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Article

The Hypothesis of the Interplay Between Air Particulate Matter PM2.5 and Acute Cellular Rejection Episodes Following Heart Transplantation

by
Tomasz Urbanowicz
1,*,
Krzysztof Skotak
2,
Dominika Konecka-Mrówka
3,
Hanna Wachowiak-Baszyńska
1,
Rafał Skowronek
3,
Jędrzej Sikora
4,
Jakub Bratkowski
2,
Jan Kaczmarek
4,
Maksymilian Misiorny
4,
Ewa Straburzyńska-Migaj
5,
Jerzy Nożyński
3 and
Marek Jemielity
1
1
Cardiac Surgery and Transplantology Department, Poznan Univeristy of Medical Sciences, 61-107 Poznan, Poland
2
Institute of Environmental Protection—National Research Institute, 02-170 Warsaw, Poland
3
Department of Histopathology, Silesian Centre for Heart Disease, Medical University of Silesia in Katowice, 41-800 Zabrze, Poland
4
Student Research Group, Medical Faculty, Poznań University of Medical Sciences, 61-107 Poznan, Poland
5
1st Cardiology Department, Poznan Univeristy of Medical Sciences, 61-107 Poznan, Poland
*
Author to whom correspondence should be addressed.
Atmosphere 2025, 16(2), 234; https://doi.org/10.3390/atmos16020234
Submission received: 27 December 2024 / Revised: 10 February 2025 / Accepted: 11 February 2025 / Published: 18 February 2025
(This article belongs to the Special Issue Cutting-Edge Developments in Air Quality and Health)
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Versions Notes

Abstract

:
Background: In end-stage HF, interventional therapy is the treatment of choice, including mechanical circulatory support and heart organ transplantation. Acute cellular rejection is considered a major impediment to the long-term survival of cardiac allografts. The aim of this study is to point out a possible relationship underlying acute cellular rejection risk in heart organ recipients. Methods: A total of 30 (25 (83%) men and 5 (17%) women) heart organ recipients with a median (Q1–Q3) age of 49 (38–60) were enrolled in the analysis. The results from repeated hospitalizations due to protocolar endomyocardial biopsies performed between one and three months following the heart transplantation in relation air pollution exposure were taken into the analysis. Results: The median (Q1–Q3) observation time after organ transplantation was 92 (82–97) days. A significant difference in PM2.5 exposure between the rejection group (16.10 (14.24–17.61)) μg/m3 and the non-rejection group (11.97 (9.85–12.97)) μg/m3 was noticed (p < 0.001). The odds ratio (95% confidence interval) for acute rejection prediction related to PM2.5 was 1.79 (1.11–2.89), p = 0.018. The reviewer operator curve for acute cellular rejection related to PM2.5 exposure was performed, and the area under the curve (AUC) was 0.873, yielding a precision of 0.600 and an f-measure of 0.545. The predicted residual plots for PM2.5 indicated a 50% increased risk for PM2.5 above 16 μg/m3 and of 91% for PM2.5 above 20 μg/m3. Conclusions: The single-center study was performed on a limited number of heart organ recipients and was related to personalized individual calculations of PM2.5 exposure. The study represents a personalized approach and indicates possible links to the hypothesis, which should be verified on a higher volume of patients.

