Diesel exhaust particles increase nasal symptoms and IL-17A in house dust mite-induced allergic mice.

Diesel exhaust particles (DEPs), traffic-related air pollutants, are considered environmental factors adversely affecting allergic diseases. However, the immunological basis for the adjuvant effects of DEP in allergic rhinitis (AR) remains unclear. Therefore, this study aimed to investigate the effect of DEP exposure on AR using a mouse model. BALB/c mice sensitized to house dust mite (HDM) were intranasally challenged with HDM in the presence and absence of DEP. Allergic symptom scores, serum total and HDM-specific immunoglobulins (Igs), eosinophil infiltration in the nasal mucosa, cytological profiles in bronchoalveolar lavage fluid (BALF), and cytokine levels in the nasal mucosa and spleen cell culture were analyzed. Mice co-exposed to HDM and DEP showed increased allergic symptom scores compared with mice exposed to HDM alone. Reduced total IgE and HDM-specific IgE and IgG1 levels, decreased eosinophil infiltration in the nasal mucosa, and increased proportion of neutrophils in BALF were found in mice co-exposed to HDM and DEP. Interleukin (IL)-17A level was found to be increased in the nasal mucosa of the co-exposure group compared with that in the HDM-exposed group. The levels of IL-4, IL-13, interferon-γ, IL-25, IL-33, and TSLP expression showed no difference between the groups with and without DEP treatment. Increased expression of IL-17A in the nasal mucosa may contribute to DEP-mediated exacerbation of AR in HDM-sensitized murine AR model.

Role of Innate Immune System in Environmental Lung Diseases.

The lung mucosa functions as a principal barrier between the body and inhaled environmental irritants and pathogens. Precise and targeted surveillance mechanisms are required at this lung-environment interface to maintain homeostasis and preserve gas exchange. This is performed by the innate immune system, a germline-encoded system that regulates initial responses to foreign irritants and pathogens. Environmental pollutants, such as particulate matter (PM), ozone (O3), and other products of combustion (NO2, SO3, etc.), both stimulate and disrupt the function of the innate immune system of the lung, leading to the potential for pathologic consequences. PURPOSE OF REVIEW: The purpose of this review is to explore recent discoveries and investigations into the role of the innate immune system in responding to environmental exposures. This focuses on mechanisms by which the normal function of the innate immune system is modified by environmental agents leading to disruptions in respiratory function. RECENT FINDINGS: This is a narrative review of mechanisms of pulmonary innate immunity and the impact of environmental exposures on these responses. Recent findings highlighted in this review are categorized by specific components of innate immunity including epithelial function, macrophages, pattern recognition receptors, and the microbiome. Overall, the review supports broad impacts of environmental exposures to alterations to normal innate immune functions and has important implications for incidence and exacerbations of lung disease. The innate immune system plays a critical role in maintaining pulmonary homeostasis in response to inhaled air pollutants. As many of these agents are unable to be mitigated, understanding their mechanistic impact is critical to develop future interventions to limit their pathologic consequences.

Impact of a pollution breach at a coke oven factory on asthma control in nearby vulnerable adults.

BACKGROUND: Previous studies have related sulfur dioxide (SO2) exposure to asthma exacerbations. We utilized the University of Pittsburgh Asthma Institute registry to study associations of asthma exacerbations between 2 geographically distinct populations of adults with asthma. OBJECTIVE: Our objective was to examine whether asthma symptoms worsened following a significant fire event that destroyed pollution control equipment at the largest coke works in the United States. METHODS: Two groups of patients with asthma, namely, those residing within 10 miles of the coke works fire (the proximal group [n = 39]) and those residing beyond that range (the control group [n = 44]), were geocoded by residential address. Concentrations of ambient air SO2 were generated by using local University of Pittsburgh Asthma Institute registry air monitoring data. Factory emissions were also evaluated. Data from a patient historical acute exposure survey and in-person follow-up data were evaluated. Inferential statistics were used to compare the groups. RESULTS: In the immediate postfire period (6-8 weeks), the level of emissions of SO2 from the factory emissions increased to 25 times more than the typical level. Following the pollution control breach, the proximal cohort self-reported an increase in medication use (risk ratio = 1.76; 95% CI = 1.1-2.8; P < .01) and more exacerbations. In a small subset of the follow-up cohort of those who completed the acute exposure survey only, asthma control metrics improved. CONCLUSIONS: Real-world exposure to a marked increase in ambient levels of SO2 from a pollution control breach was associated with worsened asthma control in patients proximal to the event, with the worsened control improving following repair of the controls. Improved spatial resolution of air pollutant measurements would enable better examination of exposures and subsequent health impacts.

