Next Article in Journal
Placing Health Warnings on E-Cigarettes: A Standardized Protocol
Next Article in Special Issue
The Epidemiology of Food Allergy in the Global Context
Previous Article in Journal
Spatial Distribution of Fine Particulate Matter in Underground Passageways
Previous Article in Special Issue
How Accurate Are the ISAAC Questions for Diagnosis of Allergic Rhinitis in Korean Children?
Open AccessReview

Aeroallergens in Canada: Distribution, Public Health Impacts, and Opportunities for Prevention

1
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada
2
Institute of Medical Science, University of Toronto, Toronto, ON M5S 3H7, Canada
3
Department of Biomedical & Molecular Sciences and Division of Allergy & Immunology, Department of Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
4
Allergy Research Unit, Kingston General Hospital, Kingston, ON K7L 2V7, Canada
5
Dalla Lana School of Public Health, University of Toronto, Toronto, ON M3H 5T4, Canada
6
Air Quality Health Index, Health Canada, Ottawa, ON K1A 0K9, Canada
7
Health and Air Quality Services, Environment and Climate Change Canada, Gatineau, QC K1A 0H3, Canada
8
Environmental Health Services, BC Centre for Disease Control, Vancouver, BC V5Z 4R4, Canada
9
School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
10
Air Health Science Division, Health Canada, Ottawa, ON K1A 0K9, Canada
11
School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON K1G 5Z3, Canada
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2018, 15(8), 1577; https://doi.org/10.3390/ijerph15081577
Received: 6 June 2018 / Revised: 4 July 2018 / Accepted: 18 July 2018 / Published: 25 July 2018
(This article belongs to the Special Issue The Epidemiology of Allergy)

Abstract

Aeroallergens occur naturally in the environment and are widely dispersed across Canada, yet their public health implications are not well-understood. This review intends to provide a scientific and public health-oriented perspective on aeroallergens in Canada: their distribution, health impacts, and new developments including the effects of climate change and the potential role of aeroallergens in the development of allergies and asthma. The review also describes anthropogenic effects on plant distribution and diversity, and how aeroallergens interact with other environmental elements, such as air pollution and weather events. Increased understanding of the relationships between aeroallergens and health will enhance our ability to provide accurate information, improve preventive measures and provide timely treatments for affected populations.
Keywords: aeroallergens; pollen; fungi; allergy; asthma; atopic march; Canada aeroallergens; pollen; fungi; allergy; asthma; atopic march; Canada

1. Introduction

Over the past 70 years, the prevalence of allergic conditions has increased in high-income countries to the point of becoming a worldwide public health concern [1]. This increase cannot be explained by genetic changes only [2]. Environmental exposure to air pollutants and aeroallergens have been hypothesized as potential causes for this steep increase, as the nature of these exposures have changed during a similar window of time [3].
Environmental factors play a key role in defining the type of sensitization and the kind of atopic disease in genetically at-risk individuals. While heredity regulates the intergenerational transmission of the susceptibility to different phenotypes of atopic responsiveness, environmental exposure is a crucial factor in the development of atopic disease. The environmental exposures linked to the development of allergies are to: (a) common aeroallergens (e.g., pollen or mold spores); and (b) pollution, like particulate matter (PM) or environmental tobacco smoke (ETS), among others [4].
The environmental exposures listed produce a specific imbalance in the immune system [5]. There are two types of T helper immune cells (Th1 and Th2) that appear imbalanced in allergic conditions [6], with a higher proportion of the Th2 cell population [7]. The hygiene hypothesis is also considered as one of the reasons for the specific imbalance in the immune system [8]. This hypothesis attributes a reduced exposure to infectious agents at key times of immune system development to the Th2 predominance. This skewed microbial exposure may be due to improved hygiene and sanitation, and increased use of disinfectants and antibiotics [9]. When an individual has this type of imbalanced immune system, repeated exposures to a myriad of specific proteins (e.g., pollen, certain molds, dust mite feces, eggs, peanuts) can induce the creation of IgE antibodies [10]. These initial encounters with the proteins produce a sensitization to these specific molecules, and subsequent exposures will trigger symptoms each time [10,11].
Allergy symptoms in response to pollen and fungal spores are driven by IgE that is specific to proteins found in these spores [12]. The allergenicity of pollen spores refers to the concentration of protein epitopes in each spore, to which specific IgE molecules produced by the plasma cells of allergic individuals may bind [13]. Certain pollen grains are known to be highly allergenic (e.g., ragweed a.k.a Ambrosia), and highly prevalent in some parts of Canada [14]. This combination of allergenicity and prevalence makes some ambient aeroallergens highly problematic due to the growing number of exposed and sensitized individuals [15]. This exposure and the physical symptoms of the immune response have a direct impact on the everyday lives of patients with allergic conditions. They also have an impact at the societal level, including costs to the health systems that address medical needs associated with allergic responses.
This review will describe the current state of our knowledge about the variety and distribution of plant and fungi-derived aeroallergens in Canada. We will also discuss allergic diseases and the health impacts that Canadian allergy sufferers experience in connection with aeroallergens and the weather and climatic conditions that enhance exposure. It is our hope that this public health-oriented review will enhance the ability of researchers, health practitioners, and governments to provide accurate information to the public and improve preventive measures and treatments.

2. Review

2.1. Introduction to Ambient Aeroallergens

Pollen grains function as a container for the male gametophytes of plants [16]. The essential reproductive event among higher plants is achieved only when the pollen grain is successfully transferred from the floral anther to the recipient stigma. The strategies that plants use in their pollen transfer are classified into two categories: entomophilous plants depend on organisms such as insects or hummingbirds to carry larger, stickier pollen grains, anemophilous plants release large quantities of pollen grains to be blown in the wind [17].
When anemophilous plants release pollen, a number of environmental factors affect how, when, and how many grains reach their final destination [18]. The aerobiology pathway of pollen (as seen on Figure 1) illustrates how pollen grains can travel from their source to interact with humans and potentially affect health. Many of these factors are affected by shifting climatic conditions [19,20].
Currently, more than 150 pollen allergens are curated by the International Union of Immunological Societies [22]. From the entire list of pollen allergens, 12 are of particular interest in Europe due to their abundance in the atmosphere [23] and allergenic potency [24] (p. 10): (1) ragweed (Ambrosia); (2) alder (Alnus); (3) mugwort (Artemisia); (4) birch (Betula); (5) goosefoots (Chenopodiaceae); (6) hazel (Corylus); (7) cypresses, including yews (Cupressaceae/Taxaceae); (8) olive (Olea); (9) plane tree (Platanus); (10) grass (Poaceae); (11) oak (Quercus); (12) and wall pellitory (Urtica/Parietaria).
In Canada, birch and grasses are more abundant than ragweed, which is found mostly in Ontario and Quebec. Cypress, olive, plane tree, and wall pellitory are not present in Canada [14].

2.2. Canadian Distribution of Plant-Derived Aeroallergens

The geographical distribution of species of plants is dependent on multiple factors, including precipitation, soil composition and moisture and average high and low temperatures [14]. Five “floristic zones” that support the growth of different aeroallergen-producing plants have been defined across Canada [14]. As seen on Figure 2, from west to east, they are: Northwest Coastal, Northern Forest, Rocky Mountain, Central Plains, and Eastern Agricultural [14]. The major allergenic plants that grow in each of the floristic zones are widely varied (Table S1 in the supplementary materials).
Trees, grasses, and ragweed are the most common allergens associated with outdoor pollen-induced allergies across Canada [25,26,27]. Short ragweed is highly cross-reactive with all other ragweed species, as well as sage and mugwort [25,26,28,29,30]. Additionally, there is substantial clinical cross-reactivity between tree and grass allergenic species [27]. For example, individuals allergic to birch pollen in Northern Sweden have also been sensitized to beech pollen (Fagus), although that species does not grow in the region [31].
Local factors can affect spatial variation within a region [32]. Examples of the local factors are: tree canopy, defined as the types of trees planted in the geographical area of interest [33]; and level of urbanization, defined considering street network coverage and quantity of vegetation [34]. The amount of pollen in the air at a particular location depends on the distance and number of source plants in the area, atmospheric conditions and plant physiological factors such as the number of accumulated degree days at which their pollen is released [35]. Pollen grains can break open to release submicronic pollen-derived bioaerosols containing allergenic proteins, particularly when the grains have been aloft for some time and/or become wet [36,37,38,39] as in thunderstorm asthma. Some increased exposure to aeroallergens is also due to human activity, such as landscaping practices that create niches favoring the growth of weeds such as ragweed [35].

2.3. Fungal Aeroallergens

Fungi are eukaryotic organisms that grow all over the world, in the presence of moisture and carbohydrates [40,41]. Currently, fungi are organized into eight phyla, three of which produce important aeroallergens: (1) Zygomycota; (2) Ascomycota; and (3) Basidiomycota [41,42,43]. Fungi produce spores on maturity, through both sexual and asexual mechanisms [44,45]. The asexual spores produced by mitosis appear to be the most allergenic [41,46]. In addition to molecules on the surfaces of spores, fungi also secrete enzymes into their environment that can act as allergens in sensitized individuals [41,47]. Fungi spores have low mass and can remain suspended in the air for varying periods of time depending on the weather [48]. Outdoor airborne fungi such as Cladosporium, Alternaria, Penicillium, and Aspergillus can trigger allergic responses in sensitized individuals [49].

2.4. Aeroallergen Measurement and Prediction

Outdoor aeroallergen sampling is largely based on microscopic examination to identify pollen and spores based on morphologic pattern recognition [50,51]. Aeroallergens must be collected and then manually counted, so it is impossible to generally offer real-time data using these methods. Furthermore, it is not yet feasible to provide dense spatial coverage or to offer sub-daily counts on a regular basis, although bi-hourly values are occasionally reported in research [52].
Aeroallergen count modeling and forecasting allows for more detailed maps that provide estimates for locations other than sampling sites. This requires knowledge of botanical and meteorological data over several years to assess the variations possible in seasonal pollen characteristics [53]. Land use regression (LUR) modelling is a mapping technique [33] that has been used to explain approximately 79% of the spatial variation in pollen measurements [54]. Results from LUR models are a potential source of relevant information for epidemiologic studies of allergic conditions [33]. Model improvements and their validation by additional local measurements are needed to provide more accurate maps and forecasts for epidemiologic studies and to help allergic individuals and their health care providers reduce the burden of illness [53].

2.5. Aeroallergen Impact on Humans

Pollen grains carry noninfectious proteins, so exposure to pollen is an innocuous event for most individuals [55]. For others, however, it triggers an allergic immune response and related symptoms. In recent decades, pollen allergy has grown increasingly prevalent, affecting as much as 40% of the population in regions of Australia, New Zealand, and the United States, and becoming widely recognized as a public health concern [56].
Because the primary mode of dispersal for pollen grains and fungi spores is via the air, humans are exposed predominantly through inhalation [57]. The respiratory system is the first point of contact between the human body and the proteins contained in pollen and fungi [48], and that is where inflammation takes place following exposure to allergens [58]. Allergies are diagnosed using ‘skin-prick tests’, which demonstrate the presence of a Type I hypersensitivity, involving IgE, at a site on the skin where a small amount of allergen is introduced through a ‘prick’ [22,59]. For seasonal allergic rhinitis, grass, and tree pollens are the most common allergens [60].
The point at which aeroallergens impact on the respiratory system depends on their size. Aeroallergen size can vary from less than 10 μm to 100 μm, and can be classified into the following groups: very small (<10 μm), small (10–25 μm), medium (26–50 μm), large (51–100 μm), and very large (>100 μm) [61]. According to Szema [62], aeroallergen grains larger than 5 μm deposit in the ocular conjunctiva and nasal mucosa and have the potential to trigger allergic reactions such as conjunctivitis or allergic rhinitis [2,63], and also to asthma exacerbation [64]. Smaller particles than <5 μm, come from allergens such as cat dander, can reach the lungs, and have been linked to asthma onset [65].

