Identifying and managing adverse environmental health effects: 5. Persistent organic pollutants

CONCERN AND AWARENESS IS GROWING about the health effects of exposures to environmental contaminants, including those found in food. Most primary care physicians lack knowledge and training in the clinical recognition and management of the health effects of environmental exposures. We have found that the use of a simple history-taking tool — the CH²OPD² mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) — can help physicians identify patients at risk of such health effects. We present an illustrative case of a mother who is concerned about eating fish and wild game because her 7-year-old son has been found to have learning difficulties and she is planning another pregnancy. Potential exposures to persistent organic pollutants (POPs) and mercury are considered. The neurodevelopmental effects of POPs on the fetus are reviewed. We provide advice to limit a patient''s exposure to these contaminants and discuss the relevance of these exposures to the learning difficulties of the 7-year-old child and to the planning of future pregnancies.CaseA 27-year-old woman who lives in a town on the shore of Lake Huron wants to have a second child but has concerns. Her 7-year-old son is being assessed by the school psychologist for a learning disorder. She tells her family physician that she saw something on television about contaminants in fish affecting children''s intelligence. She is worried that her diet may have caused her son''s learning disorder and wants advice on how to protect her second child against environmental contaminants that may cause learning problems. Her past medical history is unremarkable. She is taking no medications other than folate (0.4 mg/d). She has had only the one pregnancy. Her pregnancy and delivery of her son were uncomplicated, and the boy met the developmental milestones. The concern about a learning disorder is recent. There is no family history of congenital anomalies, early deafness or twins. Her maternal grandmother had type 2 diabetes, and her father-in-law has hypertension; the rest of the family is healthy. Because the woman is worried about environmental exposures, you take an exposure history using the CH²OPD² mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs)¹ to identify possible sources of environmental contaminants (Open in a separate windowThe environmental contaminants that can affect the neurobehavioural development of the fetus include metals (lead, mercury and manganese), nicotine, pesticides (e.g., organophosphates), dioxins, polychlorinated biphenyls (PCBs) and solvents (e.g., alcohol).^2,3 In this article we focus on persistent organic pollutants (POPs) and mercury. These are the contaminants identified in the environmental exposure history of the case subject (4POPs are carbon-containing chemicals that share several properties. They are lipophilic, accumulating in the fat of living organisms, and increase in quantity up the food chain. Most are semivolatile, which means that they can travel in the air thousands of miles from their source before they settle. They resist photolytic, biological and chemical degradation and persist in the environment, taking as long as a century to degrade.⁵ Twelve POPs, including 9 pesticides, have been identified by the United Nations Environment Programme as powerful threats to the health of humans and wildlife and have been targeted for elimination (6 In the 1970s many countries banned or severely restricted the use of the 9 pesticides and PCBs and implemented pollution control strategies to reduce the amount of dioxin and furan released in the environment. However, it is thought that all 9 pesticides and PCBs are still used in many countries today.Table 2Open in a separate windowDespite significant achievements in reducing the production and use of POPs, these pollutants remain ubiquitous, as evident by the global distribution of PCBs and organochlorine pesticides in butter samples from around the world.⁷ Most human exposure comes from dietary sources. POPs are ingested, stored in fatty tissue and excreted in feces and breast milk. The concentration of certain chemical contaminants in breast milk serves as an indicator of population exposure. From 1967 to 1992, there was a downward trend in the concentrations of organochlorine pesticides and PCB hydrocarbons in samples of Canadian breast milk during the phase-out of these chemicals.⁸ The estimated daily intake of PCBs from the current diet of the average Canadian is less than 1 μg/d.⁹Although everyone is exposed to a background level of POPs, certain people may have higher levels of POPs exposure because of their eating habits. Some people eat more fish than the general population. Southeast Asian Canadians, Native Americans, sport anglers and hunters who regularly eat large amounts of Great Lakes fatty fish or wildlife from the top of the food chain, such as waterfowl and waterfowl eggs, turtles and turtle eggs, muskrat, otter, moose and deer, may be at risk of high exposure.¹⁰ Northern Aboriginals, such as the Inuit of Nunavik, who consume the fat of seals and beluga and narwhal whales, have been found to have higher body burdens of POPs.^11,12     

