High body mass index with the risk of allergic conjunctivitis in children: a case-control study in Southwest China

Abstract

Purpose

To assess the correlation of body mass index (BMI), diet and lifestyle with allergic conjunctivitis (AC) in children.

Methods

This prospective case-control study included 105 children with AC and 105 age- and sex-matched children with no AC. Clinical data were collected, including BMI, dietary habits, physical activity, and sleep time. Multivariate regression analysis was used to analyze the risk factors for AC.

Results

Dietary habits including vitamin A supplement use (χ2 = 0.00; P = 1.00), the consumption of sweet food (χ2 = 6.70; P = 0.08), fast food (χ2 = 3.74; P = 0.29), beverages (χ2 = 1.17; P = 0.76), and seafood and fish (χ2 = 6.15; P = 0.10) and snacking before sleep (χ2 = 2.23; P = 0.53), were not associated with AC. There were significant differences in physical activity (χ2 = 12.64; P < 0.01) between the children with AC and healthy children. Physical activity of less than 1 h per day is more found among AC and more than 2 h of exercise per day is more found in healthy children. There were no differences in sleep duration (χ2 = 5.39; P = 0.07). Multivariate regression analysis revealed that a high BMI (overweight and obesity) (OR = 3.05; 95% CI: 1.30–7.20; P = 0.01) was a significant risk factor for AC. The consumption of fish oil supplements (OR = 0.38; 95% CI: 0.17–0.81; P = 0.01) and having been breastfed (OR = 0.34; 95% CI: 0.16–0.72; p = 0.005) were protective factors against AC.

Conclusion

A high BMI (overweight and obesity) can increase the incidence of AC. Breastfeeding and dietary supplementation with fish oil are recommended for children susceptible to AC.

Introduction

Allergic conjunctivitis (AC) is a progressively increasing disease that seriously decreases the quality of life of children and their parents [1, 2]. With growth in living standards and changes in lifestyle, the incidence of AC is increasing in China [3]. The prevalence of AC is reported to be as high as 40% in the United States and approximately 15–20% in Asia [4, 5], and there is increasing concern about AC in developing countries [6]. Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are the most common forms of AC, with a prevalence of 37.4% and 14.0%, respectively [7]. SAC and PAC are associated with the IgE-mediated type I hypersensitivity reaction, therefore the two forms have the same clinical features, such as itching, redness, and conjunctival swelling [8].

Allergens, smoking, and environmental pollution are recognized as important environmental factors leading to the development of allergies. Unhealthy lifestyles such as sedentary habits, high physical activity, and short sleep time were associated with allergic rhinitis [9]. A longtime watching television or video games was positively associated with asthma [10]. At the same time, a poor-quality diet involving a high caloric intake, an irregular lifestyle, overweight, and obesity in children and adolescents accelerates the occurrence and development of allergic diseases [11]. Overweight, frequent consumption of lollipops and candies, snacking, and eating before bedtime were positively associated with asthma and allergic rhinitis [10, 11]. In recent years, the prevalence of obesity has increased dramatically in China [12, 13]. Experimental and clinical studies have demonstrated that obesity is a major risk factor for the development of allergic diseases [14, 15].

Numerous risk factors, including poor nutritional status, are associated with allergic diseases in children. There was a high prevalence of malnutrition associated with poor dietary habits in patients with atopic dermatitis (AD) allergic rhinitis (AR) and asthma [16, 17]. Several studies have evaluated the beneficial effects of long-chain polyunsaturated fatty acids (LCPUFAs) and vitamin D on allergy diseases [2, 18]. Breastfeeding could be protective against some allergic phenotypes [19], such as food allergy [20] and asthma [21]. Nevertheless, no studies have evaluated the association of lifestyle, dietary habits, and nutritional status with AC in children. Thus, the purpose of this study was to assess the association of nutritional status, dietary habits and lifestyle with AC in children.

Materials and methods

Study design

This single-centre, case‒control study was carried out in the Outpatient Department of Ophthalmology at the Children’s Hospital of Chongqing Medical University from 1 February 2022 to 30 June 2022.

The sample size was calculated based on the results from previous studies on dietary habits and allergic disease. We assumed that the incidence of obesity in those with allergic diseases was 20%, assuming a power of 90% with a 2-sided test of 5%. The estimated sample size was 52 participants in each group by using PASS (Power Analysis and Sample Size) software. Considering a dropout rate of 20%, a total of 65 subjects were recommended for each group.

Subjects

Participants in this study were children younger than 16 years of age who attend the medical centre during the study period. The paediatric patients in the case group were clinically diagnosed with seasonal allergic conjunctivitis (SAC) or perennial allergic conjunctivitis (PAC) according to allergic history and slit-lamp examinations in our previous study [16]. Each patient had clinical symptoms such as ocular itching, redness, and swelling of the conjunctiva. The control group consisted of 105 age- and sex-matched healthy children without an allergy history. Other allergic diseases, such as bronchial asthma (BA), allergic rhinitis (AR) and atopic dermatitis (AD), were obtained from patients’ medical records. Allergic diseases were required to be diagnosed by a doctor from corresponding departments.

The exclusion criteria were as follows: (1) having been treated with steroids, antihistamine or antibiotic drugs in the last three months; (2) having a history of ocular trauma or ocular surgery; (3) having any active ocular infection with the potential to confound the results of the study; and (4) having a history of rheumatism, diabetes, and other metabolic, psychological or systemic diseases.

