Role In Development Of Asthma Research Articles

"Do bacteria have a role in asthma development?" J.Armann and E.von Mutius. Eur Respir J 2010; 36: 469-471.

"Do bacteria have a role in asthma development?" J.Armann and E.von Mutius. Eur Respir J 2010; 36: 469-471.

Age-related immune-modulating properties of seminal fluid that control the severity of asthma are gender specific.

Reproductive organs play a pivotal role in asthma development and progression, especially in women. Endocrine environment changes associated with the menstrual cycle, pregnancy, and menopause can exacerbate the clinical features of asthma. Factors secreted by reproductive organs may be responsible for the gender difference and age-related changes in adult asthma. Here, we show that mammalian seminal fluid has anti-asthma effects exclusively in females. Exposure to murine seminal fluid markedly reduced eosinophilic airway inflammation in 2-month-old female mice upon ovalbumin inhalation. The anti-asthma effect with seminal fluid from 10-month-old males was double that with fluid from 2-month-old males, suggesting that it depended on male sexual maturation. We further found that seminal fluid from middle-aged human volunteers had beneficial effects in asthmatic female mice; these effects were associated with transcriptional repression of osteopontin and IL-17A, which are poor prognostic factors for asthma. In 2-month-old male mice, however, human seminal fluid failed to decrease asthmatic features and even enhanced osteopontin and IL-17A transcription. Our data demonstrate that age-related seminal fluid exerts opposing effects in asthmatic male and female mice. These findings may help the development of novel approaches to control the prevalence and age-related progression of asthma in women.

The Aftermath of Bronchoconstriction.

Asthma is characterized by chronic airway inflammation, airway remodeling, and excessive constriction of the airway. Detailed investigation exploring inflammation and the role of immune cells has revealed a variety of possible mechanisms by which chronic inflammation drives asthma development. However, the underlying mechanisms of asthma pathogenesis still remain poorly understood. New evidence now suggests that mechanical stimuli that arise during bronchoconstriction may play a critical role in asthma development. In this article, we review the mechanical effect of bronchoconstriction and how these mechanical stresses contribute to airway remodeling independent of inflammation.

Small Animal Models of Respiratory Viral Infection Related to Asthma.

Respiratory viral infections are strongly associated with asthma exacerbations. Rhinovirus is most frequently-detected pathogen; followed by respiratory syncytial virus; metapneumovirus; parainfluenza virus; enterovirus and coronavirus. In addition; viral infection; in combination with genetics; allergen exposure; microbiome and other pathogens; may play a role in asthma development. In particular; asthma development has been linked to wheezing-associated respiratory viral infections in early life. To understand underlying mechanisms of viral-induced airways disease; investigators have studied respiratory viral infections in small animals. This report reviews animal models of human respiratory viral infection employing mice; rats; guinea pigs; hamsters and ferrets. Investigators have modeled asthma exacerbations by infecting mice with allergic airways disease. Asthma development has been modeled by administration of virus to immature animals. Small animal models of respiratory viral infection will identify cell and molecular targets for the treatment of asthma.

Is preterm birth associated with asthma among children from birth to 17 years old? -A study based on 2011-2012 US National Survey of Children\u2019s Health

BackgroundPreterm birth can interrupt lung development in utero and is associated with early life factors, which adversely affects the developing respiratory system. Studies on preterm birth and asthma risk are comparatively sparse and the results are not consistent.MethodsMultivariate analyses were performed on a cross-sectional data from the National Survey of Children’s Health (NSCH) collected in 2011 to 2012. The NSCH was a nationally representative telephone survey sponsored by the Maternal and Child Health Bureau and conducted by the National Center for Health Statistics. A cross-sectional analysis using data from the US on 90,721 children was conducted to examine the relationship between preterm birth and asthma risk.ResultsA total of 90,721 children under 17 years were included and 12% of the children were reported as preterm birth. The prevalence of diagnosed asthma was 15%, with a male to female ratio of 1.26:1. Children who were born preterm were 1.64 times (95% confidence interval: 1.45–1.84) more likely to develop asthma compared with those who were born term after controlling for confounders. Similarly, children who were low birth weight were 1.43 times (95% confidence interval: 1.25–1.63) more likely for asthma, and the odds ratio increased to 1.77 for those both preborn and low birth weight. Child’s gender, race/ethnicity, age, family structure, family income levels, and household smoking were significantly associated with the odds of reported asthma.ConclusionsPreterm birth was associated with increased risk of asthma among US children, supporting the notion that preterm birth may play a critical role in asthma development.

