Received: 9 March 2023 | Accepted: 4 August 2023

DOI: 10.1111/head.14632

REVIEW ARTICLE

Migraine and air pollution: A systematic review

​​
Andrea E. Portt MSc1 | Christa Orchard MPH1 | Hong Chen PhD1,2,3,4 |
Erjia Ge PhD1 | Christine Lay MD, MSc, FRCP, FAHS5,6 | Peter M. Smith PhD1,7

1
Dalla Lana School of Public Health,
University of Toronto, Toronto, Ontario, Abstract
Canada
Objective: To systematically synthesize evidence from a broad range of studies on the
2
Environmental Health Science and
Research Bureau, Health Canada, Ottawa,
association between air pollution and migraine.
Ontario, Canada Background: Air pollution is a ubiquitous exposure that may trigger migraine attacks.
3
Public Health Ontario, Environmental and There has been no systematic review of this possible association.
Occupational Health, Toronto, Ontario,
Canada Methods: We searched for empirical studies assessing outdoor air pollution and any
4
Populations & Public Health Research quantified migraine outcomes. We included short-­and long-­term studies with quanti-
Program, ICES, Toronto, Ontario, Canada
5
fied air pollution exposures. We excluded studies of indoor air pollution, perfume, or
Centre for Headache, Women's College
Hospital, Toronto, Ontario, Canada tobacco smoke. We assessed the risk of bias with the World Health Organization's
6
Temerty Faculty of Medicine, Neurology, bias assessment instrument for air quality guidelines.
University of Toronto, Toronto, Ontario,
Results: The final review included 12 studies with over 4,000,000 participants.
Canada
7
Institute for Work & Health, Toronto,
Designs included case-­crossover, case–­control, time series, and non-­randomized
Ontario, Canada pre–­post intervention. Outcomes included migraine-­related diagnoses, diary records,

Correspondence
Andrea E. Portt, Dalla Lana School of
Public Health, University of Toronto, 608-­
35 Charles Street West, Toronto, ON M4Y
2R4, Canada.
Email: andrea.portt@gmail.com
Funding information
University of Toronto Open Fellowship;
Ontario Graduate Scholarship; University
of Toronto Data Science Institute Doctoral
Fellowship
medical visits, and prescriptions. Rather than pooling the wide variety of exposures
and outcomes into a meta-­analysis, we tabulated the results.
Point estimates above 1.00 reflected associations of increased risk. In single-­pollutant
models, the percent of point estimates above 1.00 were carbon monoxide 5/5 (100%),
nitrogen dioxide 10/13 (78%), ozone 7/8 (88%), PM2.5 13/15 (87%), PM10 2/2 (100%),
black carbon 0/1 (0%), methane 4/6 (75%), sulfur dioxide 3/5 (60%), industrial toxic
waste 1/1 (100%), and proximity to oil and gas wells 6/13 (46%). In two-­pollutant
models, 16/17 (94%) of associations with nitrogen dioxide were above 1.00; however,
more than 75% of the confidence intervals included the null value.
Most studies had low to moderate risks of bias. Where differences were observed,
stronger quality articles generally reported weaker associations.
Conclusions: Balancing the generally strong methodologies with the small number of
studies, point estimates were mainly above 1.00 for associations of carbon monox-
ide, nitrogen dioxide, ozone, and particulate matter with migraine. These results were
most consistent for nitrogen dioxide.

Abbreviations: ED, emergency department; HR, hazard ratio; OR, odds ratio; PM10, particulate matter 10 microns or less in diameter; PM2.5, particulate matter 2.5 microns or less in
diameter; ppb, parts per billion; RR, risk ratio or relative risk; WHO, World Health Organization.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction
in any medium, provided the original work is properly cited and is not used for commercial purposes.
© 2023 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.

Headache. 2023;63:1203–1219.  wileyonlinelibrary.com/journal/head | 1203

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1204
KEYWORDS
ambient air pollution, emergency department visits, environment, headache, headache diary,
migraine
I NTRO D U C TI O N
Migraine is a brain disease with neurological sequelae that affects
over one billion people and is the second leading cause of years lived
with disability worldwide.1 Environmental exposures might be a con-
tributing factor to migraine attacks among those who experience
the condition; therefore, identifying and avoiding triggers whenever
possible is an important prevention strategy for many people with
2
this condition.
Air pollution is a ubiquitous exposure that impacts respiratory
and cardiovascular health, 3 and has been proposed as a poten-
tial trigger for migraine.4–­6 The potential biological mechanism
through which air pollution may trigger migraine attacks is not
yet fully understood. Most of the world's population is exposed
to elevated ozone, nitrogen oxides, sulfur oxides, carbon mon-
oxide, and particulate matter (PM), which are produced by traf-
7
fic, industrial processes, and burning fossil fuels. As we breathe,
these pollutants may enter the bloodstream via the lungs, or
move directly to the brain via the olfactory nerves. 8 After enter-
ing the body, reactive pollutant chemicals provoke inflammatory
5,9
processes that may lead to migraine attacks. In support of this
biological mechanism, an animal study found that rats exposed to
increasing levels of nitrogen dioxide within realistic air pollution
ranges displayed increasing migraine-­like behavior with higher
levels of nitrogen dioxide. 5 Understanding the relationship be-
tween air pollution and migraine is important because if certain
levels of air pollution are associated with increased frequency of
migraine attacks, it may provide opportunities for interventions
at an individual or community level to reduce migraine burden.
While respiratory risks are likely highest for children and peo-
ple with preexisting conditions, migraine peaks during the third
to fourth decades and often affects otherwise healthy individ-
10,11
uals ; therefore, people with migraine may represent a previ-
ously unconsidered group who benefit from improved air quality.
Given that individuals have limited control over the air they
breathe day-­to-­d ay,12 policy changes are the most effective way
to reduce air pollution exposure.
This review builds upon limited existing work summarizing asso-
ciations between air pollution and migraine and/or headache.13–­15
Specifically, we believe this review represents the first systematic
search for studies of air pollution and migraine, assessment of risk
of bias, and synthesis of the available data. Reflecting the studies to
date, our review includes short-­ and long-­term studies and a wide
variety of air pollution exposures and migraine outcomes. More
broadly, this work builds on the existing evidence of air pollution as a
hazard not only for individuals with preexisting respiratory or heart
conditions,16 but also for those susceptible to neurologic conditions
including migraine.
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HEADA​CHE​
M E TH O D S
Types of studies
The protocol for this review was registered with the PROSPERO In-
ternational prospective register of systematic reviews in November
2021 (registration number CRD42021275394).17 As described in the
protocol, we included peer-­reviewed studies that analyzed the as-
sociation between migraine and air pollution in humans. Recognizing
the dearth of information in this important area of headache medi-
cine, we set out to summarize as much as possible of the available
data. As such, we accepted a wide range of populations, outdoor
air pollutants, comparators, migraine outcomes, and study designs.
We did not restrict based on short-­term or long-­term exposure and
outcome measures. We limited exposures to quantitative (including
binary yes/no) measures of outdoor air pollution. Studies of indoor
air pollution, tobacco smoke, and perfume were excluded. Studies
that did not specify or quantify migraine were excluded, as were
studies that combined migraine with other headaches. Studies were
published in English up to February 2023. We excluded conference
abstracts or presentations, dissertations, case studies, editorials,
and reviews.
Search and study selection
We developed our search strategy, including key terms and data-
bases, in consultation with a librarian. We searched EMBASE and the
Allied and Complementary Medicine Database (AMED) via Ovid, the
Cochrane Library, the Latin American and Caribbean Health Sciences
Literature (LILACS) database, and the Cumulative Index to Nursing
and Allied Health Literature (CINAHL). Our key words included “mi-
graine” as well as “air pollution” and/or “ambient” and/or “ambient air.”
Two reviewers independently screened all titles and abstracts.
Where there was disagreement, the article was included in the next
screening step.
Data extraction
As well as pollution exposure and effect estimate data for single-­and
two-­pollutant models, we also extracted data on covariates. Several
studies examined effect modification by temperature, sex, age, and
time lag between exposure and outcome; therefore we extracted
these data as well. Data were extracted into an Excel document by
either C.O. or A.P., and verified by A.P.
Effect estimates included odds ratios (ORs), hazard ratios (HRs),
relative risks/risk ratios (RRs), percent changes, and percent relative