2.6. Aeroallergens and the Development of Respiratory Allergies

Worldwide, a steep increase in the prevalence of Type I hypersensitivity reactions—such as asthma and allergies—has been documented in every age group [66]. Recent studies report significant differences over such a short timespan that the findings cannot be explained by genetic changes [67,68,69,70]. Better understanding of the environmental factors that affect the development of atopic disorders and their phenotypic expression could lead to better understanding of their increased prevalence. Because pollen grains from anemophilous plants are one of the most important allergen sources in the outdoor air [57], their role in development of asthma and allergy needs further exploration. Spores from fungi are also important aeroallergens that have been linked to allergic reactions [41,46] and in some studies potentially also to the risk of asthma development [71].
Asthma is one of the most severe expressions of an adverse immune response in the respiratory system [72,73]. Moreover, researchers such as de Weger et al. [58] and von Mutius [74] acknowledge the diversity of factors that influence the health impact of aeroallergens and call for better understanding of the extrinsic influences and intrinsic factors that contribute to the new onset of the allergic conditions associated with aeroallergen exposures. Among the possible explanations for the onset of allergic conditions, the hygiene hypothesis has gained widespread acceptance [8]. This hypothesis states that the primary factor underlying increases in autoimmune diseases (including allergic conditions) is the decrease in infectious diseases due to improved hygiene and sanitation, and increased use of vaccines and antibiotics [9].
According to Gunawan et al. [23] the allergic potency of aeroallergens is linked to substances that have structural similarity to inflammatory lipid mediators including prostaglandin E2 and leukotriene B4. Lipid fractions from pollens promote chemotaxis and the activation of neutrophils and eosinophils. Additionally, allergenic pollens release proteases [75]. This proteolytic activity may also be involved in the development of allergic diseases. The combined actions of lipid mediators, proteases, and allergens in the respiratory system promote a disruption of normal cell barriers and a modification of antigen-presenting cells to exhibit predominately Th2 activity. In this microenvironment, the development of incident asthma is more likely [75].
In many children with asthma, the appearance of different allergic conditions follows a sequence that has been labelled the “atopic march” [76]. This sequence connects the different expressions of allergic diseases that vary with age, which often have transient symptoms. Typically, a large exposure to a potential allergen is followed by sensitization, according to the order in which infants are exposed to a predominant allergen: first food allergens (e.g., egg), then indoor allergens (e.g., dust mites), and finally, outdoor allergens (e.g., local anemopilous pollens) [69]. This sequence of exposures and sensitizations generally precedes the sequence of atopic symptoms that begins with food allergy and associated gastrointestinal disorders, continues with atopic dermatitis, and progresses to respiratory allergies [77].
Because the first symptoms of the allergic conditions involved in the “atopic march” sometimes emerge during the first year of life, the first possible window for the environmental exposures responsible for these cases of atopy and asthma is likely to be open during gestation and the first months of life. This window is calculated considering two factors: (1) that only exposures preceding the first symptoms of an illness “can influence its inception” [67] (p. 2231); and (2) that antigens and air components can cross the placental barrier [78].
In other cases, such as pollen-related later-onset symptoms, allergies and asthma appear later in life when individuals are exposed to:
(a)
new varieties of pollen through immigration to a new location [79,80] or through the appearance of botanical species in new geographical zones other than their native zones [81];
(b)
higher than normal exposures to pollen, including in jobs that require long periods of contact with plants [82]. Occupational allergies and bronchial asthma have been reported in agricultural populations [83,84,85], florists [86], floriculturists [87], carpenters [88], and gardeners [89].

2.7. Variability in Sensitivity

A critical question for both pollen and fungi allergy is: how much aeroallergen exposure is needed for an allergic person need to develop sensitization and or exacerbation of existing disease? Most studies of exacerbation have found non-linear responses to indoor and outdoor allergens, indicating a threshold level for response [40,90,91]. In addition to a threshold for clinical symptoms, threshold exposure levels have also been described for the release of biological and inflammatory mediators [92]. The threshold values for fungi spores are generally higher than for pollen grains and range from ≥100 spores/m3 for Alternaria, to ≥900 spores/m3 for Aspergillus/Penicillium, to ≥3000 spores/m3 for Cladosporium [93,94,95,96]. Although individuals vary widely in their reactivity to allergens, one proposed threshold for outdoor ragweed levels in the United States was estimated at 10 to 20 grains/m3 for a period of at least 15 min [40]. During peak ragweed season, concentrations in North America can reach 250 grains/m3, and they remain above 100 grains/m3 for most of the season [97]. Likewise with tree pollen in Ontario, where mean in-season values of 300 grains/m3 were recorded, with peaks reaching even higher [98]. Peaks reported for grass are somewhat lower, between 70 and 110 grains/m3 to precipitate symptoms [99].
The priming effect is another important phenomenon involved in our understanding of the induction of allergic symptoms. The priming effect describes the transition from a state of minimal symptoms out of season to noticeable/bothersome symptoms after sufficient exposure to an allergen. It is formally defined as an increase in reactivity of the nasal membrane following repeated exposure [100]. Individuals who are already experiencing symptoms due to a perennial allergen (dust, pets, etc.) [101] or to high levels of air pollution [64] are more sensitive to subsequent exposure to aeroallergens. Conversely, when individuals with multiple sensitizations are ‘primed’ by an ongoing pollen season, they react more readily to allergens found in the home environment, such as dust [10,101]. The priming effect is relevant to consider when developing pollen warning or forecasting system in conjunction with existing systems for outdoor air pollutants. It demonstrates that those who suffer from seasonal allergies may have the ability to initiate short-term treatment such as antihistamines or sublingual immunotherapy within the first 3–5 days of the season to block the development of severe symptoms. However, those who are already suffering from poorly controlled allergic rhinitis or asthma are in danger of reacting severely and almost immediately upon the arrival of pollen season due to pre-priming [102].

2.8. Development of Respiratory Allergies: Risk/Protective Factors

The most promising mechanism that can explain the development of allergies involves interactions between individual genetic susceptibility and environmental exposures [103]. For example, gene–environment interactions have been demonstrated with changes in microRNA [3] and bronchial epithelial DNA methylation, after exposures to diesel exhaust [104]. For individuals with atopy-prone or immune modulated genotypes, environmental exposures play a role in the onset of an allergic disorder [105], including exposures to aeroallergens [2,106]. However, the environmental effect may be either detrimental or protective; Tovey et al. [91] found a non-linear relationship between mite allergen exposure and sensitization and asthma, with children on the lowest and highest quintile of exposure less likely to have both sensitization and asthma compared with the middle range of exposures.

2.9. Protective Factors

An environmental exposure can be considered as a protective factor if it is linked to decreased risk of the development of a specific condition [105].

2.9.1. Animals

An increasing number of studies indicate that exposure to domestic animals (pets or livestock) in early life decreases the risk of asthma [67], aeroallergen sensitization [107], and respiratory allergic disease as a whole [108]. The immune system modulation caused by these exposures is aligned with the hygiene hypothesis in which microbial exposures shift the immune response towards Th1 predominance [8,109,110].
Early and prolonged contact with animals [111] seems to have a protective effect against sensitization to aeroallergens, particularly if the exposure happens during the two first years of life [107]. The benefit appears to continue throughout the life course [112]. Exposures to farm animals seem to reduce specific aeroallergen IgE antibody production [113], particularly with higher exposures [114].

2.9.2. Breastfeeding

Breastfeeding, defined as the consumption of human breast milk through infant suckling directly from the breast, is acknowledged as an optimal source of infant nutrition [115]. Despite the short-term clinical and societal benefits, evidence has been mixed on the role of breastfeeding in the development of atopic conditions.
Breastfeeding has been associated with decreased risk of child atopy and the different phenotypes of asthma [116]. Although some factors such as maternal atopy might confound this association [117], reduced risk is present mostly with exclusive breastfeeding when compared with consumption of expressed milk or combined breast milk and formula [115]. Risk reduction extends well into school age, but is most pronounced in children 0–2 years [116].

2.10. Risk Factors

To consider an environmental element as a risk factor, it is necessary to demonstrate a positive exposure–response relationship with the allergic outcome of interest [103]. Interactions between pollen and the following environmental conditions have been studied and linked to increased risk for the development of an allergic condition [118].

2.10.1. Weather

In northern climates such as Canada, pollen production, dispersal, and airborne lifespan are highly dependent on the weather. In general, trees bloom in the early spring, grasses bloom late spring to early summer, and weeds pollinate in the fall [40]. Ragweed is in late August until the first frost, and thus ragweed season can be cut short by an early frost [32,119]. The weather in the current year has less effect on the intensity of the tree pollen season than the weather in the previous year, because trees produce pollen in the summer and fall, then release it when a sufficient number of warm days occur in the following spring [32,119]. Thus, the amount of tree pollen released depends on the weather in the previous year, but the timing of release depends on the current spring weather [32].
Diurnal changes in pollen levels have also been observed. As ragweed pollen is released in the morning, peak concentrations are reached around noon in the absence of high winds or rain [120]. Depending on the temperature, humidity, and wind conditions, the counts may drop at night or remain elevated [40,121]. Mature pollen grains tend to be released when the relative humidity drops, and they remain airborne longer at low humidity, low wind speeds, and high atmospheric pressure [120]. Meteorological conditions also affect fungi sporulation, as many grow well when conditions are wet and they produce spores as a survival mechanism when conditions are dry [40,121].
Precipitation can temporarily clear particles and aeroallergens from the air, although some pollen grains or fungi spores may be resuspended after a brief rainfall [36,122]. Exposure to water may also increase the formation of both pollen and fungi aeroallergens in a 24-h timeframe [40]. Considering the added complexity of rainfall, it is possible that the presence of high counts may be sufficient, but not necessary, for significant aeroallergen exposure to occur, due to the ruptured aeroallergen grains that are not accurately counted during these events [40].
Thunderstorms can be associated with asthma exacerbations, with steep increases in the use of emergency services and increased mortality [123,124,125]. Thunderstorms during pollen season are known to carry whole and ruptured pollen grains at the ground level where wind outflows distribute them with larger geographic coverage than under normal conditions [126]. Climate change has been linked to an increase in frequency of thunderstorms in some areas [127].

2.10.2. Seasonality

The division of the year into four seasons (spring, summer, fall, and winter) takes into consideration variables that undergo yearly cyclical changes, such as day length, temperature, and humidity. The influence of these factors on aeroallergens can be direct and indirect [128], and all have been associated with allergic respiratory morbidity [129,130,131] and mortality [132,133]. There is some indication of an association between season of birth on the development of asthma and allergies [134]. If an individual is exposed to high aeroallergen counts in utero and/or during the sensitive immune system development period of the first months of life, there may be at risk of atopic disease later in life [135,136,137].

2.10.3. Urbanization

Living in urban areas, as opposed to rural and semi-rural areas, is a known risk factor for the development of aeroallergen-induced respiratory allergy [128,138]. There is evidence that highly allergenic species of fungi are present at higher levels in the outdoor air in cities compared with rural environments [139]. Differences between aeroallergen counts (higher in the rural areas) and species diversity (lower in urban areas) may drive some of the differences between rural and urban influence on the onset of allergies and asthma [140]. Additionally, the higher levels of air pollutants predominant in urban areas can interact with airborne pollen grains, which is likely to exacerbate allergic conditions and respiratory distress [128]. Two thirds of the global population will live in urban areas by 2020, and an increased risk for aeroallergen-induced respiratory allergy is expected [127].

2.10.4. Air Pollution

The interactions between air pollution and aeroallergens are complex and occur both in the atmosphere and in the airways [141]. Ziska et al. [142] have demonstrated that outdoor air pollution can prompt an increase in pollen production by certain herbaceous species, similar to the effects seen with increased CO2. A number of studies have also shown that air pollution may increase the allergenicity of pollen and/or fungi, because air pollutants can attach to the surface of pollen grains and potentially alter their allergenic potential and morphology by making the surface of the pollen grain coating more fragile [128,143,144]. Timing of exposure is important, and co-occurence of pollen/spore release and increased air pollution episodes appears to be the most harmful in terms of increased allergenicity. Ragweed pollen is released from early to mid-morning, peaking around noon [145]. Air pollution monitoring data from various cities has shown that traffic-related air pollution (TRAP) follows a diurnal pattern with an increase during the daily rush hours [146,147,148]. Air pollution in combination with sunlight can lead to the photochemical production of ground-level ozone, which typically peaks in the afternoon. Thus, the diurnal patterns of pollen release, TRAP, and ozone concentrations in cities may place high levels of aeroallergens in contact with relatively high daily levels of air pollution, potentially leading to ambient modifications of the allergenicity of aeroallergens [146].
In the airway, oxidative stress has been identified as a major biologic pathway for the effects of most of the air pollutants components (e.g., PM2.5, ground-level ozone, nitrogen dioxide (NO2) and sulfur dioxide (SO2) [149,150]. Air pollutants allow for easier penetration of pollen and spore allergens because they trigger damage to the airway mucociliary clearance mechanisms [128,141]. Particulate matter smaller than 2.5 μm (PM2.5) reaches deeply in the lungs and acts as an adjuvant that increases production of IgE [3,151,152]. Furthermore, exposure to diesel exhaust is known to impact DNA methylation and impaired regulatory T-cell functions, two mechanisms relevant for the immune response [104]. Changes in FEV1 following allergen exposure have also been modified by controlled diesel exhaust exposure and GST genotype in a gene–environment interaction manner [152]. These GST variants are commonly present in the general population (i.e., from 23% to 62% depending on the ethnic group, in the USA) [153], so many people might experience amplified effects of air pollution–aeroallergen co-exposures in the outdoor environment.

