Characteristics of Pediatric Allergic Rhinitis With Different Disease Severity
Abstract
Background: Although numerous studies have focused on diagnostic biomarkers to help identify allergic rhinitis (AR), data on the characteristics of pediatric AR with different severity is limited. We aimed to compare the characteristics of pediatric AR with different severity.
Methods: A total of 1054 children with AR were enrolled and classified into mild intermittent AR, mild persistent AR, moderate-to-severe intermittent AR, and moderate-to-severe persistent AR. All children were surveyed using a questionnaire that included detailed demographic information. Blood cell analysis was performed using an automatic hematology analyzer.
Results: No significant differences were observed in feeding patterns, dietary habits, outdoor activity time, total IgE, eosinophil count, and eosinophil percentage among the different AR subgroups. However, a higher prevalence of a family history of AR was noted in the moderate-to-severe persistent group. Symptoms were more likely to exacerbate when using air conditioning in children with moderate-to-severe persistent AR. Multivariate regression analysis also showed that symptom exacerbation when using air conditioning was associated with disease severity.
Conclusions: This study suggests that exacerbation of symptoms during air conditioning use can be considered a predictive factor for the severity of pediatric AR. Doctors and parents should pay special attention to these children to prevent more severe symptoms and improve the quality of life of these patients as early as possible.
1. Introduction
Allergic rhinitis (AR) is an IgE-mediated nasal mucosal immune disease caused by common allergens, characterized by increased mucus secretion and airway hyperreactivity [1]. In China, the incidence of AR has increased with the acceleration of industrialization and urbanization [2]. Population-based cross-sectional surveys conducted in various regions of China have revealed that the prevalence of AR among adults varies between 9.6% and 23.9%, with an average prevalence rate of 9.8% observed among children [3, 4]. Although AR is not life-threatening, its severity significantly impacts the quality of life of children [5].
In the Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines, experts have suggested a straightforward qualitative assessment approach to categorize AR severity based on quality-of-life factors such as sleep, learning, and physical activities. This method divides children with AR into two groups: mild (where none of these factors are affected) and moderate-to-severe (where one or more of these factors are impacted) [6].
Although numerous studies have focused on diagnostic biomarkers to help identify AR, data on the characteristics of pediatric AR with different severity is limited [7–9]. We aimed to compare the characteristics of pediatric AR with different severity.
2. Materials and Methods
2.1. Study Subjects
A total of 1054 children with comprehensive AR data, who visited our hospital between August 2015 and August 2023, were consecutively enrolled in the study. Our study has received approval from the Ethics Committee of our hospital, and all children’s guardians were required to assist in completing the informed consent form. The inclusion criteria encompassed the following: the presence of typical nasal symptoms in accordance with the ARIA Guidelines, a positive serum-specific IgE test or skin prick test for at least one type of aeroallergen (including house dust mites [HDM], cockroaches, weed pollen, fungi, cat dander, and dog dander), and an age range of 3–18 years. Children with incomplete clinical data, tumors, mental disorders, or other allergic (asthma, atopic dermatitis) and systemic diseases were excluded from the study.
AR was classified into mild intermittent AR, mild persistent AR, moderate-to-severe intermittent AR, and moderate-to-severe persistent AR based on ARIA Guidelines. Information on gender, age, height, weight, family history, dietary habits, living environment, and other relevant factors were collected.
2.2. Total Nasal Symptom and Medication Scores
The total nasal symptom score encompassed four symptoms: nasal itchiness, nasal congestion, sneezing, and rhinorrhea. Each symptom was rated on a scale from 0 to 3 based on subjective severity. A total score of >0 and ≤4 was defined as mild AR, while a score of >4 and ≤12 was defined as moderate-to-severe AR [10].
The medication scores were assigned as follows: 0 points for no medication use, 1 point for oral and/or topical antihistamines, 2 points for nasal corticosteroid spray, and 3 points for oral corticosteroids. The sum of all medication records constituted the total medication score.
2.3. Laboratory Test
Serum total IgE and allergen-specific IgE were measured using the ELISA method with the Phadia UniCAP 100 analyzer (Sweden). Blood cells were analyzed by an automatic hematology analyzer.
2.4. Statistical Analysis
Statistical analysis was done by SPSS version 23 (SPSS, Chicago, USA). Normally distributed continuous variables were described as mean ± standard deviation and analyzed by the t-test. Categorical variables were presented as rates and percentages and analyzed by the chi-square test. Logistic regression analysis was performed to explore the factors affecting the severity of AR. A p-value less than 0.05 indicated statistical significance.