H​E AD​ACH​E
risks. Percent relative risks were converted to relative risks for ease
of comparison. It is commonly accepted that ORs approximate RRs
when the incidence is less than 5%.18,19 Given the rare frequency
of migraine outcomes, we assumed that odds ratios approximated
risk ratios, and tabulated them side-­by-­side18 For simplicity, we also
included HRs and percentages in the tables.
Where clarification was required or quantitative data were miss-
ing, we emailed the corresponding authors. 20–­22
Assessment of risk of bias
We piloted an assessment tool provided by the World Health Organ-
ization (WHO), the Risk of bias assessment instrument for systematic
reviews informing the WHO global air quality guidelines, 23 with three
selected studies to identify and resolve challenges. This instru-
ment includes assessment of bias in confounding, selection, expo-
sure, outcome, missing data, and selective reporting. For short-­term
studies, critical confounders are temperatures, seasonality, day of
the week, and long-­term trends. Other potential confounders in the
WHO instrument are holidays and influenza epidemics (not used,
see modifications below). For long-­term studies, critical confound-
ers are age, sex, socioeconomic status, and body mass index. Other
potential confounders are year of enrolment, ethnicity, diet, physical
activity, marital status, and smoking. 23
We applied the WHO instrument with the following modifications:
1. Influenza epidemics are seasonal and are associated with respi-
ratory24 and cardiovascular25 outcomes and mortality26 and are
therefore included in “other potential confounders” in the WHO
instrument for air quality guidelines. Given the lack of known
or hypothesized relationship between migraine and influenza,
we did not include influenza in “other potential confounders”
in our assessment of risk of confounding bias.
2. Given the established impact of weather on air pollution, 27 and
the hypothesized association of migraine with humidity and baro-
metric pressure, 28 these two variables were considered “other
potential confounders.”
For each included study, two reviewers independently assessed
the risk of bias. Consensus was achieved through discussion.
Data synthesis
We set out to summarize the modest amount of available informa-
tion on air pollution and migraine outcomes, with the understanding
that many of the studies would not be directly comparable. Indeed,
given the wide variety of exposures and exposure ranges, outcomes,
confounding variables, effect measures, and study designs, the re-
sulting data could not reasonably be pooled for meta-­analysis; there-
fore, we tabulated the results and summarized them narratively. We
also summarized effect modification by lag, temperature, and sex.
|
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1205
Data collection templates, extracted data, and analytic code are
available upon request.
R E S U LT S
Description of studies
Our initial searches identified 124 records. After removing dupli-
cates, 118 titles and abstracts remained. We identified six more
records from searching references within initial search results and
later searches. We piloted our screening process in an open process
on the first 14 publications.
We retrieved 24 full texts for further assessment. Twelve articles
were excluded due to language, 29 study type (case study,30 edito-
rial, or review31–­33), exposure or outcome not being quantified,34,35
headache and migraine being pooled,36 or due to the data being used
in a larger, included study37–­40 (see Figure 1).
Table 1 summarizes the characteristics of the 12 remaining stud-
ies. Reporting was generally incomplete for cohort size, patient, and
migraine attack or event numbers. In terms of reported numbers
alone, the total cohort size was 4,084,937, with 112,642 patients
with migraine, and 84,919 migraine events. Note that the Chen and
Chiu papers used the same cohort and migraine sample for analysis
of different pollutants, and therefore participants and outcomes for
this pair of papers are only counted once in Table 1.
Populations included public or private insurance program pa-
tients, patients with migraine recruited from outpatient clinics
in-­person or by mailed questionnaire, and in one case, residents
of a single small town. Whereas one study specifically focused on
patients with episodic migraine, 20 characteristics of the sample
patients and their migraine conditions were otherwise largely unre-
ported (Table 1). Presumably, migraine attacks recorded in diaries at
home are often less severe than those recorded during emergency
department (ED) visits.
Table 2 summarizes exposures, comparators, outcomes, and
study designs. Exposures were quantified measures of black carbon,
carbon monoxide, methane, nitrogen dioxide, ozone, sulfur dioxide,
residential proximity to oil and gas wells, PM 10 microns or less in
diameter (PM10), and PM 2.5 microns or less in diameter (PM2.5). One
study applied closure of an industrial waste landfill as a binary proxy
for exposure to volatile organic compounds.
Outcomes were quantified migraine events: ED visits, hospital-
izations, headache diaries, reported migraine symptoms, migraine
diagnoses, migraine-­specific drug prescriptions, and estimated mi-
graine severity.
Study designs were mainly case-­crossover, but also included
case–­control, time series, repeated measures analysis, and non-­
randomized pre–­post intervention (see Table 2).
Reporting of the shape of the pollution–­outcome relationship
was incomplete across studies. Studies that did make such a report
employed either linear relationships or non-­linear relationships with
splines.
 |
1206
F I G U R E 1 PRISMA flow diagram of the systematic search for migraine and air pollution and/or ambient and/or ambient air, leading to 12
full-­text studies for review. Modified from Page et al.57 [Color figure can be viewed at wileyonlinelibrary.com]
Transient health outcomes are sometimes reported after a
delay (lag) following environmental exposures.41 Among short-­
term studies, lags varied by length and method of calculation. Lag
lengths spanned from same day to 7 days. The lagged exposures
were either calculated as simple average pollution over the given
days or as distributed lags, which parameterize the time-­response
41
relationship.
Timeframes for long-­term studies ranged from 1 to 5 years (see
Table 2).
Risk of bias
Figure 2 illustrates the proportion of the 12 included studies
within each risk of bias category. The studies were largely well
designed with minor methodological challenges resulting in mod-
erate risk categorization. Risks of bias by study are summarized in
Table 3.
In most categories of risk of bias (selection, exposure, outcome,
missing data, selective reporting) these articles fell within low or
moderate risk, with minor transgressions leading to moderate risk
ratings. For example, one study had a moderate risk of selection bias
due to low response rates in surveys,42 whereas others had a moder-
ate risk of bias from missing data due to lack of reporting of missing
data for exposures 43 or outcomes. 21
In contrast to the other bias categories, the risk of confound-
ing bias was generally moderate to high. For example, eight of
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HEADA​CHE​
the studies met the criteria for moderate risk of confounding bias
simply due to lack of control for holidays. Given that holidays are
relatively rare, this would not be expected to strongly influence
results. One short-­term study met the criteria for high risk of
confounding bias due to missing the critical confounder tempera-
ture,44 while a long-­term study from 1994 did not report on the
critical confounder body mass index.45 Finally, one study scored
low risk of bias by including all of the confounders listed as critical
or potential.46
Given the minimal variation in levels of risk of bias, our ability to
assess effect estimates according to risk of bias was limited. Arti-
cles with low risk of bias tended to report weak positive associations
between pollutant exposures and migraine outcomes. Variation in
point estimates was greater in studies with moderate or high risks of
bias (see Tables S1–­S6).
Estimated effects of pollutants
Short-­term single pollutant studies
Short-­term studies tested the hypothesis that exposure to air pollu-
tion may increase the likelihood of migraine onset or severity within
the next 0–­7 days, as measured by clinic visits, hospitalizations, ED
visits, or migraine diaries. Exposures included black carbon, carbon
monoxide, ozone, PM10 and PM2.5, nitrogen dioxide, ozone, and sul-
fur dioxide.
 H​E AD​ACH​E