Intranasal levels of lead as an exacerbation factor for allergic rhinitis in humans and mice.

BACKGROUND: Air pollutants are suspected to affect pathological conditions of allergic rhinitis (AR). OBJECTIVES: After detecting Pb (375 µg/kg) in Japanese cedar pollen, the effects of intranasal exposure to Pb on symptoms of AR were investigated. METHODS: Pollen counts, subjective symptoms, and Pb levels in nasal epithelial lining fluid (ELF) were investigated in 44 patients with Japanese cedar pollinosis and 57 controls from preseason to season. Effects of intranasal exposure to Pb on symptoms were confirmed by using a mouse model of AR. RESULTS: Pb levels in ELF from patients were >40% higher than those in ELF from control subjects during the pollen season but not before the pollen season. Pb level in ELF was positively associated with pollen counts for the latest 4 days before visiting a hospital as well as scores of subjective symptoms. Intranasal exposure to Pb exacerbated symptoms in allergic mice, suggesting Pb as an exacerbation factor. Pb levels in ELF and nasal mucosa in Pb-exposed allergic mice were higher than those in Pb-exposed nonallergic mice, despite intranasally challenging the same amount of Pb. Because the increased Pb level in the nasal mucosa of Pb-exposed allergic mice was decreased after washing the nasal cavity, Pb on the surface of but not inside the nasal mucosa may have been a source of increased Pb level in ELF of allergic mice. CONCLUSIONS: Increased nasal Pb level partially derived from pollen could exacerbate subjective symptoms of AR, indicating Pb as a novel hazardous air pollutant for AR.

Effect of PM10 on pulmonary immune response and fetus development.

Despite numerous reports that ambient particulate matter is a key determinant for human health, toxicity data produced based on physicochemical properties of particulate matters is very lack, suggesting lack of scientific evidence for regulation. In this study, we sampled inhalable particulate matters (PM10) in northern Seoul, Korea. PM10 showed atypical- and fiber-type particles with the average size and the surface charge of 1,598.1 ± 128.7 nm and -27.5 ± 2.8, respectively, and various toxic elements were detected in the water extract. On day 90 after the first pulmonary exposure, total cell number dose-dependently increased in the lungs of both sexes of mice. PM10 induced Th1-dominant immune response with pathological changes in both sexes of mice. Meanwhile, composition of total cells and expression of proteins which functions in cell-to-cell communication showed different trends between sexes. Following, male and female mice were mated to identify effects of PM10 to the next generation. PM10 remained in the lung of dams until day 21 after birth, and the levels of IgA and IgE increased in the blood of dams exposed to the maximum dose compared to control. In addition, the interval between births of fetuses, the number of offspring, the neonatal survival rate (day 4 after birth) and the sex ratio seemed to be affected at the maximum dose, and particularly, all offspring from one dam were stillborn. In addition, expression of HIF-1α protein increased in the lung tissue of dams exposed to PM10, and level of hypoxia-related proteins was notably enhanced in PM10-exposed bronchial epithelial cells compared to control. Taken together, we suggest that inhaled PM10 may induce Th1-shifting immune response in the lung, and that it may affect reproduction (fetus development) by causing lung hypoxia. Additionally, we propose that further study is needed to identify particle-size-dependent effects on development of the next generation.

Diagnostic characterization of respiratory allergies by means of a multiplex immunoassay.

Allergic sensitization is commonly assessed in patients by performing the skin prick test (SPT) or determining specific immunoglobulin (IgE) levels in blood samples with the ImmunoCAP™ assay, which measures each allergen and sample separately. This paper explores the possibility to investigate respiratory allergies with a high throughput method, the Meso Scale Discovery (MSD) multiplex immunoassay, measuring IgE levels in low volumes of blood. The MSD multiplex immunoassay, developed and optimized with standards and allergens from Radim Diagnostics, was validated against the SPT and the ImmunoCAP assay. For 18 adults (15 respiratory allergy patients and three controls), blood collection and the SPT were performed within the same hour. Pearson correlations and Bland-Altman analysis showed high comparability of the MSD multiplex immunoassay with the SPT and the ImmunoCAP assay, except for house dust mite. The sensitivity of the MSD multiplexed assay was ≥78% for most allergens compared to the SPT and ImmunoCAP assay. Additionally, the specificity of the MSD multiplex immunoassay was ≥ 87% - the majority showing 100% specificity. Only the rye allergen had a low specificity when compared to the SPT, probably due to cross-reactivity. The reproducibility of the MSD multiplex immunoassay, assessed as intra- and interassay reproducibility and biological variability between different sampling moments, showed significantly high correlations (r = 0·943-1) for all tested subjects (apart from subject 13; r = 0·65-0·99). The MSD multiplex immunoassay is a reliable method to detect specific IgE levels against respiratory allergens in a multiplexed and high-throughput manner, using blood samples as small as from a finger prick.

