 14-26, there was little remaining evidence of chronic respiratory effects in females but pronounced effects persisted in males. Mechanisms for the marked male female differences warrant further investigation along with further follow-up to see if respiratory effects continue in males.

Although it is well accepted that air pollution exposure exacerbates preexisting airway disease, it has not been firmly established that long-term pollution exposure increases the risk of new-onset asthma or chronic obstruction pulmonary disease (COPD). This Workshop brought together experts on mechanistic, epidemiological, and clinical aspects of airway disease to review current knowledge regarding whether air pollution is a causal factor in the development of asthma and/or COPD. Speakers presented recent evidence in their respective areas of expertise related to air pollution and new airway disease incidence, followed by interactive discussions. A writing committee summarized their collective findings. The Epidemiology Group found that long-term exposure to air pollution, especially metrics of traffic-related air pollution such as nitrogen dioxide and black carbon, is associated with onset of childhood asthma. However, the evidence for a causal role in adult-onset asthma or COPD remains insufficient. The Mechanistic Group concluded that air pollution exposure can cause airway remodeling, which can lead to asthma or COPD, as well as asthma-like phenotypes that worsen with long-term exposure to air pollution, especially fine particulate matter and ozone. The Clinical Group concluded that air pollution is a plausible contributor to the onset of both asthma and COPD. Available evidence indicates that long-term exposure to air pollution is a cause of childhood asthma, but the evidence for a similar determination for adult asthma or COPD remains insufficient. Further research is needed to elucidate the exact biological mechanism underlying incident childhood asthma, and the specific air pollutant that causes it.

RationaleThere are no population-based studies from sub-Saharan Africa describing longitudinal lung function in adults.ObjectivesTo explore the lung function trajectories and their determinants, including the effects of air pollution exposures and the cleaner-burning biomass-fuelled cookstove intervention of the Cooking and Pneumonia Study (CAPS), in adults living in rural Malawi.MethodsWe assessed respiratory symptoms and exposures, spirometry and measured 48-hour personal exposure to fine particulate matter (PM2.5) and carbon monoxide (CO), on three occasions over 3 years. Longitudinal data were analysed using mixed-effects modelling by maximum likelihood estimation.Measurements and main resultsWe recruited 1481 adults, mean (SD) age 43.8 (17.8) years, including 523 participants from CAPS households (271 intervention; 252 controls), and collected multiple spirometry and air pollution measurements for 654 (44%) and 929 (63%), respectively. Compared with Global Lung Function Initiative African-American reference ranges, mean (SD) FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) z-scores were -0.38 (1.14) and -0.19 (1.09). FEV1 and FVC were determined by age, sex, height, previous TB and body mass index, with FEV1 declining by 30.9 mL/year (95% CI: 21.6 to 40.1) and FVC by 38.3 mL/year (95% CI: 28.5 to 48.1). There was decreased exposure to PM2.5 in those with access to a cookstove but no effect on lung function.ConclusionsWe did not observe accelerated lung function decline in this cohort of Malawian adults, compared with that reported in healthy, non-smoking populations from high-income countries; this suggests that the lung function deficits we measured in adulthood may have origins in early life.

Background: Exposure to household air pollution generated as a result of cooking and heating is a leading contributor to global disease. The effects of cookstove-generated air pollution on adult lung function, however, remain uncertain.Objectives: We investigated acute responses in lung function following controlled exposures to cookstove-generated air pollution.Methods: We recruited 48 healthy adult volunteers to undergo six two-hour treatments: a filtered-air control and emissions from five different stoves with fine particulate matter (PM2.5) targets from 10 to 500 µg/m3. Spirometry was conducted prior to exposure and immediately, and three and 24 h post-exposure. Mixed-effect models were used to estimate differences in post-exposure lung function for stove treatments versus control.Results: Immediately post-exposure, lung function was lower compared to the control for the three highest PM2.5-level stoves. The largest differences were for the fan rocket stove (target 250 µg/m3; forced vital capacity (FVC): -60 mL, 95% confidence interval (95% CI) -135, 15; forced expiratory volume (FEV1): -51 mL, 95% CI -117, 16; mid-expiratory flow (FEF25-75): -116 mL/s, 95% CI -239, 8). At 3 h post-exposure, lung function was lower compared to the control for all stove treatments; effects were of similar magnitude for all stoves. At 24 h post-exposure, results were consistent with a null association for FVC and FEV1; FEF25-75 was lower relative to the control for the gasifier, fan rocket, and three stone fire.Conclusions: Patterns suggesting short-term decreases in lung function follow from exposure to cookstove air pollution even for stove exposures with low PM2.5 levels.