TA B L E 1 Characteristics of included studies including population and sample sizes, where reported.

Sample size

Size of Number of patients with Number of

Author Jurisdiction Year Population cohort migraine migraine events

Chen Taipei, Taiwan 2015 Random sample of National Health Insurance (NHI) program 1,000,000 NR 13,676
patients
Chiu Taipei, Taiwan 2015 Random sample of National Health Insurance (NHI) program 1,000,000 NR 13,676
patients
Dales Santiago, Chile 2009 Patients hospitalized for migraine as reported by the Instituto 2,699,000 NR NR
Nacional de Estadisticas
Elser Northern California, USA 2021 Adults with migraine covered by a single insurance company 360,139 89,575 NR
Elser California, USA 2023 Adult members of a commercial and Medicare claims database 9898 NR 5534
Koo Ansan-­city, South Korea 2010 Patients with migraine recruited from an outpatient clinic 245 33 NR
Lee Seoul, South Korea 2018 Patients who visited the ED for migraine as reported by the NR 18,921 NR
National Emergency Department Information System
Li Boston, USA 2019 Adults with episodic migraine recruited from hospitals and clinics NR 98 870
Mukamal Boston, USA 2009 Patients seen in a single ED 7054 2250 NR
Szyszkowicz Multi-­city Canada 2009 Patients who visited the ED for migraine NR NR 64,839
Tustin Pennsylvania, USA 2017 Adult clinic patients who replied to a mailed, self-­administered 7785 1765 NR
questionnaire
Zmirou Montchanin, France 1994 Residents of the town Montchanin 816 NR NR
a
Total 4,084,937 112,642 84,919

Abbreviations: ED, emergency department; NR, not reported.

a
Note that Chen 2015 and Chiu 2015 studied the same cohort and sample of migraine events.
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 TA B L E 2 Summary of study methods including designs, lags, exposures, comparators, and outcomes.
| 1208

Pollution-­
migraine
Author Year Study design Time frame Models Lag type relationship Exposure Comparator Outcome

Chen 2015 Case-­crossover Daily Logistic 3-­day average Linear PM2.5 Odds of clinic visits for migraine Clinic visits
regression on days with 75th percentile
pollution compared to 25th
percentile

Chiu 2015 Case-­crossover Daily Logistic 24-­h average Linear Carbon monoxide, Odds of clinic visits for migraine Clinic visits
regression nitrogen dioxide, on days with 75th percentile
ozone, PM10, sulfur pollution compared to 25th
dioxide percentile

Dales 2009 Time-­series Daily Mixed effects 0–­5 days Linear Carbon monoxide, Risk of hospitalization for migraine Hospitalizations
with undistributed & nitrogen dioxide, on days with 75th percentile
Poisson distributed ozone, PM2.5, PM10, pollution compared to 25th
distribution sulfur dioxide percentile

Elser 2021 Case–­control 5 years Generalized NR/NA Non-­linear: Methane, nitrogen Odds of migraine diagnosis at higher Migraine diagnosis
linear mixed Splines dioxide, oil and gas levels of residential pollutant
wells, PM2.5 exposure compared to lower

Case-­crossover 5 years Negative NR/NA Non-­linear: Methane, nitrogen Risk of migraine outcomes at higher Migraine probability,
binomial Splines dioxide, oil and gas levels of residential pollutant triptan
mixed wells, PM2.5 exposure compared to lower prescriptions,
neurology visits,
urgent care visits,
ED visits

Elser 2023 Case-­crossover Daily Logistic 7-­day average NR/NA PM2.5, overall and from Odds of ED visits for migraine on ED visits
regression wildfire days with 10 μg/m3 higher PM2.5
in the previous week compared
to days with lower PM2.5

Koo 2010 Case-­crossover Daily Logistic 0–­4 day distributed NR/NA Carbon monoxide, Hazard of self-­reported migraine Migraine diaries
regression nitrogen dioxide, in diaries on days with one
ozone, PM10, sulfur unit (ppb or μg/m3) increase in
dioxide pollution compared to days with
one unit lower pollution

Lee 2018 Case-­crossover Daily Logistic Single-­day lag and Linear Carbon monoxide, Odds of ED visits for migraine ED visits
regression moving average nitrogen dioxide, on days with 75th percentile
lag structures up ozone, PM2.5, PM10, pollution compared to 25th
to 7 days prior sulfur dioxide percentile

Li 2019 Repeated measures Daily Fixed effects 1–­3 day averages NR/NA Carbon monoxide, Odds of self-­reported migraine Migraine diaries
analysis logistic nitrogen dioxide, in diary on days with 75th
regression ozone, PM2.5, sulfur percentile pollution compared to
dioxide 25th percentile

Mukamal 2009 Case-­crossover Daily Logistic 0–­2 day distributed NR/NA Black carbon, nitrogen Odds of ED visits for migraine ED visits
regression dioxide, PM2.5, sulfur on days with 75th percentile
dioxide pollution compared to 25th
percentile
HEADA​CHE​

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H​E AD​ACH​E 1209

Our main analysis focused on results with pooled sexes and sea-

Population-­level change

Abbreviations: ED, emergency department; NR/NA, not reported or not applicable; PM2.5, particulate matter 2.5 microns or less in diameter; PM10, particulate matter 10 microns or less in diameter; ppb,
headaches in the

in migraine drug
son or temperatures. We summarized these results in Table 4. Point

past 12 months
Yes/No: Migraine

prescriptions
estimates for the likelihood of migraine events and relatively higher
carbon monoxide, nitrogen dioxide, or ozone ranged from 0.97 to
Outcome

ED visits
1.17.20–22,46–48 The portion of estimates above the null value was 6/6
(100%) for carbon monoxide, 10/13 (77%) for nitrogen dioxide, and 7/8
(88%) for ozone; however, most confidence intervals included 1.00.

