GSTP1 is a hub gene for gene–air pollution interactions on childhood asthma

There is growing evidence that multiple genes and air pollutants are associated with asthma. By identifying the effect of air pollution on the general population, the effects of air pollution on childhood asthma can be better understood. We conducted the Taiwan Children Health Study (TCHS) to investigate the influence of gene–air pollution interactions on childhood asthma. Complete monitoring data for the ambient air pollutants were collected from Taiwan Environmental Protection Agency air monitoring stations. Our results show a significant two‐way gene–air pollution interaction between glutathione S‐transferase P (GSTP1) and PM₁₀ on the risk of childhood asthma. Interactions between GSTP1 and different types of air pollutants have a higher information gain than other gene–air pollutant combinations. Our study suggests that interaction between GSTP1 and PM₁₀ is the most influential gene–air pollution interaction model on childhood asthma. The different types of air pollution combined with the GSTP1 gene may alter the susceptibility to childhood asthma. It implies that GSTP1 is an important hub gene in the anti‐oxidative pathway that buffers the harmful effects of air pollution.     

Exhaled nitric oxide in childhood asthma: a review

As an ‘inflammometer’, the fraction of nitric oxide in exhaled air (Fe _NO) is increasingly used in the management of paediatric asthma. Fe _NO provides us with valuable, additional information regarding the nature of underlying airway inflammation, and complements lung function testing and measurement of airway hyper‐reactivity. This review focuses on clinical applications of Fe _NO in paediatric asthma. First, Fe _NO provides us with a practical tool to aid in the diagnosis of asthma and distinguish patients who will benefit from inhaled corticosteroids from those who will not. Second, Fe _NO is helpful in predicting exacerbations, and predicting successful steroid reduction or withdrawal. In atopic asthmatic children Fe _NO is beneficial in adjusting steroid doses, discerning those patients who require additional therapy from those whose medication dose could feasibly be reduced. In pre‐school children Fe _NO may be of help in the differential diagnosis of respiratory symptoms, and may potentially allow for better targeting and monitoring of anti‐inflammatory treatment.     

Atopic sensitization and respiratory symptoms among Polish and Swedish school children

Allergic sensitization and symptoms from the airways in relation to air pollution were compared in 10–12-year-old school children (n= 1113) from urban Konin in central Poland and both urban and rural parts of Sundsvall in northern Sweden. The measurements included parental questionnaires, skin-prick tests and serial peak flow measurements during 2 weeks with simultaneous monitoring of outdoor air pollutants. The skin-prick test technique was validated by IgE antibody determinations. The levels of common industrial pollutants, SO₂ and smoke particles were much higher in Konin than in urban Sundsvall and the levels of NO₂ were similar. Various respiratory symptoms were more often reported among school children in Konin (except for wheezing and diagnosed asthma). Multiple logistic regression analyses yielded the following increased odds ratios for children in Konin as compared with the reference group (rural Sundsvall): chest tightness and breathlessness 348 (95% confidence interval 2.08–5.82), exercise-induced coughing attacks 3.69 (95% confidence interval 1.68–8.10), recurrent episodes of common cold 2.79 (95% confidence interval 1.53–5.09) and prolonged cough 4–89 (95% confidence interval 2.59–9.23). In contrast, as compared with rural Sundsvall, the adjusted odds ratio for a positive skin-prick test was decreased in Konin, but increased in urban Sundsvall, 0.58 (95% confidence interval 0.37–0.91) and 1.67 (95% confidence interval 1.15–2.42) respectively. The study confirms that living in urban, as compared with rural areas, is associated with an increased prevalence of respiratory symptoms and sensitization to allergens. These differences could be explained by air pollution. Respiratory symptoms were more common in a similar urban group of Polish children who were exposed to even higher levels of air pollution. These children, however, had a much lower prevalence of sensitization to allergens, as compared with the Swedish children. This indicates that differences in lifestyle and standard of living between western Europe and a former socialist country influences the prevalence of atopy.     

