Air pollutants

Air Pollutants
Thitima Kantachatvanich, M.D.
Faculty of Medicine
Chulalongkorn University

Outline
• Introduction
– Health effects
– Susceptible groups
• Classification
• Sources of air pollutants
• Air quality
• Mechanism
• Pollutant – Allergen
interactions
• Climate change effects
• Each pollutant
– Outdoor & Indoor
• Long term effects
– Trials on lung growth
• Management
• Environmental
control: Air filters
• Summary
• Examination

Introduction
:Major Health Effects
• Asthma, COPD: ↑initiation, exacerbation
• Acute lower RS infection (RS epithelium damage, MØ,
mucociliary dysfunction)
• In utero: ↓birth weight, future lung fn. effects
• Oncogenic: AdenoCA lung due to DNA damage (ROS)
• CVS: IHD (ROS, Ca2+, vascular dysfunction)
SO2, NOx, O3, PM, biologic agents: impact on asthma
(except for CO, lead)
Biomass: Polyaromatic HCs, quinones, ROS, airborne endotoxin
Particulate Matter
Middleton 8th Edition

Introduction
• Air pollutants affect especially susceptible groups
– Extreme age
– Preexisting disease: cardiopulmonary disease
– Genetic: oxidative stress response, innate immunity genes
– Lower socioeconomic: ↑exposure

Susceptible Populations
Genetic
– Inter-individual: varies
– Intra-individual: stable
– Susceptible to AW disease: oxidative responses,
TNFα
Genes: cellular and mucosal oxidant stress
– GSTs: GSTM1, GSTP1
– NQO1
– HO-1, HMOX1

Genetic Risk
• Oxidative stress
 master TF “NFE2L2” translocates to Nuc.
 bind to antioxidant response element
 transcribe antioxidant genes
• GSTM1 (null genotype): antioxidative gene
– ↑wheezing in children exposed to tobacco smoke during perinatal
period
– ↑asthma attack in response to ozone
– ↑inﬂammatory response to inhaled LPS (at 20,000 endotoxin
units): ↑IL-1β and TNF-α in the sputum
• TNF-α SNP: proinflammatory gene
• Gene-gene-environmental interaction

Classification of Air Pollutants
• Primary (directly emitted): SO2, some Nox, CO, PM10
• Secondary (form in the air): O3, some Nox, PM2.5, PM0.1
– *Emission from source of 1o α ambient conc. (but not for 2o)
– ↑O3 paradoxically if ↓NO
• Indoor
– Sources: cooking, AC, smoking, heating
– Products: CO, CO2, SVOC, microbial, organic dusts, radon
• Outdoor (point/mobile sources)
– Sources: industrial, agriculture, automobile
– Products: CO, SVOC, PM, SO2 , O3, Nox
• Gaseous: CO, SVOC, PM, SO2 , O3, Nox
• Particulate: coarse (PM10), fine(PM2.5), ultrafine(PM0.1)
Jonathan A. Bernstein, et al., Health effects of air pollution, JACI 2004

Sources of Pollutants
• In the United States,
• Point sources
– 93% of SO2
– 51% of NOx
– 9% of CO
– 52% of VOC
• Both point and mobile sources contribute to PM
production.
• Mobile sources
- 2% of SO2
- 45% of NOx
- 81% of CO
- 37% of VOC

• EPA determine “criteria air pollutants”
– Human risks from short term exposure
• Nonattainment areas: don't meet the national standard
criteria
• Lead
• Carbon Monoxide (CO)
• Nitrogen Dioxide (NO2)
• Ozone, Ground Level
• Sulfur Dioxide (SO2)
• Particulate Matter (PM)
AQI
Standards for Air Pollutants
(the US Environmental Protective Agency)
Not currently regulated (Less data is known
about PM0.1 ;may have potentially more toxic

Limitations: human variability, pollutions from elsewhere

Mechanism (Direct)
• Free radical, oxidative stress generation
– PAH on DEP, ozone, nitric dioxide
– ↑Epithelial permeability
– Inhibit the ciliary beat frequency (delayed
clearance of allergens and irritants)
G. Schiavoni et al., The dangerous liaison between pollens and
pollution in respiratory allergy, Ann Allergy Asthma Immunol 2017

Hierarchic Oxidative Stress Model
• ↑Dose of PM sequentially induce responses
• Oxidative stress: ↓ratio of glutathione/oxidized
glutathione
J.A.Bernstein, et al. Health effects of air pollution, JACI 2004