BACKGROUND: Indoor and ambient air pollution exposure is a major risk to respiratory health worldwide, particularly in low- and middle-income countries (LMICs). Interventional trials have mainly focused on alternatives to cooking stoves, with mixed results. Beyond cooking, additional sources of particulate matter also contribute to the burden of air pollution exposure. This review explores evidence from current randomised controlled trials (RCTs) on the clinical effectiveness of interventions to reduce particulate matter in LMICs.METHODS: Twelve databases and the grey literature (e.g., Government reports and policy papers) were searched. Eligible studies were RCTs conducted in LMICs aiming to reduce particulate exposure from any source and reporting on at least one clinical respiratory outcome (respiratory symptoms, lung function or clinical diagnoses). Data from relevant studies were systematically extracted, the risk of bias assessed and narrative synthesis provided.RESULTS: Of the 14 included studies, 12 tested 'improved' cookstoves, most using biomass, but solar and bioethanol cookers were also included. One trial used solar lamps and another was an integrated intervention incorporating behavioural and environmental components for the treatment and prevention of chronic obstructive pulmonary disease. Of the six studies reporting child pneumonia outcomes, none demonstrated significant benefit in intention-to-treat analysis. Ten studies reported respiratory symptom outcomes with some improvements seen, but self-reporting made these outcomes highly vulnerable to bias. Substantial inter-study clinical and methodological heterogeneity precluded calculation of pooled effect estimates.CONCLUSION: Evidence from the RCTs performed to date suggests that individual household-level interventions for air pollution exposure reduction have limited benefits for respiratory health. More comprehensive approaches to air pollution exposure reduction must be developed so their potential health benefits can be assessed.

BackgroundAsthma disproportionately affects communities of colour in the USA, but the underlying factors for this remain poorly understood. In this study, we assess the role of historical redlining as outlined in security maps created by the Home Owners' Loan Corporation (HOLC), the discriminatory practice of categorising neighbourhoods on the basis of perceived mortgage investment risk, on the burden of asthma in these neighbourhoods.MethodsWe did an ecological study of HOLC risk grades and asthma exacerbations in California using the security maps available for the following eight cities: Fresno, Los Angeles, Oakland, Sacramento, San Diego, San Jose, San Francisco, and Stockton. Each census tract was categorised into one of four risk levels (A, B, C, or D) on the basis of the location of population-weighted centroids on security maps, with the worst risk level (D) indicating historical redlining. We obtained census tract-level rates of emergency department visits due to asthma from CalEnviroScreen 3.0. We assessed the relationship between risk grade and log-transformed asthma visit rates between 2011 and 2013 using ordinary least squares regression. We included potential confounding variables from the 2010 Census and CalEnviroScreen 3.0: diesel exhaust particle emissions, PM2·5, and percent of the population living below 2 times the federal poverty level. We also built random intercept and slope models to assess city-level variation in the relationship between redlining and asthma.FindingsIn the 1431 census tracts assessed (64 [4·5%] grade A, 241 [16·8%] grade B, 719 [50·2%] grade C, and 407 [28·4%] grade D), the proportion of the population that was non-Hispanic black and Hispanic, the percentage of the population living in poverty, and diesel exhaust particle emissions all significantly increased as security map risk grade worsened (p

ObjectiveOccupational dust exposure has been associated with accelerated lung function decline, which in turn is associated with overall morbidity and mortality. In the current study, we assess potential benefits on lung function of hypothetical interventions that would reduce occupational exposure to fine particulate matter (PM2.5) while adjusting for the healthy worker survivor effect.MethodsAnalyses were performed in a cohort of 6485 hourly male workers in an aluminium manufacturing company in the USA, followed between 1996 and 2013. We used the parametric g-formula to assess lung function decline over time under hypothetical interventions while also addressing time-varying confounding by underlying health status, using a composite risk score based on health insurance claims.ResultsA counterfactual scenario envisioning a limit on exposure equivalent to the 10th percentile of the observed exposure distribution of 0.05 mg/m3 was associated with an improvement in forced expiratory volume in one second (FEV1) equivalent to 37.6 mL (95% CI 13.6 to 61.6) after 10 years of follow-up when compared with the observed. Assuming a linear decrease and (from NHANES reference values), a 20 mL decrease per year for a 1.8 m-tall man as they age, this 37.6 mL FEV1 loss over 10 years associated with observed exposure would translate to approximately a 19% increase to the already expected loss per year from age alone.ConclusionsOur results indicate that occupational PM2.5 exposure in the aluminium industry accelerates lung function decline over age. Reduction in exposure may mitigate accelerated loss of lung function over time in the industry.