Thunderstorm asthma: an overview of mechanisms and management strategies.

INTRODUCTION: Epidemic thunderstorm asthma (ETSA) is due to a complex interaction of environmental and individual susceptibility factors, with outbreaks reported globally over the last four decades. Australia has been particularly susceptible with nearly half of episodes reported internationally, culminating in the catastrophic Melbourne 2016 event. AREAS COVERED: Reported ETSA episodes are reviewed for common environmental and meteorological risk factors. Allergen aerobiology interaction with thunderstorm activity and rapid weather condition changes is examined. Assessment of the clinical and immunological data highlights risk factors for ETSA presentation, hospital admission, and intensive care admission. Risk factors associated with ETSA deaths are evaluated. Public health strategies, as well as pharmacological and immunological management approaches to reduce individual susceptibility and prevent ETSA are discussed. EXPERT OPINION: Improved understanding of the specific meteorological factors predisposing to the greatest risk of ETSA to improve forecasting is required. Better monitoring of aeroallergen levels in areas of greatest geographic risk, with further research into allergen aerobiology underpinning mechanisms of allergen exposure is needed. The role of climate change in increasing the risk of ETSA outbreaks requires further research. Public awareness and education are required to reduce exposure, and to improve uptake of pharmacological and immunological risk reduction and preventive strategies.

In vivo immune activation of splenocytes following exposure to tar from Asian sand dust.

Air pollution, especially that initiated by particulate matter (PM), has been implicated as a risk factor for several inflammatory diseases. Previously, it was reported that PM enhances immune responses. PM includes the tar fraction that contains polycyclic aromatic hydrocarbons (PAHs), which produce adverse health effects in exposed individuals. However, the influence of the tar fraction (as a component of PM) on splenocytes is not fully understood. The aim of this study was to determine the effects of the tar fraction extracted from PM collected from the atmosphere in Fukuoka, Japan, on mouse splenocytes. ICR mice were administered tar (1 or 5 µg/mouse) intratracheally 4 times at 2-week intervals, and splenocytes from the tar-treated mice were extracted and examined. The parameters determined were proliferation, cytokine concentrations and transcription factors activation. Following tar treatment, splenocyte proliferation increased relative to controls. Concanavalin A (ConA)-induced interleukin (IL)-2 formation and ConA- or lipopolysaccharide (LPS)-induced interferon-γ production were elevated in splenocytes from tar-exposed mice. However, the production of tumor necrosis factor-α and IL-6 induced by LPS was not markedly changed following tar treatment. Further, nuclear factor of activated T cells, but not nuclear factor-κB, was enhanced in splenocytes of tar-exposed mice. Data indicate that tar-activated splenocytes and PM-bound PAHs might contribute to T cell activation in the spleen.

The Role and Potential Pathogenic Mechanism of Particulate Matter in Childhood Asthma: A Review and Perspective.

Asthma, the most common chronic respiratory disease in children, affects numerous people worldwide. Accumulating evidence suggests that exposure to high levels of particulate matter (PM), either acutely or chronically, is associated with the exacerbation and incidence of pediatric asthma. However, the detailed pathogenic mechanisms by which PM contributes to the incidence of asthma remain largely unknown. In this short review, we summarize studies of relationships between PM and pediatric asthma and recent advances on the fundamental mechanisms of PM-related asthma, with emphases on cell death regulation and immune system responses. We further discuss the inadequacy of current studies and give a perspective on the prevention strategies for pediatric asthma.