3. Results
3.1. Demographic Characteristics
Our study comprised 1054 pediatric patients with AR, of which 718 (68.1%) were male and 336 (31.9%) were female. Based on the ARIA classification, 111 patients (10.5%) were diagnosed with mild intermittent rhinitis, 91 patients (8.6%) with moderate-to-severe intermittent rhinitis, 339 patients (32.2%) with mild persistent rhinitis, and 513 patients (48.7%) with moderate-to-severe persistent rhinitis (Table 1). There were no statistically significant differences in age, gender composition ratio, and BMI among different groups.
| Characteristics | AR (n = 1054) | Mild intermittent (n = 111) | Mild persistent (n = 339) | Moderate-to-severe intermittent (n = 91) | Moderate-to-severe persistent (n = 513) | p |
|---|---|---|---|---|---|---|
| Age (years) | 7.29 ± 2.544 | 7.18 ± 2.405 | 7.19 ± 2.477 | 7.66 ± 2.596 | 7.31 ± 2.606 | 0.109 |
| Sex | — | — | — | — | — | 0.722 |
| Male | 718 (68.1) | 71 (64.0) | 230 (67.8) | 61 (67.0) | 356 (69.4) | — |
| Female | 336 (31.9) | 40 (36.0) | 109 (32.2) | 30 (33.0) | 157 (30.6) | — |
| Weight | 26.95 ± 10.606 | 26.96 ± 11.971 | 27.18 ± 10.680 | 28.05 ± 10.722 | 26.60 ± 10.232 | 0.208 |
| Height | 126.85 ± 16.360 | 126.28 ± 16.769 | 127.10 ± 16.185 | 127.17 ± 16.160 | 126.75 ± 16.465 | 0.917 |
| BMI | 16.29 ± 3.775 | 16.26 ± 3.623 | 16.42 ± 4.149 | 17.05 ± 4.625 | 16.08 ± 3.347 | 0.718 |
| Allergen | ||||||
| Derf | 896 (85.0) | 84 (75.7) | 316 (93.2) | 82 (90.1) | 414 (80.7) | 0.31 |
| Derp | 785 (74.5) | 65 (58.6) | 308 (90.9) | 65 (71.4) | 347 (67.6) | 0.23 |
| Cockroach | 69 (6.5) | 17 (15.3) | 12 (3.5) | 14 (15.4) | 26 (5.1) | 0.06 |
| Cat hair | 52 (4.9) | 12 (10.8) | 15 (4.4) | 11 (12.1) | 14 (2.7) | 0.35 |
| Dog hair | 83 (7.9) | 21 (18.9) | 27 (8.0) | 19 (20.9) | 16 (3.1) | 0.12 |
| Fungus | 62 (5.9) | 15 (13.5) | 18 (5.3) | 22 (24.2) | 7 (1.4) | 0.36 |
| Weed pollen | 34 (3.2) | 11 (9.9) | 9 (2.7) | 6 (6.6) | 8 (1.6) | 0.51 |
| Seasonal symptoms | — | — | — | — | — | 0.192 |
| None | 418 (39.7) | 48 (43.2) | 147 (43.4) | 36 (39.6) | 187 (36.5) | — |
| Yes | 636 (60.3) | 63 (56.8) | 192 (56.6) | 55 (60.4) | 326 (63.5) | — |
| Nasal itching | — | — | — | — | — | <0.001 |
| 0: Slight | 470 (44.6) | 64 (57.7) | 174 (51.3) | 39 (42.9) | 193 (37.6) | — |
| 1: Moderately | 376 (35.7) | 34 (30.6) | 114 (33.6) | 35 (38.5) | 193 (37.6) | — |
| 2: Severe | 200 (19.0) | 13 (11.7) | 50 (14.7) | 16 (17.6) | 121 (23.6) | — |
| 3: Unbearable | 8 (0.8) | 0 (0.0) | 1 (0.3) | 1 (1.1) | 6 (1.2) | — |
| Sneeze | — | — | — | — | — | <0.001 |