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 in Malawian adults; whether the same would be true in children is unknown.MethodsThis cross-sectional study of children aged 6-8 years, in rural Malawi, included households from communities participating in the Cooking and Pneumonia Study (CAPS), a trial of cleaner-burning biomass-fuelled cookstoves. We assessed; chronic respiratory symptoms, anthropometry, spirometric abnormalities (using Global Lung Initiative equations) and personal carbon monoxide (CO) exposure. Prevalence estimates were calculated, and multivariable analyses were done.ResultsWe recruited 804 children (mean age 7.1 years, 51.9% female), including 476 (260 intervention; 216 control) from CAPS households. Chronic respiratory symptoms (mainly cough (8.0%) and wheeze (7.1%)) were reported by 16.6% of children. Average height-for-age and weight-for-age z-scores were -1.04 and -1.10, respectively. Spirometric abnormalities (7.1% low forced vital capacity (FVC); 6.3% obstruction) were seen in 13.0% of children. Maximum CO exposure and carboxyhaemoglobin levels (COHb) exceeded WHO guidelines in 50.1% and 68.5% of children, respectively. Children from CAPS intervention households had lower COHb (median 3.50% vs 4.85%, p=0.006) and higher FVC z-scores (-0.22 vs -0.44, p=0.05) than controls.ConclusionThe substantial burden of chronic respiratory symptoms, abnormal spirometry and air pollution exposures in children in rural Malawi is concerning; effective prevention and control strategies are needed. Our finding of potential benefit in CAPS intervention households calls for further research into clean-air interventions to maximise healthy lung development in children.

BackgroundTelomere length (TL) can serve as a potential biomarker for conditions associated with chronic oxidative stress and inflammation, such as asthma. Air pollution can induce oxidative stress. Understanding the relationship between TL, asthma, and air pollution is important for identifying risk factors contributing to unhealthy aging in children.ObjectivesWe sought to investigate associations between exposures to ambient air pollutants and TL in African American children and adolescents and to examine whether African ancestry, asthma status, and steroid medication use alter the association.MethodsLinear regression was used to examine associations between absolute telomere length (aTL) and estimated annual average residential ozone (O3) and fine particulate matter with a diameter of 2.5 μm or less (PM2.5) exposures in a cross-sectional analysis of 1072 children in an existing asthma case-control study. African ancestry, asthma status, and use of steroid medications were examined as effect modifiers.ResultsParticipants' aTLs were measured by using quantitative PCR. A 1-ppb and 1 μg/m3 increase in annual average exposure to O3 and PM2.5 were associated with a decrease in aTL of 37.1 kilo-base pair (kb; 95% CI, -66.7 to -7.4 kb) and 57.1 kb (95% CI, -118.1 to 3.9 kb), respectively. African ancestry and asthma were not effect modifiers; however, exposure to steroid medications modified the relationships between TL and pollutants. Past-year exposure to O3 and PM2.5 was associated with shorter TLs in patients without steroid use.ConclusionExposure to air pollution was associated with shorter TLs in nonasthmatic children and adolescents. This was not the case for asthmatic children as a group, but those receiving steroid medication had less shortening than those not using steroids. Reduced exposure to air pollution in childhood might help to preserve TL.

BackgroundChronic exposures to particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) and ozone pollution can affect respiratory function. ARDS, an often lethal respiratory failure, is most common among older adults. However, few epidemiology studies have investigated an association between air pollution and the risk of ARDS.MethodsThis observational study was conducted to estimate air pollution exposures at the ZIP code level and hospital admissions with ARDS among US Medicare beneficiaries aged ≥ 65 years from 2000 to 2012. A two-pollutant generalized linear mixed model, adjusting for sex, age, race, median household income, smoking, and weather, was applied.ResultsThere were a total of 1,164,784 hospital admissions with ARDS in the cohort. Increases of 1 µg/m3 in annual average PM2.5 and of 1 parts per billion in annual average ozone were associated with increases in annual hospital admission rates for ARDS of 0.72% (95% CI, 0.62-0.82) and 0.15% (95% CI, 0.08-0.22), respectively. In low-pollution regions (annual average PM2.5 level < 12 µg/m3 and annual average ozone level < 45 parts per billion), the same annual increase in PM2.5 and ozone were associated with increases in annual hospital admission rates for ARDS of 1.50% (95% CI, 1.27-1.72) and 0.27% (95% CI, 0.16-0.38).ConclusionsLong-term exposures to PM2.5 and ozone were associated with increased risk of ARDS among older adults in the United States, including exposures below current annual US National Ambient Air Quality Standards.