Airway inflammation in obese and nonobese patients with difficult-to-treat asthma

Background: Asthma and obesity are associated disorders, but the contribution of obesity to difficult‐to‐treat asthma as well as the mechanisms responsible for this relationship are unclear. The aim of this study was to investigate the relationship between obesity (body mass index ≥ 30) and factors related with asthma severity in patients with difficult‐to‐treat asthma. Methods: One hundred and thirty‐six nonsmoking asthmatic adults with persistent symptoms despite high doses of inhaled or oral corticosteroids and long‐acting bronchodilators were studied [70% female, median (range) age 44.6 (18–75) years, 32% on daily oral corticosteroids]. The association between obesity, lung function parameters [forced expiratory volume in 1 s (FEV₁), functional residual capacity/total lung capacity (FRC/TLC)], inflammatory markers [blood eosinophils, sputum eosinophils and neutrophils, exhaled nitric oxide (FE_NO), airway hyperresponsiveness, C‐reactive protein (CRP)] and aggravating co‐morbid factors (severe chronic sinus disease, gastro‐esophageal reflux, recurrent respiratory infections, psychopathology and obstructive sleep apnea) was investigated. Results: Obese patients (n = 29) had a higher FEV₁%pred (P = 0.05) and a lower FRC/TLC%pred (P < 0.01) compared with nonobese patients (n = 107). Body mass index was inversely related with sputum eosinophils (r = ?0.36, P < 0.01) and FE_NO (r = ?0.30, P < 0.01). Obese patients had an increased risk for gastro‐esophageal reflux (OR = 2.3) and sleep apnea (OR = 3.1). Conclusion: Obesity in patients with difficult‐to‐treat asthma is inversely related with sputum eosinophils and FE_NO, and positively associated with the presence of co‐morbid factors and reduced lung volumes. This suggests that other factors than airway inflammation alone explain the relationship between obesity and asthma severity.     

Effects of climate change on environmental factors in respiratory allergic diseases

A body of evidence suggests that major changes involving the atmosphere and the climate, including global warming induced by human activity, have an impact on the biosphere and the human environment. Studies on the effects of climate change on respiratory allergy are still lacking and current knowledge is provided by epidemiological and experimental studies on the relationship between asthma and environmental factors, such as meteorological variables, airborne allergens and air pollution. However, there is also considerable evidence that subjects affected by asthma are at an increased risk of developing obstructive airway exacerbations with exposure to gaseous and particulate components of air pollution. It is not easy to evaluate the impact of climate change and air pollution on the prevalence of asthma in general and on the timing of asthma exacerbations. However, the global rise in asthma prevalence and severity suggests that air pollution and climate changes could be contributing. Pollen allergy is frequently used to study the interrelationship between air pollution, rhinitis and bronchial asthma. Epidemiological studies have demonstrated that urbanization, high levels of vehicle emissions and westernized lifestyle are correlated to an increase in the frequency of pollen‐induced respiratory allergy, prevalent in people who live in urban areas compared with those who live in rural areas. Meteorological factors (temperature, wind speed, humidity, etc.) along with their climatological regimes (warm or cold anomalies and dry or wet periods, etc.), can affect both biological and chemical components of this interaction. In addition, by inducing airway inflammation, air pollution overcomes the mucosal barrier priming allergen‐induced responses. In conclusion, climate change might induce negative effects on respiratory allergic diseases. In particular, the increased length and severity of the pollen season, the higher occurrence of heavy precipitation events and the increasing frequency of urban air pollution episodes suggest that environmental risk factors will have a stronger effect in the following decades.     

Temporal relationship between air pollution and hospital admissions for asthmatic children in Hong Kong

BACKGROUND: Many epidemiological studies have shown positive association between respiratory health and current levels of outdoor air pollution in Europe and America. OBJECTIVE: The aim of this study was to investigate the association between air pollution and the number of childhood admissions for asthma in Hong Kong. METHODS: Daily counts of childhood admission for asthma to a large teaching Hospital were obtained from the computerized database for the period 1993-1994. A Poisson regression allowing for seasonal patterns and meteorological conditions was used to assess the associations between the number of Hospital admissions and the three pollutants: nitrogen dioxide, sulphur dioxide and inhalable particles (measured as PM10, particles < 10 microm in aerodynamic diameter). RESULTS: A total of 1217 children under 15 years of age were admitted for asthma during the study period. The calculated annual hospitalization rates were 283 and 178 per 100 000 for boys and girls, respectively. The mean PM10, NO2 and SO2 levels were 44.1 microg/m3, 43.3 microg/m3, and 12.2 microg/m3, respectively. Daily admission for asthma increased significantly with increasing ambient level of nitrogen dioxide (relative risk (RR) = 1.08 per 10 microg/m3 increase), sulphur dioxide (RR = 1.06) and inhalable particles (RR = 1.03). No association was found between hospital admission and humidity, temperature or atmospheric pressure. CONCLUSION: This is the first daily time series study of childhood admissions for asthma and air pollution in Hong Kong. The results support that current levels of air pollution contribute to the respiratory morbidity in asthmatic children in Hong Kong.     