1. Introduction

The epidemic of heart failure (HF) is reported as a current challenge, and its prevalence is increasing due to the aging of the population and improved survival with ischaemic heart disease [1]. It is considered a multi-faceted and potentially life-threatening syndrome [2]. The efficacy and efficiency of novel pharmacotherapies has been confirmed [3]. In end-stage HF, interventional therapy is the treatment of choice, including mechanical circulatory support and heart transplantation [4]. For optimal long-term results, patients are still assigned to organ transplantation. The shortage of heart donors, combined with marginal organ acceptance, limited efforts to expand the donor pool, and increased risks of acute rejection episodes, post-transplant malignancy, and renal dysfunction, has led to increasing suboptimal results.
Acute cellular rejection is considered a major impediment to the long-term survival of cardiac allografts [5]. The effectiveness of current immunosuppressive strategies that target recipient T cells has been reported, though these do not address innate immune response [6]. Acute cellular rejection (ACR) risk within the first year following heart transplantation is reported in up to 20% of organ recipients and is believed to represent the imbalance between a conventional versus regulatory CD4+ T cell alloimmune response [7].
Ambient air particles negatively affect human health, increasing cardiovascular, neurological, respiratory, and malignancy risk. These pollutants were found to elicit cytokines released by airway epithelium and activate hematopoietic and non-hematopoietic cells, including dendritic cells and fibroblasts [8]. In animal studies, ischemic renal reperfusion injury related to PM2.5 exposure was noted through local innate immune aggravation and mitochondrial dysfunction [9]. Ambient fine particles can lead to immune damage, emphasizing oxidative stress, inflammatory responses, and immune cells [10]. Short-term exposure to PM2.5 may even exaggerate the inflammatory response in autoimmune diseases [11]. The cardiotoxic effect of air pollution is believed to be mainly mediated by sympathovagal imbalance, oxidative stress amplification, and inflammatory and pro-aggregatory cascade activation [12]. Dendritic cell activation next to higher secretions of necrosis factor-α (TNF-α) 1-beta, and interleukins 6 and 8 (IL-1β, IL-6, IL-8) in response to PM2.5 has been already noticed [13]. The aggravation of chronic obturatory pulmonary disease (COPD) secondary to airborne PM2.5 particles was found to be related to the enhancement of autophagy in alveolar macrophages [14].
The aim of the study is to point out the possible relationship underlying acute cellular rejection risk in heart organ recipients.

2. Materials and Methods

2.1. Patients

A total of 30 (25 (83%) men and 5 (17%) women) heart transplant recipients with a median (Q1–Q3) age of 49 (38–60) were enrolled in the analysis.
The results of endomyocardial biopsies (EMBs) performed for the first 6 months following heart transplantation were examined in relation to the applied pharmacotherapy and the air pollution (measured by PM2.5 air particulate matter) in habitation places. The first two biopsies performed within the first postoperative month were excluded from the analysis to rule out the possible relation of cold ischemia-related myocardial injury. The analysis did not include recurrent acute cellular rejection (ACR) patients. None of the patients reported use of air conditioning in their habitation place.

2.2. Method

Heart transplant recipients’ and donors’ demographic and clinical preoperative characteristics were examined. The results of protocolar endomyocardial biopsies performed during repeated hospitalizations between one to three months following heart transplantation were taken into the analysis, in relation air pollution exposure.
The laboratory test results, including tacrolimus (TACR) and mycophenolate mofetil (MPA) serum concentrations in combination with transthoracic echocardiography and endomyocardial biopsies (EMBs), were considered in the analysis and compared with possible exposure to air pollutants in the habitation place.
Based on acute cellular rejection confirmed with EMB, the group was divided into a rejection (Group 1) and control group (Group 2).

2.3. Endomyocardial Biopsies

All endomyocardial biopsies (EMBs) were examined in the reference center. Biopsy fragments were fixed in a 4% buffered formaldehyde solution, and then routinely dehydrated in ethyl alcohol series and transferred to paraffin wax through xylene. Tissue slices 5 microns thick were stained H&E (hematoxylin and eosin). The rejection grade was estimated using ISHLT’s working formulation [15] (Figure 1). Acute cellular rejection (ACR) was defined as stage 2 (more focus on lymphocytic infiltrate with associated myocardial damage), 3 (multifocal or diffuse lymphocytes infiltrate with myocardial damage), or stage 4 (diffuse, polymorphous infiltrate with extensive myocyte damage, edema, vasculitis, hemorrhage) [15].

2.4. Personalized Calculations of Air Pollution Exposure in Habitation Place

To assess patients’ individual exposure to PM2.5, we used all the available air quality data. The State Environmental Monitoring (SEM) data were applied to render previous reports [16]. SEM is established based on the Act of Inspection of Environmental Protection to provide reliable data on the state of the environment [17].
Calculations involved time-dependent high-resolution bottom–up emission inventory maps stored in the Central Emission Database were elaborated based on Standard Nomenclature for Air Pollution (SNAP) categories including the main air pollutant emission sectors in Poland like residential emission, energy production, industry, transport, and agriculture [18].
Outdoor exposure to air pollution was estimated based on patients’ home addresses. The mean values for air pollution within a particular period defined by the analysis time frame were calculated based on mean values between two environmental monitoring stations and the habitation place.