Rationale: Workplace inhalational hazards remain common worldwide, even though they are ameliorable. Previous American Thoracic Society documents have assessed the contribution of workplace exposures to asthma and chronic obstructive pulmonary disease on a population level, but not to other chronic respiratory diseases. The goal of this document is to report an in-depth literature review and data synthesis of the occupational contribution to the burden of the major nonmalignant respiratory diseases, including airway diseases; interstitial fibrosis; hypersensitivity pneumonitis; other noninfectious granulomatous lung diseases, including sarcoidosis; and selected respiratory infections. Methods: Relevant literature was identified for each respiratory condition. The occupational population attributable fraction (PAF) was estimated for those conditions for which there were sufficient population-based studies to allow pooled estimates. For the other conditions, the occupational burden of disease was estimated on the basis of attribution in case series, incidence rate ratios, or attributable fraction within an exposed group. Results: Workplace exposures contribute substantially to the burden of multiple chronic respiratory diseases, including asthma (PAF, 16%); chronic obstructive pulmonary disease (PAF, 14%); chronic bronchitis (PAF, 13%); idiopathic pulmonary fibrosis (PAF, 26%); hypersensitivity pneumonitis (occupational burden, 19%); other granulomatous diseases, including sarcoidosis (occupational burden, 30%); pulmonary alveolar proteinosis (occupational burden, 29%); tuberculosis (occupational burden, 2.3% in silica-exposed workers and 1% in healthcare workers); and community-acquired pneumonia in working-age adults (PAF, 10%). Conclusions: Workplace exposures contribute to the burden of disease across a range of nonmalignant lung conditions in adults (in addition to the 100% burden for the classic occupational pneumoconioses). This burden has important clinical, research, and policy implications. There is a pressing need to improve clinical recognition and public health awareness of the contribution of occupational factors across a range of nonmalignant respiratory diseases.

BackgroundMaternal smoking during pregnancy is a risk factor for chronic disease later in life and has been associated with variability of DNA methylation at specific cytosine-phosphate-guanine (CpG) loci. We assessed the role of DNA methylation as a potential mediator of adverse effects of in utero tobacco smoke exposures on asthma outcomes in Latino children from the US mainland and Puerto Rico.MethodsRelationships between self-reported exposure and DNA methylation at CpG loci previously reported to be associated with maternal smoking were assessed in a subsample consisting of 572 children aged 8-21 years (310 cases with asthma, 262 healthy controls), sampled from a larger asthma case-control study. Subsequently, we assessed associations between top loci and asthma-related outcomes, followed by mediation analysis for loci for which associations with outcomes were observed.ResultsSelf-reported maternal smoking was associated with a -1.5% (95% confidence interval (CI) = -2.4%, -0.6%) lower methylation at CpG locus cg05575921 on the AHRR gene; a 1% increase in DNA methylation at the same locus resulted in an odds ratio (OR) of 0.90 (95% CI = 0.83, 0.96) for the odds of asthma. The OR for the indirect effect of maternal smoking on asthma mediated through methylation at the cg05575921 locus was 1.18 (95% CI = 1.07, 1.68), compared to the OR for the total effect of exposure in the parent study of 1.48 (95% CI = 1.03, 2.11).ConclusionsOur findings suggest potential mediation by DNA methylation in the association between maternal smoking during pregnancy and asthma status.

RationaleNoncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults.ObjectivesWe set out to explore the prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi.MethodsWe performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS [Cooking and Pneumonia Study]) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter

BackgroundThe prevalence of asthma and allergy is increasing in US children. In utero exposure to chemicals used in personal care products and plastics may contribute to increase in these diseases.MethodsWe quantified urinary concentrations of eight phthalate metabolites and bisphenol A in mothers twice during pregnancy in 1999-2000 in Salinas, California. We assessed probable asthma, aeroallergies, eczema, and spirometry in their children at age 7, and measured T helper 1 and T helper 2 cells in blood at ages 2, 5, and 7 (N = 392). We employed Bayesian model averaging to select confounders from additional biomarkers measured in this population and controlled for them in logistic and linear regressions.ResultsMonocarboxyisooctyl phthalate was associated with increased odds for probable asthma (odds ratio: 1.54, 95% CI: 1.12, 2.12), and with lower forced expiratory volume in one second (β: -0.09 L, 95% CI: -0.15, -0.03) and forced expiratory flow from 25% to 75% of forced vital capacity (β: -7.06 L/s, 95% CI: -11.04, -2.90). Several other associations were attenuated in final models that controlled for additional biomarkers.ConclusionMonocarboxyisooctyl phthalate was associated with lower respiratory health after controlling for related chemical exposure, which suggests that confounding by multiple chemical exposures should be considered in future research.