Airway dysfunction in nasal polyposis: a spectrum of asthmatic disease?

Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an interesting model to investigate the existence of a non‐allergic unified airway. The factors associated with airway dysfunction in CRSwNP are not fully understood. Objective To assess the impact of nasal disease on lower airway dysfunction in CRSwNP. Methods Fifty‐seven patients with CRSwNP underwent spirometry, nasal endoscopy, exhaled nitric oxide, methacholine bronchial challenge, blood sampling for total IgE, eosinophil count and radioallergosorbent testing (NCT00788749). Three phenotypic groups were identified: ‘asthma group’ (asthma diagnosis); ‘inflammatory group’ [no asthma diagnosis, but elevated fractionated exhaled nitric oxide (FE_NO) and/or bronchial‐hyperreactivity (BHR)]; and ‘non‐inflammatory group’ (no asthma diagnosis, no BHR and normal FE_NO). Group comparisons, univariate and multivariate analyses were performed to examine associations with airway dysfunction. Results FEV₁ and FEF_25?75% were reduced in asthma, but there was no difference between the non‐asthmatic groups. Total IgE and eosinophils were elevated in asthma vs. the non‐inflammatory group, but there was no difference for asthma vs. inflammatory groups. BHR was the only significant predictor of FEV₁ (P<0.001). For FEF_25?75, BHR and eosinophil count were independent predictors (P<0.001 and P=0.04). Nasal outcomes were not predictors of spirometry. Conclusion and Clinical Relevance In CRSwNP there is asymptomatic airway dysfunction suggestive of an asthmatic phenotype. Impairment of lung function is significantly associated with BHR and eosinophilia but not parameters of nasal disease suggesting that severity of airway dysfunction relates to the spectrum of asthma rather than rhinosinusitis. Lower airway dysfunction is common in CRSwNP but does not correlate to the severity of nasal disease. Signs and symptoms of asthma should be sought and treated in CRSwNP. Cite this as: P. A. Williamson, S. Vaidyanathan, K. Clearie, M. Barnes and B. J. Lipworth, Clinical & Experimental Allergy, 2011 (41) 1379–1385.     

Insights in particulate matter‐induced allergic airway inflammation: Focus on the epithelium

Outdoor air pollution is a major environmental health problem throughout the world. In particular, exposure to particulate matter (PM) has been associated with the development and exacerbation of several respiratory diseases, including asthma. Although the adverse health effects of PM have been demonstrated for many years, the underlying mechanisms have not been fully identified. In this review, we focus on the role of the lung epithelium and specifically highlight multiple cytokines in PM‐induced respiratory responses. We describe the available literature on the topic including in vitro studies, findings in humans (ie observations in human cohorts, human controlled exposure and ex vivo studies) and in vivo animal studies. In brief, it has been shown that exposure to PM modulates the airway epithelium and promotes the production of several cytokines, including IL‐1, IL‐6, IL‐8, IL‐25, IL‐33, TNF‐α, TSLP and GM‐CSF. Further, we propose that PM‐induced type 2‐promoting cytokines are important mediators in the acute and aggravating effects of PM on airway inflammation. Targeting these cytokines could therefore be a new approach in the treatment of asthma.     

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

The β₂-adrenergic receptor (β₂AR) is a transmembrane protein expressed by airway smooth muscle cells. In vitro studies have shown that polymorphisms at amino acid positions 16 and 27 alter receptor function. The aim of this study was to examine the associations between the β ₂ AR polymorphisms and risks of asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in a sample of adults. Participants were part of a cross-sectional population-based study of risk factors for respiratory disease. A total of 1,090 Caucasian participants completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of gas transfer. Genotyping for β ₂ AR polymorphisms at positions 16 and 27 was performed using the tetra-primer amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) method. Haplotype frequencies for the two polymorphisms were estimated using the E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR 5.13; 95% CI 1.40,18.8), asthma (2.44; 1.12,5.31) and symptoms of wheeze (1.84; 1.02,3.35). The Gln27 homozygotes had an increased risk of asthma (2.08; 1.05,4.13) and bronchial hyperreactivity (BHR) (1.92; 1.07,3.46). The Arg16/Gln27 haplotype was associated with asthma (1.63; 1.12,2.38) and COPD (2.91; 1.42,5.94). The Arg16/Gln27 β₂AR haplotype is important in COPD, asthma and BHR, and may be associated with more severe respiratory symptoms in middle-aged and older adults.     