Identifying and managing adverse environmental health effects: 3. Lead exposure

LEAD LEVELS IN NORTH AMERICAN CHILDREN AND ADULTS have declined in the past 3 decades, but lead persists in the environment in lead paint, old plumbing and contaminated soil. There are also a number of occupations and hobbies that carry a high risk of lead exposure. There is no evidence for a threshold below which lead has no adverse health effects. Blood lead levels previously considered safe are now known to cause subtle, chronic health effects. The health effects of lead exposure include developmental neurotoxicity, reproductive dysfunction and toxicity to the kidneys, blood and endocrine systems. Most lead exposures are preventable, and diagnosing lead poisoning is relatively simple compared with diagnosing health effects of exposures to other environmental toxins. Accurate assessment of lead poisoning requires specific knowledge of the sources, high-risk groups and relevant laboratory tests. In this article we review the multiple, systemic toxic effects of lead and provide current information on groups at risk, prevention, diagnosis and clinical treatment. We illustrate how the CH²OPD² mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) and specific screening questions are useful tools for physicians to quickly obtain an environmental exposure history and identify patients at high risk of lead exposure. By applying effective primary prevention, case-finding and treatment interventions for lead exposure, both the individual patient and the larger community reap the benefits of better health.CaseA previously healthy 2-year-old girl and her mother visit their family physician because of the daughter''s 2-month history of intermittent complaints of a mild “tummy ache.” There is no associated vomiting, weight loss, or change in appetite, bowels or diet. There are no abnormal findings on physical examination. When asked about symptom onset the mother reports that it began shortly after the family started to renovate their kitchen. They live in an old farmhouse on the outskirts of town and drink water from a drilled well on the property. The physician decides to take an environmental exposure history using the CH²OPD² mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs; for children, the occupation question refers to workplace contaminants brought into the child''s environment).¹ The child''s exposure history (Open in a separate windowQuestions surrounding this case: Is the family at risk of health effects from lead exposure? Who else might be at risk? Are other laboratory tests indicated? Where can the physician get advice on the significance of the family''s blood lead levels? How should this case of lead exposure be treated?To some extent lead is one of the small success stories of environmental health. The association of lead poisoning with cognitive impairment is well established² and has resulted in the removal of lead from gasoline, paint and food cans. Despite these preventive measures, however, silent, low-level lead exposure continues to present a problem for many communities and populations. In 1997, data from the US National Health and Nutrition Examination Surveys showed that 4.4% of children in the United States had elevated blood lead levels.³ Black children living in older housing, children living in metropolitan areas with populations of 1 million or more and poor children living in older housing were at highest risk of exposure.³In Canada children living near a point-source smelter in the South Riverdale area of Toronto were tested in 1973 and found to have an unusually high mean lead level (1.34 μmol/L).⁴ Canada''s Federal–Provincial Committee on Environmental and Occupational Health suggested in 1994 that 5%–10% of Canadian children living in urban areas have blood lead levels exceeding 0.48 μmol/L, even though they are not exposed to point sources.⁵ The Ontario government estimated in 1994 that 4% of children in the province still had blood lead levels above 0.48 μmol/L;⁶ a 1992 study found that the mean level in Ontario children had fallen from 0.91 μmol/L in 1972 to 0.29 μmol/L in 1988.⁷ A study of Vancouver children using blood lead levels collected in 1989 found that 8% had elevated levels (mean 0.29 μmol/L).⁸ A later study of the children living in Trail, BC, the site of a lead and zinc smelter, demonstrated that 50% had an elevated blood lead level.⁹     

Traffic-related air pollution and respiratory symptoms among asthmatic children,resident in Mexico City: the EVA cohort study

Background

Taffic-related air pollution has been related to adverse respiratory outcomes; however, there is still uncertainty concerning the type of vehicle emission causing most deleterious effects.

Methods

A panel study was conducted among 147 asthmatic and 50 healthy children, who were followed up for an average of 22 weeks. Incidence density of coughing, wheezing and breathing difficulty was assessed by referring to daily records of symptoms and child''s medication. The association between exposure to pollutants and occurrence of symptoms was evaluated using mixed-effect models with binary response and poisson regression.

Results

Wheezing was found to relate significantly to air pollutants: an increase of 17.4 μg/m³ (IQR) of PM_2.5 (24-h average) was associated with an 8.8% increase (95% CI: 2.4% to 15.5%); an increase of 34 ppb (IQR) of NO₂ (1-h maximum) was associated with an 9.1% increase (95% CI: 2.3% to16.4%) and an increase of 48 ppb (IQR) in O₃ levels (1 hr maximum) to an increase of 10% (95% CI: 3.2% to 17.3%). Diesel-fueled motor vehicles were significantly associated with wheezing and bronchodilator use (IRR = 1.29; 95% CI: 1.03 to 1.62, and IRR = 1.32; 95% CI: 0.99 to 1.77, respectively, for an increase of 130 vehicles hourly, above the 24-hour average).

Conclusion

Respiratory symptoms in asthmatic children were significantly associated with exposure to traffic exhaust, especially from natural gas and diesel-fueled vehicles.     

Exposure to moderate air pollution during late pregnancy and cord blood cytokine secretion in healthy neonates

Background/Objectives

Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown.

