Background:
The relationship between air pollutants, including fine particles (particulate matter [PM] < 10 μm and < 2.5 μm), and aneurysmal subarachnoid hemorrhage (SAH) has been inadequately studied, and the results remain inconclusive. In this study, we attempted to investigate the relationship between air pollutant levels and aneurysmal SAH.
Methods:
Ninety-two patients diagnosed with aneurysmal SAH were retrospectively included in the study. Medical records were reviewed, and levels of pollutants, including those of sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and PM with an aerodynamic diameter < 10 and 2.5 μm (PM10 and PM2.5), were collected from the open-source Air Korea website for a period of 4 days. Independent t-tests were conducted to identify the difference in the pollutant levels between the data obtained on the day of aneurysm rupture (D-0) and the other 3 days (D-7, D-2, and D-1).
Results:
A majority (40.2%) of the patients experienced aneurysm rupture during the fall season when the mean daily pollutant levels were 0.004 ± 0.001 (ppm, SO2), 0.517 ± 0.218 (ppm, CO), 0.02056 ± 0.012 (ppm, O3), 0.02628 ± 0.015 (ppm, NO2), 36.36957 ± 24.538 (μg/m3, PM10), and 19.75581 ± 13.494 (μg/m3, PM2.5), respectively. The level of NO2 was significantly higher on the day of aneurysm rupture (P = .035) than on the other days, while the levels of CO and O3 were nonsignificantly higher (P = .081, P = .055, respectively) on the day of aneurysm rupture than on the other days. There was no significant differences in the PM levels between the 4 days.
Conclusion:
A relationship between PM levels and aneurysm rupture was not identified. Only the levels of classic air pollutant (CO, O3, and NO2) were higher on the aneurysm rupture day than on the other days.
Keywords: aneurysm, particulate matter, pollutant, subarachnoid hemorrhage
1. Introduction
The rupture of an intracranial aneurysm is a common life-threatening disease with high rates of morbidity and mortality. It is now widely accepted that various conditions including abnormal blood pressure, smoking habits, and environmental factors can affect the occurrence of aneurysmal subarachnoid hemorrhage (SAH).[1] Research on the association between weather conditions and acute cardiovascular events has been gaining attention[2–6]; however, there is a lack of conclusive data on the relationship between air pollutants and aneurysmal SAH.[7] Recent research has highlighted that the ambient air pollution is regarded as a significant risk factor for acute vascular diseases.[8,9] Mounting evidence has suggested that adverse health effects have been most consistently associated with fine particles < 10 μm and < 2.5 μm in size.
In Korea, citizens can freely access the hourly and daily levels of particulate matter (PM) < 10 μm and < 2.5 μm, since these data have been reported on the government website since 2002 and 2015, respectively (Fig. 1). Herein, we attempted to investigate the relationship between air pollutant levels and the occurrence of aneurysmal SAH by using open-source data.
Figure 1.
An image captured from the Air Korea website showing the air pollutant levels and the location of the observatory.
2. Methods
2.1. Patients and data acquisition
Medical records of the patients who were admitted to the neurosurgical department of our hospital between Jan 2017 and Dec 2018 with a diagnosis of spontaneous SAH confirmed by brain computed tomography (CT) were retrospectively reviewed. Among the reviewed patients, several patients were excluded due to inadequate medical records (n = 3) or a diagnosis of nonaneurysmal SAH (n = 3). A total of 92 patients were enrolled; the flowchart of patient enrollment is shown in Figure 2. The current study was approved by the appropriate Institutional Review Board of our institution, and the requirement for informed consent was waived due to the retrospective design of the study.
Figure 2.
Flowchart of patient enrollment and the timing of data acquirement.
We retrospectively gathered the data of the included patients, including age, sex, past medical history, address, the day of aneurysmal rupture, location and physiology of the aneurysm, clinical features (World Federation of Neurosurgical Societies grade), and in-hospital courses. In addition, the daily average levels of pollutants, including those of sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and PM with an aerodynamic diameter < 10 μm and < 2.5 μm (PM10 and PM2.5), for a period of 4 days were retrospectively collected (Fig. 2). Pollutant levels were obtained using the average of the data for each day, which were freely available on the Air Korea website (www.airkorea.or.kr/eng).
2.2. Statistical analysis
Continuous values are presented as means and standard deviations, while categorial variables are presented as numbers and percentages. For identifying the difference between the pollutant levels, independent t-tests were conducted using the data of the rupture day (D-0) and the other 3 days (D-7, D-2, and D-1). Statistical significance was considered at P < .05. The statistical analyses were performed using a standard software (version 23.0, SPSS, IBM, Chicago, IL).