Mechanism (Direct *Imune)
• Modulate proinflammatory, chemotactic
markers from human bronchial epithelial cells
(in vitro)
– ozone  ↑PAF, IL-8, GM-CSF, TNF-α, sICAM-1
– Nitric dioxide  LTC4, GM-CSF, TNF-α, IL-8,
RANTES, sICAM-1
– DEPs  IL-8, GM-CSF, sICAM-1

Mechanism (Direct)
• Covalent modification of key protein
– Epigenetic modification
• Nocireceptor, ANS stimulation (HR, AW
reactivity): Ozone
• Procoagulant activity of ultrafine PM

Mechanism (Direct *Immune)
• Biologic compound: innate immune effects
– Endotoxin, ozone
• Suppression of defense mechanism
– Alveolar macrophage function
– Dalay ciliary work

Heat shock proteins, oxidized lipids,
ﬁbrinogen, LMW hyaluronic acid
Hyaluronic: GAGs in AW matrix
Marker of ozone induced AW inflammation

Pollutant & Allergen Interactions
• Adjuvant effects in immune systems
– DEPs, transition metals
– DEPs, polyaromatic HCs  synthesis of IgE, IL-4
(TH2 polarization)
– DEPs: ↑HLA-DR and CD86 molecules

Pollen Structure & Releasings
• TH2 polarization (IgE and non-IgE)
– PALMs (Pollen associated lipid mediators): LTB4
like
– Phytoprostanes: PGE like
• Simple count of pollen grains
– not always correlate with the prevalence of
sensitization
– Allergenic potency* (releasing, structure of
allergen): free allergen not coincide with peak
pollen counts

• Pollen allergens carried by airborne particles
(Combine aeroallergens with particles)
• Then released by hydration or pollution-
induced rupture of pollens
– ↓ Lamellation of intine
– Elicit degranulation of cytoplasmic prot. to intine
Depend on type of pollutant, pollen
*SO2 + grass  ↓degranulation of allergen e.g. East
German

Dust Agglomeration
• Birch
• Grass
• Mugwort
• Nettle pollen
• Fungal spores
(Cladosporium, Alternaria)

• Adaptation of plants to abiotic stress
• To endure environmental stress
• Measure of pollen allergenicity as a parameter of air
emissions and climate changes
• Comparative proteomics: ROS-scavenging pathway
products

Climate Change & Allergy
• Global warming = Plant stressor
– Production of greenhouse gases (mostly = CO2)
– North America: earlier(ragweed grow faster), last
longer pollen season, ↑pathogenic allergen
production
– ↑CO2 2X  ragweed production by 61%
– Tree, grass, weed, and ragweed
– ↑Potency of allergen (↑Amb a I content)
– ↑Gene corresponding allergen response to
drought (Protect flower from dehydration)

MPG = Miles Per Gallon
www.epa.gov

Smog
• Type I (classic)
– SO2, PM10
– Not associated with ↑allergy prevalence
– East Germany: industrialized farm ↓but traffic exhaust
• Type II: ↑Traffic exhaust
– NOx, PM2.5, PM0.1
– ↑ Allergy prevalence
– West Germany: traditional farm but ↑traffic exhaust
≠ Farmer Hypothesis

Farmer Hypothesis
• Asthma prevalence
– Eastern, central Europe < western
– Amish < Hutterite schoolchildren
• ↓Asthma in traditional farm (esp. animal,
↑microbial load)

Particulate Matter
Coarse PM
• 2.5-10 micron
• Abraded soil, road dust, construction debris
Fine, ultrafine PM
• Small but more absorbed and toxic
• Fine < 2.5 micron, Ultrafine < 0.1 micron
• Formed during combustion of fossil fuel
products
Vehicles of airborne pollen

Particulate Matter
• ↑Asthma exacerbations and development
• Metals in PM (e.g., copper, nickel, zinc) induce
AW inﬂammation
• Ghio and Huang: HR variability and other
systemic effects
• Ischemic cardiovascular events (MI)

Diesel Exhaust
• Diesel combustion  DEPs, NOx, O3 precursor
– Elemental carbon core (70% of mass)
– Organic compounds, transition metal coat
• Single diesel < 0.1 micron  agglomerate to
fine particles (<2.5 micron)
• Inflammation: PAHs rich > Low PAHs
• Cedar pollinosis in high traffic area
• Asthma prevalence, severity, hospitalization,
AR, sensitization, ↓lung function