Methods

In a birth cohort of 265 healthy term-born neonates, we assessed maternal exposure to particles with an aerodynamic diameter of 10 µm or less (PM₁₀), as well as to indoor air pollution during the last trimester, specifically the last 21, 14, 7, 3 and 1 days of pregnancy. As a proxy for traffic-related air pollution, we determined the distance of mothers'' homes to major roads. We measured cytokine and chemokine levels (MCP-1, IL-6, IL-10, IL-1ß, TNF-α and GM-CSF) in cord blood serum using LUMINEX technology. Their association with pollution levels was assessed using regression analysis, adjusted for possible confounders.

Results

Mean (95%-CI) PM₁₀ exposure for the last 7 days of pregnancy was 18.3 (10.3–38.4 µg/m³). PM₁₀ exposure during the last 3 days of pregnancy was significantly associated with reduced IL-10 and during the last 3 months of pregnancy with increased IL-1ß levels in cord blood after adjustment for relevant confounders. Maternal smoking was associated with reduced IL-6 levels. For the other cytokines no association was found.

Conclusions

Our results suggest that even naturally occurring prenatal exposure to moderate amounts of indoor and outdoor air pollution may lead to changes in cord blood cytokine levels in a population based cohort.     

Identifying and managing adverse environmental health effects: 1. Taking an exposure history

PUBLIC CONCERN AND AWARENESS ARE GROWING about adverse health effects of exposure to environmental contaminants. Frequently patients present to their physicians with questions or concerns about exposures to such substances as lead, air pollutants and pesticides. Most primary care physicians lack training in and knowledge of the clinical recognition, management and avoidance of such exposures. We have found that it can be helpful to use the CH²OPD² mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) as a tool to identify a patient''s history of exposures to potentially toxic environmental contaminants. In this article we discuss why it is important to take a patient''s environmental exposure history, when and how to take the history, and how to interpret the findings. Possible routes of exposure and common sources of potentially toxic biological, physical and chemical substances are identified. A case of sick-building syndrome is used to illustrate the use of the mnemonic.CaseA 40-year-old married bookkeeper presents with a 3-year history of headaches. She describes having “tight,” bitemporal headaches almost daily that resolve after taking three 325-mg tablets of ASA. She also complains of a “spacey” feeling, difficulty concentrating and remembering, fatigue, a stuffy nose and a full feeling in her ears. Her symptoms improve on weekends and over the holidays and seem to be worse in the winter. Over the past 2 years she has noticed that she gets a stuffy nose and headaches when exposed to perfumes, tobacco smoke and automobile exhaust. Her past medical history is remarkable only for infantile eczema. Her family history is unremarkable other than her mother having hypothyroidism. She is taking no medications other than ASA, does not smoke, reports having no allergies and says she is happily married with no major family, financial or social concerns. She enjoys her work and coworkers. On physical examination she has puffy, dark circles under her eyes, there is loss of light reflex on her left ear drum, and her nasal mucosa appears edematous and erythematous. There are multiple excoriated, erythematous papules 5 mm in diameter on her face, anterior chest and anterior lower legs.Questions surrounding this case: What is sick-building syndrome and how do patients commonly present? What causes or contributes to sick-building syndrome? What are the risk factors? How should cases be managed?     

Public health: Quality of indoor residential air and health

About 90% of our time is spent indoors where we are exposed to chemical and biological contaminants and possibly to carcinogens. These agents may influence the risk of developing nonspecific respiratory and neurologic symptoms, allergies, asthma and lung cancer. We review the sources, health effects and control strategies for several of these agents. There are conflicting data about indoor allergens. Early exposure may increase or may decrease the risk of future sensitization. Reports of indoor moulds or dampness or both are consistently associated with increased respiratory symptoms but causality has not been established. After cigarette smoking, exposure to environmental tobacco smoke and radon are the most common causes of lung cancer. Homeowners can improve the air quality in their homes, often with relatively simple measures, which should provide health benefits.In North America, adults spend about 87% of their time in buildings, 6% in vehicles and 7% outdoors.¹ Leech and colleagues² have reported that Canadians spend similar amounts of time indoors. Typically, more time is spent indoors in very hot or cold climates. As a result, personal exposure to airborne substances is more closely related to indoor rather than outdoor pollution.^3,4 We review the sources, health effects and control strategies for several of the most important sources of residential biological and chemical contaminants.Although outdoor and indoor environments tend to be viewed as distinct entities, some outdoor pollutants enter the home. However, less air pollution enters tightly sealed homes, such as those found in colder and hotter climates where windows and doors are more regularly closed to retain conditioned air.⁵ In addition, economically disadvantaged families may be more likely than others to live close to roadways and industry, have lower-quality housing and have less access to air conditioning, which may result in poor indoor air quality.⁶ On days with high concentrations of particulate matter, cities with a high prevalence of air conditioner use report fewer hospital admissions for cardiovascular disease, chronic obstructive pulmonary disease and pneumonia compared with cities with lower air conditioner use.⁵Indoor air pollutants include carcinogens and biological and chemical contaminants. The latter category can be divided into combustion products and gases released from indoor materials (off-gassing emissions). Several guidelines for exposure limits for indoor air contaminents have been developed by the Canadian government (Open in a separate window     

Acrolein and Asthma Attack Prevalence in a Representative Sample of the United States Adult Population 2000 – 2009

Background

Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency''s 2005 NATA (National-Scale Air Toxics Assessment) and acrolein''s comparatively potent inhalation reference concentration of 0.02 µg/m³.