in migraine drug prescriptions in

exposure to gas wells compared
the mean pollutant level change

the affected town compared to

Informal comparison of the change
Point estimates for the association between migraine and rel-
Odds of self-­reported migraine by
with 75 percentile residential
amount compared to on days
days with higher pollution by

to 25th percentile exposure

Risk of ED visits for migraine on

atively higher PM10 or PM2.5 ranged from 0.97 to 3.09. 20,22,44,46–49

nation-­wide in France
For PM10 and PM2.5, 3/3 (100%) and 10/11 (91%) of estimates, re-
with lower pollution

spectively, were above the null. Seven of the confidence intervals

excluded the null value.
Comparator

Three of the included studies reported on the association be-

tween sulfur dioxide and migraine outcomes. 20,22,46 The point es-
timates were distributed around the null value, with several falling
below 1.00 (see Table 4).
Mukamal et al.47 estimated the OR for ED visits when black car-
Industrial waste landfill
Ozone, PM2.5, PM10,

bon was relatively higher by 0.51 μg/m3 to be 1.00 (0.93, 1.07) (see
sulfur dioxide

Table 4).
Exposure

Gas wells

Long-­term single pollutant studies

Three studies tested the hypothesis that people living in areas

relationship
Pollution-­
migraine

with higher long-­term exposure to air pollution may have higher

NR/NA
Linear

Linear

numbers of migraine outcomes than those living in areas with

lower pollution. Exposures were measures of methane gas, prox-
imity to oil and gas wells, and industrial landfill closures. Outcomes
included migraine diagnoses or self-­reports, migraine probability,
migraine drug prescriptions, neurology visits, urgent care visits,
Lag type

0–­2 day

NR/NA

NR/NA

and ED visits.
Oil and gas wells release various air pollutants including methane,
nitrogen oxides, PM, petroleum hydrocarbons, sulfur oxides, and vol-
linear mixed

Multiple linear
regression

regression

atile organic compounds.42,48,50 Two studies looked at the association

Generalized

models

between oil and/or gas wells and migraine. Elser et al. found point
Logistic
Models

estimates at or below the null value for the association between 4/5
(80%) of migraine outcomes and a continuous measure of proximity
to oil and gas wells in California.48 In contrast, they reported point
after landfill
before and
12 months

estimates above 1.00 for neurology visits, urgent care visits, and ED
Time frame

closure
18 months
Previous

visits, and migraine probability using a binary measure of wells within

Daily

10 km of residence. Tustin et al. studied survey reports of migraine in

association with unconventional oil and gas well development includ-
ing fracking in Pennsylvania. Oil and gas well exposure was an aggre-
Non-­r andomized,

intervention
Case-­crossover

gate estimate including well activity dates, volume of production, and

pre–­post
Study design

Time series

proximity to participants’ residences. Compared to participants in the

lowest quartile of exposure, those in the second, third, and highest
TA B L E 2 (Continued)

quartiles had 1.14 (0.74, 1.75), 0.89 (0.58, 1.36), and 1.43 (0.94, 2.18)
odd ratios, respectively, for reporting migraine attacks42; therefore,
2009

2017

1994
Year

based on these studies, estimates of potential associations between

parts per billion.

oil and gas extraction and migraine outcomes are mixed (see Table 4).
Szyszkowicz

Point estimates by Elser et al. of the association between long-­

Author

Zmirou
Tustin

term exposure to 10,000 kg/h of methane and 6 migraine outcomes

(diagnoses, triptan prescriptions, neurology visits, urgent care visits,
 |
1210
F I G U R E 2 Results of the risk of bias assessments. Two reviewers applied the Risk of bias assessment instrument for systematic reviews
informing WHO global air quality guidelines23 to all 12 included studies. For selective reporting, missing data, outcome measurement, exposure
assessment, and selection bias, the majority of studies met the criteria for low risk of bias. In contrast, 9 of 12 studies had moderate risk of
confounding bias and two met the criteria for high risk. [Color figure can be viewed at wileyonlinelibrary.com]
ED visits, and migraine probability) were evenly distributed around
the null value 1.00 (see Table 4).
Zmirou et al. described changes in prescribing of migraine drugs
by unit per resident following closure of an industrial toxic waste
landfill in Montchanin, France, in 1988. The landfill had received ad-
hesives, varnishes, and paint waste from 1979 to 1988. Over 300
volatile organic compounds were identified at the site including
benzene, chloroform, methylene chloride (still found in conven-
tional paint strippers in some jurisdictions), trichloroethylene, chlo-
45
robenzene, 1,1,1-­trichloroethane, and 1,1-­dichloroethane. In the
18 months following the closure, the number of units of migraine
drugs prescribed per resident decreased by 17.9% in Montchanin
compared to a 1.01% decrease nationwide (see Table 4).
Effect modification in single-­pollutant models
Potential effect modifications by lag time, sex, season or tempera-
ture, and age were examined in single-­pollutant models.
Ten studies reported estimates for specific lags or long-­term
associations between single pollutant exposures and migraine out-
comes. Most point estimates for all time frames were above the null
value of 1.00. The confidence intervals from the estimates with a
48-­h lag were more likely than other timeframes to exclude the null.
This suggests that if there is an association between air pollution and
migraine outcomes, it may be strongest approximately 2 days follow-
ing exposure (see Table S7). Where distributed and non-­distributed
lags were reported, results were similar regardless of lag distribution
type.45
Dales et al. reported on effect modification by sex in all seasons.
The results showed no evidence of effect modification by sex (see
Table S8).
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HEADA​CHE​
Six studies reported on potential effect modification by season/
temperature with both sexes combined. The point estimates do not
appear to change according to temperature, with the possible ex-
ception of a stronger relationship with ozone during cold weather
(Table S9).
There were limited data to extract on potential effect modifica-
tion by age. One study reported generally higher point estimates and
tighter confidence intervals in the <40 and 40–­6 4 age groups com-
pared to the 65+ age group for carbon monoxide, nitrogen dioxide,
ozone, PM2.5, PM10, and sulfur dioxide.46 Another study reported
a stronger association with sulfur dioxide in warm weather for fe-
males, and also reported that the association with nitrogen dioxide
for males in warm weather was strongest below age 20 and above
age 40.49
We also assessed whether specific migraine outcomes were
more strongly associated with air pollution exposures. We focused
on nitrogen dioxide and PM2.5 as these pollutants were tested in re-
lation to many outcomes. We did not observe any clear pattern (see
Table S10).
Two-­pollutant studies
Four studies controlled for co-­pollutants while assessing the asso-
ciation between air pollutants and clinic visits, ED visits, or hospitali-
zations for migraine. 22,43,46,51 Overall results suggest that estimates
for the association between migraine outcomes and carbon monox-
ide, ozone, and sulfur dioxide may be confounded by co-­pollution
with nitrogen dioxide and PM. Estimates for PM may be confounded
by co-­pollution with carbon monoxide, sulfur dioxide, and nitrogen
dioxide. In contrast, estimates for nitrogen dioxide remained stable
in two-­pollutant models (see Table 5).
 |

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H​E AD​ACH​E 1211

DISCUSSION

Reporting

Moderate
Moderate

Moderate
The objective of this study was to summarize the association be-

Low
Low

Low
Low
Low

Low
Low
Low
Low
tween air pollution exposures and migraine in humans. The over-
all quality of the included studies was high. Nonetheless, the small
Missing Data

number of studies and the wide variety of pollution exposures and

Moderate

Moderate

Moderate
migraine outcomes make it difficult to draw conclusions. To sum-
marize the studies we reviewed, point estimates for single-­pollutant
Low