Diesel Exhaust
• Proinflammatory cytokines, chemokines from
bronchial epithelium
• Alter T cell response
• Murine model, in vitro human Ba,L: ↑Th2
response (↑sIgE)
– Interfere IFN-ү producing pathway
– Oxidant dependent pathway
• ↑Susceptible to viral infection (viral entry)

Sulfer Dioxide
• Water soluble gas, might form H2SO4 particle
• Bronchoconstriction (rapid onset) in healthy,
asthma (↑effect in asthma)
• Prior O3 or cold air exposure  ↑bronchial
sensitivity to SO2 in asthma
• Nasal breath: ↓effect (water solubilize)
– AR/sinusitis +/- asthma
– Exercise: should not exercise outdoor on polluted
day

Nitrogen Dioxides
• Precursor to photochemical smog (O3)
• Combustion of fossil fuels or natural gas
• Urban and industrial regions
• ↑Severe asthmatic attack, AW inflammation
• ↑Immediate, late-phase response to inhaled
allergen in atopic pt

Deficits in the Growth of FEV1
Gauderman WJ, et al.The Effect of Air Pollution on Lung
Development from 10 to 18 Years of Age, NEJM 2004

Ozone
• Stratospheric ozone is “good”, but ground
(troposphere) ozone is “bad”
• Main ingredient in “smog”
• UV sunlight + Nox, VOCs = Ozone
– Photochemical smog
– Peak level in the afternoon of sunny days
• Chest pain, coughing, throat irritation, AW
inflammation
– Pain due to nociceptor stimuli
Jonathan A. Bernstein, et al., Health effects of air pollution, JACI 2004

Ozone
• ↓FEV1, ↑Nonspecific AW hyperresponsiveness
– Sensory-neural reflexes
– Asthma exacerbation, development (chronic
expose)
– Adult onset asthma in male
• *O3 + exercise  ↓FEV1, FVC, ↑AW resistance
(avoid outdoor exercise on ↓AQI day)
https://www.epa.gov/

Ozone
• AW inflammation (ROS; NFKB, TLRs)
• Innate immune response in asthma: ↑TLR4
• ↑Immediate, late-phase response to inhaled
allergen (↑Sputum Eo after 6 hr)
• Dose dependent

Specific Volatile Organic Compounds
(SVOC)
• Subgroup of VOCs
– Polyaromatic hydrocarbon(PAH), dioxins, benzene,
aldehydes, 1,3-butadiene
• Higher Mw
• Higher boiling point temp.
https://www.epa.gov/

Indoor Pollutants
• Biomass, NO2, PM, ETS, Endotoxin
• Sources:
– Outdoor(PM2.5)
– Smoking(Cigar, E-cigarete, marijuana)
– Biomass burning (stoving, incense)
• Top 10 preventable RFs to the global burden
of disease (WHO declaration)
E.Matsui, et al.,Indoor Environmental Control Practices and
Asthma Management. Pediatrics. 2016;138(5):e20162589

Biomass
• Polyaromatic HCs, NO2, quinones, ROS,
airborne endotoxin
• Tobacco smoke, heating sources
• Predominantly in women, their children
• COPD development
• Children in Guatemala: ↑asthma symptoms
(biomass burning for cooking compared with
plancha stoves)

Biomass
• Acute lower RS infection (RS epithelium
damage, MØ, mucociliary dysfunction)
• In utero: ↓birth weight, future lung fn. effects
• Oncogenic: AdenoCA lung due to DNA damage
(ROS)

Indoor NO2
• Outdoor – traffic
• Indoor – gas heat, older wood-burning stoves,
unvented space heaters
• Higher indoor NO2: worsen asthma
• Ensuring that the stove is properly vented
• 1 RCT: ↓40-50% in indoor NO2 when a gas
stove was replaced with an electric one
– This degree reduction improve asthma?