Environmental Exposure and Genetic Predisposition as Risk Factors for Asthma in China

Asthma is the most common chronic pulmonary disease worldwide and places a considerable economic burden on society. China is the world''s largest developing country and has the largest population. China has undergone dramatic changes in the past few decades. The traditional lifestyle and living environment have changed in ways that directly affect the prevalence of asthma. The prevalence of asthma is lower in Chinese children and adults than in developed countries, but the prevalence has been on the rise during the past 30 years. The prevalence significantly varies among different parts of China. Polymorphisms of multiple genes, outdoor air pollution caused by PM2.5, PM10, SO₂, NO₂, environmental tobacco smoke, and coal, indoor pollution, and inhaled allergens, such as house dust mites, pollen, and cockroach particles, are risk factors for asthma.     

Prior SO2 exposure promotes airway inflammation and subepithelial fibrosis following repeated ovalbumin challenge

Background Exposure to allergens or air pollutants often leads to asthma exacerbations associated with aggravation of airway inflammation. Although, repeated allergen challenge often induces chronic allergic airway inflammation (CAAI) and airway remodelling, yet, the effects of brief exposure to air pollutants such as SO₂ on development of CAAI and airway remodelling remain to be clarified. Objective The aim of the experiment was to investigate the effects of acute neutrophilic airway inflammation induced by brief exposure to SO₂ on development of CAAI and subepithelial fibrosis (SEF) in a murine model of asthma. Methods Acute airway inflammation was induced by brief exposure to 50 p.p.m. SO₂ (1 h/d, 3 days). CAAI and SEF in BALB/c mice were induced by repeated challenge with ovalbumin (OVA) for 5 or 9 weeks with or without prior exposure to SO₂. Bronchoalveolar lavage fluid (BALF) eosinophilia as index of CAAI, BALF endothelin‐1 (ET‐1) and TGF‐β1 levels, morphometric evaluation of fibrotic area beneath subbasement membrane and lung hydroxyproline content (Hyp) as indexes of SEF were monitored. Results Exposure to SO₂ led to acute neutrophilic inflammation and epithelial sloughing with profound elevation of BALF ET‐1. Repeated OVA challenge resulted in CAAI and SEF along with elevation of Hyp, increase of fibrotic area beneath subbasement membrane and elevation of BALF TGF‐β1. Preceding SO₂ exposure exaggerated BALF eosinophilia, facilitated and enhanced SEF with more significant elevation of BALF ET‐1 and TGF‐β1 levels compared with OVA‐challenged mice without prior exposure to SO₂. The increase of Hyp was positively correlated with elevation of BALF TGF‐β1 during CAAI (r=0.842, P<0.01). Conclusion This data demonstrated that SEF developed in parallel with severity and time course of CAAI following repeated OVA challenge. SO₂‐induced acute epithelial injury and neutrophilic inflammation could enhance CAAI and promote SEF, probably through overexpression of ET‐1 and TGF‐β1.     

Environmental urban factors (air pollution and allergens) and the rising trends in allergic respiratory diseases

Respiratory allergic diseases such as rhinitis and bronchial asthma appear to be increasing worldwide, affecting in particular subjects living in urban areas, and the reasons for this increase are still largely unknown. Although the role played by air pollution has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions and a westernised lifestyle are linked to the rising frequency of these diseases observed in most industrialized countries. Laboratory studies confirm the epidemiological evidence that inhalation of some pollutants, either individually or in combination, adversely affect lung function in asthmatics. Air pollutants may not only increase the frequency and intensity of symptoms in already allergic patients but may promote airway sensitization to airborne allergens in predisposed subjects. By attaching to the surface of pollen grains and of plant-derived paucimicronic particles, pollutants can modify the morphology of these antigen-carrying agents and alter their allergenic potential. In addition, by inducing airway inflammation, pollutants may overcome the mucosal barrier and so 'prime' allergen-induced responses. In other words airway mucosal damage and impaired mucociliary clearance induced by air pollution may facilitate the access of inhaled allergens to the cells of the immune system.     