Low
Low

Low

Low

Low
Low
Low
Low
models between carbon monoxide, nitrogen dioxide, ozone, PM2.5,
and PM10 and migraine outcomes were mainly above the null value.
Moderate

Moderate
Outcome

In contrast to several sub-­studies37–40,49 of a larger study49 included

in our review, estimates for the effect of exposure to sulfur diox-
Low
Low
Low

Low
Low
Low
Low
Low
Low
Low
ide does not suggest increased risk of migraine outcomes. 20,22,43,46
This disagreement may be due to different co-­pollutants or ranges
Moderate

Moderate

Moderate
Moderate
Exposure

of sulfur dioxide. Individual studies found point estimates around

Other sources of bias

the null value for an association between black carbon,47 methane,48

Low
Low
Low

Low

Low
Low
Low
Low

and migraine. Also based on a single study, a population exposed

to volatile industrial waste had a relatively higher level of migraine
drug prescription.45 Results are mixed regarding proximity to oil and
Moderate

Moderate
Moderate
Selection

gas wells.42,48 A lack of available data also limits conclusions about

Low
Low
Low
Low

Low
Low
Low

Low
Low

effect modification by sex, weather, and age. Results from four stud-
ies of two-­pollutant models suggest that positive point estimates of
physical activity, marital status

association with migraine outcomes is most consistent for exposure

Year of enrolment, ethnicity, diet,
Year of enrolment, diet, physical
Missing potential confounders

to nitrogen dioxide.43,46
TA B L E 3 Summary of the studies' risks of bias, including missing critical and other potential confounders.

Holidays, barometric pressure

Holidays, barometric pressure

Holidays, barometric pressure

We chose not to meta-­analyze our results due to lack of com-

parability in comparison ranges, outcomes, and adjustment for
Diet, physical activity
activity, smoking

confounders within individual pollutants. These differences make

it difficult to pool the results and to find a single effect estimate.
Disagreements in results between studies may stem from these dif-
Holidays
Holidays
Holidays

Holidays
Holidays

ferences, or variation in pollutant sources and related unmeasured

None

co-­pollutants. Some studies unsurprisingly found limited evidence

of associations given extremely narrow exposure ranges, for exam-
ple 1 part per billion (ppb) of ozone21 or 0.6 ppb of sulfur dioxide20
(see Table 4). We recommend that future research include prelim-
inary assessments of the population's range of pollution exposure
Body mass index
Missing critical

and limit analyses to areas where the range of exposure is likely to

Temperature
confounders

be clinically relevant. Results from this review suggest that nitrogen

dioxide should be included as a potential pollutant that triggers mi-
None
None
None
None

None
None
None
None
None
None

graine attacks.
With regards to exposure-­response time frames, short-­term
Risk of confounding

studies should include 48-­h lags, as this time frame appears to be

Confounding bias

the most significant for short-­term migraine outcomes. Although

averages and distributed lags yielded similar results in these stud-
Moderate
Moderate
Moderate
Moderate

Moderate

Moderate
Moderate
Moderate
Moderate

ies, we endorse the use of distributed lags. This method parame-

High

High
Low
bias

terizes the lag-­o utcome relationship based on the data, and can
be less biased when the lag between exposure and outcome is
unknown.41
2009

2009
2009
2023
2015
2015

2021

2018
2010

2017
2019

1994
Year

Care should be taken to include the critical and potential con-

founders listed in the WHO's bias assessment instrument, 23 as well
as barometric pressure changes. Finally, we agree with previous
Szyszkowicz
Mukamal

recommendations that analysis of ED visits should be restricted to

Zmirou
Author

Tustin
Dales
Chen

migraine as the main reason for the visit, excluding secondary head-
Elser

Elser
Chiu

Koo
Lee
Li

ache disorders.52
 TA B L E 4 Summary of estimates of the association between air pollution and migraine outcomes in single-­pollutant models.
| 1212

Effect
Pollutant Author Year Type Range Units Outcome Lag Estimate (95% CI) Measure

Black carbon Mukamal 2009 Interquartile range 0.51 μg/m3 ED visits 24 h 1.00 (0.93, 1.07) OR
Carbon monoxide Lee 2018 Interquartile range 2.88 ppm ED visits 24 h 1.03 (1.01, 1.05) OR
Li 2019 Interquartile range 0.15 ppm Migraine diaries 24 h 1.05 (0.94, 1.16) OR
Li 2019 Interquartile range 0.15 ppm Migraine diaries 48 h 1.03 (0.90, 1.19) OR
Dales 2009 Interquartile range 1.15 ppm Hospitalizations 48 h 1.11 (1.06, 1.17) RR
Dales 2009 Interquartile range 1.15 ppm Hospitalizations 48 h: distributed lag 1.14 (1.04, 1.24) RR
Li 2019 Interquartile range 0.15 ppm Migraine diaries 72 h 1.02 (0.85, 1.21) OR
Gas wells Tustin 2017 Quartiles 3rd quartile Weighted distance to Self-­reported Long-­term 0.89 (0.58, 1.36) OR
wells migraine
Tustin 2017 Quartiles 2nd quartile Weighted distance to Self-­reported Long-­term 1.14 (0.74, 1.75) OR
wells migraine
Tustin 2017 Quartiles 4th quartile Weighted distance to Self-­reported Long-­term 1.43 (0.94, 2.18) OR
wells migraine
Oil and gas wells—­binary Elser 2027 Set range 1000-­unit Weighted sum of wells Triptan Long-­term 0.99 (0.94, 1.04) RR
increase within 10 km prescriptions
Elser 2031 Set range 1000-­unit Weighted sum of wells Migraine Long-­term 1.02 (0.97, 1.07) RR
increase within 10 km probability
Elser 2028 Set range 1000-­unit Weighted sum of wells Neurology visits Long-­term 1.09 (1.03, 1.16) RR
increase within 10 km
Elser 2029 Set range 1000-­unit Weighted sum of wells ED visits Long-­term 1.11 (1.00, 1.24) RR
increase within 10 km
Elser 2030 Set range 1000-­unit Weighted sum of wells Urgent care visits Long-­term 1.43 (1.21, 1.70) RR
increase within 10 km
Oil and gas wells—­continuous Elser 2026 Set range 1000-­unit Weighted sum of wells Migraine Long-­term 0.99 (0.99, 1.00) RR
increase within 10 km probability
Elser 2024 Set range 1000-­unit Weighted sum of wells ED visits Long-­term 0.99 (0.98, 1.01) RR
increase within 10 km
Elser 2025 Set range 1000-­unit Weighted sum of wells Urgent care visits Long-­term 0.99 (0.98, 1.01) RR
increase within 10 km
Elser 2023 Set range 1000-­unit Weighted sum of wells Neurology visits Long-­term 1.00 (1.00, 1.00) RR
increase within 10 km
Elser 2022 Set range 1000-­unit Weighted sum of wells Triptan Long-­term 1.00 (1.00, 1.01) RR
increase within 10 km prescriptions
Industrial waste landfill closure Zmirou 1995 Before/After Not applicable Not applicable Migraine drug Long-­term −0.010 (NA, NA) % change
Nationwide, France prescriptions
Zmirou 1994 Before/After in Not applicable Not applicable Migraine drug Long-­term −0.179 (NA, NA) % change
Montchanin, France prescriptions
HEADA​CHE​

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 TA B L E 4 (Continued)