The Prebiotic and Probiotic Properties of Human Milk: Implications for Infant Immune Development and Pediatric Asthma.

The incidence of pediatric asthma has increased substantially in recent decades, reaching a worldwide prevalence of 14%. This rapid increase may be attributed to the loss of “Old Friend” microbes from the human microbiota resulting in a less diverse and “dysbiotic” gut microbiota, which fails to optimally stimulate immune development during infancy. This hypothesis is supported by observations that the gut microbiota is different in infants who develop asthma later in life compared to those who remain healthy. Thus, early life exposures that influence gut microbiota play a crucial role in asthma development. Breastfeeding is one such exposure; it is generally considered protective against pediatric asthma, although conflicting results have been reported, potentially due to variations in milk composition between individuals and across populations. Human milk oligosaccharides (HMOs) and milk microbiota are two major milk components that influence the infant gut microbiota and hence, development of the immune system. Among their many immunomodulatory functions, HMOs exert a selective pressure within the infant gut microbial niche, preferentially promoting the proliferation of specific bacteria including Bifidobacteria. Milk is also a source of viable bacteria originating from the maternal gut and infant oral cavity. As such, breastmilk has prebiotic and probiotic properties that can modulate two of the main forces controlling the gut microbial community assembly, i.e., dispersal and selection. Here, we review the latest evidence, mechanisms and hypotheses for the synergistic and/or additive effects of milk microbiota and HMOs in protecting against pediatric asthma.

Dual Role of Toll-like Receptors in Human and Experimental Asthma Models.

Asthma is a chronic airway inflammatory disease that is influenced by the interplay between genetic factors and exposure to environmental allergens, microbes, or microbial products where toll-like receptors (TLRs) play a pivotal role. TLRs recognize a wide range of microbial or endogenous molecules as well as airborne environmental allergens and act as adjuvants that influence positively or negatively allergic sensitization. TLRs are qualitatively and differentially expressed on hematopoietic and non-hematopoietic stromal or structural airway cells that when activated by TLRs agonists exert an immune-modulatory role in asthma development. Therefore, understanding mechanisms and pathways by which TLRs orchestrate asthma outcomes may offer new strategies to control the disease. Here, we aim to review and critically discuss the role of TLRs in human asthma and murine models of allergic airway inflammation, highlighting the complexity of TLRs function in development, exacerbation, or control of airway allergic inflammation.

Role of nitric oxide synthases polymorphism in the development of comorbidity of bronchial asthma and hypertension

Present literature review highlights the current views on the role of genetic factors in the development of bronchial asthma and hypertension, indicates their role in the formation of comorbid pathology, draws attention to the role of nitric oxide and nitric oxide synthase genes in the pathogenesis. In recent years there has been increasing interest of researchers to the problem of comorbidity, in particular to a combination of asthma and hypertension. Genetic factors play a great role in pathogenesis of these diseases. Among genes that play role in development of asthma there are genes encoding antigen recognition factors and humoral immune response factors, genes encoding mediators of inflammation, chemokines and intercellular adhesion molecules, genes of receptors performing fixation of external ligand molecules on the target cell, genes of intracellular signaling molecules and transcription factors and a number of other genes. The pathogenesis of essential hypertension is associated with the genes of renin-angiotensin-aldosterone system and genes regulating endothelial status. The link between asthma and hypertension is nitric oxide, which is involved in many physiological processes, in particular, regulates vascular and respiratory tone. Polymorphism of nitric oxide synthases genes is able to violate its production in the organism and thus lead to the development of bronchial asthma and hypertension. Polymorphisms Glu298Asp, eNOS4a/b, and 786C/T of NOS3 gene are associated with development of hypertension. Polymorphisms of this gene had been studied in patients with bronchial asthma, and they have demonstrated their influence on the level of nitric oxide in patients. Thus, the NOS gene polymorphisms may participate in the formation of comorbidity of bronchial asthma and hypertension.