Objectives

Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population.

Methods

NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old) in the NHIS (National Health Interview Survey) 2000 – 2009 (n = 271,348 subjects). A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders.

Results

In the highest quintile of outdoor acrolein exposure (0.05 – 0.46 µg/m³), there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI]  = 1.08 [0.98∶1.19]) relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29]) in a model limited to never smokers (n = 153,820).

Conclusions

Chronic exposure to outdoor acrolein of 0.05 – 0.46 µg/m³ appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population.     

Pulmonary function and incident bronchitis and asthma in children: a community-based prospective cohort study

Background

Previous studies revealed that reduction of airway caliber in infancy might increase the risks for wheezing and asthma. However, the evidence for the predictive effects of pulmonary function on respiratory health in children was still inconsistent.

Methods

We conducted a population-based prospective cohort study among children in 14 Taiwanese communities. There were 3,160 children completed pulmonary function tests in 2007 and follow-up questionnaire in 2009. Poisson regression models were performed to estimate the effect of pulmonary function on the development of bronchitis and asthma.

Results

After adjustment for potential confounders, pulmonary function indices consistently showed protective effects on respiratory diseases in children. The incidence rate ratios of bronchitis and asthma were 0.86 (95% CI 0.79–0.95) and 0.91 (95% CI 0.82–0.99) for forced expiratory volume in 1 second (FEV₁). Similar adverse effects of maximal mid-expiratory flow (MMEF) were also observed on bronchitis (RR = 0.73, 95% CI 0.67–0.81) and asthma (RR = 0.85, 95% CI 0.77–0.93). We found significant decreasing trends in categorized FEV₁ (p for trend = 0.02) and categories of MMEF (p for trend = 0.01) for incident bronchitis. Significant modification effects of traffic-related air pollution were noted for FEV₁ and MMEF on bronchitis and also for MMEF on asthma.

Conclusions

Children with high pulmonary function would have lower risks on the development of bronchitis and asthma. The protective effect of high pulmonary function would be modified by traffic-related air pollution exposure.     

Asthma prevalence associated with geographical latitude and regional insolation in the United States of America and Australia

Background

It has been proposed that vitamin D deficiency may be responsible for an increase in the prevalence of allergic diseases and asthma worldwide. Human ability to generate physiologically required quantities of vitamin D through sun exposure is decreasing with increasing geographical latitude.

Objectives

Considering that vitamin D deficiency is usually due to lack of outdoor sun exposure, this study is designed to test the hypothesis that a higher prevalence of asthma should be expected at high relative to low geographical latitudes.

Methods

Linear regression analyses are performed on asthma prevalence in the U.S. adult population vs. geographical latitude, insolation, air temperature, and air pollution (PM_2.5) for 97 major metropolitan/micropolitan statistical areas of the continental United States of America and on general population asthma prevalence vs. geographical latitude in eight metropolitan areas of Australia.

Results

A 10° change in geographical latitude from southern to northern regions of the Eastern Seaboard is associated with a 2% increase in adult asthma prevalence (p<0.001). Total insolation in winter months is almost as strong as latitude in its ability to explain the observed spatial variation in the prevalence of asthma (r² = 0.43; p<0.001). Similar results are obtained using the Australian data (r² = 0.73; p<0.01), suggesting a consistent association between the latitude/insolation and asthma prevalence worldwide.

Conclusions

The results of this study suggest that, as a known modulator of the immune response closely linked with the geographical latitude and erythemal UV irradiation, vitamin D may play an important role in the development/exacerbation of asthma.     

Socioeconomic and Sociodemographic Factors Associated with Asthma Related Outcomes in Early Childhood: The Generation R Study

Rationale

Few studies have analyzed the association of socioeconomic and sociodemographic factors with asthma related outcomes in early childhood, including Fraction of exhaled Nitric Oxide (FeNO) and airway resistance (Rint). We examined the association of socioeconomic and sociodemographic factors with wheezing, asthma, FeNO and Rint at age 6 years. Additionally, the role of potential mediating factors was studied.

Methods

The study included 6717 children participating in The Generation R Study, a prospective population-based cohort study. Data on socioeconomic and sociodemographic factors, wheezing and asthma were obtained by questionnaires. FeNO and Rint were measured at the research center. Statistical analyses were performed using logistic and linear regression models.