Environmental Tobacco Smoking
• ½ pack of cigarette = PM 4 mcg/m3
• Restaurants in Paducah, Kentucky1
– 87 μg/m3 in the nonsmoking areas
– The mean PM2.5 was 177 μg/m3 in smoking areas
• 29 times higher than that in smoke-free air
• 6 times higher than local outdoor air in Paducah
• PM, non-PM (air nicotine, other gaseous pollutants)
– HEPA purifiers: filter only PM
• Control: stop smoking > home smoking free > HEPA
purifiers (home free: not eliminate exposure)
1.Jones SC, Travers MJ, Hahn EJ, et al. Secondhand smoke and indoor
public spaces in Paducah, Kentucky. J Ky Med Assoc 2006;104:281-8.
2.E.Matsui, et al.,Indoor Environmental Control Practices and

• Mainstream smoke: taken by smoker
• Sidestream smoke: burning end, exhaled from
smoker
• Cotinine = direct metabolite of nicotine, but
longer T1/2 in body
– Slower mechanism in African Americans
• Present in saliva, urine, serum, hair

• E-cigarette aerosol and tobacco: similar
amounts of ROS
– Size of the particles: respirable range (median
aerodynamic diameter of 1.03 μm)
C. Dinakar et al., The Health Effects of Electronic Cigarettes, NEJM 2016

• Epigenetic modiﬁcations (oxidative stress)
– DNA methylation and others
– Effect on children exposed in utero or during early
life (hypothesis)
• Asthma exacerbations in children
• ↑Urinary LTE4 in children
• Epidemiologic study: development of allergy
esp. in early life2
1.Middleton 8th Edition
2.Seymour BW, et al. Second-hand smoke increases bronchial hyperreactivity and
eosinophilia in a murine model of allergic aspergillosis. Clin Dev Immunol 2003;10:35-42

Endotoxin
• Tobacco smoke, PM in occupational and domestic
environments
• Effect of early LPS exposure on atopy or asthma
development is unclear
– Hygiene/Farmer hypothesis
• Inhaled LPS interacts with CD14 and TLR4
• ↑CD11b and CD14 in AW monocytes and
macrophages in asthma
• ↑Allergen response: IgE-dependent and present
to mucosal T cells

Amish environment protects against asthma
by shaping the innate immune response
(Picture from Quick Take; Asthma Risk and Farming)
M.M. Stein, et al. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children, NEJM 2016

RS Effects of Air Pollution
• Upper & lower RS symptom
• Acute changes in lung function
– O3: AW inflam & hyperresponsive, asthma, allergen
sensitize (early & late)
– PM: AW inflam, asthma, IHD
– Nox: wheezing, allergen response (early & late), AW
inflam, worsen asthma, ↑RS infection
– SO2, sulfates, acid aerosols : RS irritant,
Bronchospasm(↑exacerbation)
– ETS: asthma
J.A.Bernstein, et al. Health effects of air pollution, JACI 2004

Long-term exposure
• ↑Sensitization to allergens during childhood
– Observational study in Japan: Cedar pollinosis
– Cross-sectional: atopic children, road density
– Meta-analysis: concentrations of PM
• ↑ Asthma, allergy incidence

Decreased Lung Growth of FEV1
Related to Increased Pollutants

Proportion of Children who had low FEV1
Related to Increased Pollutants (exc. O3)

Increased Lung Growth of FEV1
Related to Decreased Pollutants (exc. O3)
Gauderman WJ, et al. Association of Improved Air
Quality with Lung Development in Children, NEJM 2015
Mean 4-Year Lung-Function Growth vs the Mean Levels of Four Pollutants

Management
• Antiinflammation
– NSAIDs: analgesics (not reverse cellular inflam)
– Sodium cromoglycate: inh LPS induced
bronchoconstriction
– ICS: blunt cellular inflame but not prevent
functional AW response
– Selective CXCR2 antagonist: O3-induced AW
neutrophilia (neutrophil-predominant diseases?)

CXCR2 Antagonist
Remo C Russo, et al. The CXCL8/IL-8 chemokine family and its
receptors in inflammatory diseases, Expert Rev. Clin. Immunol. 2014

Management
• Antioxidant
– α-tocopherol + vit C: O3-induced lung function
decrements
– Oral sulforaphane; in broccoli
• Induced phase II enz. in B cells
• Blocked DEP enhancement of IgE production

Environmental Control
• Target
– Primary: avoid sensitize, asthma development
– Secondary: Prevent asthma morbidity
• Multiple intervention over long period of time
(at least 1-2 yr)
M.Hauptman, et al., Environmental Control: The First Tanet of Allergy, JACI Pract 2018

https://www.airvisual.com/air-quality-monitor

Air Cleaning Options
in Residential Buildings
• Whole-house ﬁltration (WHF)
– Filters or cleaners installed on the central HVAC
system)
• Free-standing portable room air cleaners
Louisville, et al. Air ﬁlters and air cleaners: Rostrum by the American
Academy of Allergy, Asthma & Immunology Indoor Allergen Committee, JACI 2010