Air pollution and children's respiratory health – gaps in the global evidence

There is now convincing evidence that air pollution, especially the particulate matter (PM) fraction, adversely affects children's health. In general, the health effects of traffic‐derived PM are well described in children living in high‐income countries. Conversely, studies into the health effects of PM from biomass and solid fuels are limited to children in lower‐income countries. As PM from different combustion sources have components in common (e.g. elemental black carbon) – are we able to extrapolate from the research performed in different countries under different exposure conditions? Using lung function growth and vulnerability to infection as examples of health effects of global significance to children, this review addresses the question whether high‐income‐country research into air pollution can inform effects of pollution in low‐income countries and vice versa. Cite this as: J. Grigg, Clinical & Experimental Allergy, 2011 (41) 1072–1075.     

Environmental exposures and asthma morbidity in children living in urban neighborhoods

A substantial disparity in asthma prevalence and morbidity among urban children compared with their nonurban counterparts has been recognized for more than two decades. Because of the nature of urban neighborhoods, pest allergens, such as cockroach and mouse, are present in high concentrations in US urban housing and have both repeatedly been linked to asthma morbidity in sensitized children. In addition, there is a growing body of evidence demonstrating that concentrations of many pollutants are higher indoors than outdoors in both US and European urban communities and that exposures to indoor pollutants such as particulate matter (PM) and nitrogen dioxide (NO₂) are independently associated with symptoms in children with asthma. Although environmental interventions are challenging to implement, when they reduce relevant indoor allergen and pollutant exposures, they are associated with clear improvements in asthma. Other modifiable risk factors in urban childhood asthma that have emerged include dietary and nutritional factors. Overweight and obese children, for example, may be more susceptible to the pulmonary effects of pollutant exposure. Insufficiency of vitamin D and folate has also emerged as modifiable risk factors for asthma morbidity in children. The identification of these modifiable risk factors for urban childhood asthma morbidity offers a ripe opportunity for intervention.     

Effects of wintertime ambient air pollutants on asthma exacerbations in urban minority children with moderate to severe disease

BACKGROUND: Urban minority children with asthma are at higher risk for severe exacerbations leading to hospitalizations and deaths. Because multiple studies have reported associations between air pollution and asthma worsening, elevated levels of air pollution are cited as a possible trigger for increased asthma morbidity in urban areas. Few studies have prospectively followed panels of urban children with asthma to determine whether air pollution levels are associated with clinically relevant outcomes such as asthma exacerbations. OBJECTIVE: To determine the association between levels of ambient air pollutants and asthma exacerbations in urban poor children with moderate to severe asthma. METHODS: A school-based panel of children with difficult-to-control disease was followed over a period of 3 consecutive winters in Denver, Colo. The panel consisted of predominantly urban African American children with moderate to severe asthma. Levels of Environmental Protection Agency criteria air pollutants were measured on a daily basis with concurrent monitoring of lung function, bronchodilator use, symptoms, and asthma exacerbations. RESULTS: After controlling for time-varying factors such as upper respiratory infections and meteorologic factors, a weak association was found between ambient carbon monoxide levels and bronchodilator use. Ozone levels were associated with daytime symptoms only. No association was observed between daily air pollution concentrations and daily levels of FEV 1 , peak flow, nighttime symptom scores, or asthma exacerbations over the 3-year period. CONCLUSION: Ambient levels of Environmental Protection Agency criteria air pollutants in Denver do not lead to clinically significant asthma worsening in urban children with moderate to severe asthma during winter months when children are primarily indoors.     

Mucociliary clearance,airway inflammation and nasal symptoms in urban motorcyclists

OBJECTIVES:There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution.METHODS:In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO₂) concentration-monitoring system during the 14 days before each assessment. The associations between NO₂ and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01976039","term_id":"NCT01976039"}}NCT01976039.RESULTS:Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO₂ exposure level was 75 mg/m³ for these subjects and a significant association was observed between NO₂ and impaired mucociliary clearance (p = 0.036).CONCLUSION:Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.     