3. Results
Table 1 shows the baseline characteristics of the enrolled patients. The mean age of patients was 58 years, and one third of the patients were male. Anterior cerebral- or anterior communicating artery was the most common location of the aneurysmal rupture (41.3%), with the mean maximal diameter of the aneurysm being 4.762 ± 2.284 mm. The majority (40.2%) of the patients experienced aneurysm rupture during the fall season (Fig. 3). The mean daily levels of pollutants were 0.004 ± 0.001 (ppm, SO2), 0.517 ± 0.218 (ppm, CO), 0.02056 ± 0.012 (ppm, O3), 0.02628 ± 0.015 (ppm, NO2), 36.36957 ± 24.538 (μg/m3, PM10), and 19.75581 ± 13.494 (μg/m3, PM2.5). Surgical clipping was marginally preferred, and the recorded death rate was 6.5%.
Table 1.
Baseline characteristics of the enrolled patients.
| Parameters | Value | ||
|---|---|---|---|
| Patients | Age | 58.75 | ±14.972 |
| Sex (female) | 62 | (67.391%) | |
| History | |||
| Hypertension | 40 | (43.478%) | |
| Diabetes | 11 | (11.957%) | |
| Smoking | 26 | (28.261%) | |
| Alcohol | 40 | (43.478%) | |
| Radiologic findings | Location | ||
| ACoA, ACA | 38 | (41.304%) | |
| MCAB, MCA | 25 | (27.174%) | |
| PCoA, ICA | 22 | (23.913%) | |
| Posterior circulation | 7 | (7.609%) | |
| Geometry | |||
| Neck | 3.455 | ±1.228 | |
| Max | 4.762 | ±2.284 | |
| Width | 4.234 | ±1.817 | |
| Height | 4.638 | ±2.014 | |
| Clinical features | WFNS grade | ||
| 1 | 5 | (5.435%) | |
| 2 | 13 | (14.130%) | |
| 3 | 5 | (5.435%) | |
| 4 | 9 | (9.783%) | |
| 5 | 60 | (65.217%) | |
| Meteorological factors | Seasons | ||
| Spring | 19 | (20.652%) | |
| Summer | 22 | (23.913%) | |
| Fall | 37 | (40.217%) | |
| Winter | 14 | (15.217%) | |
| Pollutant’s level | |||
| SO2 (ppm) | 0.004 | ±0.001 | |
| CO (ppm) | 0.517 | ±0.218 | |
| O3 (ppm) | 0.02056 | ±0.012 | |
| NO2 (ppm) | 0.02628 | ±0.015 | |
| PM10 (μg/m3) | 36.36957 | ±24.538 | |
| PM2.5 (μg/m3) | 19.75581 | ±13.494 | |
| Courses | Treatment | ||
| surgical clipping | 53 | (57.609%) | |
| endovascular coiling | 38 | (41.304%) | |
| others | 1 | (1.087%) | |
| Hospital days | 35.89 | ±25.814 | |
| Hydrocephalus | 14 | (15.217%) | |
| Vasospasm | 12 | (13.043%) | |
| Recorded death | 6 | (6.522%) | |
Figure 3.
The plots of the incidence of aneurysmal subarachnoid hemorrhage according to the seasons and months.
Table 2 shows the differences in the pollutant levels between the day of rupture (D-0) and the other 3 days (D-7, D-2, and D-1). The level of NO2 was significantly higher on the day of rupture (P = .035) than on the other days, while the levels of CO and O3 were also higher than those on the other days, but without statistical significance (P = .081, P = .055, respectively). Conversely, there were no significant differences in the PM levels between the 4 days.
Table 2.
Comparison of the pollutant’s levels between the ruptured and nonruptured days.
| Pollutants | Nonruptured days (n = 276) |
Ruptured days (n = 92) |
Mean differences | 95% CI | P-value | |
|---|---|---|---|---|---|---|
| SO2 | .003578 ± .0015367 | .003552 ± .0013611 |
.0000254 | −.0003285 | .0003793 | .335 |
| CO | .51558 ± .251851 | .51739 ± .218315 | −.001812 | −.059562 | .055938 | .081* |
| O3 | .019391 ± .0129752 | .020560 ± .0121277 | −.0011685 | −.0041915 | .0018546 | .055* |
| NO2 | .025880 ± .0172086 | .026280 ± .0149060 | −.0004004 | −.0043457 | .0035450 | .035† |
| PM10 | 35.43 ± 25.081 | 36.37 ± 24.538 | −.938 | −6.844 | 4.967 | .565 |
| PM2.5 | 18.18 ± 15.483 | 18.67 ± 13.873 | −.489 | −4.079 | 3.101 | .244 |
P < .1.
P < .05.