2.11. Fundamentals of the Allergic Response

In humans, immune responses can range from diminished (i.e., immunosuppression) to heightened (i.e., allergies) [72], with a biologically appropriate response in the middle of these extremes (i.e., appropriate recognition and response to harmful pathogens) [55]. Pollen grains carry cytoplasmic granules that release a number of proteins and glycoproteins when they are exposed to water or airborne pollutants. These proteins instigate the adverse immune response in sensitized individuals (Figure 3) [128,154,155,156]. In addition, single and repeated exposures to pollen in allergic individuals have been shown to induce epigenetic changes, both in the blood and the nasal tissue [157].
The impact of aeroallergens has been documented in every section of the airway. The nose is the first point of contact with aeroallergens, and the histamine released due to interaction with aeroallergens increases tissue swelling and permeability, causing rhinitis and rhinorrhea [59]. Rhinitis is a risk factor for the development of asthma [60] and allergic rhinitis is most commonly due to pollen allergy [159].
Due to the many similarities between the nasal and bronchial mucosa and their reactions to aeroallergens, the “one airway, one disease” concept has been proposed for allergic rhinitis and allergic asthma [160]. Approximately 80% of patients with allergic asthma also have allergic rhinitis symptoms upon exposure to aeroallergens, but not all people with allergic rhinitis experience asthma symptoms [160,161,162]. Sensitization to aeroallergens is a major contributing factor to this discrepancy [163].
The hyper-responsiveness of the airways and subsequent constriction following allergen exposure are distinctive clinical findings in asthma [103,164,165]. Constriction is due to inflammatory processes and airway remodeling. Reversibility of the inflammation over time or by medication are also considered in asthma diagnosis [74]. Wheeze, cough, and paroxysmal dyspnea are less specific clinical signs of asthma. Persistent symptoms, triggered by the Th2 and IgE interactions, lead to structural changes and remodeling of the airway [166].
Asthma is a complex disease that can be understood as a syndrome, because different pathways can result in diverse phenotypes [74]. Several clinical phenotypes of asthma display differences in severity, inflammatory pattern, and comorbidity with allergic diseases (since not all asthma is atopic) [167]. Reversible bronchoconstriction, either spontaneously or after bronchodilator treatment, remains a common process in all the phenotypes [166].
Among respiratory conditions, asthma is one of the major non-communicable chronic diseases. Globally, approximately 235 million people currently suffer from asthma [168]. In high-income countries such as Canada, prevalence rose for many years from the early 1960s to 2000 [19,128] and recently seems to have reached a plateau [126,169].

2.12. Prevalence of Respiratory Allergies in Canada

Allergic rhinitis is highly prevalent in Canada, affecting approximately 20–25% of the population [170]. Asthma is estimated to affect about 3 million Canadians, and between 12% [171] to 25% of Canadian children [172,173,174]. Approximately two-thirds of people with asthma are allergic to aeroallergens, and these allergens act as triggers for asthma exacerbations [15]. Overall, approximately 7.7 million were people affected by aeroallergens in Canada in 2016 (Figure 4) [175]. High concentrations of ambient aeroallergens, including tree pollen, fungal spores, and others, have been associated with increased risk of early delivery [176], myocardial infarction [98], as well as with asthma-related emergency department visits and hospitalizations in cities across Canada, demonstrating that severe symptoms are related to aeroallergen counts across the country [177,178,179,180,181].

2.13. Economic Costs Associated with Respiratory Allergies

Atopic conditions represent a large burden on the economy. A study in British Columbia found that excess costs to the healthcare system in patients with asthma were $1028.00 per patient/year, compared with a control group [182]. This included the direct costs of asthma, as well as publicly-funded healthcare costs related to comorbid conditions in people with asthma, including allergic rhinitis [182]. Asthma is also the leading driver of health care costs for children in Canada, estimated at over $2 billion per year [183]. Recent estimates suggest that in a single year (between 2014–2015), asthma attacks triggered over 70,000 emergency room visits [184]. The costs of asthma to the Canadian economy are also expected to rise to almost $4 billion per year by 2030, more than double the current cost [185].

2.14. Effects of Climate Change on Aeroallergens

Levels of some specific aeroallergens are on the rise in particular regions, and some of this increase has been linked to anthropogenic climate change [186]. Anthropogenic climate change has been documented over the past 100 years and is projected to continue to intensify [81], driven in part by increases in temperature [138,187]. As seen on Figure 5, the increasing planetary temperatures affect plant biology through the timing and length of the growing seasons [188], increased production and allergenicity of pollen, and shifts in range of species [186,189].
Due to the warmer temperatures, pollen seasons will start earlier and end later [66,138,155,190]. Warming by latitude has been associated with increased length of the ragweed pollen season in North America, increasing by 27 days between 1995 and 2009 [149]. Earlier seasonal starts have also been found for Juniperus, Ulmus, and Morus [81]. In Western Europe, spring events have advanced by six days [191] and changes in birch pollen season [192] and Artemisia have been described [193]. Changes in length will lead to changes in human exposure [194] and potentially in sensitization [2,189].
Increased pollen counts have been associated with the current levels of CO2, when compared with CO2 levels of the previous century [195] or even between different decades (2004 and 2013 in Ariano et al.) [186,196]. Increases in the atmospheric concentrations of CO2 impact the reproductive processes in plants, leading them to produce more pollen [111,197,198] with significantly stronger allergenicity has been found in pollen [81,193,199]. This increased allergenicity is due to more diversity in the heterogeneity of the antigenic proteins in pollen grains [62].
Climate change affects many meteorological variables that participate in the pollen dispersal and deposition (i.e., humidity, precipitation, and temperature) [127]. Changes in dispersion, both region- and species-specific, can potentially expose (and sensitize) populations to novel allergens [141]. These changes in dispersion will also impact plant distribution, as species that could not survive in previously hostile environments can potentially thrive because of changes in temperature and precipitation [193]. The proliferation of anemophilous plants where those species were not previously prevalent exposes atopy-prone individuals to new pollens [200].

2.15. Environment and Health Interventions for Patients with Respiratory Allergies

Allergic asthma is managed through allergen avoidance and pharmacotherapy to achieve and maintain asthma control [201].
The Canadian guidelines state that, after their diagnoses, patients and/or caregivers should receive a written asthma action plan and self-management education [201]. Pharmacotherapy should be part of the written asthma plan and is designed to be long-term to prevent exacerbations. Thus, aside from the self-administration of short-acting beta-agonists as needed, pharmacotherapy for asthma is not typically altered based on current aeroallergen levels except to ensure that such long-term controller medications are used properly and as prescribed. For those who are allergic to seasonal aeroallergens, knowledge of current or upcoming pollen or fungi counts may aid in both avoidance and the optimization of pharmacotherapy [127]. If certain aeroallergens are known to exacerbate individual asthma symptoms, allergen avoidance is one option (although it may not always be feasible), and immunotherapy may be recommended in advance of the allergy season. Most people with allergic asthma also have allergic rhinitis, and the treatment of both disorders during times of increased aeroallergen presence has been shown to be critical to the maintenance of asthma control; therefore, supporting the optimization of allergic rhinitis therapy by providing information on aeroallergen levels may have a profound impact on many patients with allergic asthma [162].
The efficacies of most prescribed medications for allergic rhinitis are enhanced if they are taken consistently and/or before symptom onset [170]. Thus, reminders and warnings that various aeroallergen seasons, wildfire exposures, elevated air pollution episodes or thunderstorms are approaching may allow Canadians to ensure they have visited a healthcare provider, refilled prescriptions, and begun taking preventative medications according to their management plan [202].

3. Conclusions

Pollen and fungi are important allergen in the outdoor air [57]. Aeroallergens play a critical role in the development of allergic conditions through sensitization, particularly in those individuals with genetic predisposition [203].
Pollen and fungi do not act in isolation. Other environmental exposures (e.g., TRAP) also play a role in the interaction between air and respiratory tissue [103]. Environmental exposures can act as risk or protective factors in the development of allergy to aeroallergens [204]. After the sensitization takes place and the affected individual develops symptoms, further exposures to risk factors may cause symptom exacerbations that will diminish with reduced exposure or with medical treatment [67].
An aeroallergen alert system could be used to communicate with sensitized individuals and advise them to control their exposure when aeroallergen counts are high. An aeroallergen alert system would benefit from a model of aeroallergen production and dispersion that also incorporates weather-related variations and long-term impacts of climate change and could be coupled with existing air quality predictions. Given the documented clinical cross-reactivity between pollens from similar species [30], the idea of reporting total tree, grass, and ragweed pollens is better suited to the general public for simplicity and cost minimization, while counts of individual species would still have value for modeling and research.
Climate change has the potential to increase the length of aeroallergen seasons as well as pollen counts, geographical coverage, and allergenicity [19]. These increases will also increase human exposure to the allergenic proteins found in pollen grains [155,193]. Future increases in the incidence and prevalence of respiratory allergies and asthma are predicted [194], accompanied by an increase in health care expenses allotted to the care of these conditions [62]. Longitudinal studies are needed to examine long-term trends beyond the yearly variations due to variation in aeroallergen seasons. Such studies would help explain regional differences in risk and increase our understanding of the impact of climate change on pollens and fungi [18].
Better understanding of both pollen and fungi counts, phenology, geographic coverage, and interaction with air pollutants is needed to provide the information that atopic individuals could use to modify their environmental exposures [127], and also to shape government initiatives such as alert systems and landscaping in urban zones [205].

Supplementary Materials

The following is available online at https://www.mdpi.com/1660-4601/15/8/1577/s1, Table S1: Plant-Derived Aeroallergens in the Major Floristic Zones of Canada.

Author Contributions

C.S-H., M.N., D.H. and C.D. conceived the idea for this paper. S.B.H. and T.K.T. contributed with direction on the review and extensive revisions of the manuscript. A.K.E. contributed clinical and experimental perspectives on the effect of aeroallergens on people with allergies. J.B. and E.L. contributed technical expertise on aero allergen measurement and distribution, as well as review of the manuscript.

Funding

This work was supported in part by funding from the Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence (NCE), and Toronto Public Health Department. Publication of this research was funded through Simon Fraser University Open Access Fund.

Acknowledgments

Ryan Allen contributed ideas for a preliminary version of portions of this paper.

Conflicts of Interest

Subsequent to the completion of this work, Michelle North became an employee of Novartis.