| 0: None | 53 (5.0) | 9 (8.1) | 14 (4.1) | 4 (4.4) | 26 (5.1) | — |
| 1: 1–5 times | 500 (47.4) | 60 (54.1) | 194 (57.2) | 37 (40.7) | 209 (40.7) | — |
| 2: 6–10 times | 307 (29.1) | 32 (28.8) | 85 (25.1) | 32 (35.2) | 158 (30.8) | — |
| 3: ＞11 times | 194 (18.4) | 10 (9.0) | 46 (13.6) | 18 (19.8) | 120 (23.4) | — |
| Runny nose | — | — | — | — | — | <0.001 |
| 0: None | 187 (17.7) | 32 (28.8) | 65 (19.2) | 15 (16.5) | 75 (14.6) | — |
| 1: 1−5 times | 448 (42.5) | 62 (55.9) | 161 (47.5) | 38 (41.8) | 187 (36.5) | — |
| 2: 6−10 times | 199 (18.9) | 12 (10.8) | 56 (16.5) | 19 (20.9) | 112 (21.8) | — |
| 3: ＞11 times | 220 (20.9) | 5 (4.5) | 57 (16.8) | 19 (20.9) | 139 (27.1) | — |
| Nasal obstruction | — | — | — | — | — | <0.001 |
| 0: None | 69 (6.5) | 16 (14.4) | 36 (10.6) | 3 (3.3) | 14 (2.7) | — |
| 1: Mild | 405 (38.4) | 60 (54.1) | 165 (48.7) | 27 (29.7) | 153 (29.8) | — |
| 2: Moderately | 503 (47.7) | 29 (26.1) | 123 (36.3) | 51 (56.0) | 300 (58.5) | — |
| 3: Severe | 77 (7.3) | 6 (5.4) | 15 (4.4) | 10 (11.0) | 46 (9.0) | — |
| TNSS | 5.35 ± 2.083 | 4.06 ± 1.805 | 4.78 ± 1.984 | 5.68 ± 1.903 | 5.96 ± 2.005 | <0.001 |
| Eye itching | — | — | — | — | — | 0.016 |
| 0: Slight | 757 (71.8) | 91 (82.0) | 260 (76.7) | 63 (69.2) | 343 (66.9) | — |
| 1: Moderately | 189 (17.9) | 14 (12.6) | 56 (16.5) | 17 (18.7) | 102 (19.9) | — |
| 2: Severe | 102 (9.7) | 6 (5.4) | 21 (6.2) | 11 (12.1) | 64 (1.5) | — |
| 3: Unbearable | 6 (0.6) | 0 (0.0) | 2 (0.6) | 0 (0.0) | 4 (0.4) | — |
| Total symptom score | 5.74 ± 2.327 | 4.30 ± 1.933 | 5.08 ± 2.188 | 6.11 ± 2.052 | 6.43 ± 2.278 | <0.001 |
| Medication score | 1.02 ± 0.905 | 0.87 ± 0.906 | 0.99 ± 0.902 | 1.12 ± 0.905 | 1.06 ± 0.905 | 0.147 |
| Symptom-medication score | 6.76 ± 2.505 | 5.17 ± 2.157 | 6.07 ± 2.358 | 7.23 ± 2.251 | 7.49 ± 2.432 | <0.001 |
- Note: Bold for significant differences.
- Abbreviation: AR, allergic rhinitis.
3.2. Comparison of Symptoms and Medication Scores Between Different Among Various Subgroups
The moderate-to-severe group exhibited significantly higher nasal symptom scores, ocular symptom scores, total symptom scores, and symptom medication scores compared to the mild group. Although the medication scores were also higher in the moderate-to-severe group, this difference did not reach statistical significance (Table 1).
3.3. Comparison of Dietary Factors Among Various Subgroups
No significant differences were observed in feeding methods, dietary habits (frequency of seafood, poultry, and pork consumption), or outdoor activity time among the various subgroups of AR (Table 2).
