This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Temporal and geographic variation in aeroallergen
measurements across four Canadian cities from
2008-2012
by
Cecilia Sierra Heredia
M.A., University of British Columbia, 2004
B. Psych. (Hons.), Universidad Nacional Autónoma de México, 2001
Copyright in this work rests with the author. Please ensure that any reproduction or re-use is done in accordance with the relevant national copyright legislation.
ii
Approval
Name: Cecilia Sierra Heredia
Degree: Master of Science (Health Sciences)
Title: Temporal and geographic variation in aeroallergen measurements across four Canadian cities from 2008-2012
Examining Committee: Chair: Anne-Marie Nicol Associate Professor
Timothy Takaro Senior Supervisor Professor
Ryan Allen Supervisor Associate Professor
Sarah Henderson Supervisor Associate Professor, School of Population and Public Health, University of British Columbia
Robert Schellenberg External Examiner Professor, Faculty of Medicine University of British Columbia
Date Defended/Approved: March 11, 2019
iii
Ethics Statement
iv
Abstract
Fungal spores and pollen from trees, grasses, and weeds are associated with outdoor
environmental allergies in Canada. These aeroallergens typically have a distinct
temporal pattern across geographical regions. This study describes seasonal and
geographic variation in aeroallergens from 2008-2012 in the Canadian cities of
Vancouver, Edmonton, Winnipeg, and Toronto. The study period and study locations
were chosen to characterize the potential aeroallergen exposures of participants in the
Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Seasonal
exposures in Vancouver were the longest for every group of aeroallergens, except
grasses. Vancouver was also the highest for the trees pollen. Total fungal spore
concentrations were higher in Edmonton, Winnipeg, and Toronto than in Vancouver.
The differences recorded in this study across geographical regions may be significant for
the CHILD participants if they lead to distinct and clinically important windows of
exposure for infant immune response and subsequent differential risk of allergenic
Appendix. Allergenic pollen reported by country .............................................. 77
ix
List of Tables
Table 1. List of aeroallergen stations and years of data collection. ....................... 21
Table 2. Family, genus and species analyzed ...................................................... 21
Table 3. Peak values and peak dates for pollen ................................................... 28
Table 4. 5-year mean and range of pollen cumulative concentrations (grains / m3 in hundreds). .......................................................................................... 38
Table 5. 5-year mean and range of pollen season length between cities (number of days). ..................................................................................................... 38
Table 6. Peak values and peak days for spores ................................................... 39
Table 7. 5-year mean and range of spore cumulative concentrations (spores / m3 in hundreds). .......................................................................................... 46
Table 8. 5-year mean and range of spore season length between cities (number of days). ..................................................................................................... 47
x
List of Figures
Figure 1. The aerobiology pathway of pollen ........................................................... 4
Figure 2. Ecological zones of Canada. .................................................................... 7
Figure 3. Adverse immune response in the airway. ................................................. 8
Figure 4. Effects of climate change on aeroallergens ............................................ 17
Figure 5. Location of the four Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort cities and the aeroallergen stations. ....................... 19
Figure 6. Month of birth of the participants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. .................................... 20
Figure 7. Ground coverage at 20km resolution from Landsat satellite data. .......... 27
Figure 8. Weekly pollen concentrations 2008-2012 in Vancouver with Mean and Standard Deviation (SD). ....................................................................... 30
Figure 9. Weekly pollen concentrations 2008-2012 in Edmonton with Mean and Standard Deviation (SD). ....................................................................... 31
Figure 10. Weekly pollen concentrations 2008-2012 in Winnipeg with Mean and Standard Deviation (SD). ....................................................................... 33
Figure 11. Weekly pollen concentrations 2008-2012 in Toronto with Mean and
Standard Deviation (SD). ....................................................................... 34
Figure 12. Weekly aggregates of coniferous and deciduous tree pollen concentrations, average of 2008-2012 in the CHILD cities. .................... 36
Figure 13. Weekly aggregates of grass and weed pollen concentrations, average of 2008-2012 in the CHILD cities. ............................................................... 37
Figure 14. Weekly spore concentrations 2008-2012 in Vancouver with Mean and Standard Deviation (SD). ....................................................................... 41
Figure 15. Weekly spore concentrations 2008-2012 in Edmonton with Mean and Standard Deviation (SD). ....................................................................... 42
Figure 16. Weekly spore concentrations 2008-2012 in Winnipeg with Mean and Standard Deviation (SD). ....................................................................... 43
Figure 17. Weekly spore concentrations 2008-2012 in Toronto with Mean and Standard Deviation (SD). ....................................................................... 44
Figure 18. Weekly aggregates of Ascomycetes, Basydomicetes and Fungi Imperfecti spores concentrations, average of 2008-2012 in the CHILD cities. ........ 46
xi
List of Acronyms
ARL Aerobiology Research Laboratories
CHILD Canadian Healthy Infant Longitudinal Development (birth cohort)
CO2 Carbon Dioxide
ETS Environmental Tobacco Smoke
GST Glutathione-S-Transferase
H2O2 Hydrogen Peroxide
IgE Immunoglobulin E
ILC2 Innate Lymphoid cells 2
iNKT Invariant Natural Killer T Cells
NO2 Nitrogen Dioxide
PM Particulate Matter
SD Standard Deviation
SO2 Sulfur Dioxide
VOCs Volatile Organic Compounds
1
Chapter 1. Introduction
Over the past 70 years, the prevalence of allergic conditions has increased in
high-income countries 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 (1,2). Studies in countries such as Germany (3), Japan (4),
Morocco (5), Hungary (6), Mexico (7), and Australia (8) report rapid increases in the
prevalence of allergic conditions that cannot be explained by genetic changes only (9–
12). Aeroallergens and air pollutants have been hypothesized as potential causes for the
steep increase in allergic conditions, because the nature of these environmental
exposures has changed during a similar time period (13).
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. Common aeroallergens (e.g., pollen or mold spores) and air pollution, such as
particulate matter (PM) or environmental tobacco smoke (ETS); and other environmental
exposures have been associated with increased risk of atopic conditions (14).
Pollen grains and fungal spores are widely dispersed in the air so that the
respiratory system is the first point of contact between the human body and the proteins
they contain (15); therefore, the immune response (adverse immune response) to these
proteins starts in this system (16). Aeroallergens (i.e. pollen grains and fungi) carry non-
infectious proteins, so exposure to aeroallergens is an innocuous event for most
individuals because for them, these proteins do not trigger an infectious disease (17).
For others, however, the exposure to aeroallergens’ proteins triggers an allergic immune
response and the related symptoms. Allergic reactions to aeroallergens represent the
most frequent type I hypersensitivity, affecting up to 30% of the population in high-
income countries (18).
Previous research has indicated that certain pollen grains are highly allergenic
(e.g., ragweed a.k.a. Ambrosia) and exist at relatively high concentrations in some parts
of Canada (19). Spores from fungi are also important aeroallergens that have been
2
linked to allergic reactions (20,21) and in some studies potentially also to the risk of
asthma development (22). This combination of allergenicity and prevalence makes
pollen such as ragweed problematic, because the number of sensitized individuals is
increasing (23). This exposure and the physical symptoms of the immune response have
a direct impact on the everyday lives of patients who develop allergic conditions.
Researchers such as de Weger et al. (16) and von Mutius (24) acknowledge the
diversity of factors that influence the health impacts of aeroallergens and call for better
understanding of extrinsic influences, such as differences in temporal and geographical
patterns, which contribute to the new onset of the allergic conditions associated with
aeroallergen exposures. In this project, I describe the seasonal and geographic patterns
for the most common aeroallergens in four Canadian cities: Vancouver, Edmonton,
Winnipeg and Toronto, between 2008-2012.
3
Chapter 2. Background
2.1. Plant Pollen
Pollen grains are defined as “multinucleate reproductive microgametophytes of
plants” (25, p.2); they function as a container for the male gametophytes of plants (26).
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. However,
this transfer is not easily accomplished and successful pollination involves many steps.
Plants are classified into two categories according to the strategies they use for pollen
transfer (27):
1) Entomophilous plants depend on organisms such as insects or hummingbirds
to carry larger, stickier pollen grains to their receptors.
2) Anemophilous plants release large quantities of pollen grains to be blown in
the wind to their receptors.
When anemophilous plants release pollen, a number of environmental factors
affect when and how many grains reach their final destination (28). Many of these
factors are affected by shifting climatic conditions (29,30). The aerobiology pathway of
pollen illustrates how pollen grains can travel from their source to interact with humans
and potentially affect health (Figure 1).
4
Figure 1. The aerobiology pathway of pollen Adapted from (31).
Because inhalation is the predominant type of exposure for humans, the
respiratory system is the first point of impact for aeroallergens. The exact point of impact
on the respiratory system depends on the size of the inhaled pollen. Pollen size can vary
from less than 10m to more than 100m; pollen grains from trees, weeds or grass or
spores from the fungus Alternaria, that are larger than 5m, deposit in the ocular
conjunctiva and nasal mucosa and have the potential to trigger allergic reactions such as
conjunctivitis or allergic rhinitis (32). Smaller particles (<5m), like spores of moulds
such as Penicillium or Aspergillus (33), can reach the lungs and have been linked to
asthma onset or exacerbation (34).
Because anemophilous plants are present in almost every location inhabited by
humans, humans are exposed to anemophilous pollens and our bodies have the
potential to develop adverse immune responses to those pollen. Currently, more than
150 pollen allergens are curated by the International Union of Immunological Societies
(18). Each geographical region has their own list of pollen of particular interest due to
5
their abundance in the atmosphere (35) and allergenic potency (36), (p.10). In Canada,
birch and grasses are more abundant than ragweed, which is found mostly in Ontario
and Quebec (19).
The concentrations of outdoor aeroallergens are determined by sampling the
outdoor air, and largely based on microscopic examination to identify pollen and spores
based on morphologic pattern recognition (37,38). Because aeroallergens must still be
collected and manually counted, it is currently impossible to offer real-time data using
conventional methods. Furthermore, due to the large amount of resources required for
aeroallergen measurements, it is not yet feasible to routinely make measurements at
high spatial or temporal resolution, although bi-hourly values are occasionally reported in
research (39).
2.2. Fungal Aeroallergens
Fungi are eukaryotic organisms that grow all over the world, in the presence of
moisture and carbohydrates (21,40). Fungi produce spores on maturity, through both
sexual and asexual mechanisms (41,42). The asexual spores produced by mitosis
appear to be the most allergenic (20,21). In addition to molecules on the surfaces of
spores, fungi also secrete enzymes into their environment that can act as allergens in
spores have low mass and can remain suspended in the air for varying periods of time
depending on the weather, with proteins (from their secreted enzymes) in both live and
dead fungi products causing symptoms in humans (15); in some zones of North America
they can be found in the air year-round (44).
Currently, fungi are organized into eight phyla, some of which produce important
aeroallergens, such as Ascomycota, Basidiomycota and Deuteromycetes (previously
labelled Fungi Imperfecti) (21,45,46). Outdoor airborne fungi such as Cladosporium,
Alternaria, Penicillium, and Aspergillus can trigger allergic responses in sensitized
individuals (47) and were traditionally grouped in the taxa of Fungi Imperfecti if they
lacked an obvious sexual stage (21). Advances in the classification of fungi through DNA
sequencing have opened the possibility of reorganizing and relabeling this taxa (as
Zygomycota, (21), but for health-based reporting spore concentrations are still grouped
6
in the traditional three categories: Ascomycota, Basidiomycota and Fungi Imperfecti
(Personal communication, Aerobiology Research Laboratories).
2.3. Canadian Distribution of Plant-Derived Aeroallergens
The environmental factors involved in pollen dispersion, including precipitation,
soil composition and moisture, and average high and low temperature (Figure 1) also
affect the geographical distribution of plant species (19).
A climate-based classification for local climate or ecological zones shows 15
different terrestrial ecozones in Canada (Figure 2); the cities from the Canadian Healthy
Infant Longitudinal Development (CHILD) birth cohort are located in three different
ecozones: Vancouver in the Pacific Maritime, Edmonton and Winnipeg in the Prairies,
and Toronto in the Mixedwood plains. Ecological zones are defined as areas of the
Earth’s surface with uniform cover, structure, material, and human activity. Each zone is
characterized by interactive and adjusting abiotic and biotic factors that span hundreds
of meters to several kilometers in horizontal scale (48,49). Aeroallergens are one of the
biotic factors that characterize each ecological zone. These include (a) a thermal factor,
as a metric for climate-dependent ecological processes involving vegetation, and (b) a
moisture factor, to quantify the wetness of the environment corresponding with the
distribution of natural vegetation (50). The major allergenic plants that grow in each of
the Canadian ecological zones are widely varied.
7
Figure 2. Ecological zones of Canada.
(51)
Local factors can also affect spatial variation within a region (52). Examples of
these are (a) tree canopy, defined as the types of trees planted in the geographical area
of interest (53), and (b) level of urbanization, defined considering street network
coverage and quantity of vegetation (54). The amount of pollen in the air at a particular
location also depends on the proximity to and number of source plants in the area,
atmospheric conditions, and plant physiological factors such as the number of
accumulated degree days (a temperature threshold for that species) at which their pollen
are released (55). Pollen grains can break open to release submicronic pollen-derived
bioaerosols that contain allergenic proteins, particularly when the grains have been aloft
for some time and/or become wet (56–59), especially during thunderstorms. Some
increased exposure to aeroallergens is also due to human activities, such as
landscaping practices, that create niches favoring the growth of weeds such as ragweed
(55).