Results

At age 6 years, 9% (456/5084) of the children had wheezing symptoms and 7% (328/4953) had asthma. Children from parents with financial difficulties had an increased risk of wheezing (adjusted Odds Ratio (aOR) = 1.63, 95% Confidence Interval (CI):1.18–2.24). Parental low education, paternal unemployment and child''s male sex were associated with asthma, independent of other socioeconomic or sociodemographic factors (aOR = 1.63, 95% CI:1.24–2.15, aOR = 1.85, 95% CI:1.11–3.09, aOR = 1.58, 95% CI:1.24–2.01, respectively). No socioeconomic or gender differences in FeNO were found. The risks of wheezing, asthma, FeNO and Rint measurements differed between ethnic groups (p<0.05). Associations between paternal unemployment, child''s sex, ethnicity and asthma related outcomes remained largely unexplained.

Conclusions

This study showed differences between the socioeconomic and sociodemographic correlates of wheezing and asthma compared to the correlates of FeNO and Rint at age 6 years. Several socioeconomic and sociodemographic factors were independently associated with wheezing and asthma. Child''s ethnicity was the only factor independently associated with FeNO. We encourage further studies on underlying pathways and public health intervention programs, focusing on reducing socioeconomic or sociodemographic inequalities in asthma.     

Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study

Background

Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship.

Methodology/Principal Findings

30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxides (NO₂), ozone (O₃) and carbon monoxide (CO). A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM₁₀, SO₂, NO₂, O₃, and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM₁₀ (ORs = 1.36 per 31 µg/m³; 95% CI, 1.08–1.72), SO₂ (ORs = 1.38 per 21 µg/m³; 95%CI, 1.12–1.69) only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO₂ (ORs = 1.48 per 21 µg/m³; 95%CI, 1.21–1.80), NO₂ (ORs = 1.26 per 10 µg/m³; 95%CI, 1.01–1.56), and current asthma with O₃ (ORs = 1.55 per 23 µg/m³; 95%CI, 1.18–2.04) only among females.

Conclusion/Significance

Ambient air pollutions were more evident in males without an allergic predisposition and more associations were detected in females with allergic predisposition.     

Bronchodilator Responsiveness and Reported Respiratory Symptoms in an Adult Population

Background

The relationship between patient-reported symptoms and objective measures of lung function is poorly understood.

Aim

To determine the association between responsiveness to bronchodilator and respiratory symptoms in random population samples.

Methods

4669 people aged 40 years and older from 8 sites in Canada completed interviewer-administered respiratory questionnaires and performed spirometry before and after administration of 200 ug of inhaled salbutamol. The effect of anthropometric variables, smoking exposure and doctor-diagnosed asthma (DDA) on bronchodilator responsiveness in forced expiratory volume in 1 second (FEV₁) and in forced vital capacity (FVC) were evaluated. Multiple logistic regression was used to test for association between quintiles of increasing changes in FEV₁ and in FVC after bronchodilator and several respiratory symptoms.

Results

Determinants of bronchodilator change in FEV₁ and FVC included age, DDA, smoking, respiratory drug use and female gender [p<0.005 to p<0.0001 ]. In subjects without doctor-diagnosed asthma or COPD, bronchodilator response in FEV₁ was associated with wheezing [p for trend<0.0001], while bronchodilator response for FVC was associated with breathlessness. [p for trend <0.0001].

Conclusions

Bronchodilator responsiveness in FEV₁ or FVC are associated with different respiratory symptoms in the community. Both flow and volume bronchodilator responses are useful parameters which together can be predictive of both wheezing and breathlessness in the general population.     

Effects of air pollution and habitual exercise on the risk of death: a longitudinal cohort study

Background:Exercise may exacerbate the adverse health effects of air pollution by increasing the inhalation of air pollutants. We investigated the combined effects of long-term exposure to fine particle matter (PM_2.5) and habitual exercise on deaths from natural causes in Taiwan.Methods:We recruited 384 130 adults (aged ≥ 18 yr) with 842 394 medical examination records between 2001 and 2016, and followed all participants until May 31, 2019. We obtained vital data from the National Death Registry of Taiwan. We estimated PM_2.5 exposure using a satellite-based spatiotemporal model, and collected information on exercise habits using a standard self-administered questionnaire. We analyzed the data using a Cox regression model with time-dependent covariates.Results:A higher level of habitual exercise was associated with a lower risk of death from natural causes, compared with inactivity (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.80–0.88 for the moderate exercise group; HR 0.65, 95% CI 0.62–0.68 for the high exercise groups), whereas a higher PM_2.5 exposure was associated with a higher risk of death from natural causes compared with lower exposure (HR 1.02, 95% CI 0.98–1.07, and HR 1.15, 95% CI 1.10–1.20, for the moderate and high PM_2.5 exposure groups, respectively). Compared with inactive adults with high PM_2.5 exposure, adults with high levels of habitual exercise and low PM_2.5 exposure had a substantially lower risk of death from natural causes. We found a minor, but statistically significant, interaction effect between exercise and PM_2.5 exposure on risk of death (HR 1.03 95% CI 1.01–1.06). Subgroup analyses, stratified by PM_2.5 categories, suggested that moderate and high levels of exercise were associated with a lower risk of death in each PM_2.5 stratum, compared with inactivity.Interpretation:Increased levels of exercise and reduced PM_2.5 exposure are associated with a lower risk of death from natural causes. Habitual exercise can reduce risk regardless of the levels of PM_2.5 exposure. Our results suggest that exercise is a safe health improvement strategy, even for people residing in relatively polluted regions.