References

  1. Lau, S. Are asthma and allergies increasing in children and adolescents? Eur. J. Integr. Med. 2009, 1, 175. [Google Scholar] [CrossRef]
  2. Breton, M.-C.; Garneau, M.; Fortier, I.; Guay, F.; Louis, J. Relationship between climate, pollen concentrations of Ambrosia and medical consultations for allergic rhinitis in Montreal, 1994–2002. Sci. Total Environ. 2006, 370, 39–50. [Google Scholar] [CrossRef] [PubMed]
  3. Rider, C.F.; Yamamoto, M.; Günther, O.P.; Hirota, J.A.; Singh, A.; Tebbutt, S.J.; Carlsten, C. Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J. Allergy Clin. Immunol. 2016, 138, 1690–1700. [Google Scholar] [CrossRef] [PubMed]
  4. Smits, H.H.; van der Vlugt, L.E.; von Mutius, E.; Hiemstra, P.S. Childhood allergies and asthma: New insights on environmental exposures and local immunity at the lung barrier. Curr. Opin. Immunol. 2016, 42, 41–47. [Google Scholar] [CrossRef] [PubMed]
  5. Cardaba, B.; Llanes, E.; Chacartegui, M.; Sastre, B.; Lopez, E.; Molla, R.; Del Pozo, V.; Florido, F.; Quiralte, J.; Palomino, P.; et al. Modulation of allergic response by gene-environment interaction: Olive pollen allergy. J. Investig. Allergol. Clin. Immunol. 2007, 17 (Suppl. 1), 31–35. [Google Scholar] [PubMed]
  6. Huang, F.; Yin, J.-N.; Wang, H.-B.; Liu, S.-Y.; Li, Y.-N. Association of imbalance of effector T cells and regulatory cells with the severity of asthma and allergic rhinitis in children. Allergy Asthma Proc. 2017, 38, 70–77. [Google Scholar] [CrossRef] [PubMed]
  7. Sun, R.; Tang, X.-Y.; Yang, Y. Immune imbalance of regulatory T/type 2 helper cells in the pathogenesis of allergic rhinitis in children. J. Laryngol. Otol. 2016, 130, 89–94. [Google Scholar] [CrossRef] [PubMed]
  8. Sears, M.R.; Greene, J.M.; Willan, A.R.; Taylor, D.R.; Flannery, E.M.; Cowan, J.O.; Herbison, G.P.; Poulton, R. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: A longitudinal study. Lancet 2002, 360, 901–907. [Google Scholar] [CrossRef]
  9. Bach, J.-F. The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases. N. Engl. J. Med. 2002, 347, 911–920. [Google Scholar] [CrossRef] [PubMed]
  10. Ellis, A.K.; Ratz, J.D.; Day, A.G.; Day, J.H. Factors that affect the allergic rhinitis response to ragweed allergen exposure. Ann. Allergy Asthma Immunol. 2010, 104, 293–298. [Google Scholar] [CrossRef] [PubMed]
  11. Patel, D.; Lee, J.S.; Wilson, D.; Camuso, N.; Salapatek, A. Repeated Low-dose Aerosolized Dust Mite Allergen Exposure in Asthmatic and Non-asthmatic Dust Mite Allergic patients in An Environmental Exposure Chamber Induces Specific Asthma Symptoms as well as Allergic Rhinoconjunctivitis Symptoms. J. Allergy Clin. Immunol. 2011, 127, AB20. [Google Scholar] [CrossRef]
  12. Rondón, C.; Fernández, J.; López, S.; Campo, P.; Doña, I.; Torres, M.J.; Mayorga, C.; Blanca, M. Nasal inflammatory mediators and specific IgE production after nasal challenge with grass pollen in local allergic rhinitis. J. Allergy Clin. Immunol. 2009, 124, 1005–1011. [Google Scholar] [CrossRef] [PubMed]
  13. Gieras, A.; Focke-Tejkl, M.; Ball, T.; Verdino, P.; Hartl, A.; Thalhamer, J.; Valenta, R. Molecular determinants of allergen-induced effector cell degranulation. J. Allergy Clin. Immunol. 2007, 119, 384–390. [Google Scholar] [CrossRef] [PubMed]
  14. Weber, R.W. Floristic zones and aeroallergen diversity. Immunol. Allergy Clin. N. Am. 2003, 23, 357–369. [Google Scholar] [CrossRef]
  15. Lafeuille, M.-H.; Gravel, J.; Figliomeni, M.; Zhang, J.; Lefebvre, P. Burden of illness of patients with allergic asthma versus non-allergic asthma. J. Asthma 2013, 50, 900–907. [Google Scholar] [CrossRef] [PubMed]
  16. Grant-Downton, R.; Hafidh, S.; Twell, D.; Dickinson, H.G. Small RNA Pathways Are Present and Functional in the Angiosperm Male Gametophyte. Mol. Plant 2009, 2, 500–512. [Google Scholar] [CrossRef] [PubMed]
  17. Farré-Armengol, G.; Filella, I.; Llusià, J.; Peñuelas, J. Pollination mode determines floral scent. Biochem. Syst. Ecol. 2015, 61, 44–53. [Google Scholar] [CrossRef]
  18. Park, H.J.; Lee, J.-H.; Park, K.H.; Kim, K.R.; Han, M.J.; Choe, H.; Oh, J.W.; Hong, C.S. A Six-Year Study on the Changes in Airborne Pollen Counts and Skin Positivity Rates in Korea: 2008–2013. Yonsei Med. J. 2016, 57, 714–720. [Google Scholar] [CrossRef] [PubMed]
  19. D’Amato, G.; Vitale, C.; De Martino, A.; Viegi, G.; Lanza, M.; Molino, A.; Sanduzzi, A.; Vatrella, A.; Annesi-Maesano, I.; D’amato, M. Effects on asthma and respiratory allergy of Climate change and air pollution. Multidiscip. Respir. Med. 2015, 10, 39. [Google Scholar] [CrossRef] [PubMed][Green Version]
  20. Katelaris, C.H.; Beggs, P.J. Climate change: Allergens and allergic diseases. Intern. Med. J. 2018, 48, 129–134. [Google Scholar] [CrossRef] [PubMed]
  21. Lacey, J. Spore dispersal—Its role in ecology and disease: The British contribution to fungal aerobiology. Mycol. Res. 1996, 100, 641–660. [Google Scholar] [CrossRef]
  22. Pablos, I.; Wildner, S.; Asam, C.; Wallner, M.; Gadermaier, G. Pollen Allergens for Molecular Diagnosis. Curr. Allergy Asthma Rep. 2016, 16, 31. [Google Scholar] [CrossRef] [PubMed]
  23. Gunawan, H.; Takai, T.; Kamijo, S.; Wang, X.L.; Ikeda, S.; Okumura, K.; Ogawa, H. Characterization of proteases, proteins, and eicosanoid-like substances in soluble extracts from allergenic pollen grains. Int. Arch. Allergy Immunol. 2008, 147, 276–288. [Google Scholar] [CrossRef] [PubMed]
  24. Skjøth, C.A.; Šikoparija, B.; Jäger, S. EAN-Network. Pollen Sources. In Allergenic Pollen; Springer: Dordrecht, The Netherlands, 2013; pp. 9–27. Available online: http://link.springer.com/chapter/10.1007/978-94-007-4881-1_2 (accessed on 31 May 2018).
  25. Ellis, A.K.; Soliman, M.; Steacy, L.; Boulay, M.-È.; Boulet, L.-P.; Keith, P.K.; Vliagoftis, H.; Waserman, S.; Neighbour, H. The Allergic Rhinitis–Clinical Investigator Collaborative (AR-CIC): Nasal allergen challenge protocol optimization for studying AR pathophysiology and evaluating novel therapies. Allergy Asthma Clin. Immunol. 2015, 11, 16. [Google Scholar] [CrossRef] [PubMed]
  26. Ellis, A.K.; North, M.L.; Walker, T.; Steacy, L.M. Environmental exposure unit: A sensitive, specific, and reproducible methodology for allergen challenge. Ann. Allergy Asthma Immunol. 2013, 111, 323–328. [Google Scholar] [CrossRef] [PubMed]
  27. White, J.F.; Bernstein, D.I. Key pollen allergens in North America. Ann. Allergy Asthma Immunol. 2003, 91, 425–435. [Google Scholar] [CrossRef]
  28. Léonard, R.; Wopfner, N.; Pabst, M.; Stadlmann, J.; Petersen, B.O.; Duus, J.Ø.; Himly, M.; Radauer, C.; Gadermaier, G.; Razzazzi-Fazeli, E.; et al. A new allergen from ragweed (Ambrosia artemisiifolia) with homology to art v 1 from mugwort. J. Biol. Chem. 2010, 285, 27192. [Google Scholar] [CrossRef] [PubMed]
  29. Oberhuber, C.; Ma, Y.; Wopfner, N.; Gadermaier, G.; Dedic, A.; Niggemann, B.; Maderegger, B.; Gruber, P.; Ferreira, F.; Scheiner, O.; et al. Prevalence of IgE-Binding to Art v 1, Art v 4 and Amb a 1 in Mugwort-Allergic Patients. Int. Arch. Allergy Immunol. 2008, 145, 94–101. [Google Scholar] [CrossRef] [PubMed]
  30. Asero, R.; Wopfner, N.; Gruber, P.; Gadermaier, G.; Ferreira, F. Artemisia and Ambrosia hypersensitivity: Co-sensitization or co-recognition? Clin. Exp. Allergy 2006, 36, 658–665. [Google Scholar] [CrossRef] [PubMed]
  31. Eriksson, N.E.; Wihl, J.A.; Arrendal, H.; Strandhede, S.O. Tree pollen allergy. II. Sensitization to various tree pollen allergens in Sweden. A multi-centre study. Allergy 1984, 39, 610–617. [Google Scholar] [CrossRef] [PubMed]
  32. Sutherland, S. News—Pollen Season Is upon US. Who’s Getting it Bad This Year? The Weather Network. Available online: https://www.theweathernetwork.com/news/articles/pollen-season-is-upon-us-whos-getting-it-bad-this-year/66940 (accessed on 31 May 2018).
  33. Weinberger, K.R.; Kinney, P.L.; Robinson, G.S.; Sheehan, D.; Kheirbek, I.; Matte, T.D.; Lovasi, G.S. Levels and determinants of tree pollen in New York City. J. Expo. Sci. Environ. Epidemiol. 2018, 28, 119–124. [Google Scholar] [CrossRef] [PubMed]
  34. Hugg, T.T.; Hjort, J.; Antikainen, H.; Rusanen, J.; Tuokila, M.; Korkonen, S.; Weckström, J.; Jaakkola, M.S.; Jaakkola, J.J. Urbanity as a determinant of exposure to grass pollen in Helsinki Metropolitan area, Finland. PLoS ONE 2017, 12, e0186348. [Google Scholar] [CrossRef] [PubMed]
  35. Rogers, C.A. An aeropalynological study of metropolitan Toronto. Aerobiologia 1997, 13, 243–257. [Google Scholar] [CrossRef]
  36. Solomon, W.R. Airborne pollen: A brief life. J. Allergy Clin. Immunol. 2002, 109, 895–900. [Google Scholar] [CrossRef] [PubMed]
  37. Agarwal, M.K.; Swanson, M.C.; Reed, C.E.; Yunginger, J.W. Immunochemical quantitation of airborne short ragweed, Alternaria, antigen, E.; and Alt-I allergens: A two-year prospective study. J. Allergy Clin. Immunol. 1983, 72, 40–45. [Google Scholar] [CrossRef]
  38. Agarwal, M.K.; Swanson, M.C.; Reed, C.E.; Yunginger, J.W. Airborne ragweed allergens: Association with various particle sizes and short ragweed plant parts. J. Allergy Clin. Immunol. 1984, 74, 687–693. [Google Scholar] [CrossRef]
  39. Grote, M.; Vrtala, S.; Niederberger, V.; Wiermann, R.; Valenta, R.; Reichelt, R. Release of allergen-bearing cytoplasm from hydrated pollen: A mechanism common to a variety of grass (Poaceae) species revealed by electron microscopy. J. Allergy Clin. Immunol. 2001, 108, 109–115. [Google Scholar] [CrossRef] [PubMed]
  40. Portnoy, J.; Barnes, C. Clinical relevance of spore and pollen counts. Immunol. Allergy Clin. N. Am. 2003, 23, 389–410. [Google Scholar] [CrossRef]
  41. Levetin, E.; Horner, W.E.; Scott, J.A. Taxonomy of Allergenic Fungi. J. Allergy Clin. Immunol. Pract. 2016, 4, 375–385. [Google Scholar] [CrossRef] [PubMed]
  42. Hibbett, D.S.; Binder, M.; Bischoff, J.F.; Blackwell, M.; Cannon, P.F.; Eriksson, O.E.; Huhndorf, S.; James, T.; Kirk, P.M.; Lücking, R.; et al. A higher-level phylogenetic classification of the Fungi. Mycol. Res. 2007, 111, 509–547. [Google Scholar] [CrossRef] [PubMed][Green Version]