8
2.4. The Impact of Aeroallergens on Humans:
2.4.1. Immune System
In humans, aeroallergens can lead to both immunosuppression or a heightened
immune response (i.e., allergies) (60), with a biologically appropriate response in the
middle of these extremes (i.e. appropriate recognition and response to harmful
pathogens) (17). Pollen grains carry cytoplasmic granules that release different proteins
and glycoproteins when they are exposed to water or airborne pollutants. These proteins
instigate the adverse immune response in sensitized individuals (Figure 3) (25,61–63).
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 (64).
Figure 3. Adverse immune response in the airway.
Adapted from (65).
Environmental exposures to aeroallergens produce a specific imbalance in the
immune system (66) that triggers the heightened immune response. There are two types
of T helper immune cells (Th1 and Th2) that appear imbalanced in allergic conditions
(67), with a higher proportion of the Th2 cell population (68). The hygiene hypothesis is
also considered as one of the reasons for the specific imbalance in the immune system
9
(69). 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,
vaccines, and antibiotics (70). 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 (71). The initial
exposures to the proteins produce a sensitization to these specific molecules, and
subsequent exposures will trigger symptoms each time (71,72). Allergy symptoms in
response to pollen and fungal spores are driven by IgE that is specific to proteins found
in these spores (73). 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 (74).
2.4.2. Respiratory System
Trees, grasses, and ragweed are the most common allergens associated with
outdoor allergies across Canada (75,76). There is substantial clinical cross-reactivity
between tree and grass allergenic species (76). Additionally, short ragweed is highly
cross-reactive with all other ragweed species, as well as sage and mugwort (75,77–80).
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
(81). For seasonal allergic rhinitis, grass and tree pollen are the most common allergens
(82).
The impact of aeroallergens has been documented in every section of the
airway. 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 (83). The nasal passage 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 (84). Rhinitis
is a risk factor for the development of asthma (82) and allergic rhinitis is most commonly
due to pollen allergy (85). 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 (83,86,87). Sensitization to aeroallergens is a
major contributing factor to this discrepancy (88).
10
2.4.3. Asthma
Among respiratory conditions, asthma is one of the major non-communicable
chronic diseases. Globally, approximately 235 million people currently suffer from
asthma (89). In high-income countries such as Canada, prevalence rose for many years
from the early 1960s to 2000 (29,61) and recently seems to have reached a plateau
(90,91).
Asthma is one of the most severe expressions of an adverse immune response
in the respiratory system (60,92). This condition falls into the category of allergic disease
because it involves the specific IgE-mediated hypersensitivity and the subsequent
inflammatory processes in the airways (93). The hyper-responsiveness of the airways
and subsequent constriction following allergen exposure are distinctive clinical findings
in asthma (94–96). Constriction is due to inflammatory processes and airway
remodeling. The reversibility of the inflammation (over time or by medication) is also
considered in asthma diagnosis (24). 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 (97).
2.5. The Role of Aeroallergens and the Development of Respiratory Disease
2.5.1. The Relationship Between Allergies and Asthma
A link between sensitization to outdoor pollen of local plants has been reported in
many countries between 1990 and 2016 on almost every continent (complete list in
Appendix “Allergenic pollen reported by country”, p. 75). Approximately two-thirds of
people with asthma are allergic to aeroallergens, and these allergens act as triggers for
asthma exacerbations (23). In Canada, approximately 7.7 million were affected by
aeroallergens in 2016 (98), and allergic rhinitis is highly prevalent, affecting
approximately 20–25% of the population (99). Asthma is estimated to affect about three
million Canadians, and between 12% (100) to 25% of Canadian children (101–103).
Asthma is a complex disease that can be understood as a syndrome, because different
pathways can result in diverse phenotypes (24). Several clinical phenotypes of asthma
display differences in severity, inflammatory pattern, and comorbidity with allergic
11
diseases (since not all asthma is atopic) (104). Reversible bronchoconstriction, either
spontaneously or after bronchodilator treatment, remains a common process in all the
phenotypes (97).
In many children with asthma, the appearance of different allergic conditions
follows a sequence that has been labelled the “atopic march” (105). 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 pollen) (11). 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 (106).
Because the first symptoms of the allergic conditions involved in the “atopic
march” often 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” (9) (p. 2231); and (2) that antigens and air components can cross
the placental barrier (107).
In other cases, such as pollen-related later-onset symptoms, allergies and
asthma appear later in life when individuals are exposed to:
- new varieties of pollen through immigration to a new location (108,109), or
through the appearance of botanical species in new geographical zones other
than their native zones (110);
- higher than normal exposures to pollen, including in jobs that require long
periods of contact with plants (111). Occupational allergies and bronchial asthma
have been reported in agricultural populations (112–114), florists (115),
floriculturists (116), carpenters (117) who are in contact with plants such as
saffron (112), ragweed (118) or the Brassica oleracea species (i.e broccoli,
cauliflower), (114).
12
2.5.2. Thresholds of Effect
A critical question for both pollen and fungi allergy is: how much aeroallergen
exposure is needed for an allergic person to develop sensitization, or to exacerbate
existing disease? Most studies of exacerbation have found non-linear responses to
indoor and outdoor allergens, potentially signaling a minimum threshold level
(40,119,120). In addition to a threshold for clinical symptoms, threshold exposure levels
have also been described for the release of biological and inflammatory mediators (121).
The threshold values for fungi spores are generally higher than those for pollen grains,
ranging from ≥100 spores/m3 for Alternaria to ≥3000 spores/m3 for Cladosporium (122–
125); a relevant consideration here is that the proteins in the spores are the active
immunologic agent, not the spore itself, so fragmented molecules might not be counted
but still affect the immunological response in humans due to their proteins.
Although individuals vary widely in their reactivity to allergens, one proposed
threshold for outdoor ragweed levels in the United States was 10 to 20 grains/m3 for a
period of at least 15 minutes (40). During peak ragweed season, daily concentrations in
North America can reach 250 grains/m3, and they remain above 100 grains/m3 for most
of the season (126); likewise, with tree pollen in Ontario, where mean in-season daily
values of 300 grains/m3 were recorded, with daily peaks reaching even higher (127).
Peaks reported for grass are somewhat lower, between 70 and 110 grains/m3 to
precipitate symptoms (128).
2.5.3. The Priming Effect
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 (129). Individuals who are
already experiencing symptoms due to a perennial allergen (dust, pets, etc.) (130) or to
high levels of air pollution (131) 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 other allergens found in the home
environment, such as dust (71,132). The priming effect is relevant to consider when
13
developing pollen warning or forecasting systems in conjunction with existing systems
for outdoor air pollutants. It demonstrates that, for those who suffer from seasonal
allergies, the option to initiate short-term treatment (such as antihistamines or sublingual
immunotherapy) within the first 3–5 days of the season could potentially, 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 priming (133).
2.5.4. Effect Modifiers
The most promising mechanism that explains the development of allergies
involves interactions between individual genetic susceptibility and environmental
exposures (94). For example, gene–environment interactions have been demonstrated
with changes in microRNA (134) and bronchial epithelial DNA methylation, after
exposures to diesel exhaust (135). For individuals with atopy-prone or immune
modulated genotypes, environmental exposures play a role in the onset of an allergic
disorder (136), including exposures to aeroallergens (137,138). However, the
environmental effect may be either detrimental or protective: Tovey et al. (120) 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.
In the study of the development of health conditions in humans, an environmental
exposure can be considered as a protective factor if it is linked to decreased risk of the
development of a specific condition (136). Early exposure to animals and breastfeeding
are linked to decreased risk for the development of allergies to pollen and spores. To
consider an environmental component as a risk factor, it is necessary to demonstrate
that increased exposure to it is associated to an increase in the incidence of atopy (139).
Interactions between pollen and other environmental conditions such as weather,
seasons, urban environments and high concentrations of air pollution have been studied
and linked to increased risk for the development of an allergic condition. The interactions
between these environmental conditions and aeroallergens also happen at the
atmospheric level and could impact aeroallergen concentration. In this way, the
environmental conditions could be understood as effect modifiers: “a variable that
modifies the effect of the exposure of interest… through an interaction between the
14
effect modifier and the exposure.” (p.212) (140). These effect modifiers are described in
the following sections:
Effect Modifier: 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 (52,141). 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, and release them when a sufficient number of warm days
occur in the following spring (52,141).
Diurnal changes in pollen levels have also been observed. Because ragweed
pollen is released in the morning, peak concentrations are reached around noon in the
absence of high winds or rain (142). Depending on the temperature, humidity, and wind
conditions, the counts may drop at night or remain elevated (40,143). 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 (142).
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 (40,142).
Thunderstorms can be associated with asthma exacerbations, with steep
increases in the use of emergency services and increased mortality (144–146).
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 (90). Climate change has been linked to an
increase in frequency of thunderstorms in some areas (147).
Effect Modifier: 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 (61), and all have been associated with allergic respiratory morbidity (148–
15
150) and mortality (151,152). There is some indication of an association between
season of birth on the development of asthma and allergies (153). 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 (154–156).
Effect Modifier: 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 (61,157). There is
evidence that highly allergenic species of fungi are present at higher levels in the
outdoor air in cities compared with rural environments (158). Differences between
aeroallergen counts (higher in 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 (159). Additionally, the higher levels of air pollutants in urban areas
can interact with airborne pollen grains, which is likely to exacerbate allergic conditions
and respiratory distress (61). Two thirds of the global population will live in urban areas
by 2020, and an increased risk for aeroallergen-induced respiratory allergy is expected
(147).
Effect Modifier: Air Pollution
Population based studies support the hypothesis that air pollution contributes to
the etiology of respiratory allergies (160,161). Epidemiological and clinical research
have documented the chronic, adverse effects of air pollution on the pulmonary
development of children and also the relevance of the timing of exposure for the
development of asthma (162,163).
The interactions between air pollution and aeroallergens are complex and occur
both in the atmosphere and in the airways (161). Ziska et al. (164) 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 their surfaces and can alter their allergenic potential
and morphology by making the surface coating more fragile (61,165,166). Co-
occurrence of exposure is important, and the simultaneous release of pollen grains
16
and/or fungal spores and increased air pollution episodes appears to be the most
harmful in terms of increased allergenicity (167–170).
In the airway, oxidative stress has been identified as a major biologic pathway for
the effects of most of the air pollutants (171,172). Air pollutants allow for easier
penetration of pollen and spore allergens because they trigger damage to the airway
mucociliary clearance mechanisms (61,161). Particulate matter smaller than 2.5 μm
(PM2.5) reaches deeply in the lungs and acts as an adjuvant that increases production of
IgE (134,173,174). Furthermore, exposure to diesel exhaust is known to impact DNA
methylation and impaired regulatory T-cell functions, two mechanisms relevant for the
immune response (135). Decrements in lung function (measured through changes in
FEV1) following allergen exposure and controlled diesel exhaust exposure have also
been modified by the presence of the GST genotype, in a gene–environment interaction
manner (174).
2.6. Effects of Climate Change on Aeroallergens
In addition to its negative effects on human health, air pollution also shapes the
anthropogenic climate change that has been documented for several decades (175).
Atmospheric concentrations of greenhouse gases (GHG) have contributed to increasing
global temperatures, and it has been acknowledged that further increases are inevitable
(REF). Drawing on over 29,000 longitudinal data sets, the findings from an international
group of experts show that human-led activities have contributed to a global increase in
temperature and other long-term shifts in weather conditions (176–178).
Climate-related changes in the local ecosystems will present specific threats for
their human populations (179). Among the areas of human life affected by climate
change, health is prominent. The incidence, range, and seasonality of many existing
disorders will certainly be altered due to fluctuations in the average climate conditions,
the climatic variability, and other noninfectious drivers of health (180,181). Levels of
some specific aeroallergens are on the rise in particular regions (182), and some of this
increase has been linked to anthropogenic climate change (183). The increasing
planetary temperatures affect plant biology through the timing and length of the growing
seasons (184), increased production and allergenicity of pollen, and shifts in range of
species (Figure 4) (183,185).
17
Figure 4. Effects of climate change on aeroallergens
Due to the warmer temperatures, pollen seasons will start earlier and end later
(25,157,186,187). Warming by latitude has been associated with longer ragweed pollen
seasons in North America, increasing by 27 days between 1995 and 2009 (171). Earlier
seasonal starts have also been found for Juniperus, Ulmus, and Morus (110). In
Western Europe, spring events have advanced by six days (187) and changes in birch
pollen season (188) and Artemisia have been described (189). Changes in season
length will lead to changes in human exposure (190) and also in sensitization and
symptoms of allergic conditions (137,185,191).
Increased pollen counts have been associated with the current levels of CO2,
when compared with CO2 levels of the previous century (192) or even between different
decades (2004 and 2013) (183,193). Increases in the atmospheric concentrations of
CO2 impact the reproductive processes in plants, leading them to produce more pollen
(8,194,195) with significantly stronger allergenicity (110,189,196). This increased
allergenicity is due to more diversity in the heterogeneity of the antigenic proteins in
pollen grains (32).
Climate change affects many meteorological variables that participate in the
dispersal and deposition of aeroallergens (i.e., humidity, precipitation, and temperature)
(147). Changes in dispersion, both region- and species-specific, can potentially expose
18
(and sensitize) populations to novel allergens (161). These changes will also impact
plant distribution, as species that could not survive in previously hostile environments
can potentially thrive in changing temperature and precipitation regimes (189).