Air pollution and physical inactivity are both major public health challenges worldwide.¹ Air pollution was the fifth leading cause of disability related to health and accounted for 4.9 million deaths worldwide in 2017.² More than 91% of the global population lives in areas where air quality does not meet the World Health Organization (WHO) guidelines.³ In addition, physical inactivity was the fourth leading risk factor for death globally, accounting for 5.3 million deaths worldwide in 2012.⁴ The WHO has challenged its member states to reduce physical inactivity by 15% by 2030.⁵As people exercise, their ventilation rate increases, which increases the volume of air pollutants they inhale. This may exacerbate the adverse health effects of air pollutants. Thus, the risk–benefit relation between air pollution and exercise needs to be assessed to understand whether it is safe to exercise regularly in polluted regions. Indeed, some studies have shown that acute exposure to air pollution when exercising may override the benefits of exercise.^6,7 It is possible that the effects of long-term exposure to air pollution may be irreversible and cause a much larger disease burden than short-term exposure. Limited information exists on the combined effects of long-term exposure to air pollution and habitual exercise on human health, and findings have been inconsistent depending on health outcome. Three cohort studies have explored the relation between air pollution, physical activity and risk of death in Hong Kong,⁸ Denmark and the United States,⁹ with relatively small sample sizes.¹⁰ Therefore, we sought to investigate the combined effects of habitual exercise and long-term exposure to fine particle matter (PM_2.5) on the risk of death from natural causes (i.e., deaths not attributable to accident, suicide or homicide) using a longitudinal cohort of adults in Taiwan, where the annual PM_2.5 concentrations are 1.6 times higher than the WHO-recommended limit. We hypothesized that the beneficial effects of habitual exercise on risk of death may outweigh the risk of high levels of air pollutants inhaled during exercise.     

Prevalence of asthma among Chinese adolescents living in Canada and in China

Background

Studies of the prevalence of asthma among migrating populations may help in identifying environmental risk factors.

Methods

We analyzed data from Vancouver, Canada, and from Guangzhou, Beijing and Hong Kong, China, collected during phase 3 of the International Study of Asthma and Allergies in Childhood. We subdivided the Vancouver adolescents according to whether they were Chinese immigrants to Canada, Canadian-born Chinese or Canadian-born non-Chinese. We compared the prevalence of asthma and wheezing among Chinese adolescents born in Canada, Chinese adolescents who had immigrated to Canada and Chinese adolescents living in China.

Results

Of 7794 Chinese adolescents who met the inclusion criteria, 3058 were from Guangzhou, 2824 were from Beijing, and 1912 were from Hong Kong. Of 2235 adolescents in Vancouver, Canada, 475 were Chinese immigrants, 617 were Canadian-born Chinese, and 1143 were Canadian-born non-Chinese. The prevalence of current wheezing among boys ranged from 5.9% in Guangzhou to 11.2% in Canadian-born Chinese adolescents. For girls, the range was 4.3% in Guangzhou to 9.8% in Canadian-born Chinese adolescents. The prevalence of ever having had asthma ranged from 6.6% to 16.6% for boys and from 2.9% to 15.0% for girls. Prevalence gradients persisted after adjustment for other environmental variables (odds ratios for ever having had asthma among Canadian-born Chinese compared with native Chinese in Guangzhou: 2.72 [95% confidence interval 1.75–4.23] for boys and 5.50 [95% confidence interval 3.21–9.44] for girls; p < 0.001 for both). Among Chinese adolescents living in Vancouver, the prevalence of ever wheezing increased with duration of residence, from 14.5% among those living in Canada for less than 7 years to 20.9% among those living their entire life in Canada. The same pattern was observed for the prevalence of ever having had asthma, from 7.7% to 15.9%.