Although air pollution is well known to be harmful to the lung and airways, it can also damage most other organ systems of the body. It is estimated that about 500,000 lung cancer deaths and 1.6 million COPD deaths can be attributed to air pollution, but air pollution may also account for 19% of all cardiovascular deaths and 21% of all stroke deaths. Air pollution has been linked to other malignancies, such as bladder cancer and childhood leukemia. Lung development in childhood is stymied with exposure to air pollutants, and poor lung development in children predicts lung impairment in adults. Air pollution is associated with reduced cognitive function and increased risk of dementia. Particulate matter in the air (particulate matter with an aerodynamic diameter < 2.5 μm) is associated with delayed psychomotor development and lower child intelligence. Studies link air pollution with diabetes mellitus prevalence, morbidity, and mortality. Pollution affects the immune system and is associated with allergic rhinitis, allergic sensitization, and autoimmunity. It is also associated with osteoporosis and bone fractures, conjunctivitis, dry eye disease, blepharitis, inflammatory bowel disease, increased intravascular coagulation, and decreased glomerular filtration rate. Atopic and urticarial skin disease, acne, and skin aging are linked to air pollution. Air pollution is controllable and, therefore, many of these adverse health effects can be prevented.

RationaleExposure to air pollution has molecular and physiologic effects on the lung that may increase the risk of acute respiratory distress syndrome (ARDS) after injury.ObjectivesTo determine the association of short- and long-term air pollutant exposures and ARDS risk after severe trauma.MethodsWe analyzed data from a prospective cohort of 996 critically ill patients presenting with acute trauma and an injury severity score greater than 15. Exposures to ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and particulate matter less than 2.5 μm were assessed by weighted averages of daily levels from all monitors within 50 km of the geocoded location of a patient's residence. Patients were followed for 6 days for the development of ARDS according to Berlin Criteria. The association between each exposure and ARDS was determined via multivariable logistic regression adjusting for potential confounders.Measurements and main resultsARDS developed in 243 (24%) patients. None of the short-term exposures averaged over the 3 days before presentation was associated with ARDS, except sulfur dioxide, which demonstrated a nonlinear association. Nitrogen dioxide, sulfur dioxide, and particulate matter less than or equal to 2.5 μm in aerodynamic diameter exposure over the 6 weeks before presentation was significantly associated with ARDS (P

BackgroundCOPD is a common HIV comorbidity, and HIV-infected individuals have a higher incidence and earlier onset of COPD compared to HIV-uninfected individuals. While the pathogenesis of HIV-associated COPD is largely unknown, chronic inflammation may contribute. Four pneumoproteins known to be markers of lung injury and inflammation have been associated with COPD in HIV-uninfected individuals: PARC/CCL-18, SP-D, CC-16, and sRAGE.ObjectiveTo determine whether these pneumoproteins are also associated with pulmonary function and COPD Assessment Test (CAT) scores in HIV-infected individuals.MethodsAssociations between plasma pneumoprotein levels and pulmonary function were determined in a cross-sectional study of otherwise healthy HIV-infected individuals enrolled between September 2016 and June 2017. Covariates included HIV-associated (antiretroviral therapy, CD4 count, and viral load) and COPD-associated (smoking and BMI) covariates.ResultsAmong 65 participants, 78.5% were male, 50.8% had undetectable viral load, and 76.9% were ever-smokers. Mean post-bronchodilator FEV1/FVC was 0.71, and mean DLco%predicted was 61%. Higher PARC/CCL-18 was associated with lower DLco%predicted and higher CAT score. Higher CC-16 was associated with lower DLco%predicted and lower FVC%predicted.ConclusionsThis exploratory analysis is the first to characterize associations between these four pneumoproteins and pulmonary function in an HIV-infected cohort. Our findings suggest the pathogenesis of HIV-associated COPD may differ from that of non-HIV-associated COPD due to HIV-specific inflammatory changes affecting DLco. PARC/CCL-18 is associated with structural and functional pulmonary abnormalities and may be an important COPD biomarker candidate in HIV infection. Our study is a preliminary step toward finding clinically relevant COPD biomarkers in high-risk populations.