Alternatively, native species or species with limited adaptive capacity might not survive
the hotter and drier conditions forecasted (177). The proliferation of anemophilous plants
where those species were not previously prevalent exposes atopy-prone individuals to
new pollens (197).
2.7. Knowledge Gaps and Challenges
With the documented changes over time in environmental factors, it is expected
that pollen concentrations in different locations within Canada will display differences in
temporal and geographical patterns. More research is needed in order to understand
these differences (171) and to contribute to better understanding of basic environment-
health associations (198). The Canadian Healthy Infant Longitudinal Development
(CHILD) birth cohort aims to increase our understanding of the environment-health
interactions that occur during the prenatal and early childhood windows of development
for allergic conditions (199). In this study, I describe the temporal and geographic
variations for the most common aeroallergens (1) during the years in which the CHILD
participants were born (i.e. 2008-2012) and (2) in the four cities where they live:
Vancouver, Edmonton, Winnipeg and Toronto. The exposure data will support
subsequent epidemiologic analyses of allergic disease outcomes.
19
Chapter 3. Methods
3.1. Study Setting
I used pollen and spore concentration data collected in the four CHILD cities,
from 2008 through 2012 (Figure 5). These cities are located in different ecological zones
in Canada: Vancouver is in the Pacific Maritime, Edmonton and Winnipeg are in the
Prairies, and Toronto is in the Mixedwood plains.
Figure 5. Location of the four Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort cities and the aeroallergen stations.
Aeroallergen stations: One station in Edmonton and Toronto, and two stations in Vancouver (one active in 2008 and 2009 and a second active from 2010 through 2012) and Winnipeg (one active in 2011 and a second active from 2008 through 2010 and 2012).
20
3.2. Data Collection
I obtained and analyzed data collected between January 1, 2008 and December
31, 2012 during the period of pregnancies and deliveries in the CHILD birth cohort
(Figure 6).
Figure 6. Month of birth of the participants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort.
Pollen and fungi concentrations were measured by Aerobiology Research
Laboratories (ARL) at one station in Edmonton and Toronto and at two stations in
Vancouver (one for 2008 and 2009 and a second for 2010 through 2012) and Winnipeg
(one for 2011 and a second for 2008 through 2010 and 2012; Figure 5 and Table 1).
Aeroallergen samplers are located in neighborhoods that have been identified by ARL to
be representative of the biota in an approximate 50-mile (80 km) radius (Personal
communication, ARL May 2018). Samplers are located at approximately 6-7 feet above
the ground, a height chosen to be representative of human breathing zones (127). All
samplers are located away from structures and as far away as possible from the local
21
trees in order to allow atmospheric mixing to make the collections more representative of
the flora present in the location (137). Private residences are often used for the
collection stations where the samplers are installed so the exact coordinates are
confidential.
Rotation impaction samplers (Model GRIPST 2009) were used to collect pollen
grains and fungal spores. These samplers are considered suitable for the collection of
pollen and spores as small as 2-3m (200). Sampling was conducted on a 10% duty
cycle over each 24-hr period (Personal communication, ARL). Pollen grains and fungal
spores: (1) adhered to the silicon grease-coated sample rods of the samplers, (2) were
identified by trained palynologists with microscopic morphology, (3) grouped according
to taxa, and (4) counted to establish the number of particles per cubic meter of air
sampled.
Table 1. List of aeroallergen stations and years of data collection.
Station Province Years
E Vancouver BC 2008 - 2009
W Vancouver BC 2010-2012
Edmonton AB 2008-2012
N Winnipeg MB 2008-2010, 2012
S Winnipeg MB 2011
Toronto ON 2008-2012
Pollen season is defined as the days in which pollen is measurable in the air
(201). Daily aeroallergen concentrations for each taxon were collected by ARL after
measurable counts of pollen were recorded for five consecutive days and until
measurable pollen counts were not recorded for five consecutive days (131). The peak
value was defined as the maximum concentration in each year, and the date when that
concentration was reached was defined as peak date (202). Each specie of pollen grains
and fungal spores was grouped in a genus and a family (Table 2).
Because of the diversity in specific allergenic plants that grow in each floristic
zone in Canada, I analyzed pollen and spores by taxa in order to have adequate
concentrations and variation. For example, a preliminary analysis of a single genus
(Ragweed, Ambrosia) showed high levels in some cities (Toronto and Winnipeg) and
extremely low levels in others (Vancouver and Edmonton), prohibiting the comparative
analysis of this genus in all four cities. Spores considered highly allergenic such as
Alternaria, Aspergillus and Cladosporium were grouped by ARL in the taxa of Fungi
Imperfecti. The analysis was done with the following categories: Deciduous trees pollen,
Coniferous trees pollen, Weeds pollen, Grasses pollen; and Ascomycetes,
Basydiomicetes and Fungi Imperfecti spores (Table 2).
The data manipulation and descriptive statistical analyses were performed in R
(203) and RStudio (Version 1.0.143) using the plyr (204), broom (205), dplyr (206),
ggplot2 (207), zoo (208), and lubridate (209) packages.
When data were missing for periods of less than four days, I used the R package
zoo (208) to interpolate the missing data with the approx function. This function uses
linear interpolation with the contiguous existing values to fill in the missing data. In
Vancouver, Edmonton, Winnipeg and Toronto I interpolated 11, 10, 56, and 10 days of
non-consecutive data, respectively. Winnipeg has two long periods of 16 days and nine
consecutive days during which samples were not readable or the sampler
malfunctioned. Data were not interpolated for those two time periods.
I used satellite images from Landsat 5 and Landsat 7 to visualize seasonal
variations in vegetation in the 20 km surrounding the pollen measurement stations in
each city. Landsat images are space-based moderate-resolution land remote sensing
data, collected by the U.S. Geological Survey (USGS) and the National Aeronautics and
Space Administration (NASA) (210). Landsat images are considered useful for capturing
seasonal and annual changes in vegetation type that alter pollen production (211). A
figure displaying Landsat imagery for 20km around the monitoring locations throughout
the year was included in order to show the differences in greenness between the cities
going through the seasons (Figure 7).
25
Descriptive statistics were calculated for both within-station (seasonal) and
between-station (geographical) differences, data were expressed as: average
cumulative concentrations (and minimum and maximum values for the five-year period,
tables 4 and 7); average number of days in the season (also with minimum and
maximum values for the five-year period, tables 5 and 8); and peak values and dates
(Tables 3 and 6). Cumulative concentrations were chosen in order to reflect both the
level of grains and spores and the seasons length. Within-station differences were
described with one graph per city that displayed the weekly aggregates of the daily
concentrations, as well as the mean and standard deviation, for each taxon for pollen
(figures 8-11) and spores (figures 14-17) per year.
Between-station differences were described with a plot that grouped the four
cities and displayed the average of the five-years weekly aggregates for: 1) the
coniferous and deciduous pollen (figure 12), 2) the grass and weeds pollen (figure 13)
and 3) the spore taxa (figure 18). Further details were provided for:
1) Cumulative concentrations: Average and range for the five years in each city
is listed separately for pollen (table 4) and spore taxa (table 7).
2) Season length: Average and range for the five years in each city is listed
separately for pollen (table 5) and spores taxa (table 8).
With the data provided by ARL, which had one start and end date for all the taxa,
I used two definitions of the aeroallergen seasons for each taxa, which yielded different
season lengths (Tables 5 and 8):
a) the period between the days when the 5% and the 95% of the total pollen
was collected, and
b) the period between the days when the 1% and the 99% of the total pollen
was collected.
26
Chapter 4. Results
Consistent with the more moderate climates, Vancouver had a longer season for
every group of pollen but grass, where Toronto had the longest season. Toronto also
had the second longest season for weeds, deciduous and coniferous pollen (Table 5).
Vancouver had the highest average values for the cumulative concentrations for
coniferous and deciduous trees, with over ten times more than Edmonton for coniferous
pollen (Table 4).
The distinctive patterns of the seasons lengths for the aeroallergens studied for
each city are consistent with the differences in greenness and snow coverage observed
in the Landsat images of the four participant cities (Figure 7), and to the ecological
zones where each city is located (Figure 5).
27
Figure 7. Ground coverage at 20km resolution from Landsat satellite data. Jagged edges mark the edge of the image from the satellite. Approximate location of the aeroallergen samplers is depicted with red dots: One station in Edmonton and Toronto, and two stations in Vancouver (one active during 2008 and 2009 and one active for 2010 through 2012) and Winnipeg (one active during 2011 and a second active from 2008 through 2010 and 2012).
28
4.1. Within-Station Differences for Pollen
The pollen levels for coniferous and deciduous trees, grasses, and weeds
showed yearly variations in the four cities and peak concentrations were highly varied
across the time periods studied (Figures 8-11, Table 3).
Table 3. Peak values and peak dates for pollen
Vancouver
Coniferous Deciduous Grass Weeds
Date: 2008 February 25 March 6 June 12 August 3
grains / m3 1104 591 54 40
Date: 2009 April 21 March 20 June 13 June 04
grains / m3 3427 1721 70 28
Date: 2010 February 23 March 1st July 7 May 24
grains / m3 1305 4509 81 23
Date: 2011 March 10 March 24 June 21 June 8
grains / m3 1006 5155 96 48
Date: 2012 March 3 March 23 June 20 July 1
grains / m3 1254 3060 96 19
Edmonton
Coniferous Deciduous Grass Weeds
Date: 2008 May 31 May 15 July 12 July 11
grains / m3 149 533 312 129
Date: 2009 June 17 May 5 July 21 August 29
grains / m3 435 1096 74 108
Date: 2010 June 28 April 21 July 18 July 31
grains / m3 96 616 64 100
Date: 2011 June 28 May 09 July 15 July 20
grains / m3 257 319 286 240
Date: 2012 July 8 May 4 June 21 July 14
grains / m3 131 503 235 58
Winnipeg
Coniferous Deciduous Grass Weeds
Date: 2008 June 10 May 23 June 9 August 30
grains / m3 597 1117 249 250
Date: 2009 June 15 May 6 June 24 September 2
grains / m3 910 748 108 155
Date: 2010 May 22 April 19 July 3 August 22
grains / m3 997 2724 54 218
Date: 2011 April 24 May 20 June 18 August 12
grains / m3 794 2355 140 126
Date: 2012 March 18 March 31 June 3 August 23
grains / m3 274 858 30 99
29
Toronto
Coniferous Deciduous Grass Weeds
Date: 2008 April 20 April 20 June 7 August 31
grains / m3 388 1426 110 244
Date: 2009 June 24 April 25 June 22 August 21
grains / m3 395 902 44 126
Date: 2010 March 25 April 3 May 30 September 1
grains / m3 320 1296 86 300
Date: 2011 April 12 May 12 June 8 September 2
grains / m3 1470 1624 70 133
Date: 2012 March 22 March 22 May 25 August 31
grains / m3 129 720 55 209
In Vancouver, coniferous trees and deciduous trees showed similar values for
the five-year mean of the cumulative concentrations (21026 and 21830 grains / m3,
respectively, Table 4) and these were the highest concentrations for the pollen taxa in
this city; however, the season length for coniferous trees was longer (98 days for the 5-
95% values and 151 days for the 1-99% values, Table 5) than for deciduous trees (58
days for the 5-95% values and 96 days for the 1-99% values, table 5. Both coniferous
and deciduous trees concentrations reached peak values before May (Figure 8),
although only the concentrations for coniferous trees display two peaks each year (with
the second before July).
For grass pollen, the five-year mean of the cumulative concentrations was 1497
grains / m3 (Table 4). Season length for grass pollen lasted on average 75 days (for the
5-95% values) and 124 days (for the 1-99% values, Table 5). Grass pollen
concentrations reached peak values later in the year (between June and July) compared
with the trees pollen (Figure 8, Table 3).
Weeds pollen had a five-year mean of the cumulative concentrations of 821
grains / m3 (Table 4), the lowest values of all the pollen taxa for Vancouver. Season
length for weeds pollen lasted on average 103 days (for the 5-95% definition) and 130
days (for the 1-99% definition, Table 5). The months for peak values for weeds pollen
concentration are between May and August (Figure 8, Table 3).
30
Figure 8. Weekly pollen concentrations 2008-2012 in Vancouver with Mean and Standard Deviation (SD).
In Edmonton, the five-year mean of the cumulative concentrations of coniferous
trees pollen was 2024 grains / m3 (Table 4), deciduous trees pollen had the highest
cumulative concentrations of all pollen taxa in this city (5330 grains / m3, Table 3).
Season length for coniferous trees was longer (57 days for the 5-95% definition and 95
days for the 1-99% definition, Table 5) than for deciduous trees (39 days for the 5-95%
definition and 64 days for the 1-99% definition, Table 5). In each year of the period
analyzed (2008-2012), coniferous trees pollen concentrations reached peak values
between June and July (with some peaks happening as early as late May); deciduous
trees pollen concentrations reached peak values earlier in the year, between late April
and May (Figure 9, Table 3).
For grass pollen, the five-year mean of the cumulative concentrations in
Edmonton was 1523 grains / m3 (Table 4). Season length for grass pollen lasted on
average 54 days (for the 5-95% values) and 101 days (for the 1-99% values, this is the
longest season for this city, Table 5). Grass pollen concentrations reached peak values
31
later in the year (in July, almost every year) compared with the deciduous trees peaks
(Figure 9, Table 3).