Airborne pollen calendar of Portugal: a 15-year survey (2002-2017)

INTRODUCTION: Data about the occurrence of airborne pollen enables the creation of pollen calendars with an approximation of flowering periods for the most common allergenic plant species in a specific area. The aim of this work is to provide pollen calendar for each of the seven monitoring regions of Portugal based on 15 years of airborne sampling, in order to chart the seasonal behaviour of the main allergenic pollen types. MATERIAL AND METHODS: Airborne pollen monitoring (2002-2017) was carried out by the Portuguese Aerobiology Network (RPA), using Hirst-type volumetric spore traps, following well-established guidelines. RESULTS: A total of 14 airborne pollen types were recorded at RPA monitoring stations, of which 64.2% belong to trees, 28.5% to herbs and 7.1% to weeds. The airborne pollen spectrum is dominated by important allergenic pollen types such as Poaceae, Quercus spp., Urticaceae and Cupressaceae. The average pollen index was 42.557 in mainland Portugal and 3.818 in the Islands. There was an increased trend in the airborne pollen levels over the years, namely in Coimbra, Évora and Porto, compared to the remaining regions. CONCLUSION: This report provides accessible information about the main allergenic airborne pollen types occurring in the course of the year. The pollen calendars charted for each Portuguese region showed that the occurrence of most allergenic taxa was centred from March to July. Pollen peak concentrations were detected earlier in the Centre and Lisbon and Tagus Valley regions, and later in the remaining regions

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Trends of sensitization to aeroallergens in patients with allergic rhinitis and asthma in the city of Bursa, South Marmara Sea Region of Turkey

Background/aim: Allergic rhinitis (AR) and asthma are the most common allergic disorders worldwide. Aeroallergens are critical causative factors in the pathogenesis of these disorders and sensitization to aeroallergens differs in various countries and regions. Identification of the most common aeroallergen sensitization is crucial in the diagnosis and management of AR and asthma. We examined the distribution of aeroallergen sensitizations detected by skin prick tests (SPTs) in adult patients with AR and/or asthma in the city of Bursa. Materials and methods: Five hundred forty-five patients who underwent a SPT and were diagnosed with rhinitis and/or asthma in the Uludag University Faculty of Medicine's Department of Immunology and Allergic Diseases Outpatient Clinic from March 2018 to August 2018 were retrospectively evaluated. SPTs with standard extracts including house dust mites, pollens, molds, animal dander, and latex were performed for patients. Results: A total of 545 patients were included and most of the patients (270; 49.5%) were between 30 and 49 years of age. The prevalence of atopy was 57.9%. The most common aeroallergens detected in SPTs were Dermatophagoides farinae (50%) and D. pteronyssinus (44%), followed by grass-rye mix (43%), grass mix (38.6%), olive (33.2%), and wheat (32.3%). The sensitization to olive pollen was higher in cases of mild asthma (52%), while sensitization to D. farinae was higher in patients with mild and moderate asthma (54.5%, 54.2%) (P < 0.05) . Conclusions: Our study revealed that house dust mite was the most common sensitizing aeroallergen in patients with AR and asthma while pollens were the most common allergen in patients with only AR. The sensitization to grass and olive pollen was higher in cases of mild asthma than moderate and severe. Regional allergy panels may provide important clinical clues for characteristics and courses of allergic diseases.

Brake dust exposure exacerbates inflammation and transiently compromises phagocytosis in macrophages.

Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4-25 µg ml-1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.

Subcutaneous immunotherapy with aeroallergens Evaluation of adherence in real life.

Summary: Introduction. Adherence in allergen immunotherapy is crucial for its efficacy. At least 3 years of treatment are recommended for achieving a long-term modifying effect. Objectives. To assess patient's adherence and to identify determinant factors for allergen subcutaneous immunotherapy (SCIT) suspension in patients with respiratory allergy. Methods. Retrospective analysis of the medical record of patients submitted to SCIT between January 2013 and December 2016 in our Department. Results. 323 patients were included: 52% female; mean age 30±13 years; average treatment time 19±13 months. 52 patients (16%) stopped SCIT: 54% female; mean age 30±9 years; average treatment time 12±6 months; 67% dropped the treatment during the 1st year, 27% in the 2nd and 6% during the 3rd year of treatment. Adherence rate determined was 77%. The most frequent reasons for withdrawal were due to economic reasons (47.9%), followed by patients' perception of no clinical improvement (23%) and change to sublingual immunotherapy (11.6%). Conclusion. Adherence rate in our study was 77%. Economic reasons were the main cause of abandonment in the first year, while the perception of non improvement was the main reason for abandonment in subsequent years. Adequate information on SCIT prescribing and rigorous monitoring of patients during the treatment can improve adherence.