The microbial environment and its influence on asthma prevention in early life

There is accumulating evidence to suggest that the environmental microbiome plays a significant role in asthma development. The very low prevalence of asthma in populations highly exposed to microbial environments (farm children and Amish populations) highlights its preventive potential. This microbial diversity might be necessary to instruct a well-adapted immune response and regulated inflammatory responses to other inhaled and ingested environmental elements, such as allergens, particles, and viruses. Like the internal gut microbiome, which is increasingly recognized as an important instructor of immune maturation, the external environmental microbiome might shape immune responses on the skin, airway mucosal surfaces, and potentially also the gut early in life. The diversity of the external microbial world will ensure that of the many maladapted pathways leading to asthma development, most, if not all, will be counterbalanced. Likewise, important contributors to asthma, such as allergen sensitization and allergic manifestations early in life, are being suppressed. Thus the facets of innate immunity targeted by microbes and their compounds and metabolites might be the master switch to asthma and allergy protection, which has been found in environments rich in microbial exposures.

The obesity's role in asthma development in pediatric population - literature review

The obesity's role in asthma development in pediatric population - literature review

Infections in Children with Asthma

Asthma is one of the most common chronic disorders in childhood. Asthma symptoms normally find in first three years of a life when the growth and remodeling of lungs is at maximum pace. There is always a common concern regarding different forms of asthma and how to cure them. Studies showed us in US about 20 million people are suffering from asthma and out of which 9 millions are children. Globally around 70% of asthmatic children are suffering from Wheeze which is mostly a symptom of viral infection. This is also one of the global burdens due to respiratory viral infections imposed by asthma. The various types of infections include rhinovirus infections which plays a crucial role in asthma development; respiratory syncytial virus which cause lower respiratory tract infection such as bronchiolitis; influenza and par- influenza viruses; pertussis, one of the major reason of death for children below 3 months of age; epiglottitis; bronchiolitis which effects mainly children below age of 2; and pneumonia caused by bacteria, fungi, parasites or due to virus. In this article we will shed some light on the relationship of chest infections with asthma and how they impact the course of asthma disease in children. The most important factor is how several vitamins like Vitamin D plays a crucial role for asthma patients. General studies show prevention and long term control is major key in stopping asthma attacks. There are various medications available to avoid asthma attacks but it generally depends upon the patient’s symptoms, age and the various triggering factors. Further we will see how a balanced diet helps like pro-biotic supplements, bacterial derived product, OM-85 etc helps in controlling asthma infections.

The Effect of Aerobic Exercise on Asthma-related Responses in Adults

RationaleIncreasing evidence indicates that decreased physical activity may play a role in asthma development (Lucas & Platts-Mills, 2005). In light of this evidence, this study has examined the effect of moderate intensity aerobic exercise on asthmatic responses in adult patients.MethodsWe have completed a randomized, parallel group proof of concept study in which sixteen adults (33 - 78yrs) with mild to moderate persistent asthma were assigned randomly to either: i) a 12-week protocol of moderate intensity aerobic exercise plus usual care or ii) a 12-week protocol of usual care only. All participants had evidence of reversibility via spirometry as performed by the ATS guidelines. Exercise participants completed a walking program at a frequency of 3x/wk, 60 - 75% of age-predicted HRmax.ResultsBefore and after protocol completion, participants were monitored for differences in asthma control, lung function, and pro-inflammatory targets in peripheral blood and nasal lavage. Results suggest that participants in the exercise group exhibited a trend toward improved fitness levels, including increased VO2 peak and total treadmill time. Subjects in both groups exhibited improved asthma control; no changes were observed in lung function or pro-inflammatory mediator levels. As indicated by heart rate monitors and exercise logs, adherence in the exercise group was 86%.ConclusionsThis study has demonstrated the feasibility of the protocol and measurements, established proof of concept, and generated preliminary data for a larger, clinical efficacy trial that will test the efficacy of exercise as an adjunct therapy for the treatment of asthma. RationaleIncreasing evidence indicates that decreased physical activity may play a role in asthma development (Lucas & Platts-Mills, 2005). In light of this evidence, this study has examined the effect of moderate intensity aerobic exercise on asthmatic responses in adult patients. Increasing evidence indicates that decreased physical activity may play a role in asthma development (Lucas & Platts-Mills, 2005). In light of this evidence, this study has examined the effect of moderate intensity aerobic exercise on asthmatic responses in adult patients. MethodsWe have completed a randomized, parallel group proof of concept study in which sixteen adults (33 - 78yrs) with mild to moderate persistent asthma were assigned randomly to either: i) a 12-week protocol of moderate intensity aerobic exercise plus usual care or ii) a 12-week protocol of usual care only. All participants had evidence of reversibility via spirometry as performed by the ATS guidelines. Exercise participants completed a walking program at a frequency of 3x/wk, 60 - 75% of age-predicted HRmax. We have completed a randomized, parallel group proof of concept study in which sixteen adults (33 - 78yrs) with mild to moderate persistent asthma were assigned randomly to either: i) a 12-week protocol of moderate intensity aerobic exercise plus usual care or ii) a 12-week protocol of usual care only. All participants had evidence of reversibility via spirometry as performed by the ATS guidelines. Exercise participants completed a walking program at a frequency of 3x/wk, 60 - 75% of age-predicted HRmax. ResultsBefore and after protocol completion, participants were monitored for differences in asthma control, lung function, and pro-inflammatory targets in peripheral blood and nasal lavage. Results suggest that participants in the exercise group exhibited a trend toward improved fitness levels, including increased VO2 peak and total treadmill time. Subjects in both groups exhibited improved asthma control; no changes were observed in lung function or pro-inflammatory mediator levels. As indicated by heart rate monitors and exercise logs, adherence in the exercise group was 86%. Before and after protocol completion, participants were monitored for differences in asthma control, lung function, and pro-inflammatory targets in peripheral blood and nasal lavage. Results suggest that participants in the exercise group exhibited a trend toward improved fitness levels, including increased VO2 peak and total treadmill time. Subjects in both groups exhibited improved asthma control; no changes were observed in lung function or pro-inflammatory mediator levels. As indicated by heart rate monitors and exercise logs, adherence in the exercise group was 86%. ConclusionsThis study has demonstrated the feasibility of the protocol and measurements, established proof of concept, and generated preliminary data for a larger, clinical efficacy trial that will test the efficacy of exercise as an adjunct therapy for the treatment of asthma. This study has demonstrated the feasibility of the protocol and measurements, established proof of concept, and generated preliminary data for a larger, clinical efficacy trial that will test the efficacy of exercise as an adjunct therapy for the treatment of asthma.