Weeds pollen had a five-year mean of the cumulative concentrations of 1431
grains / m3 (Table 4), the lowest values of all the pollen taxa for Edmonton. Season
length for weeds pollen lasted on average 65 days (for the 5-95% values this is the
longest season for this city) and 95 days (for the 1-99% values, Table 5). Peak values
for weeds pollen concentration were reached in July most years and August (in 2009,
Figure 9, Table 3).
Figure 9. Weekly pollen concentrations 2008-2012 in Edmonton with Mean and Standard Deviation (SD).
In Winnipeg, coniferous trees showed lower values for the five-year mean of the
cumulative concentrations than deciduous trees (3228 and 13628 grains / m3,
respectively, table 4), deciduous trees had the highest cumulative concentrations of all
the pollen taxa in this city. The season length for coniferous trees was longer (66 days
for the 5-95% definition and 90 days for the 1-99% definition, Table 5) than for
32
deciduous trees (45 days for the 5-95% definition and 55 days for the 1-99% definition,
table 5), which was the shortest pollen season for all the pollen taxa in this city.
Coniferous trees concentrations reached peak values between March and early June
(Figure 10, Table 3), with three years (2008, 2011 and 2012) displaying two peaks each
year. Deciduous trees concentrations reached peak values between late March and May
(Figure 10, Table 3).
For grass pollen, the five-year mean of the cumulative concentrations was 1564
grains / m3 (Table 4), the lowest values of all the pollen taxa for Winnipeg. Season length
for grass pollen lasted on average 71 days (for the 5-95% values) and 115 days (for the
1-99% values, Table 5). Grass pollen concentrations reached peak values later in the
year (between June and July) compared with the trees pollen (Figure 10, Table 3).
Weeds pollen had a five-year mean of the cumulative concentrations of 2912
grains / m3 (Table 4). Season length for weeds pollen lasted on average 72 days (for the
5-95% values) and 100 (for the 1-99% values, Table 5). Peak values for weeds pollen
concentration were reached in August and early September (Figure 10, Table 3).
33
Figure 10. Weekly pollen concentrations 2008-2012 in Winnipeg with Mean and Standard Deviation (SD).
In Toronto, coniferous trees showed much lower values for the five-year mean of
the cumulative concentrations compared with the deciduous trees (3600 and 13056
grains / m3, respectively, Table 4); however, the average season length for coniferous
trees was longer (82 days for the 5-95% definition and 130 days for the 1-99% definition,
Table 5) than for deciduous trees (56 days for the 5-95% definition and 74 days for the
1-99% definition, Table 5). Coniferous trees concentrations reached peak values
between late March and June (Figure 11, Table 3) and displayed two peaks each year.
Deciduous trees concentrations displayed peak values between late March and May and
did not have two peaks (Figure 11, Table 3).
For grass pollen, the five-year mean of the cumulative concentrations was 991
grains / m3 (Table 4), the lowest values of all the pollen taxa for Toronto. Season length
for grass pollen lasted on average 107 days (for the 5-95% values) and 141 days (for the
1-99% values, Table 5), the longest season length for all the pollen taxa in Toronto.
Grass pollen concentrations reached peak values later in the year (between June and
34
July, sometimes as early as late May) compared with the deciduous trees pollen (Figure
11, Table 3).
Weeds pollen had a five-year mean of the cumulative concentrations of 3138
grains / m3 (Table 4). Season length for weeds pollen lasted on average 90 days (for the
5-95% values) and 126 (for the 1-99% values, Table 5). Weeds pollen concentration
displayed two peak values, a small one between June and July (with values under 50
grains per m3), and a higher one (with values between 50 and 150 grains / m3) in August
(Figure 11, Table 3).
Figure 11. Weekly pollen concentrations 2008-2012 in Toronto with Mean and Standard Deviation (SD).
35
4.2. Between-Station Differences for Pollen
Weekly aggregates for 2008-2012 showed that Vancouver had the highest peaks
for coniferous trees and for deciduous trees, with peak values in Vancouver (3427 grains
/ m3) being 2-4 times higher than those in the other cities (435, 997, 1470 for Edmonton,
Winnipeg and Toronto, respectively, Figure 12, Table 3). Coniferous trees showed
consistent earlier starts in Vancouver (between February 14 and March 7 for the 5-95%
definition and February 10 and March 2 for the 1-99% definition) than in Edmonton (April
18 and May 27 for the 5-95% definition, and April 2 and April 27 for the 1-99%
definition), Winnipeg (March 18, April 24 for the 5-95% definition, and March 16, April 19
for the 1-99% definition), and Toronto (March 15, April 10, for the 5-95% definition, and
March 5 and April 1 for the 1-99% definition, Figure 12, Table 5). Coniferous trees, in
particular, showed more than one peak in each year in all the cities; the separate peaks
could indicate different species reaching their peak concentration at different times.
Deciduous trees showed consistent earlier starts and peaks in Vancouver
(between February 6 and March 13 for the 5-95% definition and January 30 and March 3
for the 1-99% definition) than in Edmonton (April 9 and April 26 for the 5-95% definition,
and March 28 and April 22 for the 1-99% definition), Winnipeg (March 22, April 27 for the
5-95% definition, and March 18, April 24 for the 1-99% definition) and Toronto (March
17, April 16, for the 5-95% definition, and March 13 and April 7 for the 1-99% definition,
Figure 12, Table 5).
36
Figure 12. Weekly aggregates of coniferous and deciduous tree pollen concentrations, average of 2008-2012 in the CHILD cities.
Grass pollen peaked consistently between June and August in most of the years
assessed (with the exceptions of 2008 and 2010-2012 in Toronto and 2012 year in
Vancouver, Table 3). For grasses, longer seasons were often accompanied by higher
peaks. Edmonton had the highest peak concentrations for grass pollen (312 grains / m3)
compared to the other three cities (96 grains / m3, 249 grains / m3, 110 grains / m3, for
Vancouver, Winnipeg and Toronto, respectively, Table 3) and all four cities were above
100 grains / m3, a threshold for clinical response in adults (Lebel et al., 1988). Winnipeg
showed the highest values for weed pollen (250 grains / m3) and the second highest for
grass pollen. Toronto had the second highest values for weed pollen (Figure 13, Table
3).
Weed pollen had an earlier season start in Vancouver during the five years
studied (between May 19 and June 5 for the 5-95% definition and May 9 and May 23 for
the 1-99% definition) than in Edmonton (July 1 and July 12 for the 5-95% definition, and
June 15 and July 6 for the 1-99% definition), Winnipeg (June 26, July 9 for the 5-95%
37
definition, and June 14, June 28 for the 1-99% definition) and Toronto (June 15, June
26, for the 5-95% definition, and May 26 and June 14 for the 1-99% definition, Figure
12). Edmonton and Winnipeg had their weed pollen season during the third quarter of
the year (Figure 13). Toronto displayed two peaks, with different concentrations, both
within the second and third quarter of the year, potentially indicating two separate genus
peaking at different times (Figure 13).
Figure 13. Weekly aggregates of grass and weed pollen concentrations, average of 2008-2012 in the CHILD cities.
38
Table 4. 5-year mean and range of pollen cumulative concentrations (grains /
Our findings point to unique aeroallergen season lengths in each city, with
similarities in the cities located within the same ecological zone (i.e. Edmonton and
Winnipeg). There are some distinctive features that are worth highlighting such as the
fact that Vancouver had the longest season for tree and weed pollen, as well as for all
the spore taxa. Toronto had the longest season for grass pollen and the second longest
season for trees and weed pollen, as well as for the fungi spores. The cumulative
concentration of aeroallergens also displayed unique distributions, with Vancouver
recording the highest concentrations for Ascomycetes, Basidiomycetes, Fungi
Imperfecti, coniferous and deciduous trees and Toronto for weed pollen. Local abiotic
factors (i.e. temperature, topography or precipitation) that affect the temporal and spatial
variation in each region are likely responsible for the particular season lengths and
aeroallergen levels (biotic elements) in the three different ecological zones where the
four CHILD cities are located (52).
Concentration and season length are important determinants of human exposure
to aeroallergens (161), along with the species present in the environment. The
differences recorded in our study, in exposure and season length, and across
geographical regions may be significant if, along with other factors, they lead to different,
clinically important, windows of exposure for infant immune response for the CHILD
participants. Although the thresholds of aeroallergen exposure for asthma exacerbations
and for asthma development are likely to be different, it is important to consider what
levels of pollen and fungal spore exposure contribute to aeroallergen sensitization that
increases the risk of asthma and allergy in childhood (161,212). The peaks shown in our
graphs point to specific points in time when thresholds may have been crossed and
participants of the CHILD study were exposed to high concentrations during suspected
windows of immune system development. The season’s length and cumulative
concentration for each one of the aeroallergens studied have created unique patterns of
exposure for the participants from the each one of the cities in the CHILD study.
Because sensitization to aeroallergens is related to long-term exposure (213), and the
participants have been exposed to different amounts of each aeroallergen during
different periods in a sensitive developmental stage of their lives (i.e. in utero), this
environmental exposure might affect a) the incidence of atopic conditions in each city
49
and b) the specific aeroallergens that the participants are sensitized to. The exposure to
aeroallergens will interact with the genetic backgrounds of exposed individuals (94) and
with other relevant exposures such as pets (214) or air pollution (173), which is likely to
modify the risk for the development of allergic diseases.
5.1. Limitations
There are several limitations of this study. Earlier starts and longer pollen
seasons are attributed to overall higher temperatures observed with climate change
(171,175), and increased pollen counts (184). One limitation for our study is that there
were too few years in our analyses to enable exploration of the potential effects of
climate change in these Canadian cities. In some Canadian cities, data have been
collected by ARL for over 20 years. The analysis of long-term data trends using these
datasets will increase our understanding of the effects of climate change on
aeroallergens, and on the impact of these changes on the development of atopic
conditions and its exacerbations.
A second limitation was the fact that, during each year studied, the available data
came from only one station per city. The paucity of spatial information meant I could not
assess within-city exposure variation or explore the correlation of data collected at
different sites during the same period of time. Unfortunately, most cities in Canada
currently have only one active station. Increasing the number of monitoring sites that
collect data continuously has been highlighted as important for both practical and
mechanistic research in this area (161). Efforts to apply land use regression models for
aeroallergen exposure are promising (53,215) and would also require simultaneous
collection of data from multiple stations in each city, for validation. Previous studies (200)
compared daily concentrations in two sites (Toronto and Brampton) separated at a
similar distance as the stations for Winnipeg and Vancouver (approximately 15km in
each city), over a period of ten years, also by ARL. Brubacher et al (200) calculated the
Pearson’s correlation between the two datasets; their findings show correlations higher
than .70 for pollens and .60 for spores, which points to moderately correlated timing of
pollination periods between the two sites. In Vancouver and Winnipeg, two different
collection stations were used during the time period studies; based on Brubacher et al
(200) results, similar moderate correlations between the data collected in the different
stations within each city, could be expected in this study.
50
The definition of the pollen season is another limitation for our study. The criteria
to start the sampling period inevitably leads to some seasons where the collection
clearly begins after the season has started giving an arbitrary nature to the date (131)
(p.229). Data for all the aeroallergens were collected during the same period of time in
each city, no individual definition of the start and end of the season was considered;
therefore, in some cases our graphs show rising concentrations at the very beginning of
the season which creates some error due to underestimation into season length
calculations.
5.2. Strengths
To our knowledge, this is the first study that provides a description of the
aeroallergen concentrations and seasons lengths in four Canadian cities with the
differences in greenness observed through the Landsat images to this description; this is
a significant contribution to the understanding of the aeroallergens temporal and
geographical patterns. Differences in concentrations of pollen were representative of the
differences in the greenness and in the three ecological zones of the four cities, as it has
been reported to happen with pollen concentrations and phytogeographical and climatic
maps of a country (216). Even when the selection of sites does not represent all the
ecological zones within this country, our findings regarding season length and
concentration of aeroallergens can be useful to allergists and atopic individuals
(202).Ariano et al (193) and Fuertes et al. (217) reported the use of different
geographical locations for studies of pollen concentrations in Italy and Germany
respectively, and Emberlin et al (188) found significant regional contrasts with their six
bio geographical situations chosen in Europe. In Canada, Coates & Jurgens (218) used
pollen concentrations exclusively and found differences in key events of the pollen
season, such as the start and end dates (by up to a month in 30 sites), and also
significant variance on the pollen season from year to year, making the case for
continued data collection to monitor and analyze said variance.
One strength of this study is that, in line with the current standards
(193,219,220), the pollen concentrations collected were the daily average concentrations
from 0 to 24 hours. With the daily data points, I calculated the weekly aggregates and
seasons lengths for each taxon. This level of detail enables observation of the
thresholds and windows of exposure to specific concentrations of known clinical
51
relevance. Our description of aeroallergen seasons follows McInnes et al (221)
recommendation to consider the timing of pollen release when analyzing the impact of
pollen grains on human health. The detailed descriptions presented in this paper will
constitute the basis to calculate exposure of CHILD participants and further improve our
models to assess the relevance of early exposure to aeroallergens as risk factors for the
development of sensitization and atopic conditions. Studies of pollen diversity provide
useful information regarding atopic conditions (222) and in Canada, some have linked
changes in pollen and fungal concentrations with asthma morbidity (223,224),
conjunctivitis and rhinitis (137,225) and even with earlier delivery among term births
(220).