Prenatal and early-life exposure to indoor air-polluting factors and allergic sensitization at 2 years of age.

BACKGROUND: Previous studies have suggested that exposures to indoor air-polluting factors during pregnancy and early life can influence childhood allergy development. These exposures have been investigated in singularity; however, the effect of simultaneous exposure to multiple factors remains unclear. OBJECTIVE: To evaluate the effect of prenatal and early-life exposure to 7 air-polluting factors on allergic sensitization at 2 years of age. METHODS: Mother-child pairs (n = 108) enrolled in the Kingston Allergy Birth Cohort were followed up from birth to 2 years of age. Exposure to air fresheners, candles, mold, cats, dogs, carpet, and environmental tobacco smoke (ETS) during the prenatal, 6-month, 1-year, and 2-year time points were obtained. A skin prick test (SPT) was performed on both the mother and the 2-year-old child. RESULTS: Exposure to candles during the prenatal window, cats during the 6-month window, and ETS at 2 years significantly increased the odds ratio (OR) of a positive SPT result (candles: OR, 5.096; 95% CI, 1.69-13.86; P = .006; cat: OR, 4.267; 95% CI, 1.096-15.68; P = .048; and ETS: OR, 3.78; 95% CI, 1.189-11.18; P = .04). Children with a positive SPT result had significantly more exposures than SPT-negative children (prenatal P = .005, 1-year P = .03, and 2-year P = .008). As the total number of exposures increased, the percentage of SPT-positive children increased (prenatal P = .005, 1-year P = .03, and 2-year P = .01). CONCLUSION: We have provided evidence supporting the role of the indoor environment on atopic disease development. The combined effect of multiple exposures may be more influential to allergy development than a single exposure.

Air pollution significantly associated with severe ocular allergic inflammatory diseases.

Ambient air pollution is a well-recognized risk for various diseases including asthma and heart diseases. However, it remains unclear whether air pollution may also be a risk of ocular allergic diseases. Using a web-based, nation-wide, cross-sectional study design, we examined whether the level of ambient air pollution is significantly associated with the prevalence of ocular allergic diseases. A web-based questionnaire was posted to invite the participants who are members of the Japan Ophthalmologist Association and their family members. The answers from 3004 respondents were used to determine whether there were significant associations between the level of the pollutants and the prevalence of ocular allergic diseases. The study period was between March to May 2017. The data of the air pollutants during 2012 to 2016 were obtained from the National Institute for Environmental Studies. The prevalence of allergic diseases was calculated by post stratification and examined for significant associations with the level of pollutants using multiple logistic regression analyses. The prevalence of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC) in Japan was 45.4%, 14.0%, 5.3%, and 1.2%, respectively. The high prevalence of the severe forms of allergic conjunctivitis, including AKC and VKC, were significantly associated with the levels of the air pollutants. The prevalence of AKC was significantly associated with the levels of NO2 with an odds ratio (OR) of 1.23 (per quintile). The prevalence of VKC was significantly associated with the levels of NOx and PM10 with ORs of 1.72 and 1.54 respectively. The significant associations between the prevalence of AKC and VKC and the levels of air pollutants indicate that clinicians need to be aware that air pollutants may pose serious risks of vision threatening severe ocular allergy.

Risk factors for asthma among schoolchildren who participated in a case-control study in urban Uganda.

Data on asthma aetiology in Africa are scarce. We investigated the risk factors for asthma among schoolchildren (5-17 years) in urban Uganda. We conducted a case-control study, among 555 cases and 1115 controls. Asthma was diagnosed by study clinicians. The main risk factors for asthma were tertiary education for fathers (adjusted OR (95% CI); 2.32 (1.71-3.16)) and mothers (1.85 (1.38-2.48)); area of residence at birth, with children born in a small town or in the city having an increased asthma risk compared to schoolchildren born in rural areas (2.16 (1.60-2.92)) and (2.79 (1.79-4.35)), respectively; father's and mother's history of asthma; children's own allergic conditions; atopy; and cooking on gas/electricity. In conclusion, asthma was associated with a strong rural-town-city risk gradient, higher parental socio-economic status and urbanicity. This work provides the basis for future studies to identify specific environmental/lifestyle factors responsible for increasing asthma risk among children in urban areas in LMICs.