Whole-house filtration (WHF)
• Heating, Ventilation, Air Conditioning (HVAC) system
• MERV: minimum efficiency reporting value
– Tested by 12 particle sizes 0.3-10 micron as ASHRAE standard
testing method ver 52.2-2007
• Adequate airflow for ventilation
– Residential filters: airflow velocity 300 ft/min (MERV 1-12)
– System’s fan remain on for maximum benefit
• Media filters: maintain efficacy after use
– Loss electrostatic activity

Residential and ofﬁce: MERV 1-12
Ductwork length > 10 ft (3m): MERV ≥ 6

Whole-house filtration (WHF)
1. Panel filters (Inexpensive to higher efficenct)
2. Washable/reuseable filters
3. High-efficiency particulate air (HEPA) filters
4. EACs
5. Hybrid combinations of the prior types

Panel Filters
Inexpensive panel ﬁlters
• No beneﬁt to small particulate
• Capturing and dumping particulates
downstream
• No/very low MERV 1 – 2

Panel Filters
Panel furnace higher-efficiency filters
• The most effective are usually of non-woven
materials, e.g. polyolefin
– Can reach MERV of 11 - 12 in 1-in pleated panel
– American Lung Association Health House
recommends MERV ≥ 11
– Filter change intervals: q 3 mo for residential use with
annual replacement
– Custom installed 2- to 5-in filters: ↑capacity but
expensive

Panel Filters
Washable panel filters
– Metal or woven nylon filament
– If charged materials coated  ↓efficiency
dramatically
– Inadequate washing might leave residual damp
dirt  substrate for mold or bacterial growth

HEPA HVAC Filters
• Minimum particle collection efﬁciency =
99.97% on 0.3 micron of speciﬁed aerosol
– Better greater than and less than that size
• Term HEPA: particulate > 0.3 micron
– Misuse: ‘‘HEPA-type’’ or ‘‘HEPA-like’’ may not
meet performance

HEPA HVAC Filters
• HEPA filters for HVAC systems require bypass
systems
– Up to 80% of the air intake not pass filter because
of high airflow resistance
• Furnace HEPAs: highly efficient in closed
systems

Powered Electronic Filters
• EACs or Electronic Precipitators
• Entering dust, air are ionized in a high-voltage
electric ﬁeld
• Precipitated onto collecting surfaces
• ↓Efﬁciency: the plates load, covered with
dust  recommend clean q 1 month
• Produce low levels of ozone

Composite Component Systems
• EACs
• Standard disposable elements to UV lights
(germicidal effects)
• Coatings for catalytic conversion of ozone

Portable Air Cleaners
• Clean air delivery rate: decay of the presence
of these aerosols (as AHAM standard)
– Cigarette smoke: 0.09 – 1 micron particle size
– Fine calibrated test dust: 0.5 – 3 micron
– Mulberry pollen: 5 – 11 micron
• Label with the clean-air delivery rate numbers
– The higher, the faster cleans

Portable Air Cleaners
• Ionizer air cleaners or purifiers
• HEPA room air cleaners
• Non-HEPA room air cleaners that contain disposable
or washable filters
• Composite of above
‘‘Purifiers’’ (like the EACs): means of an electronic field
Limitation: 1. Unionized particle released
2. Ionization can also produce ozone
(although ozone-to-oxygen converters are now added on many of
these devices)

HEPA Room Air Cleaners
• High-Efficiency Particulate Air
• Filter only particulate (not for gaseous)
• Many RCTs  symptom reduction
• ↓Indoor PM concentration: 25-50%
– ↓Asthma symptoms, exacerbation
• Little evidence to support efficacy in ↓airborne
animal allergens, pollen
• *Nonionizing HEPA purifiers with ↑clean air
delivery rates (room size appropriate)

WHF trail: mostly positive

Need sufficient duration & combined multi-intervention

Summary
Pollutants + climatic changes
= plant, human stressors
• Direct: Inflammation + ↑susceptibility to allergen
• Indirect
– Combining aeroallergens with particles (diesel
exhaust): spreading
– Adaptation of plants to abiotic stress: ↑ qualitative &
quantitative allergenicity

Summary
• History taking: home, + of relatives, school,
daycare, transportation
• Measures
– Source removal
– Source control
– Mitigating strategies

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