The use of remote sensing imagery is another strength of this study. Remote
sensing imagery, such as the images captured by Landsat satellites, is considered
accurate at providing estimates of the seasonal changes and location of different pollen
sources (226), vegetation coverage (227) and land-use type (228); it is also considered
the primary tool for monitoring changes in vegetation activity (i.e. Floristic pollen
production and season length) (229). Data from remote sensing imagery has been
analyzed in connection to health outcomes such as allergic outcomes in children, with
closer proximity to greenness considered as having a greater aeroallergen exposure
(217). Future projects could use images from Landsat satellites or other data to identify
vegetation types (229) or land-use (228) if such images with higher resolution become
available for the years and cities studied in this project.
5.3. Recommendations
Better understanding of both pollen and fungi concentrations, phenology,
geographic coverage, and interaction with air pollutants is needed to provide the
information that atopic individuals could use to modify their environmental exposures
(147); it is also needed, to understand the public health impacts of these exposures now
and into the future. The available methods for data collection on aeroallergens already
produce large amounts of information; however, many challenges remain and should be
addressed in order to provide a more accurate picture. One of these challenges is the
fact that fractured grains or spores are not regularly counted in the taxon concentrations;
however, when inhaled, they are still capable of triggering an immune response, due to
their allergenic proteins. While existing technology is not yet capable of addressing this
52
challenge or even of quantifying the likely magnitude of this undeterminable particles,
future developments in profiling with genetic or molecular analysis could provide the
solution. Additionally, the limitations described in the discussion also point to the need
for: (a) a long-term collection plan; (b) an increased number of monitoring stations per
city; (c) continuous aeroallergen collection throughout the year; (d) open access to
historical and current aerobiological data worldwide.
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 pollen and fungi and the other biotic and abiotic factors that shape the
environmental exposures in urban areas (28). Climate change has the potential to
increase the length of aeroallergen seasons as well as pollen counts, geographical
coverage, and allergenicity (29). These escalations will also increase human exposure to
the allergenic proteins found in pollen grains and fungal spores (25,189). Future
increases in the incidence and prevalence of respiratory allergies and asthma are
predicted (190), accompanied by an increase in health care expenses allotted to the
care of these conditions (32). More extreme weather events (e.g. wildfires, floods,
thunderstorms) have been predicted in light of the forecasted climate change, and these
events will also worsen our exposure to aeroallergens and other risk factors such as air
pollution. Climate change should be considered in government initiatives for
aeroallergens such as alert systems (similar to the ones in place for air quality) and for
landscaping in urban zones (7). Given the demonstrated differences on concentration
and seasons lengths between each city, any initiative should be tailor-made at the
municipal level, but also integrated with other initiatives at the provincial and national
level. It is likely that atopy-prone individuals will be sensitized to the aeroallergens of the
local plants and fungi, but all the species present in Canada have the potential to change
their geographical locations in the future due to the increasing temperatures associated
with climate change.
Given the high costs associated with the health impacts of atopic conditions and
its high prevalence in Canada, there is a pressing need for public health programs that
acknowledge that exposure to aeroallergens often aggravates these conditions. Public
health programs for atopic conditions should be designed to prevent the development of
these conditions due to sensitization to aeroallergens and also the exacerbations on
53
patients who have already developed an atopic condition. Widespread use of an
aeroallergen alert system with detailed info as the one available from the Weather
Channel, and as comprehensive as the Air Quality Health Index, could be used to
communicate with sensitized individuals and advise them to reduce their exposure when
aeroallergen concentrations start to rise. Considering that aeroallergens have different
season lengths and different start and end dates, the alert system should issue separate
alerts for each aeroallergen, so that the priming of the immune system can be curtailed
before symptoms are developed. This alert system, that could provide local
concentrations daily (however, not in real-time), 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 (80), 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.
54
Chapter 6. Conclusion
Aeroallergens are an important type of particulate matter in the outdoor air (230),
and humans are often exposed to these aeroallergens due to their means of
environmental dispersion. Pollen grains and fungal spores are produced as part of the
reproductive cycle, and inhalation by humans and other animals is an unplanned event
in their pathway of dispersion (31).2
Aeroallergens play a critical role in the development of allergic conditions through
sensitization, particularly in those individuals with genetic predisposition (231). However,
spores and pollen grains do not act in isolation; there are other biotic and abiotic factors
present in the environment and distinctive of each ecological zone. The biotic and abiotic
factors also represent an environmental exposures (e.g., air pollution) and play a role in
the interaction between air and respiratory tissue (94). Environmental exposures can act
as risk or protective effect modifiers in the development of allergy to aeroallergens (232)
and have special relevance during specific periods of time such as pregnancy or the first
year after birth. After the sensitization takes place and the affected individual develops
symptoms, further exposures to risk factors and / or allergens may cause symptom
exacerbations that will start in the respiratory system and subsequently involve the
immune system too (9).
The seasonal and geographic differences in aeroallergen concentrations
highlighted in this thesis suggest specific exposure patterns for each city, which may
lead to differential risks of disease. For the CHILD participants, the concentrations and
aeroallergen season lengths create a unique pattern of a relevant environmental
exposure, during suspected windows of susceptibility, that could be linked to their
potential development of atopic conditions and asthma. The unique pattern of
environmental exposures described could be generalized to other atopy-prone
individuals living in the same cities and years. In the near future, our environmental
2 It is interesting to consider, given the negative impacts in sensitized or atopy prone
humans, that for plants pollen inhalation by humans represents a waste of their resources, since
it decreases their possibilities of successful reproduction.
55
exposures will be altered by the human activities that drive climate change; unless
effective actions are taken to slow temperature increase and further decrease air
pollution, it is likely that the environmental conditions described will worsen and cause
an increase in the negative health impacts in humans, specifically in atopic conditions.
56
References
1. Graham-Rowe D. Lifestyle: When allergies go west. Nature. 2011;479(7374):S2.
2. Lau S. Are asthma and allergies increasing in children and adolescents? European Journal of Integrative Medicine. 2009 Dec 1;1(4):175.
3. Weiland S., von Mutius E, Hirsch, T., Duhme, H. Prevalence of respiratory and atopic disorders among children in the East and West of Germany five years after unification. Eur Respir J. 1999;14:862±870.
4. Ebisawa M, Nishima S, Ohnishi H, Kondo N. Pediatric allergy and immunology in Japan. Pediatr Allergy Immunol. 2013 Nov;24(7):704–14.
5. 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 Aug;72(4):221–7.
6. Endre L, Lang S, Vamos A, Bobvos J, Paldy A, Farkas I, et al. [Increase in prevalence of childhood asthma in Budapest between 1995 and 2003: correlation with air pollution data and total pollen count]. Orv Hetil. 2007 Feb 4;148(5):211–6.
7. Palma-Gomez S, Gonzalez-Diaz SN, Arias-Cruz A, Macias-Weinmann A, Amaro-Vivian LE, Perez-Vanzzini R, et al. [Effects of reforestation on tree pollen sensitization in inhabitants of Nuevo Leon, Mexico]. Rev Alerg Mex. 2014 Sep;61(3):162–7.
8. Taylor PE, Jacobson KW, House JM, Glovsky MM. Links between pollen, atopy and the asthma epidemic. Int Arch Allergy Immunol. 2007;144(2):162–70.
9. Eder W, Ege MJ, von Mutius E. The Asthma Epidemic. N Engl J Med. 2006 Nov 23;355(21):2226–35.
10. Armentia A, Banuelos C, Arranz ML, Del Villar V, Martin-Santos JM, Gil FJ, et al. Early introduction of cereals into children’s diets as a risk-factor for grass pollen asthma. Clin Exp Allergy. 2001 Aug;31(8):1250–5.
11. Halken S. Prevention of allergic disease in childhood: clinical and epidemiological aspects of primary and secondary allergy prevention. Pediatr Allergy Immunol. 2004 Jun;15 Suppl 16:4–5, 9–32.
12. Warner JA, Jones AC, Miles EA, Colwell BM, Warner JO. Prenatal origins of asthma and allergy. Ciba Found Symp. 1997;206:220–8; discussion 228-232.
57
13. Pinkerton, K., Rom, W., Akpinar-Elci, M., Balmes, J., Bayram, H., Brandli, O., . . . Takaro, T. An Official American Thoracic Society Workshop Report: Climate Change and Human Health. Proceedings of the American Thoracic Society. 2012;9(1):3–8.
14. Smits HH, van der Vlugt LE, von Mutius E, Hiemstra PS. Childhood allergies and asthma: New insights on environmental exposures and local immunity at the lung barrier. Current Opinion in Immunology. 2016 Oct 1;42:41–7.
15. Singh AB. Pollen and Fungal Aeroallergens Associated with Allergy and Asthma in India. Global Journal of Immunology and Allergic Diseases. 2014 Jun 30;2(1):19–28.
16. de Weger LA, Bergmann KC, Rantio-Lehtimäki A, Dahl Å, Buters J, Déchamp C, et al. Impact of Pollen. In: Sofiev M, Bergmann K-C, editors. Allergenic Pollen [Internet]. Dordrecht: Springer Netherlands; 2013 [cited 2018 May 31]. p. 161–215. Available from: http://link.springer.com/10.1007/978-94-007-4881-1_6
17. Esser C. Principles of the Immune System: Players and Organization. In: Environmental Influences on the Immune System. Vienna: Springer; 2016. p. 1–17.
18. Pablos I, Wildner S, Asam C, Wallner M, Gadermaier G. Pollen Allergens for Molecular Diagnosis. Curr Allergy Asthma Rep. 2016 Apr;16(4):31.
19. Weber RW. Floristic zones and aeroallergen diversity. Immunol Allergy Clin North Am. 2003 Aug;23(3):357–69.
20. Taylor J, Jacobson D, Fisher M. The Evolution of Asexual Fungi: Reproduction, Speciation and Classification. Annu Rev Phytopathol. 1999 Sep 1;37(1):197–246.
21. Levetin E, Horner WE, Scott JA. Taxonomy of Allergenic Fungi. The Journal of Allergy and Clinical Immunology: In Practice. 2016;4(3):375-385.e1.
22. Duffy DL, Mitchell CA, Martin NG. Genetic and environmental risk factors for asthma: a cotwin-control study. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):840–5.
23. 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 Oct;50(8):900–7.
24. von Mutius E. Gene-environment interactions in asthma. Journal of Allergy and Clinical Immunology. 2009;123(1):3–11.
58
25. Traidl-Hoffmann C, Kasche A, Menzel A, Jakob T, Thiel M, Ring J, et al. Impact of pollen on human health: more than allergen carriers? Int Arch Allergy Immunol. 2003 May;131(1):1–13.
26. Grant-Downton R, Hafidh S, Twell D, Dickinson HG. Small RNA Pathways Are Present and Functional in the Angiosperm Male Gametophyte. Molecular Plant. 2009 May 1;2(3):500–12.
27. Farré-Armengol G, Filella I, Llusià J, Peñuelas J. Pollination mode determines floral scent. Biochemical Systematics and Ecology. 2015 Aug 1;61:44–53.
28. Park HJ, Lee J-H, Park KH, Kim KR, Han MJ, Choe H, et al. A Six-Year Study on the Changes in Airborne Pollen Counts and Skin Positivity Rates in Korea: 2008-2013. Yonsei Med J. 2016 May;57(3):714–20.
29. D’Amato G, Vitale C, De Martino A, Viegi G, Lanza M, Molino A, et al. Effects on asthma and respiratory allergy of Climate change and air pollution. Multidiscip Respir Med. 2015;10:39.
30. Katelaris CH, Beggs PJ. Climate change: allergens and allergic diseases. Intern Med J. 2018 Feb 1;48(2):129–34.
31. Lacey J. Spore dispersal — its role in ecology and disease: the British contribution to fungal aerobiology. Mycological Research. 1996 Jun 1;100(6):641–60.
32. Szema AM. Asthma, Hay Fever, Pollen, and Climate Change. In: Pinkerton KE, Rom WN, editors. Global Climate Change and Public Health [Internet]. Springer New York; 2014 [cited 2016 Jul 14]. p. 155–65. (Respiratory Medicine). Available from: http://link.springer.com.proxy.lib.sfu.ca/chapter/10.1007/978-1-4614-8417-2_9
33. Shripad A, Eric Caulton. Aerobiology – Applications of Airborne Pollen Studies in Allergy. In: Pollen and Spores Applications with Special Emphasis on Aerobiology and Allergy. Science Publishers; 2009.
34. De Blay F, Bessot JC, Pauli G. [New aero-allergens]. Rev Pneumol Clin. 1996;52(2):79–87.
35. Gunawan H, Takai T, Kamijo S, Wang XL, Ikeda S, Okumura K, et al. Characterization of proteases, proteins, and eicosanoid-like substances in soluble extracts from allergenic pollen grains. Int Arch Allergy Immunol. 2008;147(4):276–88.
39. Crouzy B, Stella M, Konzelmann T, Calpini B, Clot B. All-optical automatic pollen identification: Towards an operational system. Atmospheric Environment. 2016;140:202–12.
40. Portnoy J, Barnes C. Clinical relevance of spore and pollen counts. Immunol Allergy Clin North Am. 2003 Aug;23(3):389–410, vi.
41. Aukrust L. Mold allergy. Introduction. Clin Rev Allergy. 1992;10(3):147–51.
42. Burge HA. Classification of the fungi. Clin Rev Allergy. 1992;10(3):153–63.
43. Crameri R, Zeller S, Glaser AG, Vilhelmsson M, Rhyner C. Cross-reactivity among fungal allergens: a clinically relevant phenomenon? Mycoses. 2009 Mar 1;52(2):99–106.
44. Long DL, Kramer CL. Air spora of two contrasting ecological sites in Kansas. Journal of Allergy and Clinical Immunology. 1972 May 1;49(5):255–66.