  43. McLaughlin, D.J.; Hibbett, D.S.; Lutzoni, F.; Spatafora, J.W.; Vilgalys, R. The search for the fungal tree of life. Trends Microbiol. 2009, 17, 488–497. [Google Scholar] [CrossRef] [PubMed]
  44. Aukrust, L. Mold allergy. Introduction. Clin. Rev. Allergy 1992, 10, 147–151. [Google Scholar] [PubMed]
  45. Burge, H.A. Classification of the fungi. Clin. Rev. Allergy 1992, 10, 153–163. [Google Scholar] [PubMed]
  46. Taylor, J.; Jacobson, D.; Fisher, M. The Evolution of Asexual Fungi: Reproduction, Speciation and Classification. Annu. Rev. Phytopathol. 1999, 37, 197–246. [Google Scholar] [CrossRef] [PubMed]
  47. Crameri, R.; Zeller, S.; Glaser, A.G.; Vilhelmsson, M.; Rhyner, C. Cross-reactivity among fungal allergens: A clinically relevant phenomenon? Mycoses 2009, 52, 99–106. [Google Scholar] [CrossRef] [PubMed]
  48. Singh, A.B. Pollen and Fungal Aeroallergens Associated with Allergy and Asthma in India. Glob. J. Immunol. Allerg. Dis. 2014, 2, 19–28. [Google Scholar] [CrossRef]
  49. Akiyama, K. The role of fungal allergy in bronchial asthma. Nihon Ishinkin Gakkai Zasshi Jpn. J. Med. Mycol. 2000, 41, 149–155. [Google Scholar] [CrossRef]
  50. Weber, R.W. Outdoor aeroallergen sampling: Not all that simple. Ann. Allergy Asthma Immunol. 2007, 98, 505–506. [Google Scholar] [CrossRef]
  51. Weber, R.W. Pollen Identification. Ann. Allergy Asthma Immunol. 1998, 80, 141–148. [Google Scholar] [CrossRef]
  52. Crouzy, B.; Stella, M.; Konzelmann, T.; Calpini, B.; Clot, B. All-Optical automatic pollen identification: Towards an operational system. Atmos. Environ. 2016, 140, 202–212. [Google Scholar] [CrossRef]
  53. Levetin, E.; Van de Water, P.K. Pollen count forecasting. Immunol. Allergy Clin. N. Am. 2003, 23, 423–442. [Google Scholar] [CrossRef]
  54. Hjort, J.; Hugg, T.T.; Antikainen, H.; Rusanen, J.; Sofiev, M.; Kukkonen, J.; Jaakkola, M.S.; Jaakkola, J.J. Fine-Scale Exposure to Allergenic Pollen in the Urban Environment: Evaluation of Land Use Regression Approach. Environ. Health Perspect. 2016, 124, 619–626. [Google Scholar] [CrossRef] [PubMed][Green Version]
  55. Esser, C. Principles of the Immune System: Players and Organization. In Environmental Influences on the Immune System; Springer: Vienna, Austria, 2016; pp. 1–17. Available online: http://link.springer.com/chapter/10.1007/978-3-7091-1890-0_1 (accessed on 31 May 2018).
  56. Graham-Rowe, D. Lifestyle: When allergies go west. Nature 2011, 479, S2–S4. [Google Scholar] [CrossRef]
  57. Cecchi, L. Introduction. In Allergenic Pollen; Springer: Dordrecht, The Netherlands, 2013; pp. 1–7. Available online: http://link.springer.com/chapter/10.1007/978-94-007-4881-1_1 (accessed on 31 May 2018).
  58. De Weger, L.A.; Bergmann, K.C.; Rantio-Lehtimäki, A.; Dahl, Å.; Buters, J.; Déchamp, C.; Belmonte, J.; Thibaudon, M.; Cecchi, L.; Besancenot, J.P.; et al. Impact of Pollen. In Allergenic Pollen; Sofiev, M., Bergmann, K.-C., Eds.; Springer: Dordrecht, The Netherlands, 2013; pp. 161–215. Available online: http://link.springer.com/10.1007/978-94-007-4881-1_6 (accessed on 31 May 2018).
  59. Cantani, A. Allergic Rhinitis. In Pediatric Allergy, Asthma and Immunology; Springer: Berlin, Germany, 2008; pp. 875–910. Available online: http://link.springer.com.proxy.lib.sfu.ca/chapter/10.1007/978-3-540-33395-1_12 (accessed on 18 July 2016).
  60. Vaitla, P.M.; Drewe, E. Identifying the culprit allergen in seasonal allergic rhinitis. Practitioner 2011, 255, 27–31. [Google Scholar] [PubMed]
  61. Hesse, M.; Halbritter, H.; Zetter, R.; Weber, M.; Buchner, R.; Frosch-Radivo, A.; Ulrich, S.; Zetter, R. Pollen Morphology. In Pollen Terminology an Illustrated Handbook; Springer: Wien, Austria, 2009. [Google Scholar]
  62. Szema, A.M. Asthma, Hay Fever, Pollen, and Climate Change. In Global Climate Change and Public Health; Pinkerton, K.E., Rom, W.N., Eds.; Springer: New York, NY, USA, 2014; pp. 155–165. Available online: http://link.springer.com.proxy.lib.sfu.ca/chapter/10.1007/978-1-4614-8417-2_9 (accessed on 15 July 2016).
  63. Green, B.J.; Beezhold, D.H.; Gallinger, Z.; Barron, C.S.; Melvin, R.; Bledsoe, T.A.; Kashon, M.L.; Sussman, G.L. Allergic sensitization in Canadian chronic rhinosinusitis patients. Allergy Asthma Clin. Immunol. 2014, 10, 15. [Google Scholar] [CrossRef] [PubMed][Green Version]
  64. Cakmak, S.; Dales, R.E.; Coates, F. Does air pollution increase the effect of aeroallergens on hospitalization for asthma? J. Allergy Clin. Immunol. 2011, 129, 228–231. [Google Scholar] [CrossRef] [PubMed]
  65. Sandin, A.; Bjorksten, B.; Braback, L. Development of atopy and wheezing symptoms in relation to heredity and early pet keeping in a Swedish birth cohort. Pediatr. Allergy Immunol. 2004, 15, 316–322. [Google Scholar] [CrossRef] [PubMed]
  66. D’Amato, G.; Vitale, C.; Lanza, M.; Molino, A.; D’Amato, M. Climate change, air pollution, and allergic respiratory diseases: An update. Curr. Opin. Allergy Clin. Immunol. 2016, 16, 434–440. [Google Scholar] [CrossRef] [PubMed]
  67. Eder, W.; Ege, M.J.; von Mutius, E. The Asthma Epidemic. N. Engl. J. Med. 2006, 355, 2226–2235. [Google Scholar] [CrossRef] [PubMed]
  68. Armentia, A.; Banuelos, C.; Arranz, M.L.; Del Villar, V.; Martin-Santos, J.M.; Gil, F.J.; Gil, F.M.; Vega, J.M.; Callejo, A.; Paredes, C. Early introduction of cereals into children’s diets as a risk-factor for grass pollen asthma. Clin. Exp. Allergy 2001, 31, 1250–1255. [Google Scholar] [CrossRef] [PubMed]
  69. Halken, S. Prevention of allergic disease in childhood: Clinical and epidemiological aspects of primary and secondary allergy prevention. Pediatr. Allergy Immunol. 2004, 15, 9–32. [Google Scholar] [CrossRef] [PubMed]
  70. Bardei, F.; Bouziane, H.; Kadiri, M.; Rkiek, B.; Tebay, A.; Saoud, A. Skin sensitisation profiles to inhalant allergens for patients in Tetouan city (North West of Morocco). Rev. Pneumol. Clin. 2016, 72, 221–227. [Google Scholar] [CrossRef] [PubMed]
  71. Duffy, D.L.; Mitchell, C.A.; Martin, N.G. Genetic and environmental risk factors for asthma: A cotwin-control study. Am. J. Respir. Crit. Care Med. 1998, 157, 840–845. [Google Scholar] [CrossRef] [PubMed]
  72. Horvath, A.; Balashazy, I.; Farkas, A.; Sarkany, Z.; Hofmann, W.; Czitrovszky, A.; Dobos, E. Quantification of airway deposition of intact and fragmented pollens. Int. J. Environ. Health Res. 2011, 21, 427–440. [Google Scholar] [CrossRef] [PubMed]
  73. Liu, L.; Li, G.; Sun, Y.; Li, J.; Tang, N.; Dong, L. Airway wall thickness of allergic asthma caused by weed pollen or house dust mite assessed by computed tomography. Respir. Med. 2015, 109, 339–346. [Google Scholar] [CrossRef] [PubMed]
  74. Von Mutius, E. Gene-environment interactions in asthma. J. Allergy Clin. Immunol. 2009, 123, 3–11. [Google Scholar] [CrossRef] [PubMed]
  75. Vinhas, R.; Cortes, L.; Cardoso, I.; Mendes, V.M.; Manadas, B.; Todo-Bom, A.; Pires, E.; Verissimo, P. Pollen proteases compromise the airway epithelial barrier through degradation of transmembrane adhesion proteins and lung bioactive peptides. Allergy 2011, 66, 1088–1098. [Google Scholar] [CrossRef] [PubMed]
  76. Tran, M.M.; Lefebvre, D.L.; Dharma, C.; Dai, D.; Lou, W.Y.W.; Subbarao, P.; Becker, A.B.; Mandhane, P.J.; Turvey, S.E.; Sears, M.R.; et al. Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study. J. Allergy Clin. Immunol. 2017, 141, 601–607. [Google Scholar] [CrossRef] [PubMed]
  77. Bergmann, R.L.; Wahn, U.; Bergmann, K.E. The allergy march: From food to pollen. Environ. Toxicol. Pharmacol. 1997, 4, 79–83. [Google Scholar] [CrossRef]
  78. Warner, J.A.; Jones, C.A.; Jones, A.C.; Warner, J.O. Prenatal origins of allergic disease. J. Allergy Clin. Immunol. 2000, 105, S493–S498. [Google Scholar] [CrossRef]
  79. Leung, R.C.; Carlin, J.B.; Burdon, J.G.; Czarny, D. Asthma, allergy and atopy in Asian immigrants in Melbourne. Med. J. Aust. 1994, 161, 418–425. [Google Scholar] [PubMed]
  80. Ventura, M.T.; Munno, G.; Giannoccaro, F.; Accettura, F.; Chironna, M.; Lama, R.; Hoxha, M.; Panetta, V.; Ferrigno, L.; Rosmini, F.; et al. Allergy, asthma and markers of infections among Albanian migrants to Southern Italy. Allergy 2004, 59, 632–636. [Google Scholar] [CrossRef] [PubMed]
  81. Beggs, P.J. Impacts of climate change on aeroallergens: Past and future. Clin. Exp. Allergy 2004, 34, 1507–1513. [Google Scholar] [CrossRef] [PubMed]
  82. De Jong, N.W.; Vermeulen, A.M.; Gerth van Wijk, R.; de Groot, H. Occupational allergy caused by flowers. Allergy 1998, 53, 204–209. [Google Scholar] [CrossRef] [PubMed]
  83. Anguita, J.L.; Palacios, L.; Ruiz-Valenzuela, L.; Bartolome, B.; Lopez-Urbano, M.J.; Saenz de San Pedro, B.; Cano, E.; Quiralte, J. An occupational respiratory allergy caused by Sinapis alba pollen in olive farmers. Allergy 2007, 62, 447–450. [Google Scholar] [CrossRef] [PubMed]
  84. Garcia-Ortega, P.; Bartolome, B.; Enrique, E.; Gaig, P.; Richart, C. Allergy to Diplotaxis erucoides pollen: Occupational sensitization and cross-reactivity with other common pollens. Allergy 2001, 56, 679–683. [Google Scholar] [CrossRef] [PubMed]
  85. Hermanides, H.K.; Lahey-de Boer, A.M.; Zuidmeer, L.; Guikers, C.; van Ree, R.; Knulst, A.C. Brassica oleracea pollen, a new source of occupational allergens. Allergy 2006, 61, 498–502. [Google Scholar] [CrossRef] [PubMed]
  86. Swierczyniska-Machura, D.; Krakowiak, A.; Palczynski, C. Occupational allergy caused by ornamental plants. Med. Pr. 2006, 57, 359–364. [Google Scholar] [PubMed]
  87. Miesen, W.M.A.J.; Van der Heide, S.; Kerstjens, H.A.M.; Dubois, A.E.J.; de Monchy, J.G.R. Occupational asthma due to IgE mediated allergy to the flower Molucella laevis (Bells of Ireland). Occup. Environ. Med. 2003, 60, 701–703. [Google Scholar] [CrossRef] [PubMed][Green Version]
  88. Eire, M.A.; Pineda, F.; Losada, S.V.; de la Cuesta, C.G.; Villalva, M.M. Occupational rhinitis and asthma due to cedroarana (Cedrelinga catenaeformis Ducke) wood dust allergy. J. Investig. Allergol. Clin. Immunol. 2006, 16, 385–387. [Google Scholar] [PubMed]