2.5. Statistical Analysis

The normality of the distribution of variables was tested with the Shapiro–Wilk test. The t-test, Cochran–Cox test or Mann–Whitney test, or Fisher’s exact test were used where applicable to compare the variables between the two groups. ANOVA tests evaluated the repeated measures. The odds ratio was calculated with 95% confidence intervals for acute cellular rejection in relation to PM2.5 exposure. The receiver operator curve (ROC), alongside the precision and f-measure, was calculated to predict ACR due to PM2.5. Statistical analysis was performed using JASP version 0.14.1 (University of Amsterdam, Netherlands), with the significance level set at p < 0.05 (https://jasp-stats.org, accessed on 5 February 2025).
The sample was estimated using the minimum sample size estimation tool of the PQStat software (v. 1.8.6). Based on the assumption of an undetermined target population size, α = 0.05 and β = 0.2, the minimum sample size was estimated at 24 participants. Hence, the authors decided to collect full data from at least 30 participants.

2.6. Bioethics Committee

The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Ethics Committee of Poznan University of Medical Sciences, Poznan, Poland (protocol code 694/20 on 4 November 2020), for studies involving humans.

3. Results

There were neither fatal events nor clinical presentations of acute cellular rejection in the presented group throughout the study period. The median (Q1–Q3) observation time after organ transplantation was 92 (82–97) days.
Laboratory tests combined with transthoracic echocardiography were performed prior to EMB at the following intervals: 21 (17–28) days, 35 (31–42) days, 69 (57–77) days, and 92 (82–97) days after transplantation. If the EMB confirmed ACR, the standard protocol included a 3000 mg parenteral infusion of methylprednisolone, followed by an increase in oral steroid therapy and a control EMB within 7 days. Only the original results, without one week post-ACR EMB steroid therapy effects, were considered in the analysis.
There were eight patients with EMB-confirmed acute myocardial rejection, and they were treated with standard steroid therapy, including parenteral infusion of an overall amount of three grams of methylprednisolone within three days. Based on acute cellular rejection confirmed with EMB, the group was divided into a rejection (Group 1) and control group (Group 2). The demographic and clinical characteristics of the heart organ recipients in both subgroups are presented in Table 1.
Four consecutive protocolar EMB results in relation to applied anti-rejection pharmacotherapy were considered, as presented in Table 2.
There were no significant changes in tacrolimus serum concentrations in the whole group (p = 0.017), nor between the rejection and non-rejection subpopulations (p = 0.554), as presented in Figure 2.
There were significant changes in mycophenolate mofetil acid serum concentrations within the whole group (p = 0.447) and also between rejection and non-rejection subpopulations (p = 0.059), as presented in Figure 3.
The peripheral blood count results, including myocardial injury markers such as Troponin-I serum concentration, were considered in analysis and found to be inconclusive for ACR prediction within the whole group (p = 0.412) and also between rejection and non-rejection subgroups (p = 0.955).
Inflammatory markers like C-reactive protein (CRP) were analyzed throughout the study period. They did not reveal any significant differences for ACR prediction between the rejection and non-rejection subgroups (p = 0.647), as shown in Figure 4.
The air pollution exposure related to particulate matter PM2.5 was individually calculated for each heart transplant recipient. The mean values of the air PM2.5 concentration throughout the study period were examined and compared between both groups. A significant difference in PM2.5 exposure between the rejection group (16.10 (14.24–17.61)) μg/m3 and the non-rejection group (11.97 (9.85–12.97)) μg/m3 was noticed (p < 0.001) (Figure 5).
The possible relation between air pollution particles and acute rejection risk was examined for PM2.5, PM10, and NO2, as presented in Table 3.
The odds ratio (95% confidence interval) for acute rejection prediction related to PM2.5 was 1.79 (1.11–2.89), p = 0.018. The reviewer operator curve for acute cellular rejection related to PM2.5 exposure was performed, and the area under the curve (AUC) was 0.873, yielding a precision of 0.600 and an f-measure of 0.545. The predicted residual plots for PM2.5 indicated a 50% increased risk for PM2.5 above 16 μg/m3 and 91% for PM2.5 above 20 μg/m3, respectively, as presented in Figure 6.