45. Hibbett DS, Binder M, Bischoff JF, Blackwell M, Cannon PF, Eriksson OE, et al. A higher-level phylogenetic classification of the Fungi. Mycological Research. 2007;111(5):509–47.
46. McLaughlin DJ, Hibbett DS, Lutzoni F, Spatafora JW, Vilgalys R. The search for the fungal tree of life. Trends Microbiol. 2009 Nov;17(11):488–97.
47. Akiyama K. [The role of fungal allergy in bronchial asthma]. Nihon Ishinkin Gakkai Zasshi. 2000;41(3):149–55.
48. Stewart ID, Oke TR. Local Climate Zones for Urban Temperature Studies. Bull Amer Meteor Soc. 2012 May 25;93(12):1879–900.
49. Marshall, I.B., Schut, P.H., and Ballard, M. National Ecological Framework (3 of 23) [Internet]. A National Ecological Framework for Canada: Attribute Data. 1999 [cited 2018 Dec 5]. Available from: http://sis.agr.gc.ca/cansis/nsdb/ecostrat/1999report/framework.html#ecogen
60
50. Elguindi N, Grundstein A, Bernardes S, Turuncoglu U, Feddema J. Assessment of CMIP5 global model simulations and climate change projections for the 21stcentury using a modified Thornthwaite climate classification. Climatic Change. 2014 Feb 1;122(4):523–38.
51. Government of Canada. National Ecological Framework for Canada: Ecozones Dataset. [Internet]. Government of Canada; 2017. Available from: http://sis.agr.gc.ca/cansis/nsdb/ecostrat/gis_data.html
52. Sutherland S. News - Pollen season is upon us. Who’s getting it bad this year? - The Weather Network [Internet]. 2016 [cited 2018 May 31]. Available from: https://www.theweathernetwork.com/news/articles/pollen-season-is-upon-us-whos-getting-it-bad-this-year/66940
53. Weinberger KR, Kinney PL, Robinson GS, Sheehan D, Kheirbek I, Matte TD, et al. Levels and determinants of tree pollen in New York City. J Expo Sci Environ Epidemiol. 2018 Mar;28(2):119–24.
54. Hugg TT, Hjort J, Antikainen H, Rusanen J, Tuokila M, Korkonen S, et al. Urbanity as a determinant of exposure to grass pollen in Helsinki Metropolitan area, Finland. PLoS ONE. 2017;12(10):e0186348.
55. Rogers CA. An aeropalynological study of metropolitan Toronto. Aerobiologia. 1997 Dec 1;13(4):243–57.
56. Solomon WR. Airborne pollen: A brief life. Journal of Allergy and Clinical Immunology. 2002 Jun 1;109(6):895–900.
57. Agarwal MK, Swanson MC, Reed CE, Yunginger JW. Immunochemical quantitation of airborne short ragweed, Alternaria, antigen E, and Alt-I allergens: a two-year prospective study. J Allergy Clin Immunol. 1983 Jul;72(1):40–5.
58. Agarwal MK, Swanson MC, Reed CE, Yunginger JW. Airborne ragweed allergens: association with various particle sizes and short ragweed plant parts. J Allergy Clin Immunol. 1984 Nov;74(5):687–93.
59. 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. The Journal of Allergy and Clinical Immunology. 2001;108(1):109–15.
60. Horvath A, Balashazy I, Farkas A, Sarkany Z, Hofmann W, Czitrovszky A, et al. Quantification of airway deposition of intact and fragmented pollens. Int J Environ Health Res. 2011 Dec;21(6):427–40.
61
61. D’Amato G, Cecchi L. Effects of climate change on environmental factors in respiratory allergic diseases. Clin Exp Allergy. 2008 Aug;38(8):1264–74.
62. Boldogh I. ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. Journal of Clinical Investigation. 2005 Aug 1;115(8):2169–79.
63. Abou Chakra O, Rogerieux F, Poncet P, Sutra J-P, Peltre G, Senechal H, et al. Ability of pollen cytoplasmic granules to induce biased allergic responses in a rat model. Int Arch Allergy Immunol. 2011;154(2):128–36.
64. North ML, Jones MJ, Macisaac JL, Morin AM, Steacy LM, Gregor A, et al. Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit. Allergy. 2018;73(1):196–205.
65. Holtzman MJ, Byers DE, Alexander-Brett J, Wang X. The role of airway epithelial cells and innate immune cells in chronic respiratory disease. Nature Reviews Immunology. 2014 Oct;14(10):686–98.
66. Cardaba B, Llanes E, Chacartegui M, Sastre B, Lopez E, Molla R, et al. Modulation of allergic response by gene-environment interaction: olive pollen allergy. J Investig Allergol Clin Immunol. 2007;17 Suppl 1:31–5.
67. 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 And Asthma Proceedings. 2017 Nov 1;38(6):70–7.
68. Sun R, Tang X-Y, Yang Y. Immune imbalance of regulatory T/type 2 helper cells in the pathogenesis of allergic rhinitis in children. The Journal of Laryngology & Otology. 2016;130(1):89–94.
69. Sears MR, Greene JM, Willan AR, Taylor DR, Flannery EM, Cowan JO, et al. Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet. 2002 Sep 21;360(9337):901–7.
70. Bach J-F. The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases. The New England Journal of Medicine. 2002;347(12):911–20.
71. Ellis AK, Ratz JD, Day AG, Day JH. Factors that affect the allergic rhinitis response to ragweed allergen exposure. Annals of Allergy, Asthma & Immunology. 2010;104(4):293–8.
72. Patel D, Lee JS, Wilson D, Camuso N, Salapatek A. Repeated Low-dose Aerosolized Dust Mite Allergen Exposure In Asthmatic And Non-asthmatic
62
Dust Mite Allergic Patients In An Environmental Exposure Chamber Induces Specific Asthma Symptoms As Well As Allergic Rhinoconjunctivitis Symptoms. Journal of Allergy and Clinical Immunology. 2011 Feb 1;127(2, Supplement):AB20.
73. Rondón C, Fernández J, López S, Campo P, Doña I, Torres MJ, et al. Nasal inflammatory mediators and specific IgE production after nasal challenge with grass pollen in local allergic rhinitis. Journal of Allergy and Clinical Immunology. 2009 Nov 1;124(5):1005-1011.e1.
74. Gieras A, Focke-Tejkl M, Ball T, Verdino P, Hartl A, Thalhamer J, et al. Molecular determinants of allergen-induced effector cell degranulation. J Allergy Clin Immunol. 2007 Feb;119(2):384–90.
75. Ellis AK, Soliman M, Steacy L, Boulay M-È, Boulet L-P, Keith PK, et al. The Allergic Rhinitis - Clinical Investigator Collaborative (AR-CIC): nasal allergen challenge protocol optimization for studying AR pathophysiology and evaluating novel therapies. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2015;11(1):16.
76. White JF, Bernstein DI. Key pollen allergens in North America. Annals of Allergy, Asthma & Immunology. 2003 Nov 1;91(5):425–35.
77. Ellis AK, North ML, Walker T, Steacy LM. Environmental exposure unit: a sensitive, specific, and reproducible methodology for allergen challenge. Annals of Allergy, Asthma & Immunology. 2013;111(5):323–8.
78. Léonard R, Wopfner N, Pabst M, Stadlmann J, Petersen BO, Duus JØ, et al. A new allergen from ragweed (Ambrosia artemisiifolia) with homology to art v 1 from mugwort. The Journal of biological chemistry. 2010;285(35):27192.
79. Oberhuber C, Ma Y, Wopfner N, Gadermaier G, Dedic A, Niggemann B, et al. Prevalence of IgE-Binding to Art v 1, Art v 4 and Amb a 1 in Mugwort-Allergic Patients. International Archives of Allergy and Immunology. 2008;145(2):94–101.
80. Asero R, Wopfner N, Gruber P, Gadermaier G, Ferreira F. Artemisia and Ambrosia hypersensitivity: co-sensitization or co-recognition? Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2006;36(5):658.
81. Eriksson NE, Wihl JA, Arrendal H, Strandhede SO. Tree pollen allergy. II. Sensitization to various tree pollen allergens in Sweden. A multi-centre study. Allergy. 1984;39(8):610.
63
82. Vaitla PM, Drewe E. Identifying the culprit allergen in seasonal allergic rhinitis. Practitioner. 2011 May;255(1740):27–31, 2.
83. Bachert C, Vignola AM, Gevaert P, Leynaert B, Van Cauwenberge P, Bousquet J. Allergic rhinitis, rhinosinusitis, and asthma: one airway disease. Immunol Allergy Clin North Am. 2004 Feb;24(1):19–43.
84. Cantani, A. Allergic Rhinitis. In: Pediatric Allergy, Asthma and Immunology [Internet]. Springer Berlin Heidelberg; 2008 [cited 2016 Jul 18]. p. 875–910. Available from: http://link.springer.com.proxy.lib.sfu.ca/chapter/10.1007/978-3-540-33395-1_12
85. 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 Aug 16;13:764.
86. 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 Nov;108(5 Suppl):S147-334.
87. Kim H, Bouchard J, Renzix P. The link between allergic rhinitis and asthma: A role for antileukotrienes? Can Respir J. 2008 Mar;15(2):91–8.
88. Egan M, Bunyavanich S. Allergic rhinitis: the “Ghost Diagnosis” in patients with asthma. Asthma Res Pract [Internet]. 2015 Sep 7 [cited 2018 May 31];1. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142399/
89. World Health Organization. Asthma [Internet]. World Health Organization. 2017 [cited 2018 May 31]. Available from: http://www.who.int/news-room/fact-sheets/detail/asthma
90. D’Amato G, Annesi Maesano I, Molino A, Vitale C, D’Amato M. Thunderstorm-related asthma attacks. Journal of Allergy and Clinical Immunology. 2017 Jun 1;139(6):1786–7.
91. Hertzen L., Haahtela T. Signs of reversing trends in prevalence of asthma. Allergy. 2005 Jan 28;60(3):283–92.
92. 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 Mar;109(3):339–46.
93. Brown CW, Hawkins L. Allergy prevalence and causal factors in the domestic environment: results of a random population survey in the United Kingdom. Ann Allergy Asthma Immunol. 1999 Sep;83(3):240–4.
64
94. Subbarao P, Becker A, Brook JR, Daley D, Mandhane PJ, Miller GE, et al. Epidemiology of asthma: risk factors for development. Expert Rev Clin Immunol. 2009 Jan;5(1):77–95.
95. Ciprandi G, Buscaglia S, Scordamaglia A, Canonica GW. Allergen-specific conjunctival challenge in asthma. An additional diagnostic tool to define sensitization. Int Arch Allergy Immunol. 1997 Mar;112(3):247–50.
96. 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 Aug;128(4):336–43.
97. Cantani, A. Asthma. In: Pediatric Allergy, Asthma and Immunology [Internet]. Springer Berlin Heidelberg; 2008 [cited 2016 Jul 18]. p. 725–873. Available from: http://link.springer.com.proxy.lib.sfu.ca/chapter/10.1007/978-3-540-33395-1_11
98. Statistics Canada. Population by Sex and Age Group, Population as of July 1 [Internet]. Statistics Canada, CANSIM, table 051-0001; 2016 [cited 2016 Oct 18]. Available from: http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/demo10a-eng.htm
99. Keith PK, Desrosiers M, Laister T, Schellenberg RR, Waserman S. The burden of allergic rhinitis (AR) in Canada: perspectives of physicians and patients. Allergy, Asthma & Clinical Immunology [Internet]. 2012 Dec [cited 2019 Feb 5];8(1). Available from: https://aacijournal.biomedcentral.com/articles/10.1186/1710-1492-8-7
100. Government of Canada SC. Asthma, by age group and sex (Percent) [Internet]. 2016 [cited 2018 May 31]. Available from: https://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/health49b-eng.htm
101. Gershon AS, Guan J, Wang C, To T. Trends in Asthma Prevalence and Incidence in Ontario, Canada, 1996–2005: A Population Study. American Journal of Epidemiology. 2010;172(6):728–36.
102. Asher MI, Montefort S, Björkstén B, Lai CK, Strachan DP, Weiland SK, et al. 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. The Lancet. 2006;368(9537):733–43.
103. Ismaila AS, Sayani AP, Marin M, Su Z. Clinical, economic, and humanistic burden of asthma in Canada: a systematic review. BMC pulmonary medicine. 2013;13:70.
65
104. Hesselmar B, Bergin A-M, Park H, Hahn-Zoric M, Eriksson B, Hanson L-A, et al. Interleukin-4 receptor polymorphisms in asthma and allergy: relation to different disease phenotypes. Acta Paediatr. 2010 Mar;99(3):399–403.
105. Tran MM, Lefebvre DL, Dharma C, Dai D, Lou WYW, Subbarao P, et al. Predicting the atopic march: Results from the Canadian Healthy Infant Longitudinal Development Study. Journal of Allergy and Clinical Immunology [Internet]. 2017 Nov 15; Available from: http://www.sciencedirect.com/science/article/pii/S009167491731480X
106. Bergmann RL, Wahn U, Bergmann KE. The allergy march: from food to pollen. Environ Toxicol Pharmacol. 1997 Nov;4(1–2):79–83.
107. Warner JA, Jones CA, Jones AC, Warner JO. Prenatal origins of allergic disease. J Allergy Clin Immunol. 2000 Feb;105(2 Pt 2):S493-498.