Interaction between filaggrin null mutations and tobacco smoking in relation to asthma

The mechanisms underlying the association between filaggrin (FLG) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development. We sought to investigate possible interactions between FLG null mutations and tobacco smoking in relation to asthma. A total of 3471 adults from a general population sample participated in a health examination. Lung function and serum specific IgE levels to inhalant allergens were measured, and information on asthma and smoking was obtained by means of questionnaire. Participants were genotyped for the 2 most common FLG null mutations in white subjects: R501X and 2282del4. Another Danish population was used for replication. The FLG null mutation genotype was significantly associated with a higher prevalence of asthma and decreased FEV(1)/forced vital capacity ratio. In logistic regression analyses with asthma as the outcome, a significant interaction was found between FLG null mutations and smoking status (P= .02). This interaction was confirmed, although it was not statistically significant, in another Danish population study. Interactions between FLG genotype and cumulated smoking exposure were found in relation to asthma (P= .03) and decreased FEV(1)/forced vital capacity ratio (P= .03). A3-way interaction was found among FLG genotype, smoking, and asthma, suggesting that the FLG-smoking interaction mainly played a role in nonatopic subjects. FLG null mutations modified the effects of smoking on the risk of asthma. This finding might have implications for risk stratification of the population.

Relevance and implication of genetic determinants to asthma pathophysiology

The number of single nucleotide polymorphisms (SNPs) found to be associated with asthma and related phenotypes outnumbers those with functional impacts. In this review we briefly described some of the approaches used to investigate functionality of SNPs, and summarized recent findings related to the characterization of functional SNPs in asthma. For disease-associated SNPs residing in the promoter or 3' untranslated regions, differential protein binding affinity between the major and minor alleles is often the first logical area of investigation. In this review, we described SNPs associated with asthma or related phenotypes in five genes which in the past 12 months have new data implicating potential mechanisms in asthma development. Variability in treatment responses poses a great challenge in asthma management. It is established that the genetic makeup of individuals plays a role in asthma development, yet the mechanisms remain unclear. Investigations on the functional impacts of disease-associated SNPs will help us gain insights into potential disease mechanisms, and ultimately lead to effective therapies for those who suffer from asthma.