Environmental risk factors and allergic bronchial asthma

The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic potential. In addition, by inducing airway inflammation, which increases airway permeability, pollutants overcome the mucosal barrier and could be able to "prime" allergen-induced responses. There are also observations that a thunderstorm occurring during pollen season can induce severe asthma attacks in pollinosis patients. After rupture by thunderstorm, pollen grains may release part of their cytoplasmic content, including inhalable, allergen-carrying paucimicronic particles.     

An economic evaluation of NIOX MINO airway inflammation monitor in the United Kingdom

Background: Fractional exhaled nitric oxide (FE_NO), a marker of eosinophilic airway inflammation, is easily measured by noninvasive means. The objective of this study was to determine the cost‐effectiveness of FE_NO measurement using a hand‐held monitor (NIOX MINO), at a reimbursement price of £23, for asthma diagnosis and management in the UK. Methods: We constructed two decision trees to compare FE_NO measurement with standard diagnostic testing and guideline recommendations for management. For asthma diagnosis, we compared FE_NO measurement with lung function and reversibility testing, bronchial provocation and sputum eosinophil count. For asthma management, we evaluated the impact on asthma control, including inhaled corticosteroid use, exacerbations and hospitalizations, of monitoring with FE_NO measurement vs symptoms and lung function as in standard care. Resource use and health outcomes were evaluated over a 1‐year time frame. Direct costs were calculated from a UK health‐care payer perspective (2005 £). Results: An asthma diagnosis using FE_NO measurement cost £43 less per patient as compared with standard diagnostic tests. Asthma management using FE_NO measurement instead of lung function testing resulted in annual cost‐savings of £341 and 0.06 quality‐adjusted life‐years gained for patients with mild to severe asthma and cost‐savings of £554 and 0.004 quality‐adjusted life‐years gained for those with moderate to severe asthma. Conclusions: Asthma diagnosis based on FE_NO measurement with NIOX MINO alone is less costly and more accurate than standard diagnostic methods. Asthma management based on FE_NO measurement is less costly than asthma management based on standard guidelines and provides similar health benefits.     

Genetic variation in biotransformation enzymes,air pollution exposures,and risk of spina bifida

Spina bifida is a birth defect characterized by incomplete closure of the embryonic neural tube. Genetic factors as well as environmental factors have been observed to influence risks for spina bifida. Few studies have investigated possible gene‐environment interactions that could contribute to spina bifida risk. The aim of this study is to examine the interaction between gene variants in biotransformation enzyme pathways and ambient air pollution exposures and risk of spina bifida. We evaluated the role of air pollution exposure during pregnancy and gene variants of biotransformation enzymes from bloodspots and buccal cells in a California population‐based case‐control (86 cases of spina bifida and 208 non‐malformed controls) study. We considered race/ethnicity and folic acid vitamin use as potential effect modifiers and adjusted for those factors and smoking. We observed gene‐environment interactions between each of the five pollutants and several gene variants: NO (ABCC2), NO₂ (ABCC2, SLC01B1), PM₁₀ (ABCC2, CYP1A1, CYP2B6, CYP2C19, CYP2D6, NAT2, SLC01B1, SLC01B3), PM_2.5 (CYP1A1 and CYP1A2). These analyses show positive interactions between air pollution exposure during early pregnancy and gene variants associated with metabolizing enzymes. These exploratory results suggest that some individuals based on their genetic background may be more susceptible to the adverse effects of pollution.     

Respiratory health effects of air pollution: update on biomass smoke and traffic pollution

Mounting evidence suggests that air pollution contributes to the large global burden of respiratory and allergic diseases, including asthma, chronic obstructive pulmonary disease, pneumonia, and possibly tuberculosis. Although associations between air pollution and respiratory disease are complex, recent epidemiologic studies have led to an increased recognition of the emerging importance of traffic-related air pollution in both developed and less-developed countries, as well as the continued importance of emissions from domestic fires burning biomass fuels, primarily in the less-developed world. Emissions from these sources lead to personal exposures to complex mixtures of air pollutants that change rapidly in space and time because of varying emission rates, distances from source, ventilation rates, and other factors. Although the high degree of variability in personal exposure to pollutants from these sources remains a challenge, newer methods for measuring and modeling these exposures are beginning to unravel complex associations with asthma and other respiratory tract diseases. These studies indicate that air pollution from these sources is a major preventable cause of increased incidence and exacerbation of respiratory disease. Physicians can help to reduce the risk of adverse respiratory effects of exposure to biomass and traffic air pollutants by promoting awareness and supporting individual and community-level interventions.