108. Leung RC, Carlin JB, Burdon JG, Czarny D. Asthma, allergy and atopy in Asian immigrants in Melbourne. Med J Aust. 1994 Oct 3;161(7):418–25.
109. Ventura MT, Munno G, Giannoccaro F, Accettura F, Chironna M, Lama R, et al. Allergy, asthma and markers of infections among Albanian migrants to Southern Italy. Allergy. 2004 Jun;59(6):632–6.
110. Beggs PJ. Impacts of climate change on aeroallergens: past and future. Clin Exp Allergy. 2004 Oct;34(10):1507–13.
111. de Jong NW, Vermeulen AM, Gerth van Wijk R, de Groot H. Occupational allergy caused by flowers. Allergy. 1998 Feb;53(2):204–9.
112. Anguita JL, Palacios L, Ruiz-Valenzuela L, Bartolome B, Lopez-Urbano MJ, Saenz de San Pedro B, et al. An occupational respiratory allergy caused by Sinapis alba pollen in olive farmers. Allergy. 2007 Apr;62(4):447–50.
113. 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 Jul;56(7):679–83.
114. Hermanides HK, Lahey-de Boer AM, Zuidmeer L, Guikers C, van Ree R, Knulst AC. Brassica oleracea pollen, a new source of occupational allergens. Allergy. 2006 Apr;61(4):498–502.
115. Swierczyniska-Machura D, Krakowiak A, Palczynski C. [Occupational allergy caused by ornamental plants]. Med Pr. 2006;57(4):359–64.
116. Miesen WMAJ, van der Heide S, Kerstjens HAM, Dubois AEJ, de Monchy JGR. Occupational asthma due to IgE mediated allergy to the flower Molucella laevis (Bells of Ireland). Occup Environ Med. 2003 Sep;60(9):701–3.
66
117. Eire MA, Pineda F, Losada SV, de la Cuesta CG, Villalva MM. Occupational rhinitis and asthma due to cedroarana (Cedrelinga catenaeformis Ducke) wood dust allergy. J Investig Allergol Clin Immunol. 2006;16(6):385–7.
118. Brandt O, Zuberbier T, Bergmann K-C. Risk of sensitization and allergy in Ragweed workers - a pilot study. Allergy Asthma Clin Immunol. 2014;10(1):42.
119. Barbato A, Pisetta F, Norbiato M, Ragusa A, Mesirca P, Pesenti P, et al. Influence of aeroallergens on bronchial reactivity in children sensitized to grass pollens. Ann Allergy. 1986 Feb;56(2):138–41.
120. Tovey ER, Almqvist C, Li Q, Crisafulli D, Marks GB. Nonlinear relationship of mite allergen exposure to mite sensitization and asthma in a birth cohort. The Journal of Allergy and Clinical Immunology. 2008;122(1):114-118.e5.
121. Lebel B, Bousquet J, Morel A, Chanal I, Godard P, Michel FB. 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 Nov;82(5 Pt 1):869–77.
122. Twaroch TE, Curin M, Valenta R, Swoboda I. Mold allergens in respiratory allergy: from structure to therapy. Allergy Asthma Immunol Res. 2015 May;7(3):205–20.
123. D’Amato G, Spieksma FT. Aerobiologic and clinical aspects of mould allergy in Europe. Allergy. 1995 Nov;50(11):870–7.
124. 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 Feb;6(1):55–62.
125. Baxter DM, Perkins JL, McGhee CR, Seltzer JM. A regional comparison of mold spore concentrations outdoors and inside “clean” and “mold contaminated” Southern California buildings. J Occup Environ Hyg. 2005 Jan;2(1):8–18.
126. Nolte H, Hébert J, Berman G, Gawchik S, White M, Kaur A, et al. Randomized controlled trial of ragweed allergy immunotherapy tablet efficacy and safety in North American adults. Ann Allergy Asthma Immunol. 2013 Jun;110(6):450-456.e4.
127. Weichenthal S, Lavigne E, Villeneuve PJ, Reeves F. Airborne Pollen Concentrations and Emergency Room Visits for Myocardial Infarction: A Multicity Case-Crossover Study in Ontario, Canada. Am J Epidemiol. 2016 Apr 1;183(7):613–21.
67
128. Durham SR, Emminger W, Kapp A, de Monchy JGR, Rak S, Scadding GK, 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 Mar;129(3):717-725.e5.
129. Connell JT. Quantitative intranasal pollen challenges. 3. The priming effect in allergic rhinitis. J Allergy. 1969 Jan;43(1):33–44.
130. Jacobs RL, Andrews CP, Ramirez DA, Rather CG, Harper N, Jimenez F, et al. Symptom dynamics during repeated serial allergen challenge chamber exposures to house dust mite. The Journal of Allergy and Clinical Immunology. 2015;135(4):1071–5.
131. Cakmak S, Dales RE, Coates F. Does air pollution increase the effect of aeroallergens on hospitalization for asthma? The Journal of Allergy and Clinical Immunology. 2011;
132. Jacobs RL, Andrews CP, Ramirez DA, Rather CG, Harper N, Jimenez F, et al. Symptom dynamics during repeated serial allergen challenge chamber exposures to house dust mite. Journal of Allergy and Clinical Immunology. 2015 Apr 1;135(4):1071–5.
133. O’Hehir RE, Varese NP, Deckert K, Zubrinich CM, van Zelm MC, Rolland JM, et al. Epidemic Thunderstorm Asthma Protection with Five-grass Pollen Tablet Sublingual Immunotherapy. Am J Respir Crit Care Med [Internet]. 2018 Feb 20; Available from: https://www.atsjournals.org/doi/abs/10.1164/rccm.201711-2337LE
134. Rider CF, Yamamoto M, Günther OP, Hirota JA, Singh A, Tebbutt SJ, et al. Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. Journal of Allergy and Clinical Immunology. 2016;138(6):1690–700.
135. Clifford RL, Jones MJ, MacIsaac JL, McEwen LM, Goodman SJ, Mostafavi S, et al. Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. Journal of Allergy and Clinical Immunology. 2017;139(1):112–21.
136. Gershwin. Infectious and Environmental Triggers of Asthma. In: Current Clinical Practice: Bronchial Asthma: A Guide for Practical Understanding and Treatment. 5th ed. Totowa, NJ: Humana Press Inc.,; 2006.
137. 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. Science of The Total Environment. 2006 Oct 15;370(1):39–50.
68
138. Parameswaran K, Hildreth AJ, Taylor IK, Keaney NP, Bansal SK. Predictors of asthma severity in the elderly: results of a community survey in Northeast England. J Asthma. 1999 Oct;36(7):613–8.
139. Aleraj B, Tomic B. [Epidemiology of allergic diseases]. Acta Med Croatica. 2011;65(2):147–53.
140. Armstrong, Ben, Basagaña, Xavier. Exposure Measurement Error. Consequences and Design Issues. In: Exposure assessment in environmental epidemiology. 2nd ed. USA: Oxford University Press; 2015. p. 201–26.
141. North ML, Soliman M, Walker T, Steacy LM, Ellis AK. Controlled Allergen Challenge Facilities and Their Unique Contributions to Allergic Rhinitis Research. Curr Allergy Asthma Rep. 2015 Apr;15(4):11.
142. Barnes C, Pacheco F, Landuyt J, Hu F, Portnoy J. Hourly variation of airborne ragweed pollen in Kansas City. Ann Allergy Asthma Immunol. 2001 Feb;86(2):166–71.
143. Weber RW. Meteorologic variables in aerobiology. Immunology and Allergy Clinics of North America. 2003 Aug 1;23(3):411–22.
144. Andrew E, Nehme Z, Bernard S, Smith K. 6 Characteristics of thunderstorm asthma EMS attendances in victoria, australia. BMJ Open. 2017 May 1;7(Suppl 3):A2.
145. Cockcroft DW, Davis BE, Blais CM. Thunderstorm asthma: An allergen-induced early asthmatic response. Annals of Allergy, Asthma & Immunology. 2018;120(2):120–3.
146. Lee J, Kronborg C, O’Hehir RE, Hew M. Who’s at risk of thunderstorm asthma? The ryegrass pollen trifecta and lessons learnt from the Melbourne thunderstorm epidemic. Respiratory Medicine. 2017 Nov 1;132:146–8.
147. D’Amato G, Holgate ST, Pawankar R, Ledford DK, Cecchi L, Al-Ahmad M, 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(1):25.
148. Valero A, Chivato T, Justicia JL, Navarro AM. Diagnosis and treatment of grass pollen-induced allergic rhinitis in specialized current clinical practice in Spain. Allergy Asthma Proc. 2011 Oct;32(5):384–9.
149. Canonica GW, Ciprandi G, Pesce GP, Buscaglia S, Paolieri F, Bagnasco M. ICAM-1 on epithelial cells in allergic subjects: a hallmark of allergic inflammation. Int Arch Allergy Immunol. 1995 Jun;107(1–3):99–102.
69
150. Ogi K, Takabayashi T, Sakashita M, Susuki D, Yamada T, Manabe Y, et al. Effect of Asian sand dust on Japanese cedar pollinosis. Auris Nasus Larynx. 2014 Dec;41(6):518–22.
151. Weeke ER. Epidemiology of allergic diseases in children. Rhinol Suppl. 1992 Sep;13:5–12.
152. D’Amato G, Liccardi G, D’Amato M, Holgate S. Environmental risk factors and allergic bronchial asthma. Clin Exp Allergy. 2005 Sep;35(9):1113–24.
153. Carinanos P, Sanchez-Mesa JA, Prieto-Baena JC, Lopez A, Guerra F, Moreno C, et al. Pollen allergy related to the area of residence in the city of Cordoba, south-west Spain. J Environ Monit. 2002 Oct;4(5):734–8.
154. Knudsen TB, Thomsen SF, Ulrik CS, Fenger M, Nepper-Christensen S, Backer V. Season of birth and risk of atopic disease among children and adolescents. J Asthma. 2007 May;44(4):257–60.
155. 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 Feb;20(1):15–22.
156. Lowe AJ, Olsson D, Bråbäck L, Forsberg B. Pollen exposure in pregnancy and infancy and risk of asthma hospitalisation - a register based cohort study. Allergy Asthma Clin Immunol. 2012 Nov 7;8(1):17.
157. D’Amato G, Bergmann KC, Cecchi L, Annesi-Maesano I, Sanduzzi A, Liccardi G, et al. Climate change and air pollution: Effects on pollen allergy and other allergic respiratory diseases. Allergo J Int. 2014;23(1):17–23.
158. Guinea J, Peláez T, Alcalá L, Bouza E. Outdoor environmental levels of Aspergillus spp. conidia over a wide geographical area. Med Mycol. 2006 Jun;44(4):349–56.
159. Bosch-Cano F, Bernard N, Sudre B, Gillet F, Thibaudon M, Richard H, et al. Human exposure to allergenic pollens: A comparison between urban and rural areas. Environmental Research. 2011 Jul;111(5):619–25.
160. Clark NA, Demers PA, Karr CJ, Koehoorn M, Lencar C, Tamburic L, et al. Effect of Early Life Exposure to Air Pollution on Development of Childhood Asthma. Environmental Health Perspectives. 2010;118(2):284–90.
161. Reid CE, Gamble JL. Aeroallergens, allergic disease, and climate change: impacts and adaptation. Ecohealth. 2009 Sep;6(3):458–70.
162. Gauderman WJ, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, et al. The Effect of Air Pollution on Lung Development from 10 to 18 Years of Age. N Engl J Med. 2004 Sep 9;351(11):1057–67.
70
163. Nishimura KK, Galanter JM, Roth LA, Oh SS, Thakur N, Nguyen EA, et al. Early-Life Air Pollution and Asthma Risk in Minority Children. The GALA II and SAGE II Studies. American Journal of Respiratory and Critical Care Medicine. 2013 Aug 1;188(3):309–18.
164. Ziska LH, Gebhard DE, Frenz DA, Faulkner S, Singer BD, Straka JG. Cities as harbingers of climate change: common ragweed, urbanization, and public health. J Allergy Clin Immunol. 2003 Feb;111(2):290–5.
165. Majd A, Chehregani A, Moin M, Gholami M, Kohno S, Nabe T, et al. The Effects of Air Pollution on Structures, Proteins and Allergenicity of Pollen Grains. Aerobiologia. 2004;20(2):111–8.
166. Pasqualini S, Tedeschini E, Frenguelli G, Wopfner N, Ferreira F, D’Amato G, et al. Ozone affects pollen viability and NAD(P)H oxidase release from Ambrosia artemisiifolia pollen. Environmental Pollution. 2011 Oct 1;159(10):2823–30.
167. Raynor GS, Ogden EC, Hayes JV. Dispersion and Deposition of Ragweed Pollen from Experimental Sources. J Appl Meteor. 1970 Dec 1;9(6):885–95.
168. Ying Z, Tie X, Li G. Sensitivity of ozone concentrations to diurnal variations of surface emissions in Mexico City: A WRF/Chem modeling study. Atmospheric Environment. 2009 Feb 1;43(4):851–9.
169. Lazić L, Urošević MA, 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. Atmospheric Environment. 2016;141:347–60.
170. Masiol M, Hopke PK, Felton HD, Frank BP, Rattigan OV, Wurth MJ, et al. Analysis of major air pollutants and submicron particles in New York City and Long Island. Atmospheric Environment. 2017;148:203–14.
171. Takaro TK, Knowlton K, Balmes JR. Climate change and respiratory health: current evidence and knowledge gaps. Expert Rev Respir Med. 2013 Aug;7(4):349–61.