| Items | AR (n = 1054) | Mild intermittent (n = 111) | Mild persistent (n = 339) | Moderate-to-severe intermittent (n = 91) | Moderate-to-severe persistent (n = 513) | p |
|---|---|---|---|---|---|---|
| Feeding method | — | — | — | — | — | 0.155 |
| Powdered milk | 383 (36.3) | 39 (35.1) | 128 (37.8) | 33 (36.3) | 183 (35.7) | — |
| Breast milk | 623 (59.1) | 62 (55.9) | 198 (58.4) | 51 (56.0) | 312 (60.8) | — |
| Combinations | 48 (4.6) | 10 (9.0) | 13 (3.8) | 7 (7.7) | 18 (3.5) | — |
| Seafood | — | — | — | — | — | 0.468 |
| None | 781 (74.1) | 82 (73.9) | 241 (71.1) | 69 (75.8) | 389 (75.8) | — |
| Yes | 273 (25.9) | 29 (26.1) | 98 (28.9) | 22 (24.2) | 124 (24.2) | — |
| Poultry | — | — | — | — | — | 0.924 |
| None | 435 (41.3) | 46 (41.4) | 135 (39.8) | 39 (42.9) | 215 (41.9) | — |
| Yes | 619 (58.7) | 65 (58.6) | 204 (60.2) | 52 (57.1) | 298 (58.1) | — |
| Pork | — | — | — | — | — | — |
| None | 139 (13.2) | 10 (9.0) | 38 (11.2) | 11 (12.1) | 80 (15.6) | 0.136 |
| Yes | 915 (86.8) | 101 (91.0) | 301 (88.8) | 80 (87.9) | 433 (84.4) | — |
| Outdoor activity time (h/day) | — | — | — | — | — | 0.095 |
| ≤1 h | 471 (44.7) | 44 (39.6) | 142 (41.9) | 44 (48.4) | 241 (47.0) | — |
| 2–3 h | 404 (38.3) | 47 (42.3) | 125 (36.9) | 30 (33.0) | 202 (39.4) | — |
| >3 h | 179 (17.0) | 20 (18.0) | 72 (21.2) | 17 (18.7) | 70 (13.6) | — |
- Abbreviation: AR, allergic rhinitis.
3.4. Comparison of Genetic and Environmental Factors Among Various Subgroups
A higher proportion of children with a family history of AR was observed in the moderate-to-severe persistent group. Symptoms were more likely to exacerbate when using air conditioning in children with moderate-to-severe persistent AR. However, no statistically significant differences were found in living environment, region, pet, and plush toy ownership, passive smoking history, air conditioning usage frequency, bedding cleaning frequency, bedroom occupancy time, and carpet ownership among the various subgroups of AR (Table 3). Multivariate regression analysis revealed that only symptom exacerbation when using air conditioning was significantly associated with disease severity (Table 4).
| Factors | AR (n = 1054) | Mild intermittent (n = 111) | Mild persistent (n = 339) | Moderate-to-severe intermittent (n = 91) | Moderate-to-severe persistent (n = 513) | p |
|---|---|---|---|---|---|---|
| Parents’ allergy history | — | — | — | — | — | 0.049 |
| None | 444 (42.1) | 60 (54.1) | 143 (42.2) | 38 (41.8) | 203 (39.6) | — |
| Yes | 610 (57.9) | 51 (45.9) | 196 (57.8) | 53 (58.2) | 310 (60.4) | — |
| Type of residence | — | — | — | — | — | 0.057 |
| Single-story house | 44 (4.2) | 1 (0.9) | 15 (4.4) | 8 (8.8) | 20 (3.9) | — |
| Multi-story building | 1010 (95.8) | 110 (99.1) | 324 (95.6) | 83 (91.2) | 493 (96.1) | — |
| Residential area | — | — | — | — | — | 0.354 |
| Rural | 107 (10.2) | 15 (13.5) | 38 (11.2) | 10 (11.0) | 44 (8.6) | — |
| Urban | 947 (89.8) | 96 (86.5) | 301 (88.8) | 81 (89.0) | 469 (91.4) | — |
| Pet ownership | — | — | — | — | — | 0.774 |
| None | 982 (93.2) | 106 (95.5) | 315 (92.9) | 84 (92.3) | 477 (93.0) | — |
| Yes | 72 (6.8) | 5 (4.5) | 24 (7.1) | 7 (7.7) | 36 (7.0) | — |
| Plush toy ownership | — | — | — | — | — | 0.822 |
| None | 293 (27.8) | 32 (28.8) | 92 (27.1) | 22 (24.2) | 147 (28.7) | — |
| Yes | 761 (72.2) | 79 (71.2) | 247 (72.9) | 69 (75.8) | 366 (71.3) | — |
| Parents’ smoking habits | — | — | — | — | — | 0.653 |
| None | 681 (64.6) | 70 (63.1) | 228 (67.3) | 59 (64.8) | 324 (63.2) | — |