Effect
Pollutant Author Year Type Range Units Outcome Lag Estimate (95% CI) Measure
H​E AD​ACH​E

Methane Elser 2021 Set range 100,000 kg/h ED visits Long-­term 0.88 (0.63, 1.21) RR
Elser 2021 Set range 100,000 kg/h Neurology visits Long-­term 0.95 (0.85, 1.05) RR
Elser 2021 Set range 100,000 kg/h Migraine Long-­term 1.01 (0.94, 1.09) RR
probability
Elser 2021 Set range 100,000 kg/h Triptan Long-­term 1.03 (0.95, 1.12) RR
prescriptions
Elser 2021 No 100,000 kg/h Migraine diagnosis Long-­term 1.04 (1.00, 1.08) OR
Elser 2021 Set range 100,000 kg/h Urgent care visits Long-­term 1.12 (0.92, 1.36) RR
Nitrogen dioxide Mukamal 2009 Interquartile range 8.1 ppm ED visits 24 h 0.97 (0.89, 1.06) OR
Lee 2018 Interquartile range 17.58 ppb ED visits 24 h 1.05 (1.02, 1.09) OR
Li 2019 Interquartile range 11.7 ppb Migraine diaries 24 h 1.05 (0.93, 1.19) OR
Mukamal 2010 Interquartile range 8.1 ppm ED visits 48 h 1.07 (1.00, 1.14) OR
Li 2019 Interquartile range 11.7 ppb Migraine diaries 48 h 1.09 (0.93, 1.28) OR
Dales 2009 Interquartile range 15.43 ppb Hospitalizations 48 h 1.11 (1.06, 1.17) RR
Dales 2009 Interquartile range 15.43 ppb Hospitalizations 48 h: distributed lag 1.19 (1.06, 1.31) RR
Elser 2021 Set range 5.0 ppb Neurology visits Long-­term 0.99 (0.94, 1.05) RR
Elser 2021 Set range 5.0 ppb Migraine Long-­term 1.00 (0.96, 1.05) RR
probability
Elser 2021 Set range 5.0 ppb Triptan Long-­term 1.01 (0.98, 1.06) RR
prescriptions
Elser 2021 Set range 5.0 ppb Migraine diagnosis Long-­term 1.02 (1.00, 1.05) OR
Elser 2021 Set range 5.0 ppb ED visits Long-­term 1.16 (1.05, 1.29) RR
Elser 2021 Set range 5.0 ppb Urgent care visits Long-­term 1.22 (1.02, 1.46) RR
Ozone Li 2019 Interquartile range 14.0 ppb Migraine diaries 24 h 1.17 (1.00, 1.36) OR
Koo 2010 Set range 1.0 ppb Migraine diaries 48 h 1.01 (0.97, 1.05) HR
Li 2019 Interquartile range 14.0 ppb Migraine diaries 48 h 1.15 (0.95, 1.39) OR
Dales 2009 Interquartile range 69.51 ppb Hospitalizations 48 h 1.17 (1.08, 1.26) RR
Koo 2010 Set range 1.0 ppb Migraine diaries 72 h 1.00 (0.97, 1.04) HR
Lee 2018 Interquartile range 21.9 ppb ED visits 72 h 1.03 (1.00, 1.07) OR
Li 2019 Interquartile range 14.0 ppb Migraine diaries 72 h 1.17 (0.93, 1.47) OR
Koo 2010 Set range 1.0 ppb Migraine diaries 96 h 1.01 (0.98, 1.05) HR
3
PM10 Lee 2018 Interquartile range 29.23 μg/m ED visits 144 h 1.03 (1.01, 1.06) OR
Dales 2009 Interquartile range 37.79 μg/m3 Hospitalizations 48 h 1.10 (1.04, 1.15) RR
|

3
Dales 2010 Interquartile range 37.79 μg/m Hospitalizations 48 h: distributed lag 1.11 (1.04, 1.18) RR
1213

(Continues)

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 TA B L E 4 (Continued)
| 1214

Effect
Pollutant Author Year Type Range Units Outcome Lag Estimate (95% CI) Measure

PM2.5 Szyszkowicz 2009 Mean pollutant level 8.3 μg/m3 ED visits 24 h 1.02 (1.00, 1.03) RR
change
Mukamal 2009 Interquartile range 6.7 μg/m3 ED visits 24 h 1.02 (0.96, 1.09) OR
Li 2019 Interquartile range 3.6 μg/m3 Migraine diaries 24 h 1.03 (0.93, 1.15) OR
Li 2019 Interquartile range 3.6 μg/m3 Migraine diaries 48 h 1.02 (0.90, 1.17) OR
3
Lee 2018 Interquartile range 15.22 μg/m ED visits 48 h 1.03 (1.01, 1.05) OR
Dales 2009 Interquartile range 21.51 μg/m3 Hospitalizations 48 h 1.11 (1.00, 1.19) RR
3
Dales 2009 Interquartile range 21.51 μg/m Hospitalizations 48 h: distributed lag 1.14 (0.98, 1.30) RR
Szyszkowicz 2009 Mean pollutant level 8.3 μg/m3 ED visits 72 h 1.02 (1.00, 1.03) RR
change
Li 2019 Interquartile range 3.6 μg/m3 Migraine diaries 72 h 1.05 (0.90, 1.23) OR
Elser 2023 Set range 10.0 μg/m3 ED visits 168 h (7-­day) 0.97 (0.86, 1.10) OR
average
Elser 2021 Set range 5.0 μg/m3 Migraine diagnosis Long-­term 1.00 (0.97, 1.10) OR
3
Elser 2021 Set range 5.0 μg/m Triptan Long-­term 1.03 (0.97, 1.10) RR
prescriptions
Elser 2021 Set range 5.0 μg/m3 Migraine Long-­term 1.14 (1.07, 1.22) RR
probability
Elser 2021 Set range 5.0 μg/m3 Neurology visits Long-­term 1.18 (1.09, 1.29) RR
3
Elser 2021 Set range 5.0 μg/m Urgent care visits Long-­term 3.09 (2.28, 4.2) RR
PM2.5—­Wildfire Elser 2023 Set range 10.0 μg/m3 ED visits 168 h (7-­day) 1.07 (0.83, 1.37) OR
average
Sulfur dioxide Li 2019 Interquartile range 0.6 ppb Migraine diaries 24 h 1.01 (0.93, 1.09) OR
Lee 2018 Interquartile range 2.37 ppb ED visits 24 h 1.02 (0.99, 1.05) OR
Dales 2009 Interquartile range 6.2 ppb Hospitalizations 48 h 1.10 (1.04, 1.17) RR
Dales 2009 Interquartile range 6.2 ppb Hospitalizations 48 h: distributed lag 1.13 (1.05, 1.22) RR

Abbreviations: CI, confidence interval; ED, emergency department; NA, not applicable; OR, odds ratio; ppb, parts per billion; ppm, parts per million; RR, risk ratio or relative risk.
HEADA​CHE​

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 |

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H​E AD​ACH​E 1215

TA B L E 5 Summary of estimates of the association between air pollution and migraine outcomes in two-­pollutant models.