Mitochondrial genetic background plays a role in increasing risk to asthma

A number of studies suggest that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To shed light for the first time on the role of the mitochondrial genome in the etiology of asthma we analyzed the mitochondrial tRNA genes and part of their flanking regions in patients with asthma compared with a set of healthy controls. We found a total of 10 mutations in 56 out of 76 asthmatic patients. Four of these mutations were not found in the control group, five were observed at a significantly lower frequency in controls, but none of the combinations of mutations detected in asthma patients was observed in the controls. Furthermore, we observed that 27.6% of the asthma patients (vs. 4% of the controls) belonged to the haplogroup U (Fisher test P=0.00) and a positive significant correlation was found between the occurrence of the haplogroup U and the severity of the disease (Fisher test P=0.02). Whereas further studies in larger cohorts are needed to confirm these observations we suggest that the mitochondrial genetic background plays a key role in asthma development.

Krüppel-like factor 6 regulates transforming growth factor-β gene expression during human respiratory syncytial virus infection

BackgroundHuman respiratory syncytial virus (RSV) infection is associated with airway remodeling and subsequent asthma development. Transforming growth factor-beta (TGF) plays a crucial role in asthma development. The mechanism regulating TGF gene expression during RSV infection is not known. Kruppel-like factor family of transcription factors are critical regulators of cellular/tissue homeostasis. Previous studies have shown that Kruppel-like factor 6 (KLF6) could function as a trans-activator of TGF gene; however, whether KLF members play a role during infection is unknown. In the current study we have evaluated the role of KLF6 during TGF expression in RSV infected cells.FindingsSilencing KLF6 expression by shRNA led to drastic inhibition in TGF production during RSV infection, as assessed by ELISA analysis of medium supernatants. RT-PCR analysis revealed loss of TGF expression in KLF6 silenced cells. Chromatin-immunoprecipitation assay conducted with RSV infected cells showed binding of KLF6 protein to the TGF promoter during RSV infection. We further observed reduced RSV infectivity in KLF6 silenced cells and in cells incubated with TGF neutralizing antibody. In contrast, enhanced RSV infection was noted in cells incubated with purified TGF.ConclusionWe have identified KLF6 as a key transcription factor required for trans-activation of TGF gene during RSV infection. Moreover, TGF production is required for efficient RSV infection and thus, KLF6 is also required for efficient RSV infection by virtue of KLF6 dependent TGF production during infection.

A comparison of the allergic responses induced by Penicillium chrysogenum and house dust mite extracts in a mouse model

A report by the Institute of Medicine suggested that more research is needed to better understand mold effects on allergic disease, particularly asthma development. We compared the ability of the fungal Penicillium chrysogenum (PCE) and house dust mite (HDM) extracts to induce allergic responses in BALB/c mice. The extracts were administered by intratracheal aspiration (IA) at several doses (0, 2.5, 5, 10, 20, 40, and 80 μg) four times over a 4-week period. Three days after the last IA exposure, serum and bronchoalveolar lavage fluid (BALF) were collected. The relative allergenicity of the extracts was evaluated based on the lowest dose able to induce a significant response compared to control (0 μg) and the robustness of the response. PCE induced the most robust response at the lowest dose for most endpoints examined: BALF total, macrophage, neutrophil, and eosinophil cell counts, and antigen-specific IgE. Taken together, our data suggest that PCE may induce a more robust allergic and inflammatory response at lower doses than HDM. Our data suggest that Penicillium chrysogenum is a robust allergen and may be a more potent allergen source than house dust mite (HDM) in this mouse model. Two critical factors in the development of human allergic disease, exposure levels and sensitization thresholds, are unknown for most allergens including molds/fungi. Human exposure levels are not within the scope of this article. However, the data presented suggest a threshold dose for the induction of allergic responsiveness to P. chrysogenum. Additionally, P. chrysogenum as well as other molds may play an important role in asthma development in our society.

Do bacteria have a role in asthma development?