| Yes | 373 (35.4) | 41 (36.9) | 111 (32.7) | 32 (35.2) | 189 (36.8) | — |
| Air conditioner usage frequency | — | — | — | — | — | 0.067 |
| <3 months/year | 82 (7.8) | 2 (1.8) | 29 (8.6) | 10 (11.0) | 41 (8.0) | — |
| ≥3 months/year | 972 (92.2) | 109 (98.2) | 310 (91.4) | 81 (89.0) | 472 (92.0) | — |
| Symptoms worsen with air conditioner usage | — | — | — | — | — | <0.001 |
| None | 318 (30.2) | 49 (44.1) | 123 (36.3) | 27 (29.7) | 119 (23.2) | — |
| Yes | 736 (69.8) | 62 (55.9) | 216 (63.7) | 64 (70.3) | 394 (76.8) | — |
| Bedding washing frequency (times/month) | — | — | — | — | — | 0.948 |
| ≤1 time/month | 362 (34.3) | 39 (35.1) | 118 (34.8) | 33 (36.3) | 172 (33.5) | — |
| >1 time/month | 692 (65.7) | 72 (64.9) | 221 (65.2) | 58 (63.7) | 341 (66.5) | — |
| Time spent in bedroom (h) | — | — | — | — | — | 0.592 |
| <12 h/day | 846 (80.3) | 93 (83.8) | 271 (79.9) | 76 (83.5) | 406 (79.1) | — |
| ≥12 h/day | 208 (19.7) | 18 (16.2) | 68 (20.1) | 15 (16.5) | 107 (20.9) | — |
| Carpet | — | — | — | — | — | 0.052 |
| None | 955 (90.6) | 108 (97.3) | 307 (90.6) | 79 (86.8) | 461 (89.9) | — |
| Yes | 99 (9.4) | 3 (2.7) | 32 (9.4) | 12 (13.2) | 52 (10.1) | — |
- Note: Bold for significant differences.
- Abbreviation: AR, allergic rhinitis.
| Items | OR | Lower limit of 95% CI | Upper limit of 95% CI | p |
|---|---|---|---|---|
| Parents’ allergy history | 0.806 | −0.448 | 0.015 | 0.067 |
| Symptoms worsen with air conditioner usage | 0.524 | −0.893 | −0.399 | <0.001 |
- Note: Bold for significant differences.
3.5. Comparison of Hematological-Related Indicators Among Various Subgroups
No significant differences were observed in total IgE, eosinophil count, and eosinophil percentage among various subgroups of AR (Table 5).
| Indexes | AR (n = 1054) | Mild intermittent (n = 111) | Mild persistent (n = 339) | Moderate-to-severe intermittent (n = 91) | Moderate-to-severe persistent (n = 513) | p |
|---|---|---|---|---|---|---|
| Total IgE | 235 (18–873) | 315 (25–694) | 278 (81–561) | 261 (18–873) | 342 (17–476) | 0.12 |
| EOS counts | 121 (11–1370) | 89 (60–950) | 133 (5–1370) | 157 (22–795) | 53 (45–813) | 0.071 |
| Proportion of EOS | 2.3 (0.4–4.7) | 1.6 (0.2–2.8) | 1.3 (0.5–4.1) | 0.9 (0.4–3.8) | 1.9 (0.8–3.6) | 0.36 |
- Abbreviation: AR, allergic rhinitis.
4. Discussion
In recent years, the incidence of pediatric AR has been on the rise annually, fueled by rapid economic development and increasing environmental changes. An epidemiological study conducted in 2005, utilizing cluster stratified sampling methods, surveyed 23,791 children aged 6–13 years across eight provincial capital cities in four regions. The results revealed that the average prevalence of AR among these children was 9.8% [4]. Additionally, a cross-sectional survey conducted between October 2008 and May 2009 found that the self-reported prevalence of AR was 14.46%, 20.42%, and 7.83% in Beijing, Chongqing, and Guangzhou, respectively [11]. AR significantly impacts children’s health and quality of life and poses a substantial burden on society, making it a global health concern.
The clinical manifestations of AR vary significantly. Mild cases may occur sporadically, with minimal impact on daily life and learning, whereas severe cases can impair breathing and sleep, resulting in lethargy and a substantial decline in quality of life. Consequently, identifying the factors that contribute to the progression of childhood AR from mild to severe holds significant clinical and research value.