Pollutant Co-­pollutant Author Year Season Interquartile range Units Estimate (95% CI) Effect measure

Carbon None Chiu 2015 Cold 0.29 ppm 1.02 (0.98, 1.07) OR
monoxide Lee 2018 All 2.88 ppm 1.03 (1.01, 1.05) OR
Chiu 2015 Warm 0.29 ppm 1.20 (1.14, 1.26) OR
Nitrogen dioxide Chiu 2015 Cold 0.29 ppm 0.76 (0.69, 0.84) OR
Lee 2018 All 2.88 ppm 1.02 (0.98, 1.05) OR
Chiu 2015 Warm 0.29 ppm 1.18 (1.06, 1.30) OR
Ozone Lee 2018 All 2.88 ppm 1.03 (1.01, 1.05) OR
Chiu 2015 Cold 0.29 ppm 1.15 (1.09, 1.21) OR
Chiu 2015 Warm 0.29 ppm 1.19 (1.14, 1.25) OR
PM10 Chiu 2015 Cold 0.29 ppm 0.99 (0.93, 1.04) OR
Lee 2018 All 2.88 ppm 1.02 (0.99, 1.05) OR
Chiu 2015 Warm 0.29 ppm 1.19 (1.12, 1.27) OR
PM2.5 Lee 2018 All 2.88 ppm 1.01 (0.98, 1.04) OR
Sulfur dioxide Lee 2018 All 2.88 ppm 1.04 (1.01, 1.07) OR
Chiu 2015 Cold 0.29 ppm 1.09 (1.03, 1.16) OR
Chiu 2015 Warm 0.29 ppm 1.22 (1.15, 1.28) OR
Nitrogen dioxide None Lee 2018 All 17.58 ppb 1.05 (1.02, 1.09) OR
Chiu 2015 Cold 8.49 ppb 1.1 (1.05, 1.15) OR
Chiu 2015 Warm 8.49 ppb 1.16 (1.11, 1.21) OR
Carbon monoxide Chiu 2015 Warm 8.49 ppb 1.02 (0.94, 1.11) OR
Lee 2018 All 17.58 ppb 1.06 (1.02, 1.11) OR
Chiu 2015 Cold 8.49 ppb 1.40 (1.27, 1.55) OR
Ozone Chiu 2015 Cold 8.49 ppb 0.98 (0.93, 1.03) OR
Lee 2018 All 17.58 ppb 1.05 (1.02, 1.08) OR
Chiu 2015 Warm 8.49 ppb 1.15 (0.99, 1.09) OR
PM10 Lee 2018 All 17.58 ppb 1.05 (1.01, 1.08) OR
Chiu 2015 Cold 8.49 ppb 1.09 (1.03, 1.14) OR
Chiu 2015 Warm 8.49 ppb 1.15 (1.08, 1.21) OR
PM2.5 Lee 2018 All 17.58 ppb 1.04 (1.00, 1.08) OR
Sulfur dioxide Lee 2018 All 17.58 ppb 1.06 (1.03, 1.1) OR
Chiu 2015 Cold 8.49 ppb 1.20 (1.13, 1.27) OR
Chiu 2015 Warm 8.49 ppb 1.20 (1.14, 1.27) OR
Ozone None Lee 2018 All 21.9 ppb 1.03 (1.00, 1.07) OR
Chiu 2015 Warm 12.5 ppb 1.07 (1.02, 1.12) OR
Chiu 2015 Cold 12.5 ppb 1.23 (1.16, 1.31) OR
Carbon monoxide Lee 2018 All 21.9 ppb 1.03 (1.00, 1.07) OR
Chiu 2015 Warm 12.5 ppb 1.05 (1.00, 1.10) OR
Chiu 2015 Cold 12.5 ppb 1.36 (1.26, 1.47) OR
Nitrogen dioxide Chiu 2015 Warm 12.5 ppb 1.02 (0.97, 1.08) OR
Lee 2018 All 21.9 ppb 1.03 (1.00, 1.06) OR
Chiu 2015 Cold 12.5 ppb 1.43 (1.33, 1.54) OR
PM10 Chiu 2015 Warm 12.5 ppb 1.03 (0.97, 1.08) OR
Lee 2018 All 21.9 ppb 1.03 (1.00, 1.06) OR
Chiu 2015 Cold 12.5 ppb 1.24 (1.16, 1.32) OR
PM2.5 Lee 2018 All 21.9 ppb 1.03 (0.99, 1.06) OR
Sulfur dioxide Lee 2018 All 21.9 ppb 1.03 (1.00, 1.07) OR
Chiu 2015 Warm 12.5 ppb 1.06 (1.01, 1.11) OR
Chiu 2015 Cold 12.5 ppb 1.22 (1.14, 1.31) OR

(Continues)
 |

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1216 HEADA​CHE​

TA B L E 5 (Continued)

Pollutant Co-­pollutant Author Year Season Interquartile range Units Estimate (95% CI) Effect measure
3
PM10 None Lee 2018 All 29.23 μg/m 1.03 (1.01, 1.06) OR
Chiu 2015 Cold 26.81 μg/m3 1.05 (1.01, 1.10) OR
Chiu 2015 Warm 26.81 μg/m3 1.11 (1.06, 1.17) OR
Carbon monoxide Chiu 2015 Warm 26.81 μg/m3 1.01 (0.95, 1.07) OR
3
Lee 2018 All 29.23 μg/m 1.03 (1.00, 1.05) OR
Chiu 2015 Cold 26.81 μg/m3 1.06 (1.01, 1.11) OR
Nitrogen dioxide Chiu 2015 Warm 26.81 μg/m3 1.02 (0.95, 1.08) OR
Lee 2018 All 29.23 μg/m3 1.02 (1.00, 1.05) OR
Chiu 2015 Cold 26.81 μg/m3 1.03 (0.98, 1.07) OR
Ozone Lee 2018 All 29.23 μg/m3 1.03 (1.01, 1.06) OR
Chiu 2015 Cold 26.81 μg/m3 1.06 (1.02, 1.10) OR
3
Chiu 2015 Warm 26.81 μg/m 1.10 (1.04, 1.16) OR
Sulfur dioxide Lee 2018 All 29.23 μg/m3 1.03 (1.01, 1.06) OR
Chiu 2015 Warm 26.81 μg/m3 1.11 (1.05, 1.18) OR
Chiu 2015 Cold 26.81 μg/m3 1.13 (1.07, 1.18) OR
PM2.5 None Chen 2015 Cold 17.48 μg/m3 1.02 (0.98, 1.07) OR
Lee 2018 All 15.22 μg/m3 1.03 (1.01, 1.05) OR
3
Chen 2015 Warm 17.48 μg/m 1.13 (1.08, 1.19) OR
Carbon monoxide Chen 2015 Cold 17.48 μg/m3 1.02 (0.96, 1.08) OR
Chen 2015 Warm 17.48 μg/m3 1.03 (0.97, 1.09) OR
Lee 2018 All 15.22 μg/m3 1.04 (1.01, 1.07) OR
Nitrogen dioxide Chen 2015 Cold 17.48 μg/m3 0.97 (0.92, 1.02) OR
Lee 2018 All 15.22 μg/m3 1.02 (1.00, 1.05) OR
3
Chen 2015 Warm 17.48 μg/m 1.03 (0.97, 1.10) OR
Ozone Chen 2015 Cold 17.48 μg/m3 1.03 (0.98, 1.08) OR
Lee 2018 All 15.22 μg/m3 1.03 (1.01, 1.05) OR
Chen 2015 Warm 17.48 μg/m3 1.13 (1.07, 1.20) OR
Sulfur dioxide Lee 2018 All 15.22 μg/m3 1.04 (1.02, 1.07) OR
Chen 2015 Cold 17.48 μg/m3 1.13 (1.06, 1.20) OR
Chen 2015 Warm 17.48 μg/m3 1.15 (1.09, 1.22) OR
Sulfur dioxide None Chiu 2015 Cold 2.14 ppb 0.94 (0.89, 0.99) OR
Lee 2018 All 2.37 ppb 1.02 (0.99, 1.05) OR
Chiu 2015 Warm 2.14 ppb 1.05 (1.00, 1.10) OR
Carbon monoxide Chiu 2015 Cold 2.14 ppb 0.88 (0.82, 0.94) OR
Chiu 2015 Warm 2.14 ppb 0.97 (0.92, 1.02) OR
Lee 2018 All 2.37 ppb 1.01 (0.97, 1.04) OR
Nitrogen dioxide Chiu 2015 Cold 2.14 ppb 0.84 (0.79, 0.89) OR
Chiu 2015 Warm 2.14 ppb 0.93 (0.88, 0.99) OR
Lee 2018 All 2.37 ppb 1.00 (0.97, 1.03) OR
Ozone Chiu 2015 Cold 2.14 ppb 0.98 (0.93, 1.03) OR
Lee 2018 All 2.37 ppb 1.02 (0.99, 1.05) OR
Chiu 2015 Warm 2.14 ppb 1.04 (0.99, 1.09) OR
PM10 Chiu 2015 Cold 2.14 ppb 0.86 (0.8, 0.92) OR
Chiu 2015 Warm 2.14 ppb 1.00 (0.95, 1.06) OR
Lee 2018 All 2.37 ppb 1.00 (0.97, 1.04) OR
PM2.5 Lee 2018 All 2.37 ppb 0.99 (0.96, 1.03) OR