The relationship between the microbial world and asthma is not well understood. Although we know that the most potent triggers of wheezing attacks are viruses, we do not understand whether and how they contribute to disease onset and progression. Even less is known about the relationship between asthma and bacteria. The clearest evidence stems from studying asthma exacerbations or wheezing episodes. In clinical studies viruses can be detected in up to 90% of such episodes 1, with rhinovirus being most commonly identified, followed by respiratory syncytial virus (RSV) in the first years of life. Other viruses such as parainfluenza, metapneumovirus, coronavirus, adenovirus, influenza and enteroviruses have also been implicated, mostly in older patients. In ∼10% of episodes multiple viruses were found 2. Most recently, the H1N1 virus has been reported to be more prevalent among asthmatics than other patients 3. In a recent high-risk birth cohort, children with wheezing illnesses triggered by rhinovirus infections early in life were at risk for the subsequent development of asthma up to 6 yrs of age 2. However, it remains unclear whether viral infections are causal factors for the new onset of disease by impacting on the host's immune response or whether they merely unmask a host's underlying susceptibility to develop asthma by triggering exacerbations. It has been proposed that asthmatics may have subtle deficiencies in their immune response resulting in reduced antiviral activity and increased susceptibility for viral infections, especially of the lower respiratory tract. Corne et al. 4 recruited 76 cohabiting couples where only one partner had asthma and compared the frequency, severity and duration of rhinovirus infection between them. The authors found that asthmatics develop more severe and longer lasting respiratory symptoms following rhinovirus infections than their spouses 4. Message et al. 5 experimentally infected adult …

Arginase 1 and arginase 2 variations associate with asthma, asthma severity and β2 agonist and steroid response

Arginase probably plays an important role in asthma development, severity and progression. Polymorphisms in arginase 1 and arginase 2 genes have been associated with childhood asthma and FEV1 reversibility to beta2 agonists. We investigated the association between arginase 1 and arginase 2 polymorphisms and adult asthma, asthma severity and treatment response in a longitudinal cohort of 200 asthma patients. Patients were studied during 1962-1975 and reexamined during 1990-1999, together with their families. Longitudinal data on lung function and treatment were extracted from medical records. Associations between haplotype-tagging polymorphisms in arginase 1 (n=3) and arginase 2 (n=8) and asthma, asthma severity, acute response to bronchodilators and chronic response to inhaled corticosteroids were analyzed. Two polymorphisms in arginase 2 (rs17249437 and rs3742879) were associated with asthma and with more severe airway obstruction. Increased airway hyperresponsiveness and lower beta2 agonist reversibility, but not anticholinergic reversibility, were associated with both arginase 1 and arginase 2. Inhaled corticosteroids slowed down the annual FEV1 decline, which was significantly less effective in homozygote carriers of the C-allele of the arginase 1 polymorphism, rs2781667. We show that previously reported associations between arginase polymorphisms and childhood asthma are also present in adult asthma and the previously found associations with lower reversibility are specific for beta2 agonists. Furthermore, we identified associations of arginase 1 and arginase 2 genes with asthma severity, as reflected by a lower lung function, more severe airway hyperresponsiveness, and less long-term response to inhaled corticosteroids. Studies on the functionality of the polymorphisms are warranted to further unravel the complex mechanisms underlying these observations.

Effect of Early Life Exposure to Air Pollution on Development of Childhood Asthma

BackgroundThere is increasing recognition of the importance of early environmental exposures in the development of childhood asthma. Outdoor air pollution is a recognized asthma trigger, but it is unclear whether exposure influences incident disease. We investigated the effect of exposure to ambient air pollution in utero and during the first year of life on risk of subsequent asthma diagnosis in a population-based nested case–control study.MethodsWe assessed all children born in southwestern British Columbia in 1999 and 2000 (n = 37,401) for incidence of asthma diagnosis up to 3–4 years of age using outpatient and hospitalization records. Asthma cases were age- and sex-matched to five randomly chosen controls from the eligible cohort. We estimated each individual’s exposure to ambient air pollution for the gestational period and first year of life using high-resolution pollution surfaces derived from regulatory monitoring data as well as land use regression models adjusted for temporal variation. We used logistic regression analyses to estimate effects of carbon monoxide, nitric oxide, nitrogen dioxide, particulate matter ≤ 10 μm and ≤ 2.5 μm in aerodynamic diameter (PM10 and PM2.5), ozone, sulfur dioxide, black carbon, woodsmoke, and proximity to roads and point sources on asthma diagnosis.ResultsA total of 3,482 children (9%) were classified as asthma cases. We observed a statistically significantly increased risk of asthma diagnosis with increased early life exposure to CO, NO, NO2, PM10, SO2, and black carbon and proximity to point sources. Traffic-related pollutants were associated with the highest risks: adjusted odds ratio = 1.08 (95% confidence interval, 1.04–1.12) for a 10-μg/m3 increase of NO, 1.12 (1.07–1.17) for a 10-μg/m3 increase in NO2, and 1.10 (1.06–1.13) for a 100-μg/m3 increase in CO. These data support the hypothesis that early childhood exposure to air pollutants plays a role in development of asthma.