Interpretation

Asthma symptoms in Chinese adolescents were lowest among residents of mainland China, were greater for those in Hong Kong and those who had immigrated to Canada, and were highest among those born in Canada. These findings suggest that environmental factors and duration of exposure influence asthma prevalence.The prevalence of asthma symptoms exhibits large geographic variations, even among genetically similar groups,^1,2 which suggests that differences may reflect variation in environmental factors. Epidemiologic studies have demonstrated associations between asthma and exposure to household allergens,³ pets,⁴ environmental tobacco smoke⁵ and environmental pollution,⁶ as well as sex,⁷ obesity,⁸ number of siblings and birth order,⁹ and maternal education.¹⁰ Increasing “westernization” of environmental factors (such as changes in maternal diet, smaller family size, fewer infections during infancy, increased use of antibiotics and vaccination, less exposure to rural environments and improved sanitation) has been associated with an increased risk of childhood asthma.¹¹ Conversely, the hygiene hypothesis proposed by Strachan in 1989 suggested that infections and contact with older siblings may reduce the risk of allergic diseases.¹²Migration studies examining children of the same ethnic background living in different environments for part or all of their lives may help to identify factors relevant to the development of diseases and may explain some of the observed geographic variations in prevalence. In the International Study of Asthma and Allergies in Childhood, prevalence rates for asthma in Canada were among the highest in the world, whereas those in China were among the lowest.² This difference could reflect genetic or environmental factors. China has been and continues to be a major source of international migration.^13,14 Of immigrants in Vancouver, Canada, who landed between 1985 and 2001, half were born in East Asia, mainly Hong Kong and mainland China.¹⁵ Few studies on the prevalence of asthma among immigrants have been undertaken in Canada,¹⁶ and data for Chinese people living in Canada are not available.We hypothesized that the prevalence of asthma would be highest among Canadian-born Chinese adolescents, lower among Chinese adolescents who had immigrated to Canada and lowest among Chinese adolescents living in China. We further hypothesized that, among Chinese immigrants to Canada, prevalence rates of asthma would relate to duration of residence in Canada.     

Associations of Different Phenotypes of Wheezing Illness in Early Childhood with Environmental Variables Implicated in the Aetiology of Asthma

Rationale

Asthma is a complex heterogeneous disease that has increased in prevalence in many industrialised countries. However, the causes of asthma inception remain elusive. Consideration of sub-phenotypes of wheezing may reveal important clues to aetiological risk factors.

Methods

Longitudinal phenotypes capturing population heterogeneity in wheezing reports from birth to 7 years were derived using latent class analysis in the Avon Longitudinal Study of Parents and Children (ALSPAC). Probability of class membership was used to examine the association between five wheezing phenotypes (transient early, prolonged early, intermediate-onset, late-onset, persistent) and early life risk factors for asthma.

Results

Phenotypes had similar patterns and strengths of associations with early environmental factors. Comparing transient early with prolonged early wheezing showed a similar pattern of association with most exposure variables considered in terms of the direction of the effect estimates but with prolonged early wheezing tending to have stronger associations than transient early wheezing except for parity and day care attendance.

Conclusions

Associations with early life risk factors suggested that prolonged early wheeze might be a severe form of transient early wheezing. Although differences were found in the associations of early life risk factors with individual phenotypes, these did not point to novel aetiological pathways. Persistent wheezing phenotype has features suggesting overlap of early and late-onset phenotypes.     

Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis

Background

Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth.

Methods and Findings

Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%.Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding.

Conclusions

There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions.

Review Registration

PROSPERO CRD42013004965 Please see later in the article for the Editors'' Summary     

Performance of two Picea abies (L.) Karst. stands at different stages of decline

Summary Photosynthetic rates and nutrient contents of spruce needles were measured in a region with high levels of air pollution in NE Bavaria, Germany (FRG), and compared to spruce grown under clean air conditions at Craigieburn, in the South Island of New Zealand (NZ). The absolute rates of CO₂ uptake, the slope of the CO₂ response curve at 240 l l^–1 internal CO₂ concentration, and the change of photosynthetic rates with needle age at ambient and saturated CO₂ concentrations were virtually identical at both measuring sites. These results confirm an earlier conclusion, that there is no long-term effect of atmospheric pollutants directly on photosynthetic CO₂ uptake rates with persistent exposure at the FRG site to high levels of anthropogenic air pollution. Photosynthetic capacity at saturating CO₂ concentration was three times higher in the NZ spruce. Needles with high photosynthetic capacity in NZ had lower nitrogen and higher calcium concentrations per unit dry weight but higher concentrations of nitrogen, phosphorus, potassium, magnesium and calcium per unit leaf area, and twice the specific leaf weight.     