Abbreviations: OR, odds ratio; PM2.5, particulate matter 2.5 microns or less in diameter; PM10, particulate matter 10 microns or less in diameter; ppb,
parts per billion; ppm, parts per million.

We hope that laboratory studies with animals or humans will possibly via inflammatory mediators.4,5 Most studies reported re-
further improve our understanding of the biological mechanisms un- sults using interquartile ranges for individual pollutant exposures.
derlying possible triggers including air pollution to migraine onset, Reporting relationships between exposures and outcomes using

H​E AD​ACH​E
specific intervals would have increased comparability across studies;
however, research in other outcomes suggests that since the inter-
quartile range represents deviation from local norms, it may be more
physiologically relevant to triggering adverse reactions.53
Another area that remains unclear is the effect of co-­pollution.
Future multi-­pollutant modeling would increase clarity about the in-
dividual and additive impacts of the complex chemical mixtures in
the air we breathe. Measurement of co-­pollutants beyond those re-
ported here is often challenging; however, interesting work is being
carried out to estimate the reactive oxygen potential of air pollu-
tion,54 which could be applicable to migraine.4,6,9
Two recent publications have briefly reviewed associations be-
tween air pollution and headache and/or migraine.13,55 The overall
conclusions of these papers are in agreement with our results. A
scoping review that included a summary of air pollution and head-
ache55 reported point estimates above the null value for associations
between migraine outcomes and carbon monoxide, nitrogen diox-
ide, ozone, PM2.5, and PM10. A recent narrative review of air pollu-
tion and headache disorders56 cited 10 studies in total in relation to
headache. Two reported on headache as opposed to or combined
with migraine, and two were excluded from our review as sub-­
37,38 49
analyses of a larger study. They also included seven of the 12
articles included in our review.
As with any review, there are potential biases in our process. The
WHO risk of bias instrument is not designed for migraine outcomes23;
our modifications may not completely adjust for differences between
the included migraine outcomes and established air pollution-­related
outcomes such as cardiovascular morbidity or all-­cause mortality.
We were unable to properly screen an article published in Arabic,
we were not able to contact some corresponding authors, and some
requested supplementary data were no longer available.21,22
CO N C LU S I O N
Overall, our systematic review provides initial evidence that in addi-
tion to well-­established cardiovascular and respiratory risks,16 air pol-
lution may trigger neurologic effects in the form of migraine attacks. If
air pollution does trigger migraine attacks, both policy and individual
factors would impact migraine frequency. Policy changes are the most
effective way to reduce air pollution exposure. Despite downward
trends, population-­weighted exposure to traffic-­related nitrogen diox-
ide remains high in Europe and North America.3 On an individual level,
the take-­home message is that if these results are confirmed in future
studies, clinicians and patients may begin to consider air pollution ex-
posure as a potential migraine trigger. Patients may take steps to (1)
reduce exposure, for example by choosing active transport over driv-
ing when possible and monitoring air quality reports12; or (2) mitigate
air pollution impacts through acute or preventive treatment.
AU T H O R C O N T R I B U T I O N S
Study concept and design: Andrea E. Portt, Peter M. Smith. Acquisition
of data: Christa Orchard, Andrea E. Portt. Analysis and interpretation
|
15264610, 2023, 9, Downloaded from https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.14632 by Cochrane Hungary, Wiley Online Library on [31/12/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1217
of data: Christa Orchard, Andrea E. Portt, Peter M. Smith. Drafting
of the manuscript: Andrea E. Portt. Revising it for intellectual con-
tent: Hong Chen, Erjia Ge, Christine Lay, Christa Orchard, Andrea
E. Portt, Peter M. Smith. Final approval of the completed manuscript:
Hong Chen, Erjia Ge, Christine Lay, Christa Orchard, Andrea E. Portt,
Peter M. Smith.
AC K N OW L E D G M E N T S
We are grateful to Ms. Maggie Tiong, Manager of Library Services
at the Institute for Work & Health, for her support with the search
strategy.
F U N D I N G I N FO R M AT I O N
Andrea E. Portt is financially supported by the University of Toronto
Open Fellowship. Christa Orchard is financially supported by the
University of Toronto Open Fellowship, the University of Toronto
Data Science Institute Doctoral Fellowship, and the Ontario Gradu-
ate Scholarship.
C O N F L I C T O F I N T E R E S T S TAT E M E N T
Dr. Christine Lay participated in advisory boards for Lundbeck,
TEVA, Miravo, and AbbVie and has received research grants from
Lundbeck, Teva, Miravo, Lilly, and AbbVie. Ms. Andrea E. Portt, Ms.
Christa Orchard, Dr. Hong Chen, Dr. Erjia Ge, and Dr. Peter M. Smith
have no conflicts of interest to declare.
P R OTO C O L R EG I S T R AT I O N
The protocol for this review was registered with the PROSPERO In-
ternational prospective register of systematic reviews in November
2021. Systematic review registration number: CRD42021275394.
ORCID
Andrea E. Portt https://orcid.org/0000-0002-3393-1448
Christa Orchard https://orcid.org/0000-0002-2868-5748
Hong Chen https://orcid.org/0000-0003-0353-3622
Erjia Ge https://orcid.org/0000-0002-3622-3287
Christine Lay https://orcid.org/0000-0002-6281-4857
Peter M. Smith https://orcid.org/0000-0001-8286-4563
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