  89. Blanco, C.; Ortega, N.; Castillo, R.; Alvarez, M.; Dumpierrez, A.G.; Carrillo, T. Carica papaya pollen allergy. Ann. Allergy Asthma Immunol. 1998, 81, 171–175. [Google Scholar] [CrossRef]
  90. Barbato, A.; Pisetta, F.; Norbiato, M.; Ragusa, A.; Mesirca, P.; Pesenti, P.; Marcer, G. Influence of aeroallergens on bronchial reactivity in children sensitized to grass pollens. Ann. Allergy 1986, 56, 138–141. [Google Scholar] [PubMed]
  91. Tovey, E.R.; Almqvist, C.; Li, Q.; Crisafulli, D.; Marks, G.B. Nonlinear relationship of mite allergen exposure to mite sensitization and asthma in a birth cohort. J. Allergy Clin. Immunol. 2008, 122, 114–118. [Google Scholar] [CrossRef] [PubMed]
  92. Lebel, B.; Bousquet, J.; Morel, A.; Chanal, I.; Godard, P.; Michel, F.B. Correlation between symptoms and the threshold for release of mediators in nasal secretions during nasal challenge with grass-pollen grains. J. Allergy Clin. Immunol. 1988, 82, 869–877. [Google Scholar] [CrossRef]
  93. Twaroch, T.E.; Curin, M.; Valenta, R.; Swoboda, I. Mold allergens in respiratory allergy: From structure to therapy. Allergy Asthma Immunol. Res. 2015, 7, 205–220. [Google Scholar] [CrossRef] [PubMed]
  94. D’Amato, G.; Spieksma, F.T. Aerobiologic and clinical aspects of mould allergy in Europe. Allergy 1995, 50, 870–877. [Google Scholar] [CrossRef] [PubMed]
  95. Bernardis, P.; Agnoletto, M.; Puccinelli, P.; Parmiani, S.; Pozzan, M. Injective versus sublingual immunotherapy in Alternaria tenuis allergic patients. J. Investig. Allergol. Clin. Immunol. 1996, 6, 55–62. [Google Scholar] [PubMed]
  96. Baxter, D.M.; Perkins, J.L.; McGhee, C.R.; Seltzer, J.M. A regional comparison of mold spore concentrations outdoors and inside “clean” and “mold contaminated” Southern California buildings. J. Occup. Environ. Hyg. 2005, 2, 8–18. [Google Scholar] [CrossRef] [PubMed]
  97. Nolte, H.; Hébert, J.; Berman, G.; Gawchik, S.; White, M.; Kaur, A.; Liu, N.; Lumry, W.; Maloney, J. Randomized controlled trial of ragweed allergy immunotherapy tablet efficacy and safety in North American adults. Ann. Allergy Asthma Immunol. 2013, 110, 450–456. [Google Scholar] [CrossRef] [PubMed]
  98. Weichenthal, S.; Lavigne, E.; Villeneuve, P.J.; Reeves, F. Airborne Pollen Concentrations and Emergency Room Visits for Myocardial Infarction: A Multicity Case-Crossover Study in Ontario, Canada. Am. J. Epidemiol. 2016, 183, 613–621. [Google Scholar] [CrossRef] [PubMed][Green Version]
  99. Durham, S.R.; Emminger, W.; Kapp, A.; de Monchy, J.G.; Rak, S.; Scadding, G.K.; Wurtzen, P.A.; Andersen, J.S.; Tholstrup, B.; Riis, B.; et al. SQ-standardized sublingual grass immunotherapy: Confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J. Allergy Clin. Immunol. 2012, 129, 717–725. [Google Scholar] [CrossRef] [PubMed]
  100. Connell, J.T. Quantitative intranasal pollen challenges. 3. The priming effect in allergic rhinitis. J. Allergy 1969, 43, 33–44. [Google Scholar] [CrossRef]
  101. Jacobs, R.L.; Andrews, C.P.; Ramirez, D.A.; Rather, C.G.; Harper, N.; Jimenez, F.; Martinez, H.; Manoharan, M.; Carrillo, A.; Gerardi, M.; et al. Symptom dynamics during repeated serial allergen challenge chamber exposures to house dust mite. J. Allergy Clin. Immunol. 2015, 135, 1071–1075. [Google Scholar] [CrossRef] [PubMed]
  102. O’Hehir, R.E.; Varese, N.P.; Deckert, K.; Zubrinich, C.M.; van Zelm, M.C.; Rolland, J.M.; Hew, M. Epidemic Thunderstorm Asthma Protection with Five-grass Pollen Tablet Sublingual Immunotherapy. Am. J. Respir. Crit. Care Med. 2018, 198, 126–128. [Google Scholar] [CrossRef] [PubMed]
  103. Subbarao, P.; Becker, A.; Brook, J.R.; Daley, D.; Mandhane, P.J.; Miller, G.E.; Turvey, S.E.; Sears, M.R. Epidemiology of asthma: Risk factors for development. Expert Rev. Clin. Immunol. 2009, 5, 77–95. [Google Scholar] [CrossRef] [PubMed]
  104. Clifford, R.L.; Jones, M.J.; MacIsaac, J.L.; McEwen, L.M.; Goodman, S.J.; Mostafavi, S.; Kobor, M.S.; Carlsten, C. Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. J. Allergy Clin. Immunol. 2017, 139, 112–121. [Google Scholar] [CrossRef] [PubMed][Green Version]
  105. Gershwin, L.J. Infectious and Environmental Triggers of Asthma. In Current Clinical Practice: Bronchial Asthma: A Guide for Practical Understanding and Treatment, 5th ed.; Humana Press Inc.: Totowa, NJ, USA, 2006. [Google Scholar]
  106. Parameswaran, K.; Hildreth, A.J.; Taylor, I.K.; Keaney, N.P.; Bansal, S.K. Predictors of asthma severity in the elderly: Results of a community survey in Northeast England. J. Asthma 1999, 36, 613–618. [Google Scholar] [CrossRef] [PubMed]
  107. Anyo, G.; Brunekreef, B.; de Meer, G.; Aarts, F.; Janssen, N.A.H.; van Vliet, P. Early, current and past pet ownership: Associations with sensitization, bronchial responsiveness and allergic symptoms in school children. Clin. Exp. Allergy 2002, 32, 361–366. [Google Scholar] [CrossRef] [PubMed]
  108. Galli, L.; Facchetti, S.; Raffetti, E.; Donato, F.; D’Anna, M. Respiratory diseases and allergic sensitization in swine breeders: A population-based cross-sectional study. Ann. Allergy Asthma Immunol. 2015, 115, 402–407. [Google Scholar] [CrossRef] [PubMed]
  109. Waser, M.; von Mutius, E.; Riedler, J.; Nowak, D.; Maisch, S.; Carr, D.; Eder, W.; Tebow, G.; Schierl, R.; Schreuer, M.; et al. Exposure to pets, and the association with hay fever, asthma, and atopic sensitization in rural children. Allergy 2005, 60, 177–184. [Google Scholar] [CrossRef] [PubMed]
  110. Gassner-Bachmann, M.; Wuthrich, B. Farmers’ children suffer less from hay fever and asthma. Dtsch. Med. Wochenschr. 2000, 125, 924–931. [Google Scholar] [CrossRef] [PubMed]
  111. Bjerg, A.; Ekerljung, L.; Eriksson, J.; Naslund, J.; Sjolander, S.; Ronmark, E.; Dahl, Å.; Holmberg, K.; Wennergren, G.; Torén, K.; et al. Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood. Clin. Exp. Allergy 2016, 46, 1328–1336. [Google Scholar] [CrossRef] [PubMed][Green Version]
  112. Leynaert, B.; Neukirch, C.; Jarvis, D.; Chinn, S.; Burney, P.; Neukirch, F. Does living on a farm during childhood protect against asthma, allergic rhinitis, and atopy in adulthood? Am. J. Respir. Crit. Care Med. 2001, 164, 1829–1834. [Google Scholar] [CrossRef] [PubMed]
  113. Braun-Fahrlander, C.; Gassner, M.; Grize, L.; Neu, U.; Sennhauser, F.H.; Varonier, H.S.; Vuille, J.C.; Wüthrich, B. Prevalence of hay fever and allergic sensitization in farmer’s children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution. Clin. Exp. Allergy 1999, 29, 28–34. [Google Scholar] [CrossRef] [PubMed]
  114. Stein, M.M.; Hrusch, C.L.; Gozdz, J.; Igartua, C.; Pivniouk, V.; Murray, S.E.; Ledford, J.G.; Marques dos Santos, M.; Anderson, R.L.; Metwali, N.; et al. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. N. Engl. J. Med. 2016, 375, 411–421. [Google Scholar] [CrossRef] [PubMed][Green Version]
  115. Klopp, A.; Vehling, L.; Becker, A.B.; Subbarao, P.; Mandhane, P.J.; Turvey, S.E.; Lefebvre, D.L.; Sears, M.R.; Azad, M.B.; CHILD Study Investigators. Modes of Infant Feeding and the Risk of Childhood Asthma: A Prospective Birth Cohort Study. J. Pediatr. 2017, 190, 192–199. [Google Scholar] [CrossRef] [PubMed]
  116. Dogaru, C.M.; Nyffenegger, D.; Pescatore, A.M.; Spycher, B.D.; Kuehni, C.E. Breastfeeding and Childhood Asthma: Systematic Review and Meta-Analysis. Am. J. Epidemiol. 2014, 179, 1153–1167. [Google Scholar] [CrossRef] [PubMed][Green Version]
  117. Azad, M.B.; Becker, A.B.; Guttman, D.S.; Sears, M.R.; Scott, J.A.; Kozyrskyj, A.L. Gut microbiota diversity and atopic disease: Does breast-feeding play a role? J. Allergy Clin. Immunol. 2013, 131, 247–248. [Google Scholar] [CrossRef] [PubMed]
  118. Rosas, I.; McCartney, H.A.; Payne, R.W.; Calderón, C.; Lacey, J.; Chapela, R.; Ruiz-Velazco, S. Analysis of the relationships between environmental factors (aeroallergens, air pollution, and weather) and asthma emergency admissions to a hospital in Mexico City. Allergy 2007, 53, 394–401. [Google Scholar] [CrossRef]
  119. North, M.L.; Soliman, M.; Walker, T.; Steacy, L.M.; Ellis, A.K. Controlled Allergen Challenge Facilities and Their Unique Contributions to Allergic Rhinitis Research. Curr. Allergy Asthma Rep. 2015, 15, 11. [Google Scholar] [CrossRef] [PubMed]
  120. Barnes, C.; Pacheco, F.; Landuyt, J.; Hu, F.; Portnoy, J. Hourly variation of airborne ragweed pollen in Kansas City. Ann. Allergy Asthma Immunol. 2001, 86, 166–171. [Google Scholar] [CrossRef]
  121. Weber, R.W. Meteorologic variables in aerobiology. Aerobiology 2003, 23, 411–422. [Google Scholar] [CrossRef]
  122. Barnes, C.; Pacheco, F.; Landuyt, J.; Hu, F.; Portnoy, J. The effect of temperature, relative humidity and rainfall on airborne ragweed pollen concentrations. Aerobiologia 2001, 17, 61–68. [Google Scholar] [CrossRef]
  123. Andrew, E.; Nehme, Z.; Bernard, S.; Smith, K. 6 Characteristics of thunderstorm asthma EMS attendances in Victoria, Australia. BMJ Open 2017, 7 (Suppl. 3), A2–A3. [Google Scholar]
  124. Cockcroft, D.W.; Davis, B.E.; Blais, C.M. Thunderstorm asthma: An allergen-induced early asthmatic response. Ann. Allergy Asthma Immunol. 2018, 120, 120–123. [Google Scholar] [CrossRef] [PubMed]
  125. Lee, J.; Kronborg, C.; O’Hehir, R.E.; Hew, M. Who’s at risk of thunderstorm asthma? The ryegrass pollen trifecta and lessons learnt from the Melbourne thunderstorm epidemic. Respir. Med. 2017, 132, 146–148. [Google Scholar] [CrossRef] [PubMed]
  126. D’Amato, G.; Annesi Maesano, I.; Molino, A.; Vitale, C.; D’Amato, M. Thunderstorm-related asthma attacks. J. Allergy Clin. Immunol. 2017, 139, 1786–1787. [Google Scholar] [CrossRef] [PubMed]
  127. D’Amato, G.; Holgate, S.T.; Pawankar, R.; Ledford, D.K.; Cecchi, L.; Al-Ahmad, M.; Al-Enezi, F.; Al-Muhsen, S.; Ansotegui, I.; Baena-Cagnani, C.E.; et al. Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization. World Allergy Organ. J. 2015, 8, 25. [Google Scholar] [CrossRef] [PubMed]