BackgroundPersonal care product chemicals may be contributing to risk for asthma and other atopic illnesses. The existing literature is conflicting, and many studies do not control for multiple chemical exposures.MethodsWe quantified concentrations of three phthalate metabolites, three parabens, and four other phenols in urine collected twice during pregnancy from 392 women. We measured T helper 1 (Th1) and T helper 2 (Th2) cells in their children's blood at ages two, five, and seven, and assessed probable asthma, aeroallergies, eczema, and lung function at age seven. We conducted linear and logistic regressions, controlling for additional biomarkers measured in this population as selected by Bayesian Model Averaging.ResultsThe majority of comparisons showed null associations. Mono-n-butyl phthalate (MnBP) was associated with higher Th2% (RR: 10.40, 95% CI: 3.37, 17.92), and methyl paraben was associated with lower Th1% (RR: -3.35, 95% CI: -6.58, -0.02) and Th2% at borderline significance (RR: -4.45, 95% CI: -8.77, 0.08). Monoethyl phthalate was associated with lower forced expiratory flow from 25 to 75% of forced vital capacity (FEF25-75%) (RR: -3.22 L/s, 95% CI: -6.02, -0.34). Propyl paraben (OR: 0.86, 95% CI: 0.74, 0.99) was associated with decreased odds of probable asthma.ConclusionsWhile some biomarkers, particularly those from low molecular weight phthalates, were associated with an atopic cytokine profile and poorer lung function, no biomarkers were associated with a corresponding increase in atopic disease.

BackgroundDNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation (Foxp3 and IL10) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites. We recruited subjects from Fresno, California, an area known for high levels of AAPs. Blood samples and responses to questionnaires were obtained (n = 188), and in a subset of subjects (n = 33), repeat samples were collected 2 years later. Average measures of AAPs were obtained for 1, 15, 30, 90, 180, and 365 days prior to each blood draw to estimate the short-term vs. long-term effects of the AAP exposures.ResultsAsthma was significantly associated with higher differentially methylated regions (DMRs) of the Foxp3 promoter region (p = 0.030) and the IL10 intronic region (p = 0.026). Additionally, at the 90-day time period (90 days prior to the blood draw), Foxp3 methylation was positively associated with NO2, CO, and PM2.5 exposures (p = 0.001, p = 0.001, and p = 0.012, respectively). In the subset of subjects retested 2 years later (n = 33), a positive association between AAP exposure and methylation was sustained. There was also a negative correlation between the average Foxp3 methylation of the promoter region and activated Treg levels (p = 0.039) and a positive correlation between the average IL10 methylation of region 3 of intron 4 and IL10 cytokine expression (p = 0.030).ConclusionsShort-term and long-term exposures to high levels of CO, NO2, and PM2.5 were associated with alterations in differentially methylated regions of Foxp3. IL10 methylation showed a similar trend. For any given individual, these changes tend to be sustained over time. In addition, asthma was associated with higher differentially methylated regions of Foxp3 and IL10.

BackgroundSecondhand smoke (SHS) exposures have been linked to asthma-related outcomes but quantitative dose-responses using biomarkers of exposure have not been widely reported.ObjectivesAssess dose-response relationships between plasma cotinine-determined SHS exposure and asthma outcomes in minority children, a vulnerable population exposed to higher levels of SHS and under-represented in the literature.MethodsWe performed analyses in 1172 Latino and African-American children with asthma from the mainland USA and Puerto Rico. We used logistic regression to assess relationships of cotinine levels ≥0.05 ng/mL with asthma exacerbations (defined as asthma-related hospitalisations, emergency room visits or oral steroid prescription) in the previous year and asthma control. The shape of dose-response relationships was assessed using a continuous exposure variable in generalised additive logistic models with penalised splines.ResultsThe OR for experiencing asthma exacerbations in the previous year for cotinine levels ≥0.05 ng/mL, compared with

Household air pollution is estimated to cause half a million deaths from pneumonia in children worldwide. The Cooking and Pneumonia Study (CAPS) was conducted to determine whether the use of cleaner-burning biomass-fueled cookstoves would reduce household air pollution and thereby the incidence of pneumonia in young children in rural Malawi. Here we report a cross-sectional assessment of carbon monoxide (CO) exposure and carboxyhemoglobin (COHgB) levels at recruitment to CAPS. Mean (SD; range) 48-h CO exposure of 1928 participating children was 0.90 (2.3; 0⁻49) ppm and mean (SD; range) COHgB level was 5.8% (3.3; 0⁻20.3). Higher mean CO and COHgB levels were associated with location (Chikhwawa versus Chilumba) (OR 3.55 (1.73⁻7.26)); (OR 2.77 (1.08⁻7.08)). Correlation between mean CO and COHgB was poor (Spearman's ρ = 0.09, p < 0.001). The finding of high COHgB levels in young children in rural Malawi that are at levels at which adverse neurodevelopmental and cognitive effects occur is of concern. Effective approaches for reducing exposure to CO and other constituents of air pollution in rural sub-Saharan African settings are urgently needed.