4. Discussion
Based on our results, there was no relationship between PM levels and aneurysm rupture. Only levels of the classic air pollutants (CO, O3, NO2) were higher on the day of aneurysm rupture than on the other days.
The influence of weather conditions (especially air pollution) on variations in the onset of vascular disease has been highlighted in previous studies. However, to our knowledge, data on the relationship between aneurysmal SAH and PM levels are rare in the literature. Previous reports have focused on classic meteorological parameters including SO2, O3, NO2, and CO levels. In our study, several informative findings were observed which are discussed below.
Seasonal differences were observed in our cohort, and a majority of the patients experienced aneurysm rupture during the fall season. Further, the lowest incidence was observed during the winter, which was contradictory to the findings of previous reports.[10–12] This variation might be associated with the characteristic temperature fluctuations during fall in Korea. Gill et al reported that temperature fluctuations (from cold to warm to cold) during fall and spring are associated with increased incidence of aneurysmal SAH.[13]
Further, we also observed that several important pollutants such as NO2, CO, and O3 might be associated with aneurysm rupture. Nitrogen dioxide is an oxidizing free radical which can initiate a variety of destructive pathways, especially in living systems; several diseases are suspected to be related to both exogenously and endogenously formed NO2.[14] Since NO2-derived free radicals initially come in contact with the lung parenchyma and then get absorbed into the blood vessels, NO2 is highly associated with respiratory as well as cardiovascular disease.[15] Besides, it freely passes though the vascular system and initiates destructive mechanisms in the arterial walls, which can cause acute as well as chronic vessel wall diseases. Thus, we can infer that the NO2-derived free radicals can also affect the vulnerable walls of cerebral aneurysms, resulting in a rupture. O3 also has functions similar to those of NO2-derived free radicals. It is a powerful oxidant that can accelerate the oxidation of vessel walls and may be associated with cerebral aneurysm rupture.[16]
Moreover, carbon monoxide is a well-known endogenous gas with an important physiological role in circulation. The release of CO by vascular cells exerts both paracrine and autocrine effects on the vascular smooth muscle cells and circulating blood cells. Furthermore, CO regulates blood flow rate and fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation.[17] Excess blood CO levels may be associated with the overexpression of the smooth muscle cells and their proliferation in the media and platelet aggregation in the intima of the cerebral aneurysm, which might promote inflammatory changes in the vessel wall.
We were unable to verify the association between PM and aneurysmal SAH due to several reasons. The current study was a single-institutional study, and hence the enrolled patients with aneurysmal SAH were limited to the local area. Population, aneurysmal SAH incidence, and regional PM levels should be simultaneously considered to identify the association between PM and aneurysmal SAH. Further, the small number of included patients was inadequate for verifying the hypothesis. Aneurysmal rupture is known to be affected by multifactorial reasons, and perhaps a nation-wide dataset is necessary for reducing the confounding parameters. Finally, our study was retrospectively designed, and thus, the results cannot be generalized. Aneurysmal SAH incidence tracing according to PM levels and alterations and fluctuations in temperature can be studied using prospective studies in the future.
5. Conclusion
No relationship between the PM levels and aneurysm rupture was identified. Further, levels of the classic air pollutants (CO, O3, NO2) were higher on the day of aneurysmal rupture than on other days.
Author contributions
Conceptualization: JH Kim, SH Lee, DH Park Formal analysis: JH Kim, SH Park Funding acquisition: JH Kim, DH Park Methodology: JH Kim, SH Lee, SH Park Software: JH Kim Supervision: DJ Lim, DH Park Validation: JH Kim, DJ Lim, DH Park Visualization: JH Kim, SH Lee Writing – original draft: JH Kim Writing – review & editing: JH Kim, DH Park.
Abbreviations:
- CT =
- computed tomography
- PM =
- particulate matter
- SAH =
- subarachnoid hemorrhage.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Statement of ethics: The current study was approved by the Institutional Review Board of the Human Research Center of the institution, and requirement for informed consent was waived due to the study’s retrospective design.
Conflict of interest statement: The authors have no conflicts of interests to disclose.
Funding source: The study was supported in part by Korea University Grants (JH Kim: K2211771, DH Park: K2111291).
How to cite this article: Kim JH, Lee SH, Park SH, Lim DJ, Park DH. The relationship between air pollutant levels and aneurysmal subarachnoid hemorrhage. Medicine 2022;101:36(e30373).
Contributor Information
Jang Hun Kim, Email: jhkimns@naver.com.
Sang-Hoon Lee, Email: pibada106@hanmail.net.
Se-Heum Park, Email: doctorns@korea.com.
Dong-Jun Lim, Email: djlim@korea.ac.kr.
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