  128. D’Amato, G.; Cecchi, L. Effects of climate change on environmental factors in respiratory allergic diseases. Clin. Exp. Allergy 2008, 38, 1264–1274. [Google Scholar] [CrossRef] [PubMed]
  129. Valero, A.; Justicia, J.L.; Anton, E.; Dordal, T.; Fernandez-Parra, B.; Lluch, M.; Montoro, J.; Navarro, A.M. Epidemiology of allergic rhinitis caused by grass pollen or house-dust mites in Spain. Am. J. Rhinol. Allergy 2011, 25, e123–e128. [Google Scholar] [CrossRef] [PubMed]
  130. Canonica, G.W.; Ciprandi, G.; Pesce, G.P.; Buscaglia, S.; Paolieri, F.; Bagnasco, M. ICAM-1 on epithelial cells in allergic subjects: A hallmark of allergic inflammation. Int. Arch. Allergy Immunol. 1995, 107, 99–102. [Google Scholar] [CrossRef] [PubMed]
  131. Ogi, K.; Takabayashi, T.; Sakashita, M.; Susuki, D.; Yamada, T.; Manabe, Y.; Fujieda, S. Effect of Asian sand dust on Japanese cedar pollinosis. Auris Nasus Larynx 2014, 41, 518–522. [Google Scholar] [CrossRef] [PubMed]
  132. Weeke, E.R. Epidemiology of allergic diseases in children. Rhinol. Suppl. 1992, 13, 5–12. [Google Scholar] [PubMed]
  133. D’Amato, G.; Liccardi, G.; D’Amato, M.; Holgate, S. Environmental risk factors and allergic bronchial asthma. Clin. Exp. Allergy 2005, 35, 1113–1124. [Google Scholar] [CrossRef] [PubMed]
  134. Carinanos, P.; Sanchez-Mesa, J.A.; Prieto-Baena, J.C.; Lopez, A.; Guerra, F.; Moreno, C.; Domínguez, E.; Galan, C. Pollen allergy related to the area of residence in the city of Cordoba, south-west Spain. J. Environ. Monit. 2002, 4, 734–738. [Google Scholar] [CrossRef] [PubMed]
  135. Knudsen, T.B.; Thomsen, S.F.; Ulrik, C.S.; Fenger, M.; Nepper-Christensen, S.; Backer, V. Season of birth and risk of atopic disease among children and adolescents. J. Asthma 2007, 44, 257–260. [Google Scholar] [CrossRef] [PubMed]
  136. Vovolis, V.; Grigoreas, C.; Galatas, I.; Vourdas, D. Is month of birth a risk factor for subsequent development of pollen allergy in adults? Allergy Asthma Proc. 1999, 20, 15–22. [Google Scholar] [CrossRef] [PubMed]
  137. Lowe, A.J.; Olsson, D.; Bråbäck, L.; Forsberg, B. Pollen exposure in pregnancy and infancy and risk of asthma hospitalization—A register based cohort study. Allergy Asthma Clin. Immunol. 2012, 8, 17. [Google Scholar] [CrossRef] [PubMed]
  138. D’Amato, G.; Bergmann, K.C.; Cecchi, L.; Annesi-Maesano, I.; Sanduzzi, A.; Liccardi, G.; Vitale, C.; Stanziola, A.; D’Amato, M. Climate change and air pollution: Effects on pollen allergy and other allergic respiratory diseases. Allergo J. Int. 2014, 23, 17–23. [Google Scholar] [CrossRef] [PubMed]
  139. Guinea, J.; Peláez, T.; Alcalá, L.; Bouza, E. Outdoor environmental levels of Aspergillus spp. conidia over a wide geographical area. Med. Mycol. 2006, 44, 349–356. [Google Scholar] [CrossRef] [PubMed][Green Version]
  140. Bosch-Cano, F.; Bernard, N.; Sudre, B.; Gillet, F.; Thibaudon, M.; Richard, H.; Badot, P.M.; Ruffaldi, P. Human exposure to allergenic pollens: A comparison between urban and rural areas. Environ. Res. 2011, 111, 619–625. [Google Scholar] [CrossRef] [PubMed][Green Version]
  141. Reid, C.E.; Gamble, J.L. Aeroallergens, allergic disease, and climate change: Impacts and adaptation. EcoHealth 2009, 6, 458–470. [Google Scholar] [CrossRef] [PubMed]
  142. Ziska, L.H.; Gebhard, D.E.; Frenz, D.A.; Faulkner, S.; Singer, B.D.; Straka, J.G. Cities as harbingers of climate change: Common ragweed, urbanization, and public health. J. Allergy Clin. Immunol. 2003, 111, 290–295. [Google Scholar] [CrossRef] [PubMed]
  143. Majd, A.; Chehregani, A.; Moin, M.; Gholami, M.; Kohno, S.; Nabe, T.; Shariatzade, M.A. The Effects of Air Pollution on Structures, Proteins and Allergenicity of Pollen Grains. Int. J. Aerobiol. 2004, 20, 111–118. [Google Scholar] [CrossRef]
  144. Pasqualini, S.; Tedeschini, E.; Frenguelli, G.; Wopfner, N.; Ferreira, F.; D’Amato, G.; Ederli, L. Ozone affects pollen viability and NAD(P)H oxidase release from Ambrosia artemisiifolia pollen. Environ. Pollut. 2011, 159, 2823–2830. [Google Scholar] [CrossRef] [PubMed]
  145. Raynor, G.S.; Ogden, E.C.; Hayes, J.V. Dispersion and Deposition of Ragweed Pollen from Experimental Sources. J. Appl. Meteorol. 1970, 9, 885–895. [Google Scholar] [CrossRef]
  146. Ying, Z.; Tie, X.; Li, G. Sensitivity of ozone concentrations to diurnal variations of surface emissions in Mexico City: A WRF/Chem modeling study. Atmos. Environ. 2009, 43, 851–859. [Google Scholar] [CrossRef]
  147. Lazić, L.; Urošević, M.A.; Mijić, Z.; Vuković, G.; Ilić, L. Traffic contribution to air pollution in urban street canyons: Integrated application of the OSPM, moss biomonitoring and spectral analysis. Atmos. Environ. 2016, 141, 347–360. [Google Scholar] [CrossRef]
  148. Masiol, M.; Hopke, P.K.; Felton, H.D.; Frank, B.P.; Rattigan, O.V.; Wurth, M.J.; LaDuke, G.H. Analysis of major air pollutants and submicron particles in New York City and Long Island. Atmos. Environ. 2017, 148, 203–214. [Google Scholar] [CrossRef]
  149. Takaro, T.K.; Knowlton, K.; Balmes, J.R. Climate change and respiratory health: Current evidence and knowledge gaps. Expert Rev. Respir. Med. 2013, 7, 349–361. [Google Scholar] [CrossRef] [PubMed]
  150. Romieu, I.; Moreno-Macias, H.; London, S.J. Gene by Environment Interaction and Ambient Air Pollution. Proc. Am. Thorac. Soc. 2010, 7, 116–122. [Google Scholar] [CrossRef] [PubMed][Green Version]
  151. Peltre, G. Inter-relationship between allergenic pollens and air pollution. Allergie Immunol. 1998, 30, 324–326. [Google Scholar]
  152. Zhang, X.; Hirota, J.A.; Yang, C.; Carlsten, C. Effect of GST variants on lung function following diesel exhaust and allergen co-exposure in a controlled human crossover study. Free Radic. Biol. Med. 2016, 96, 385–391. [Google Scholar] [CrossRef] [PubMed]
  153. Alexis, N.E.; Zhou, H.; Lay, J.C.; Harris, B.; Hernandez, M.L.; Lu, T.-S.; Bromberg, P.A.; Diaz-Sanchez, D.; Devlin, R.B.; Kleeberger, S.R.; et al. The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in human subjects. J. Allergy Clin. Immunol. 2009, 124, 1222–1228. [Google Scholar] [CrossRef] [PubMed]
  154. Boldogh, I. ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J. Clin. Investig. 2005, 115, 2169–2179. [Google Scholar] [CrossRef] [PubMed][Green Version]
  155. Traidl-Hoffmann, C.; Kasche, A.; Menzel, A.; Jakob, T.; Thiel, M.; Ring, J.; Behrendt, H. Impact of pollen on human health: More than allergen carriers? Int. Arch. Allergy Immunol. 2003, 131, 1–13. [Google Scholar] [CrossRef] [PubMed]
  156. Abou Chakra, O.; Rogerieux, F.; Poncet, P.; Sutra, J.-P.; Peltre, G.; Senechal, H.; Lacroix, G. Ability of pollen cytoplasmic granules to induce biased allergic responses in a rat model. Int. Arch. Allergy Immunol. 2011, 154, 128–136. [Google Scholar] [CrossRef] [PubMed]
  157. North, M.L.; Jones, M.J.; Macisaac, J.L.; Morin, A.M.; Steacy, L.M.; Gregor, A.; Kobor, M.S.; Ellis, A.K. Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit. Allergy 2018, 73, 196–205. [Google Scholar] [CrossRef] [PubMed]
  158. Holtzman, M.J.; Byers, D.E.; Alexander-Brett, J.; Wang, X. The role of airway epithelial cells and innate immune cells in chronic respiratory disease. Nat. Rev. Immunol. 2014, 14, 686–698. [Google Scholar] [CrossRef] [PubMed][Green Version]
  159. Broms, K.; Norback, D.; Eriksson, M.; Sundelin, C.; Svardsudd, K. Prevalence and co-occurrence of parentally reported possible asthma and allergic manifestations in pre-school children. BMC Public Health 2013, 13, 764. [Google Scholar] [CrossRef] [PubMed]
  160. Bachert, C.; Vignola, A.M.; Gevaert, P.; Leynaert, B.; Van Cauwenberge, P.; Bousquet, J. Allergic rhinitis, rhinosinusitis, and asthma: One airway disease. Immunol. Allergy Clin. N. Am. 2004, 24, 19–43. [Google Scholar] [CrossRef]
  161. Bousquet, J.; Van Cauwenberge, P.; Khaltaev, N.; Aria Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J. Allergy Clin. Immunol. 2001, 108, S147–S334. [Google Scholar] [CrossRef] [PubMed]
  162. Kim, H.; Bouchard, J.; Renzix, P. The link between allergic rhinitis and asthma: A role for antileukotrienes? Can. Respir. J. 2008, 15, 91–98. [Google Scholar] [CrossRef] [PubMed]
  163. Egan, M.; Bunyavanich, S. Allergic rhinitis: The “Ghost Diagnosis” in patients with asthma. Asthma Res. Pract. 2015, 1, 8. [Google Scholar] [CrossRef] [PubMed]
  164. Ciprandi, G.; Buscaglia, S.; Scordamaglia, A.; Canonica, G.W. Allergen-specific conjunctival challenge in asthma. An additional diagnostic tool to define sensitization. Int. Arch. Allergy Immunol. 1997, 112, 247–250. [Google Scholar] [CrossRef] [PubMed]
  165. Boulay, M.-E.; Boulet, L.-P. Influence of natural exposure to pollens and domestic animals on airway responsiveness and inflammation in sensitized non-asthmatic subjects. Int. Arch. Allergy Immunol. 2002, 128, 336–343. [Google Scholar] [CrossRef] [PubMed]
  166. Cantani, A. Asthma. In Pediatric Allergy, Asthma and Immunology; Springer: Berlin/Heidelberg, Germany, 2008; pp. 725–873. Available online: http://link.springer.com.proxy.lib.sfu.ca/chapter/10.1007/978-3-540-33395-1_11 (accessed on 18 July 2016).
  167. Hesselmar, B.; Bergin, A.-M.; Park, H.; Hahn-Zoric, M.; Eriksson, B.; Hanson, L.-A.; Padyukov, L. Interleukin-4 receptor polymorphisms in asthma and allergy: Relation to different disease phenotypes. Acta Paediatr. 2010, 99, 399–403. [Google Scholar] [CrossRef] [PubMed]
  168. World Health Organization. Asthma. World Health Organization: Geneva, Switzerland, 2017. Available online: http://www.who.int/news-room/fact-sheets/detail/asthma (accessed on 31 May 2018).
  169. Hertzen, L.; Haahtela, T. Signs of reversing trends in prevalence of asthma. Allergy 2005, 60, 283–292. [Google Scholar] [CrossRef] [PubMed][Green Version]
  170. Keith, P.K.; Desrosiers, M.; Laister, T.; Schellenberg, R.R.; Waserman, S. The burden of allergic rhinitis (AR) in Canada: Perspectives of physicians and patients. Allergy Asthma Clin. Immunol. 2012, 8, 7. [Google Scholar] [CrossRef] [PubMed]