4. Discussion

The novelty of our analysis is based on the possible relationship between increased acute cellular rejection risk following heart organ transplantation and ambient air pollution. This personalized analysis suggests that environmental factors may possibly trigger an inflammatory host response that results in ACR. According to our results, ambient pollution related to PM2.5 may influence ACR risk, especially when the PM2.5 concentration exceeds 20 μg/m3.
This analysis indicates the possible role of non-traditional acute rejection factors linked to excessive immunological activation.
Heart organ transplantation is considered the optimal therapeutic resort for patients with end-stage heart failure. Among the main post-transplant complications, acute rejection episodes, even with satisfactory serum levels of immunosuppression, followed by opportunistic infection risk and eminent malignancy risk, are reported [19]. Noninvasive markers for clinically silent graft rejection have been proposed [20,21].
The pharmacological immunosuppressive agents applied after organ transplantation either inhibit cytokine release or the cell cycle. The anti-rejection regimen following heart transplantation is calcineurin inhibitor-based therapy, which blocks interleukin 2 transcription via FKBP12 [22,23]. Interleukin 2 and its receptors play a substantial role in cell-mediated immunity, particularly T lymphocyte proliferation and activation. Typically, calcineurin inhibitors combined with mycophenolate mofetil and steroids are considered the first-line therapy of choice. Mycophenolate mophetil suppresses T-cell proliferation by restraining guanosine nucleotide synthesis [24]. The mycophenolate is administered as a pro-drug [25]. The third drugs included in the standard immunosuppressive protocol are corticosteroids. They display immunomodulatory and anti-inflammatory characteristics by decreasing the number of circulating CD4+ T lymphocytes, interacting with antigen-presenting dendritic cells [26]. We thoroughly investigated the applied drug dosages and levels when estimating the rejection risk. The therapeutic serum levels of anti-rejection drugs were achieved throughout the monitoring period in the analyzed group [27,28].
Ambient particulate matter below 2.5 microns in diameter (PM2.5) comprises solid and liquid particles that are mostly the product of industrial activity, gasoline combustion, cigarette smoke, and biomass burning [29]. The two possible methods of immunological system irritation by PM2.5 inhalation are related to inflammatory cell activation, which releases various mediators, and particle translocation via the pulmonary epithelium to the bloodstream, leading to oxidative stress and vascular dysfunction [30]. Our analysis suggests a 50% increase in rejection risk among heart recipients exposed to ambient PM2.5 above 15 µg/m3. The acute cellular rejection risk among patients chronically exposed to PM2.5 above 20 µg/m3 increased to over 90%.
The respiratory system is particularly vulnerable to PM2.5 as these particles may trigger oxidative stress via mitochondrial dysfunction, oxidases, and metabolic enzyme activation [31]. PM2.5-induced lipid peroxidation and endothelial cell injury are believed to recruit innate immunity cells and propagate atherosclerosis [32]. Our previous analysis revealed the relationship between air pollutant exposure and premature epicardial artery disease development [33,34]. The beneficiary role of immunosuppressive drugs on PM2.5-generated inflammatory activation has been reported in animal studies [35].
There is a growing awareness of the possible modulatory role of ambient pollution on organ recipient outcomes. Previous reports [36] suggested a relationship between 1-year acute rejection in kidney recipients and PM2.5, highlighting the importance of environmental exposure on post-transplant outcomes. A recent epidemiological study [37] indicated an association between ambient PM2.5 levels and an increased risk of either graft failure or fatal events in lung transplant recipients. In the cohort study by Chan et al. [38], PM2.5 exposure was reported as an independent risk factor associated with adverse outcomes following kidney transplantation. Airborne fine particles may enact their negative impact on solid organ recipients as early as in the first three postoperative months [39]. Al-Kindi et al. [40] investigated long-term survival in heart transplant patients, pointing out an estimated mortality hazard ratio per 10 μg/m3 increment in annual exposure to PM2.5.
In the analyzed population, the rejection group was older. A higher rejection rate is generally associated with younger patients, as the innate and adaptive immunological response declines with age [41,42]. The presented possible relation to air pollution may be even more extensive in older heart recipients, which should be confirmed through studies with a higher volume of participants.
Air pollutant exposure can be related to geographical factors, as we found significant differences in coronary artery disease risk, secondary to inflammatory reactions triggered related to habitation place urbanization [43]. As we did not include patients who are professionally active or living in air-conditioned accommodations in the analysis, the presented results can be regarded free from influence from these factors. A multivariable analysis in a larger cohort of patients is required to confirm the presented phenomenon.