BackgroundAir pollution exposure is associated with acute exacerbation, disease progression, and mortality in patients with idiopathic pulmonary fibrosis (IPF). The objective of this study was to describe the impact of air pollution exposures on disease severity, as well as changes in lung function, in patients with IPF.MethodsUsing home spirometers and symptom diaries, 25 patients with IPF prospectively recorded FVC weekly for up to 40 weeks. Residential addresses were geocoded to estimate weekly mean air pollution exposures for ground-level ozone (O3), nitrogen dioxide (NO2), and particulate matter < 2.5 or 10 μm in aerodynamic diameter (PM2.5 and PM10, respectively). The dependence of weekly clinical measurements on preceding levels of each pollutant was assessed with the use of linear mixed models, yielding beta-coefficients with 95% CIs, using varying lag times.ResultsLower mean FVC % predicted was consistently associated with increased mean exposures to PM10 in the 2 to 5 weeks preceding clinical measurements (range, -0.46 to -0.39 [95% CI, -0.73 to -0.13]; P < .005). Lower mean FVC % predicted over the study period was inversely related to mean levels of NO2 (-0.45 [95% CI, -0.85 to -0.05]; P = .03), PM2.5 (-0.45 [95% CI, -0.84 to -0.07]; P = .02), and PM10 (-0.57 [95% CI, -0.92 to -0.21]; P = .003), averaged over the study. Weekly changes in FVC and changes over 40 weeks were independent of pollution exposures.ConclusionsHigher air pollution exposures were associated with lower lung function, but not changes in lung function, in patients with IPF. Further studies are needed to characterize the mechanisms underlying this relationship.

ObjectivesTo examine the relationship between residential proximity to agricultural fumigant use and respiratory symptoms and lung function in 7-year old children.MethodsParticipants were 294 children living in the agricultural Salinas Valley, California and enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study. We obtained information on respiratory symptoms and asthma medication use from maternal questionnaires and children performed spirometry to determine the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25-75% (FEF25-75) at 7-years of age. We estimated agricultural fumigant use within 3, 5 and 8 km of residences during pregnancy and from birth to age 7 using California's Pesticide Use Report data. We evaluated the association between prenatal and postnatal residential proximity to agricultural use of methyl bromide, chloropicrin, metam sodium and 1,3-dichloropropene with respiratory symptoms and use of asthma medication with logistic regression models and continuous lung function measurements with linear regression models adjusted for confounders.ResultsThere were no significant associations between residential proximity to use of fumigants and respiratory symptoms or use of asthma medication. We did not observe any adverse relationships between residential proximity to fumigant use and lung function measurements. Unexpectedly, we observed suggestive evidence of improved FEV1 and FEF25-75 with higher use of methyl bromide and chloropicrin during the prenatal period. For example, for each 10-fold increase in methyl bromide use during the prenatal development period we observed higher FEV1 (β = 0.06 L/s; 95% CI: 0.00, 0.12) and higher FEF25-75 (β = 0.15 L/s; 95% CI: 0.03, 0.27). Maternal report of child allergies (runny nose without a cold during the previous year) modified the relationship between FEV1 and prenatal proximity to methyl bromide use (p = .07) and we only observed higher FEV1 among children without allergies (β = 0.08 L/s; 95% CI: 0.02, 0.14 for a 10-fold increase in methyl bromide use during the prenatal period).ConclusionsResidential proximity to agricultural fumigant use during pregnancy and childhood did not adversely affect respiratory health in the children through 7 years of age. These findings should be explored in larger studies.

Community-level approaches for pediatric asthma management rely on locally collected information derived primarily from two sources: claims records and school-based surveys. We combined claims and school-based surveillance data, and examined the asthma-related risk patterns among adolescent students. Symptom data collected from school-based asthma surveys conducted in Oakland, CA were used for case identification and determination of severity levels for students (high and low). Survey data were matched to Medicaid claims data for all asthma-related health care encounters for the year prior to the survey. We then employed recursive partitioning to develop classification trees that identified patterns of demographics and healthcare utilization associated with severity. A total of 561 students had complete matched data; 86.1% were classified as high-severity, and 13.9% as low-severity asthma. The classification tree consisted of eight subsets: three indicating high severity and five indicating low severity. The risk subsets highlighted varying combinations of non-specific demographic and socioeconomic predictors of asthma prevalence, morbidity and severity. For example, the subset with the highest class-prior probability (92.1%) predicted high-severity asthma and consisted of students without prescribed rescue medication, but with at least one in-clinic nebulizer treatment. The predictive accuracy of the tree-based model was approximately 66.7%, with an estimated 91.1% of high-severity cases and 42.3% of low-severity cases correctly predicted. Our analysis draws on the strengths of two complementary datasets to provide community-level information on children with asthma, and demonstrates the utility of recursive partitioning methods to explore a combination of features that convey asthma severity.