  171. Government of Canada, S.C. Asthma, by Age Group and Sex (Percent). 2016. Available online: https://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/health49b-eng.htm (accessed on 31 May 2018).
  172. Gershon, A.S.; Guan, J.; Wang, C.; To, T. Trends in Asthma Prevalence and Incidence in Ontario, Canada, 1996–2005: A Population Study. Am. J. Epidemiol. 2010, 172, 728–736. [Google Scholar] [CrossRef] [PubMed]
  173. Asher, M.I.; Montefort, S.; Björkstén, B.; Lai, C.K.; Strachan, D.P.; Weiland, S.K.; Williams, H.; ISAAC Phase Three Study Group. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006, 368, 733–743. [Google Scholar] [CrossRef]
  174. Ismaila, A.S.; Sayani, A.P.; Marin, M.; Su, Z. Clinical, economic, and humanistic burden of asthma in Canada: A systematic review. BMC Pulm. Med. 2013, 13, 70. [Google Scholar] [CrossRef] [PubMed]
  175. Statistics Canada. Population by Sex and Age Group, Population as of July 1. Statistics Canada, CANSIM, Table 051-0001. 2016. Available online: http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo10a-eng.htm (accessed on 18 October 2016).
  176. Lavigne, E.; Gasparrini, A.; Stieb, D.M.; Chen, H.; Yasseen, A.S.; Crighton, E.; To, T.; Weichenthal, S.; Villeneuve, P.J.; Cakmak, S.; et al. Maternal Exposure to Aeroallergens and the Risk of Early Delivery. Epidemiology 2017, 28, 107–115. [Google Scholar] [CrossRef] [PubMed][Green Version]
  177. Dales, R.E.; Cakmak, S.; Judek, S.; Coates, F. Tree pollen and hospitalization for asthma in urban Canada. Int. Arch. Allergy Immunol. 2008, 146, 241–247. [Google Scholar] [CrossRef] [PubMed]
  178. Dales, R.E.; Cakmak, S.; Burnett, R.T.; Judek, S.; Coates, F.; Brook, J.R. Influence of ambient fungal spores on emergency visits for asthma to a regional children’s hospital. Am. J. Respir. Crit. Care Med. 2000, 162, 2087–2090. [Google Scholar] [CrossRef] [PubMed]
  179. Héguy, L.; Garneau, M.; Goldberg, M.S.; Raphoz, M.; Guay, F.; Valois, M.-F. Associations between grass and weed pollen and emergency department visits for asthma among children in Montreal. Environ. Res. 2008, 106, 203–211. [Google Scholar] [CrossRef] [PubMed]
  180. Cakmak, S.; Dales, R.E.; Burnett, R.T.; Judek, S.; Coates, F.; Brook, J.R. Effect of airborne allergens on emergency visits by children for conjunctivitis and rhinitis. Lancet 2002, 359, 947–948. [Google Scholar] [CrossRef]
  181. Dales, R.E.; Cakmak, S.; Judek, S.; Dann, T.; Coates, F.; Brook, J.R.; Burnett, R.T. Influence of outdoor aeroallergens on hospitalization for asthma in Canada. J. Allergy Clin. Immunol. 2004, 113, 303–306. [Google Scholar] [CrossRef] [PubMed]
  182. Tavakoli, H.; Fitzgerald, J.M.; Chen, W.; Lynd, L.; Kendzerska, T.; Aaron, S.; Gershon, A.; Marra, C.; Sadatsafavi, M.; Canadian Respiratory Research Network. Ten-year trends in direct costs of asthma: A population-based study. Allergy 2017, 72, 291–299. [Google Scholar] [CrossRef] [PubMed]
  183. To, T.; Cicutto, L.; Degani, N.; McLimont, S.; Beyene, J. Can a community evidence-based asthma care program improve clinical outcomes? A longitudinal study. Med. Care 2008, 46, 1257–1266. [Google Scholar] [CrossRef] [PubMed]
  184. Canadian Institute for Health Information. Asthma Emergency Department Visits: Volume and Median Length of Stay. 2015. Available online: http://indicatorlibrary.cihi.ca/display/HSPIL/Asthma+Emergency+Department+Visits%3A+Volume+and+Median+Length+of+Stay (accessed on 31 May 2018).
  185. Theriault, L.; Hermus, G.; Goldfarb, D.; Stonebridge, C.; Bounajm, B. Cost Risk Analysis for Chronic Lung Disease in Canada. 2012. Available online: http://www.conferenceboard.ca/e-library/abstract.aspx?did=4585&AspxAutoDetectCookieSupport=1 (accessed on 31 May 2018).
  186. Ariano, R.; Canonica, G.W.; Passalacqua, G. Possible role of climate changes in variations in pollen seasons and allergic sensitizations during 27 years. Ann. Allergy Asthma Immunol. 2010, 104, 215–222. [Google Scholar] [CrossRef] [PubMed]
  187. Intergovernmental Panel on Climate Change. Climate Change 2014 Impacts, Adaptation, and Vulnerability Part A: Global and Sectoral Aspects; Cambridge University Press: New York, NY, USA, 2014.
  188. Ziska, L.H.; Beggs, P.J. Anthropogenic climate change and allergen exposure: The role of plant biology. J. Allergy Clin. Immunol. 2012, 129, 27–32. [Google Scholar] [CrossRef] [PubMed]
  189. Bonofiglio, T.; Orlandi, F.; Ruga, L.; Romano, B.; Fornaciari, M. Climate change impact on the olive pollen season in Mediterranean areas of Italy: Air quality in late spring from an allergenic point of view. Environ. Monit. Assess. 2013, 185, 877–890. [Google Scholar] [CrossRef] [PubMed]
  190. Rice, M.B.; Thurston, G.D.; Balmes, J.R.; Pinkerton, K.E. Climate Change. A Global Threat to Cardiopulmonary Health. Am. J. Respir. Crit. Care Med. 2014, 189, 512–519. [Google Scholar] [CrossRef] [PubMed][Green Version]
  191. D’Amato, G.; Pawankar, R.; Vitale, C.; Lanza, M.; Molino, A.; Stanziola, A.; Vatrella, A.; D’Amato, M. Climate Change and Air Pollution: Effects on Respiratory Allergy. Allergy Asthma Immunol. Res. 2016, 8, 391–395. [Google Scholar] [CrossRef] [PubMed]
  192. Emberlin, J.; Detandt, M.; Gehrig, R.; Jaeger, S.; Nolard, N.; Rantio-Lehtimaki, A. Responses in the start of Betula (birch) pollen seasons to recent changes in spring temperatures across Europe. Int. J. Biometeorol. 2002, 46, 159–170. [Google Scholar] [PubMed]
  193. Stach, A.; Garcia-Mozo, H.; Prieto-Baena, J.C.; Czarnecka-Operacz, M.; Jenerowicz, D.; Silny, W.; Galán, C. Prevalence of Artemisia species pollinosis in western Poland: Impact of climate change on aerobiological trends, 1995–2004. J. Investig. Allergol. Clin. Immunol. 2007, 17, 39–47. [Google Scholar] [PubMed]
  194. Takaro, T.; Henderson, S. Climate change and the new normal for cardiorespiratory disease. Can. Respir. J. 2015, 22, 1–4. [Google Scholar] [CrossRef] [PubMed]
  195. Ahdoot, S.; Pacheco, S.E. Global Climate Change and Children’s Health. Pediatrics, 26 October 2015. Available online: http://pediatrics.aappublications.org/content/early/2015/10/21/peds.2015-3233.abstract (accessed on 31 March 2017).
  196. Ariano, R.; Berra, D.; Chiodini, E.; Ortolani, V.; Cremonte, L.G.; Mazzarello, M.G.; Galdi, E.; Calosso, C.; Ciprandi, G. Ragweed allergy: Pollen count and sensitization and allergy prevalence in two Italian allergy centers. Allergy Rhinol. 2015, 6, 177–183. [Google Scholar] [CrossRef] [PubMed][Green Version]
  197. Taylor, P.E.; Jacobson, K.W.; House, J.M.; Glovsky, M.M. Links between pollen, atopy and the asthma epidemic. Int. Arch. Allergy Immunol. 2007, 144, 162–170. [Google Scholar] [CrossRef] [PubMed]
  198. Shea, K.M.; Truckner, R.T.; Weber, R.W.; Peden, D.B. Climate change and allergic disease. J. Allergy Clin. Immunol. 2008, 122, 443–453. [Google Scholar] [CrossRef] [PubMed]
  199. Singer, B.D.; Ziska, L.H.; Frenz, D.A.; Gebhard, D.E.; Straka, J.G. Increasing Amb a 1 content in common ragweed (Ambrosia artemisiifolia) pollen as a function of rising atmospheric CO2 concentration. Funct. Plant Biol. 2005, 32, 667–670. [Google Scholar] [CrossRef]
  200. Sommer, J.; Plaschke, P.; Poulsen, L.K. Allergic disease—Pollen allergy and climate change. Ugeskr. Laeger 2009, 171, 3184–3187. [Google Scholar] [PubMed]
  201. Lougheed, M.D.; Lemière, C.; Dell, S.D.; Ducharme, F.M.; FitzGerald, J.M.; Leigh, R.; Licskai, C.; Rowe, B.H.; Bowie, D.; Becker, A.; et al. Canadian Thoracic Society Asthma Management Continuum—2010 Consensus Summary for Children Six Years of Age and Over, and Adults. Can. Respir. J. 2010, 17, 15–24. [Google Scholar] [CrossRef] [PubMed]
  202. Johnston, F.H.; Wheeler, A.J.; Williamson, G.J.; Campbell, S.L.; Jones, P.J.; Koolhof, I.S.; Lucani, C.; Cooling, N.B.; Bowman, D.M.J.S. Using smartphone technology to reduce health impacts from atmospheric environmental hazards. Environ. Res. Lett. 2018, 13, 044019. [Google Scholar] [CrossRef][Green Version]
  203. Magnan, A.; Romanet, S.; Vervloet, D. Asthma and allergy. Rev. Prat. 2001, 51, 511–516. [Google Scholar] [PubMed]
  204. D’Amato, G.; Liccardi, G.; D’Amato, M.; Cazzola, M. The role of outdoor air pollution and climatic changes on the rising trends in respiratory allergy. Respir. Med. 2001, 95, 606–611. [Google Scholar] [CrossRef] [PubMed]
  205. Palma-Gomez, S.; Gonzalez-Diaz, S.N.; Arias-Cruz, A.; Macias-Weinmann, A.; Amaro-Vivian, L.E.; Perez-Vanzzini, R.; Gutiérrez-Mujica, J.J.; Yong-Rodríguez, A. Effects of reforestation on tree pollen sensitization in inhabitants of Nuevo Leon, Mexico. Rev. Alerg. Méx. 2014, 61, 162–167. [Google Scholar] [PubMed]
Figure 1. The aerobiology pathway of pollens, adapted from [21].
Figure 1. The aerobiology pathway of pollens, adapted from [21].
Ijerph 15 01577 g001
Figure 2. Floristic zones of North America, from [14].
Figure 2. Floristic zones of North America, from [14].
Ijerph 15 01577 g002
Figure 3. Adverse immune response in the airway, adapted from [158].
Figure 3. Adverse immune response in the airway, adapted from [158].
Ijerph 15 01577 g003
Figure 4. Total Canadian population affected by aeroallergens. This estimation of the total allergic population is based on the conservative estimate that 20% of the Canadian population is affected by allergic rhinitis, and the total population of Canada used in this calculation was based on 2016 data from Statistics Canada [175].
Figure 4. Total Canadian population affected by aeroallergens. This estimation of the total allergic population is based on the conservative estimate that 20% of the Canadian population is affected by allergic rhinitis, and the total population of Canada used in this calculation was based on 2016 data from Statistics Canada [175].
Ijerph 15 01577 g004
Figure 5. Effects of climate change on aeroallergens.
Figure 5. Effects of climate change on aeroallergens.
Ijerph 15 01577 g005
Back to TopTop