Study Limitations

The single-center study was performed on a limited number of heart organ recipients and was related to personalized individual calculations of PM2.5 exposure. The study represents a personalized approach and indicates possible links to the hypothesis that should be verified in a longitudinal multi-center, high-volume study that incorporates additional biomarkers in order to better to understand the immune response to air pollutant particles and to confirm the suggested relationship using multivariable models.
This study was performed as a single-center analysis on a relatively small sample size, which limits its statistical power and generalizability. The relatively short observation period might not have captured the long-term effects of PM2.5 exposure. The analysis was based on outdoor air pollutant exposure in habitation places. We did not investigate the long-term consequences of acute rejection episodes on chronic graft dysfunction or mortality.

5. Conclusions

This study’s results present the hypothesis of a possible relation between acute rejection episodes in heart transplant recipients and personalized PM2.5 exposure. This hypothesis may help to understand the phenomenon of ACR in solid-organ donors undergoing adequate immunosuppressive therapy. Further studies are required to confirm the proposed link.

Author Contributions

Conceptualization, T.U. and K.S.; methodology, K.S., D.K.-M., R.S., J.N. and J.B.; validation, K.S. and J.B.; formal analysis, T.U., K.S. and J.B.; investigation, J.S., H.W.-B., J.K., M.M., D.K.-M., R.S. and J.N.; resources, H.W.-B., J.S., J.K. and M.M.; data curation, K.S., J.K., M.M., E.S.-M. and M.J.; writing—original draft preparation, T.U.; writing—review and editing, K.S., H.W.-B., R.S., J.S., J.K., M.M., E.S.-M., J.N. and M.J.; visualization, T.U., D.K.-M., R.S. and J.N.; supervision, M.J.; project administration, T.U. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of Poznan University of Medical Sciences, Poznan, Poland (protocol code 694/20 on 4 November 2020) for studies involving humans.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Data supporting the obtained results will be available upon reasonable request via the corresponding authors’ e-mail contact within 3 years following the publication.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. The histopathologic confirmation of no-acute cellular rejection: grade 0 (a) and grade 1a (b).
Figure 1. The histopathologic confirmation of no-acute cellular rejection: grade 0 (a) and grade 1a (b).
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Figure 2. The tacrolimus serum concentration in the ACR group (1) and control group (0).
Figure 2. The tacrolimus serum concentration in the ACR group (1) and control group (0).
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Figure 3. The mycophenolate mofetil serum concentration in the ACR group (1) and control group (0).
Figure 3. The mycophenolate mofetil serum concentration in the ACR group (1) and control group (0).
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Figure 4. The C-reactive protein (CRP) level in the ACR group (1) and control group (0).
Figure 4. The C-reactive protein (CRP) level in the ACR group (1) and control group (0).
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Figure 5. The PM2.5 median exposure in the ACR group (1) and control group (0).
Figure 5. The PM2.5 median exposure in the ACR group (1) and control group (0).
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Figure 6. ACR prediction in relation to PM2.5 exposure.
Figure 6. ACR prediction in relation to PM2.5 exposure.
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Table 1. Group demographic and clinical characteristics.
Table 1. Group demographic and clinical characteristics.
ParametersWhole Group
n = 30		Rejection Group
n = 8		Control Group
n = 22		p
Rejection vs. Control
Group
Recipients
Demographic:
Age (years) (median (Q1–Q3)49 (38–60)60 (55–62)46 (38–57)0.046
Sex (male (%)/female (%))25 (83)/5 (17)5 (62)/3 (38)20 (91)/2 (9)0.075
BMI (kg/m2) (median (Q1–Q3)25.3 (23.5–28.7)25.1 (24.3–26.5)26.1 (22.6–29.7)0.639
Primary diagnosis:
DCM (n (%))17 (57)2 (25)15 (68)0.041
ICM (n (%))6 (20)4 (50)2 (9)0.016
Other (n (%))7 (23)2 (25)5 (23)1.000
Co-morbidities:
Arterial hypertension (n (%))10 (33)3 (38)7 (32)0.796
Dyslipidemia (n (%))9 (30)3 (38)6 (27)0.616
Kidney dysfunction (n (%))6 (20)1 (13)5 (23)0.565
Diabetes mellitus (n (%))5 (17)2 (50)3 (14)0.490
COPD (n (%))3 (10)0 (0)3 (14)0.545
Smoking (n (%))6 (20)0 (0)6 (27)0.155
Donors
Demographic:
Age (years) (median (Q1–Q3)31 (26–41)30 (25–38)32 (27–43)0.756
Sex (male (%)/female (%))27 (90)/3 (10)7 (87)/1 (13)20 (91)/2 (9)1.000
BMI (kg/m2) (median (Q1–Q3)23 (20–25)23 (21–24)23 (19–25)0.812
Abbreviations: BMI—body mass index; COPD—chronic pulmonary obstructive disease; DCM—dilated cardiomyopathy; ICM—ischemic cardiomyopathy; kg—kilogram; m—meter; n—number; Q—quartile.
Table 2. Laboratory, echocardiographic, and endomyocardial biopsy (EMB) results.
Table 2. Laboratory, echocardiographic, and endomyocardial biopsy (EMB) results.
ParametersWhole Group
n = 30		Rejection Group
n = 8		Control Group
n = 22		p
Rejection vs. Control
Group
1st EMB
Time after HTX (days) (median (Q1–Q3)21 (17–28)20 (19–28)22 (17–28)0.925
Immunosupression:
TACR daily dose (mg) (median (Q1–Q3)6.0 (4.0–7.8)6.0 (3.0–6.3)6.0 (4.0–8.0)0.523
TACR serum concetration (ng/mL) (median (Q1–Q3)13.9 (11.5–17.9)17.6 (11.6–22.1)13.6 (11.5–17.0)0.341
MMF daily dose (g) (median (Q1–Q3)2.5 (1.6–3.0)2.0 (1.5–2.6)2.5 (2.0–3.0)0.239
MMF level (ug/mL) (median (Q1–Q3)2.9 (1.8–4.8)4.90 (2.48–5.23)2.75 (1.88–3.68)0.273
Steroid daily dose45 (30–65)55 (30–60)45 (21.3–62.5)0.918
Echocardiography
LVEDD (mm) (median (Q1–Q3)45 (43–48)43 (41–47)45 (44–48)0.945
LVEF (%) (median (Q1–Q3)65 (65–68)65 (65–68)66 (65–68)1.000
EMB results:
no-ACR (n (%))27 (90)5 (63)22 (100)0.014
ACR (n (%))3 (10)3 (37)0 (0)
2nd EMB
Time after HTX (days) (median (Q1–Q3)35 (31–42)32 (29–36)36 (30–44)0.118
Immunosupression:
TACR daily dose (mg) (median (Q1–Q3)6.0 (5.0–7.8)5.8 (5.0–7.0)6.0 (4.3–7.8)0.687
TACR serum concetration (ng/mL) (median (Q1–Q3)15.3 (11.4–18.4)17.7 (16.2–20.6)13.9 (11.0–18.3))0.079
MMF daily dose (g) (median (Q1–Q3)2.0 (1.5–2.5)1.8 (1.5–2.1)2.0 (1.5–2.9)0.466
MMF level (ug/mL) (median (Q1–Q3)2.7 (1.8–3.9)1.8 (1.4–2.8)2.8 (1.9–4.3)0.184
Steroid daily dose35 (15–50)45 (28–55)35 (16–44)
Echocardiography
LVEDD (mm) (median (Q1–Q3)43 (41–46)42 (42–44)43 (40–47)0.439
LVEF (%) (median (Q1–Q3)68 (65–68)65 (62–67)68 (65–68)0.092
EMB results:
no-ACR (n (%))29 (90)7 (88)22 (100)0.267
ACR (n (%))1 (10)1 (12)0 (0)
3rd EMB
Time after HTX (days) (median (Q1–Q3)69 (57–77)68 (54–76)70 (58–78)0.205
Immunosupression:
TACR daily dose (mg) (median (Q1–Q3)5.0 (4.0–7.0)3.5 (2.8–5.8)5.0 (4.3–7.0)0.228
TACR serum concetration (ng/mL) (median (Q1–Q3)13.2 (10.9–16.0)15.7 (13.2–16.7)12.7 (10.9–15.2)0.270
MMF daily dose (g) (median (Q1–Q3)1.5 (1.5–2.0)2.0 (1.5–2.0)1.5 (1.5–2.1)0.889
MMF level (ug/mL) (median (Q1–Q3)2.8 (1.7–3.8)2.4 (0.8–3.5)2.4 (1.7–4.2)0.366
Steroid daily dose25 (15–40)40 (30–40)23 (11–30)0.076
Echocardiography
LVEDD (mm) (median (Q1–Q3)45 (42–49)43 (39–47)46 (43–50)0.519
LVEF (%) (median (Q1–Q3)65 (65–68)65 (63–67)68 (65–70)0.321
EMB results:
no-ACR (n (%))28 (93)6 (75)22 (100)0.064
ACR (n (%))2 (7)2 (25)0 (0)
4th EMB
Time after HTX (days) (median (Q1–Q3)92 (82–97)79 (67–96)92 (90–99)0.259
Immunosupression:
TACR daily dose (mg) (median (Q1–Q3)3.8 (3.2–5.2)3.3 (3.0–5.5)4.0 (3.3–5.0)0.867
TACR serum concetration (ng/mL) (median (Q1–Q3)12.8 (11.0–15.2)12.9 (11.2–14.7)12.7 (10.4–16.2)0.729
MMF daily dose (g) (median (Q1–Q3)1.8 (1.5–1.9)2.0 (1.5–2.0)1.5 (1.5–2.1)0.077
MMF level (ug/mL) (median (Q1–Q3)4.6 (3.2–6.1)4.0 (2.9–5.5)5.0 (4.0–7.0)0.213
Steroid daily dose15.7 (14–20)17.5 (15–20)15 (13–20)0.639
Echocardiography
LVEDD (mm) (median (Q1–Q3)45 (42–49)43 (39–47)45 (42–50)0.174
LVEF (%) (median (Q1–Q3)65 (63–68)65 (62–67)65 (63–68)0.899
EMB results:
no-ACR (n (%))28 (93)6 (75)22 (100)0.064
ACR (n (%))2 (7)2 (25)0 (0)
Abbreviations: ACR—acute cellular rejection; EMB—endomyocardial biopsy; HTX—heart transplantation; LVEDD—left ventricular end-diastolic diameter; LVEF—left ventricular ejection fraction; MMF—mycophenolate mofetil; TACR—tacrolimus; mm—millimeter; n—number; Q—quartile.
Table 3. The predictive value of air pollutants on acute rejection episodes.
Table 3. The predictive value of air pollutants on acute rejection episodes.
Air PollutantsOR95% CIp
PM2.51.791.11–2.890.018
PM101.940.87–3.210.174
NO26.930.65–12.560.167
Abbreviations: CI—confidence interval; OR—odds ratio; PM2.5—airborne particle matter at least 2.5 um of diameter; PM10—airborne particle matter at least 10 um of diameter; NO2—airborne nitric dioxide.
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Urbanowicz, T.; Skotak, K.; Konecka-Mrówka, D.; Wachowiak-Baszyńska, H.; Skowronek, R.; Sikora, J.; Bratkowski, J.; Kaczmarek, J.; Misiorny, M.; Straburzyńska-Migaj, E.; et al. The Hypothesis of the Interplay Between Air Particulate Matter PM2.5 and Acute Cellular Rejection Episodes Following Heart Transplantation. Atmosphere 2025, 16, 234. https://doi.org/10.3390/atmos16020234