Wildland forest fire smoke: health effects and intervention evaluation,Hoopa, California, 1999

Objectives To assess the health effects of exposure to smoke fromthe fifth largest US wildfire of 1999 and to evaluate whether participation ininterventions to reduce smoke exposure prevented adverse lower respiratorytract health effects among residents of the Hoopa Valley National IndianReservation in northwestern California. Design Observational study:epidemiologists from the Centers for Disease Control and Preventionretrospectively reviewed medical records at the local medical center andconducted survey interviews of reservation residents. Setting HumboldtCounty, California. Participants Interviews were completed with 289 of385 residents, representing 26% of the households on the reservation. Of the289 participants, 92 (31.8%) had preexisting cardiopulmonary conditions.Results During the weeks of the forest fire, medical visits forrespiratory illnesses increased by 217 visits (from 417 to 634 visits, or by52%) over the previous year. Survey results indicated that although 181(62.6%) of 289 participants reported worsening lower respiratory tractsymptoms, those with preexisting cardiopulmonary conditions reported moresymptoms before, during, and after the smoke episode. An increased duration ofthe use of high-efficiency particulate air cleaners and the recollection ofpublic service announcements were associated with a reduced odds of reportingadverse health effects of the lower respiratory tract. No protective effectswere observed for duration of mask use or evacuation. ConclusionsTimely actions undertaken by the clinical staff of the local medical centerappeared beneficial to the respiratory health of the community. Futureprograms that reduce economic barriers to evacuation during smoke episodes mayalso improve intervention participation rates and decrease smoke exposures.Although promising, the effectiveness of these and other interventions need tobe confirmed in a prospective community intervention trial.Community smoke exposures resulting from wildland forest fires have beenassociated with increased emergency department and hospital admissions forchronic obstructive pulmonary disease, bronchitis, asthma, and chestpain.^1,2,3Although population expansion into wildland environments continues,interventions to prevent these smoke-related adverse health effects have notbeen validated under conditions of typicaluse.⁴In 1999, the fifth largest wildfire in the United States burned from August23 to November 3 near the Hoopa Valley National Indian Reservation in northernCalifornia. On 15 days, smoke from the fire produced ambient concentrations ofparticulate matter (PM₁₀) on the reservation that exceeded the USEnvironmental Protection Agency''s 24-hour air quality standard of 150μg/m³ of air. On October 21 and 22, particulate concentrationsexceeded the agency''s 24-hour hazardous level of 500 μg/m³.Concern over the health effects of the smoke prompted local officials andmedical officers to implement several interventions to reduce smoke exposurein the community. However, medical personnel were frustrated over the lack ofa scientific basis that could have been used to set public action levels or torecommend appropriate precautionary measures during this emergency. As aresult, on November 5, 1999, the Hoopa Valley Tribal Council requested thatthe Centers for Disease Control and Prevention (CDC) assist them inretrospectively assessing local adverse health effects and evaluating theinterventions that were implemented during the smoke episode.     

Using urine metabolomics to understand the pathogenesis of infant respiratory syncytial virus (RSV) infection and its role in childhood wheezing

Background

Respiratory syncytial virus (RSV) infection in infants causes significant morbidity and is the strongest risk factor associated with asthma. Metabolites, which reflect the interactions between host cell and virus, provide an opportunity to identify the pathways that underlie severe infections and asthma development.

Objective

To study metabolic profile differences between infants with RSV infection, and human rhinovirus (HRV) infection, and healthy infants. To compare infant metabolic differences between children who do and do not wheeze.

Methods

In a term birth cohort, urine was collected while healthy and during acute viral respiratory infection with RSV and HRV. We used ¹H-NMR to identify urinary metabolites. Multivariate and univariate statistics were used to discriminate metabolic profiles of infants with either RSV ARI, or HRV ARI, and healthy infants. Multivariable logistic regression was used to assess the association of urine metabolites with 1st-, 2nd-, and 3rd-year recurrent wheezing.

Results

Several metabolites in nicotinate and nicotinamide metabolism pathways were down-regulated in infants with RSV infection compared to healthy controls. There were no significant differences in metabolite profiles between infants with RSV infection and infants with HRV Infection. Alanine was strongly associated with reduced risk of 1st-year wheezing (OR 0.18[0.0, 0.46]) and 2nd-year wheezing (OR 0.31[0.13, 0.73]), while 2-hydroxyisobutyric acid was associated with increased 3rd-year wheezing (OR 5.02[1.49, 16.93]) only among the RSV infected subset.

Conclusion

The metabolites associated with infant RSV infection and recurrent-wheezing are indicative of viral takeover of the cellular machinery and resources to enhance virulence, replication, and subversion of the host immune-response, highlighting metabolic pathways important in the pathogenesis of RSV infection and wheeze development.

     

Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

Background

Arginase overexpression contributes to airways hyperresponsiveness (AHR) in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR.

Methods

To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA) and challenged with nebulized PBS (OVA/PBS) or OVA (OVA/OVA) for three consecutive days (sub-acute model) or 12 weeks (chronic model), which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O₃), or HEPA-filtered air (FA), for 4 hours. After the CAP+O₃ exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC) or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent^®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization.

Results

Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O₃-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O₃-induced increase in AHR in both models.

Conclusions

This study demonstrates that arginase is upregulated following environmental exposures in murine models of asthma, and contributes to the pollution-induced exacerbation of airways responsiveness. Thus arginase may be a therapeutic target to protect susceptible populations against the adverse health effects of air pollution, such as fine particles and ozone, which are two of the major contributors to smog.