Purpose of reviewGiven racial disparities in ambient air pollution (AAP) exposure and asthma risk, this review offers an overview of the literature investigating the ambient air pollution-asthma relationship in children of color between 2013 and 2017.Recent findingsAAP is likely a key contributor to the excess burden of asthma in children of color due to pervasive exposure before birth, at home, and in school. Recent findings suggest that psychosocial stressors may modify the relationship between AAP and asthma. The effect of AAP on asthma in children of color is likely modulated by multiple unique psychosocial stressors and gene-environment interactions. Although children of color are being included in asthma studies, more research is still needed on impacts of specific criteria pollutants throughout the life course. Additionally, future studies should consider historical factors when analyzing current exposure profiles.

IntroductionAmbient air quality standards are not designed to protect people occupationally exposed to outdoor air pollution on a routine basis. This study aimed to assess the effect of exceeding the US ambient air quality standard for carbon monoxide (CO) on motorcycle taxi drivers respiratory health.MethodsA cross-sectional study of 85 current motorcycle taxi drivers with at least 5 years of job tenure in Cotonou (Benin) was conducted. Personal CO was measured with a portable CO data logger for 8 hours per day during working hours. A questionnaire on respiratory symptoms was administered to participants and spirometry was performed. Participants were divided into two groups, those with exposure to CO >9 ppm and ≤9 ppm, according to the US Environmental Protection Agency (EPA) National Ambient Air Quality Standard which is an 8-hour average of 9ppm. 8 and 10 ppm were also used an exposure limit. Analysis was done using these two groups.ResultsSocio-demographic characteristics were well balanced between the two study groups. The drivers with a CO exposure of more than 9ppm had non-significantly more respiratory symptoms (OR=1.67; 95%CI:0.26,10.74), lower FVC and FEV1 compared to the less exposed group but they have a significant lower PEF (-10%, p=0.02). When we used an exposure limit of 8 or 10 ppm the results were not statistically different.ConclusionDrivers with a CO exposure >9 ppm tend to have more respiratory problems. More research is needed to reinforce this result in order to improve air quality standards to protect workers occupationally exposed to outdoor air pollution.

Exposure to household air pollution (HAP) from solid fuel combustion affects almost half of the world population. Adverse respiratory outcomes such as respiratory infections, impaired lung growth and chronic obstructive pulmonary disease have been linked to HAP exposure. Solid fuel smoke is a heterogeneous mixture of various gases and particulates. Cell culture and animal studies with controlled exposure conditions and genetic homogeneity provide important insights into HAP mechanisms. Impaired bacterial phagocytosis in exposed human alveolar macrophages possibly mediates several HAP-related health effects. Lung pathological findings in HAP-exposed individuals demonstrate greater small airways fibrosis and less emphysema compared with cigarette smokers. Field studies using questionnaires, air pollution monitoring and/or biomarkers are needed to better establish human risks. Some, but not all, studies suggest that improving cookstove efficiency or venting emissions may be associated with reduced respiratory symptoms, lung function decline in women and severe pneumonia in children. Current studies focus on fuel switching, stove technology replacements or upgrades and air filter devices. Several governments have initiated major programmes to accelerate the upgrade from solid fuels to clean fuels, particularly liquid petroleum gas, which provides research opportunities for the respiratory health community.

BackgroundAsthma is a common childhood disease that leads to many missed days of school and parents' work. There are multiple environmental contributors to asthma symptoms and understanding the potential factors inside children's homes is crucial.MethodsThis is a dual cohort study measuring household particulate matter (PM2.5), behaviors, and factors that influence air quality and asthma symptoms in the urban homes of children (ages 6-10) with asthma; one cohort had cigarette smoke exposure in the home (n = 13) and the other did not (n = 22). Exposure data included measurements every 5 minutes for a month.ResultsIn the entire study population, a large contributor to elevations in indoor PM2.5 above 35 μg/m3 was not using the stove hood when cooking (8.5% higher, CI 3.1-13.9%, p