AMA Style

Urbanowicz T, Skotak K, Konecka-Mrówka D, Wachowiak-Baszyńska H, Skowronek R, Sikora J, Bratkowski J, Kaczmarek J, Misiorny M, Straburzyńska-Migaj E, et al. The Hypothesis of the Interplay Between Air Particulate Matter PM2.5 and Acute Cellular Rejection Episodes Following Heart Transplantation. Atmosphere. 2025; 16(2):234. https://doi.org/10.3390/atmos16020234

Chicago/Turabian Style

Urbanowicz, Tomasz, Krzysztof Skotak, Dominika Konecka-Mrówka, Hanna Wachowiak-Baszyńska, Rafał Skowronek, Jędrzej Sikora, Jakub Bratkowski, Jan Kaczmarek, Maksymilian Misiorny, Ewa Straburzyńska-Migaj, and et al. 2025. "The Hypothesis of the Interplay Between Air Particulate Matter PM2.5 and Acute Cellular Rejection Episodes Following Heart Transplantation" Atmosphere 16, no. 2: 234. https://doi.org/10.3390/atmos16020234

APA Style

Urbanowicz, T., Skotak, K., Konecka-Mrówka, D., Wachowiak-Baszyńska, H., Skowronek, R., Sikora, J., Bratkowski, J., Kaczmarek, J., Misiorny, M., Straburzyńska-Migaj, E., Nożyński, J., & Jemielity, M. (2025). The Hypothesis of the Interplay Between Air Particulate Matter PM2.5 and Acute Cellular Rejection Episodes Following Heart Transplantation. Atmosphere, 16(2), 234. https://doi.org/10.3390/atmos16020234

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