Consistent with previous studies, our data revealed that the incidence of AR among boys was significantly higher than among girls, but there was no difference among subgroups, indicating that boys and girls have an equivalent risk of developing severe AR [4]. According to the ARIA classification, only 10.5% of our study population had mild intermittent rhinitis, one-third had mild persistent rhinitis, and over half suffered moderate-to-severe AR, highlighting the significant impact of AR on the majority of children. Although almost all of our subjects were sensitized to mites, ~20% still experienced seasonal symptoms, potentially due to variations in indoor allergen concentrations resulting from seasonal changes in air humidity in Guangzhou.
All nasal symptoms intensified with increasing severity, with severe nasal congestion (a score of 2 or above) affecting nearly 70% of children with moderate-to-severe AR. This suggests that nasal congestion is a prominent manifestation of severe AR in pediatric patients. Interestingly, most children with AR across various severity levels in our study displayed mild ocular pruritus symptoms. This finding may be attributed to our study population consisting of children from southern China, who are predominantly sensitized to mites. Conversely, children sensitized to pollen are more prone to developing ocular pruritus symptoms. Consistent with our results, previous studies have also demonstrated that nasal symptoms are more pronounced in children sensitive to HDM, whereas pollen allergy tends to cause ocular and systemic symptoms [12]. Regarding medication use, although the medication scores were higher in the moderate-to-severe group compared to the mild group, the difference did not reach statistical significance.
A systematic review conducted by Obbagy et al. [13] revealed insufficient and inconsistent evidence to support a correlation between feeding patterns, dietary habits, and the development of AR. Similarly, our study found no association between infant feeding patterns, current dietary habits, and the severity of childhood AR. Moreover, we did not observe significant differences in outdoor activity time among various subgroups.
The occurrence of AR is strongly linked to genetics, with studies indicating a higher risk for children whose parents have AR [14, 15]. This is especially notable in moderate-to-severe AR cases. Our findings also showed a higher proportion of children with a family history of AR in the moderate-to-severe persistent group compared to mild intermittent AR, although there were no significant differences among other groups. However, multivariate regression analysis revealed that family history was not a statistically significant factor.
We found that living environment (flat/apartment) and region (urban/rural) have no significant impact on AR severity, which may be attributed to the fact that ~90% of our subjects come from urban areas and apartments. Environmental factors, such as pets, plush toys, passive smoking, air-conditioner use, bedding cleaning frequency, bedroom duration, and carpet use, did not significantly differ among AR subgroups. Furthermore, total IgE, eosinophil count, and eosinophil percentage were similar across subgroups, indicating that AR severity in children may be more related to local immune changes than systemic changes.
We found that the exacerbation of symptoms during air-conditioner use was the only factor associated with AR severity. Previous studies have identified air-conditioner use in summer is a risk factor for the occurrence and progression of AR [16]. However, some studies suggest air-conditioners protect against wheezing by reducing outdoor allergen exposure [17, 18]. Given mites are a major allergen in southern China; air-conditioner use may expose children with AR to higher mite levels. Therefore, doctors and parents should closely monitor children with AR whose symptoms worsen when using an air-conditioner, as this may indicate a higher initial severity.
This study also has several limitations. First, its single-center design may introduce bias. Second, the focus on mite-allergic children limits the generalizability of findings to regions where pollen or other allergens dominate. Third, some relevant factors were not examined and require further research.
In conclusion, our findings suggest that symptom exacerbation during air-conditioner use can predict AR severity in children. Therefore, doctors and parents should closely monitor such children to prevent symptom progression and improve their quality of life.
Conflicts of Interest
The authors declare no conflicts of interest.
Author Contributions
Yinhui Zeng, Ting Lin, Wanhua Xie, and Shengli Gao contributed equally to this work.
Funding
This research was supported by the National Natural Science Grant of China (82271142), Guangdong Special Support Plan for Top Young Talents, Guangdong Province Natural Science Grant (2024A1515012386), the Science and Technology Program of Guangzhou (2023A03J0909, 2024A03J0141, 2024A03J1095, and 2024A03J1246), Scientific Research Capacity Improvement Project of Guangzhou Medical University (02-410-2302151XM), Guangxi Natural Science Foundation (2024GXNSFBA010264), Guangzhou Health Technology General Guidance Project (20221A011100), and 2024 Joint Funding Project by Guangzhou City, Universities (Institutes), and Enterprises (2024A03J0141).
Open Research
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