172. Romieu I, Moreno-Macias H, London SJ. Gene by Environment Interaction and Ambient Air Pollution. Proceedings of the American Thoracic Society. 2010 May 1;7(2):116–22.
173. Peltre G. [Inter-relationship between allergenic pollens and air pollution]. Allerg Immunol (Paris). 1998 Dec;30(10):324–6.
174. Zhang X, Hirota JA, Yang C, Carlsten C. Effect of GST variants on lung function following diesel exhaust and allergen co-exposure in a controlled
71
human crossover study. Free Radical Biology and Medicine. 2016 Jul;96:385–91.
175. 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 Oct;16(5):434–40.
176. Intergovernmental Panel on Climate Change. Climate Change 2007: Impacts, Adaptation and Vulnerability. Cambridge University Press: New York; 2007.
177. Intergovernmental Panel on Climate Change. Climate Change 2014 Impacts, Adaptation, and Vulnerability Part A: Global and Sectoral Aspects [Internet]. Cambridge University Press: New York; 2014. Available from: http://www.ipcc.ch/report/ar5/wg2/
178. Wu, X., Lu, Y., Chen, L., Xu, B. Impact of climate change on human infectious diseases: Empirical evidence and human adaptation. Environment International. 2016;86:14–23.
179. Gould, S., Rudolph, L. Challenges and Opportunities for Advancing Work on Climate Change and Public Health. Int J Environ Res Public Health. 2015;12:15649–72.
180. Jones, A., La Fleur, V., Purvis, N. Double Jeopardy: What the climate crisis means for the poor. In: Climate Change and Global Poverty. Washington D.C.: Brookings Institution Press; 2009.
181. McMichael, A., Friel, S., Nyong, A., Corvalan, C. Global Environmental Change and Health: Impacts, inequalities, and the health sector. BMJ. 2008;336:191–4.
182. Ziska LH, Makra L, Harry SK, Bruffaerts N, Hendrickx M, Coates F, et al. Temperature-related changes in airborne allergenic pollen abundance and seasonality across the northern hemisphere: a retrospective data analysis. The Lancet Planetary Health. 2019 Mar 1;3(3):e124–31.
183. Ariano, R., Canonica GW, Passalacqua G. Possible role of climate changes in variations in pollen seasons and allergic sensitizations during 27 years. Annals of Allergy, Asthma & Immunology,. 2010 Mar;Volume 104,(Issue 3,):Pages 215-222.
184. Ziska LH, Beggs PJ. Anthropogenic climate change and allergen exposure: The role of plant biology. Journal of Allergy and Clinical Immunology. 2012 Jan 1;129(1):27–32.
185. Bonofiglio T, Orlandi F, Ruga L, Romano B, Fornaciari M. Climate change impact on the olive pollen season in Mediterranean areas of Italy: air
72
quality in late spring from an allergenic point of view. Environ Monit Assess. 2013 Jan;185(1):877–90.
186. Rice MB, Thurston GD, Balmes JR, Pinkerton KE. Climate Change. A Global Threat to Cardiopulmonary Health. American Journal of Respiratory and Critical Care Medicine. 2014 Mar 1;189(5):512–9.
187. D’Amato G, Pawankar R, Vitale C, Lanza M, Molino A, Stanziola A, et al. Climate Change and Air Pollution: Effects on Respiratory Allergy. Allergy Asthma Immunol Res. 2016 Sep;8(5):391–5.
188. 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 Sep;46(4):159–70.
189. Stach A, Garcia-Mozo H, Prieto-Baena JC, Czarnecka-Operacz M, Jenerowicz D, Silny W, et al. Prevalence of Artemisia species pollinosis in western Poland: impact of climate change on aerobiological trends, 1995-2004. J Investig Allergol Clin Immunol. 2007;17(1):39–47.
190. Takaro, T., Henderson, S. Climate change and the new normal for cardiorespiratory disease. Can Respir J. 2015;Vol 22(No X):1–4.
191. Sapkota A, Murtugudde R, Curriero FC, Upperman CR, Ziska L, Jiang C. Associations between alteration in plant phenology and hay fever prevalence among US adults: Implication for changing climate. PLOS ONE. 2019 Mar 28;14(3):e0212010.
192. Ahdoot S, Pacheco SE. Global Climate Change and Children’s Health. Pediatrics [Internet]. 2015 Oct 26; Available from: http://pediatrics.aappublications.org/content/early/2015/10/21/peds.2015-3233.abstract
193. Ariano R, Berra D, Chiodini E, Ortolani V, Cremonte LG, Mazzarello MG, et al. Ragweed allergy: Pollen count and sensitization and allergy prevalence in two Italian allergy centers. Allergy Rhinol (Providence). 2015 Jan;6(3):177–83.
194. Bjerg A, Ekerljung L, Eriksson J, Naslund J, Sjolander S, Ronmark E, et al. Increase in pollen sensitization in Swedish adults and protective effect of keeping animals in childhood. Clin Exp Allergy. 2016 Oct;46(10):1328–36.
195. Shea KM, Truckner RT, Weber RW, Peden DB. Climate change and allergic disease. The Journal of Allergy and Clinical Immunology. 2008;122(3):454–5.
73
196. Singer BD, Ziska LH, Frenz DA, Gebhard DE, Straka JG. Increasing Amb a 1 content in common ragweed (Ambrosia artemisiifolia) pollen as a function of rising atmospheric CO2 concentration. Functional Plant Biol. 2005 Jul 26;32(7):667–70.
197. Sommer J, Plaschke P, Poulsen LK. [Allergic disease--pollen allergy and climate change]. Ugeskr Laeger. 2009 Oct 26;171(44):3184–7.
198. Costello A, Abbas M, Allen A, Ball S, Bell S, Bellamy R, et al. Managing the health effects of climate change: and University College London Institute for Global Health Commission. The Lancet. 2009;373(9676):1693–733.
199. Subbarao P, Anand SS, Becker AB, Befus AD, Brauer M, Brook JR, et al. The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma. Thorax [Internet]. 2015 Jun 11; Available from: http://thorax.bmj.com/content/early/2015/06/11/thoraxjnl-2015-207246.abstract
200. Brubacher, J., Bassil, K., Chhetri, B., Coates, F., Gower, S., Kwong, J., et al. Climate change, asthma and allergy risk in Toronto (CCAART). Report: Toronto Public Health, SFU.;
201. Dahl, Åslög, Galán C, Hajkova, Lenka, Pauling, Andreas, Sikoparija, Branlo, Smith, Matt, et al. The onset, course and intensity of the pollen season. In: Allergenic Pollen A review of the production, release, distribution and health impacts. Berlin: Springer; 2013. p. 29–70.
202. Frenz DA. Volumetric ragweed pollen data for eight cities in the continental United States. Annals of Allergy, Asthma & Immunology. 1999 Jan 1;82(1):41–6.
203. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria.; 2016.
204. Wickham H. The Split-Apply-Combine Strategy for Data Analysis. Journal of Statistical Software. 2011;40(1):1–29.
205. Robinson, D. Broom: Convert Statistical Analysis Objects into Tidy Data Frames. R package version 0.4.2 [Internet]. 2017. Available from: https://CRAN.R-project.org/package=broom
206. Wickham H, Francois, R., Henry, L., Müller, K. dplyr: A Grammar of Data Manipulation. R package version 0.7.4. 2017.
207. Wickham, Hadley. ggplot2: Elegant Graphics for Data Analysis. In New York: Springer-Verlag; 2009.
74
208. Zeilieis, A., Grothendieck, G. zoo: S3 Infrastructure for Regular and Irregular Time Series. Journal of Statistical Software. 2005;14(6):1–27.
209. Grolemund, G., Wickham, Hadley. Dates and Times made easy with lubridate. Journal of Statistical Software. 2011;40(3):1–25.
210. USGS. Landsat 7 Data Users Handbook - Section 1 | Landsat Missions [Internet]. [cited 2018 Oct 3]. Available from: https://landsat.usgs.gov/landsat-7-data-users-handbook-section-1
211. Asrar G, Zhou Y. Developing Pollen Allergy Risk Maps from Remote Sensing Observations for Public Health Advisories and Warning. In AMS; 2017 [cited 2018 Oct 10]. Available from: https://ams.confex.com/ams/97Annual/webprogram/Paper315012.html
212. Sierra-Heredia C, North M, Brook J, Daly C, Ellis . Anne, Henderson D, et al. Aeroallergens in Canada: Distribution, Public Health Impacts, and Opportunities for Prevention. International Journal of Environmental Research and Public Health. 2018;15(8).
213. Lake, I., Jones, N., Agnew, M., Goodess, C., Giorgi, F., Hamaoui-Laguel, L. Climate Change and Future Pollen Allergy in Europe. Environmental Health Perspectives. 2017 Mar;125(3):385–91.
214. Anyo G, Brunekreef B, de Meer G, Aarts F, Janssen NAH, van Vliet P. Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children. Clin Exp Allergy. 2002 Mar;32(3):361–6.
215. Hjort J, Hugg TT, Antikainen H, Rusanen J, Sofiev M, Kukkonen J, et al. Fine-Scale Exposure to Allergenic Pollen in the Urban Environment: Evaluation of Land Use Regression Approach. Environ Health Perspect. 2016;124(5):619–26.
216. Ramon GD, Arango N, Barrionuevo LB, Reyes MS, Adamo M, Molina O, et al. Comparison of Grass Pollen Levels in 5 Cities of Argentina. Journal of Allergy and Clinical Immunology. 2016 Feb 1;137(2, Supplement):AB122.
217. Fuertes E, Markevych I, von Berg A, Bauer C-P, Berdel D, Koletzko S, et al. Greenness and allergies: evidence of differential associations in two areas in Germany. J Epidemiol Community Health. 2014 Aug 1;68(8):787.
218. Coates F, Jurgens D. Annual Fluctuations of Outdoor Allergen Seasons. Journal of Allergy and Clinical Immunology. 2016 Feb 1;137(2, Supplement):AB120.
75
219. Emberlin J, Bartle J, Bryant C. Not just a spring fever... Information and advice to help families with hay fever sufferers. J Fam Health Care. 2011 Jun;21(3):23–8.
220. Lavigne E, Gasparrini A, Stieb DM, Chen H, Yasseen AS, Crighton E, et al. Maternal Exposure to Aeroallergens and the Risk of Early Delivery. Epidemiology. 2017;28(1):107–15.
221. McInnes RN, Hemming D, Burgess P, Lyndsay D, Osborne NJ, Skjøth CA, et al. Mapping allergenic pollen vegetation in UK to study environmental exposure and human health. Science of The Total Environment. 2017 Dec 1;599–600:483–99.
222. Aira MJ, Almaguer Chávez M, Fernández-González M, Rodríguez-Rajo FJ. Pollen diversity in the atmosphere of Havana, Cuba. Aerobiologia. 2018 Sep 1;34(3):389–403.
223. Dales RE, Cakmak S, Judek S, Coates F. Tree pollen and hospitalization for asthma in urban Canada. Int Arch Allergy Immunol. 2008;146(3):241–7.
224. Ito K, Weinberger KR, Robinson GS, Sheffield PE, Lall R, Mathes R, et al. The associations between daily spring pollen counts, over-the-counter allergy medication sales, and asthma syndrome emergency department visits in New York City, 2002-2012. Environ Health. 2015 Aug 27;14:71.
225. Cakmak S, Dales RE, Burnett RT, Judek S, Coates F, Brook JR. Effect of airborne allergens on emergency visits by children for conjunctivitis and rhinitis. Lancet. 2002 Mar 16;359(9310):947–8.
226. Devadas R, Huete AR, Vicendese D, Erbas B, Beggs PJ, Medek D, et al. Dynamic ecological observations from satellites inform aerobiology of allergenic grass pollen. Science of The Total Environment. 2018 Aug 15;633:441–51.
227. Wolter PT, Berkley EA, Peckham SD, Singh A, Townsend PA. Exploiting tree shadows on snow for estimating forest basal area using Landsat data. Remote Sensing of Environment. 2012 Jun 1;121:69–79.
228. Ebisu K, Holford TR, Bell ML. Association between greenness, urbanicity, and birth weight. Science of The Total Environment. 2016 Jan 15;542:750–6.
229. Scheifinger, H., Belmonte, J., Buters, J., Celenk, S., Damialis, A., Dechamp, C., et al. Monitoring, Modelling and Forecasting of the Pollen Season. In: Sofiev, M., Bergmann KC, editors. Allergenic Pollen. Dordrecht: Springer; 2013.
76
230. Cecchi L. Introduction. In: Allergenic Pollen [Internet]. Springer, Dordrecht; 2013 [cited 2018 May 31]. p. 1–7. Available from: http://link.springer.com/chapter/10.1007/978-94-007-4881-1_1
231. Magnan A, Romanet S, Vervloet D. [Asthma and allergy]. Rev Prat. 2001 Mar 15;51(5):511–6.
232. 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 Jul;95(7):606–11.
77
Appendix. Allergenic pollen reported by country
Country Pollen Reference
Pakistan Mixed pollen, thresher dust and raw cotton
(Ahmed, Minhas, Micheal & Ahmad, 2011)
Mexico
Guadalajara Oaks and ashes, in weeds was mugwort, in grasses was Zea mays
Ragweed of Ambrosia species and grasses of the Poaceae family, such as timothy (Phleum pratense), rye (Lolium species), Kentucky blue grass (Poa pratensis), orchard grass (Dactylis glomerata), Bermuda grass (Cynodon dactylon)