Body mass index (BMI)

Body height was measured by a stadiometer, and body mass was measured with an electronic scale by a nurse during the first visit. Body mass index (BMI) was calculated by the following formula: body mass in kilograms divided by the square of height in meters (kg/m²). Obesity was defined as BMI-for-age greater than 2 standard deviations above the WHO growth reference median, as recommended by the WHO [17]. In this analysis, BMI was calculated as weight/height². Sex- and age-specific BMI z scores were calculated using the equation from Cole et al. [18] based on the centile curves for Chinese children and adolescents [19]. Overweight/obesity was defined according to both the Working Group on Obesity in China (WGOC) [20] and the International Obesity Task Force (IOTF) BMI cut-offs for children [18].

Dietary habits

According to Chinese dietary habits, the researchers designed a questionnaire based on the items of the Food Frequency Questionnaire (FFQ) [21] and Children’s Dietary Questionnaire [22]. The questionnaires were completed by parents, assessing the diet of children in the last 12 months. The questionnaires collected information on dietary habits, such as consumption of sugar and other sweeteners (syrups, sweet spreads, sweets and marshmallows, chocolate and bars, ice cream, jelly desserts, sweet sauces, sweet baking ingredients), fast food (hamburger, pizza, takeaways, fried chicken and chips), and sugar-sweetened beverages (sweetened fruit juice drinks and nectars, soft drinks/sodas, sweetened teas and waters, instant beverages, sweetened sport drink).

Physical activity and sleep time

Lifestyle was evaluated according to the amount of time spent participating in physical activity (none, ≤ 1 h per day, 2 ~ 3 h per day, > 3 h per day) and sleeping (< 8 h/d, 8 ~ 10 h/d, > 10 h/d).

Statistical analysis

Data were analyzed using SPSS version 18.0 software (SPSS, Inc., Chicago, IL, USA). Values for continuous variables are presented as the mean ± the standard deviation. The quantitative data between the groups were compared using the Student’s t-test. Categorical variables were compared with the chi-square test. Ordered categorical data were analyzed by trend chi-square test. The odds ratios (ORs) and 95% confidence intervals were analyzed by logistic regression to evaluate the factors related to AC. For univariate analysis, the occurrence of AC and possible confounding variables including age, sex, family history of smoking, breastfeeding, items in dietary habits, sleeping time, physical exercise, and BMI were compared. Variables with a statistical significance of P < 0.01 in the univariate analysis were included in the multivariate model. Statistical significance was defined as P < 0.05.

Results

Patients

A total of 105 children with clinically diagnosed SAC or PAC and 105 healthy children aged 4–12 years were enrolled in this study (Fig. 1). The basic characteristics of the patients are shown in Table 1. There was no difference in age or sex between the two groups. The incidence of AR (χ² = 24.94; P < 0.001) and AD (χ² = 30.35; P < 0.001) were significantly higher in the AC group than in the control group. The average weight in the AC group was higher than that in the control group (χ² = 2.44, P < 0.05); however, no difference was found in height between the two groups (χ² = 1.30, P = 0.20). BMI in the AC group was obviously higher than that in the control group (χ² = 6.90, P < 0.01). More children in the control group were breastfed than those in the AC group (χ² = 6.20, P < 0.05). Family history of allergy and incidence of AR and AD were significantly higher in the AC group than in the control group (P < 0.01).

Fig. 1.

The flow chart of the study

Table 1.

The basic characteristic of children in the case group and the control group

Basic characteristic		AC group (n = 105)	Control group (n = 105)	χ 2	P-value
Age (year)		6.51 ± 2.44	6.11 ± 2.91	1.09	0.28
Sex	Female	45(42.86)	39(37.14)	0.71	0.40
(n, %)	Male	60(57.14)	66(62.86)
Family history of smoking		61 (58.1)	46 (43.81)	4.29	0.04*
Residence		63 (60.00)	42 (40.00)	8.40	< 0.01**
Weight (kg)		32.14 ± 9.57	28.64 ± 11.16	2.44	0.02*
Height (cm)		116.20 ± 16.63	119.45 ± 19.48	1.30	0.20
BMI (kg/m2)		23.64 ± 4.35	19.65 ± 4.03	6.90	< 0.01**
Breast feeding (n, %)		47(44.76)	65(61.9)	6.20	0.01*
Bronchial Asthma (n, %)		30(28.57)	21(20)	2.10	0.15
Allergic Rhinitis (n, %)		44(41.9)	12(11.43)	24.940	< 0.0001***
Atopic Dermatitis (n, %)		42(40)	8(7.62)	30.35	< 0.0001***

*P<0.05, **P<0.01, ***P<0.001

Dietary habits

The assessments of dietary habits are presented in Table 2. The proportion of consumption of fish oil supplements was significantly higher in the control group (43.81%) than in the AC group (27.62%), and the difference was statistically significant (χ² = 2.45; P = 0.01). However, consumption of vitamin A supplements (χ² = 0.00; P = 1.00) and other dietary habits, such as consumption of sweet food (χ² = 6.70; P = 0.08), fast food (χ² = 3.74; P = 0.29), beverages (χ² = 1.17; P = 0.80), and seafood and fish (χ² = 6.15; P = 0.10) and snacking before sleep (χ² = 2.23; P = 0.53), were not significantly different between the two groups.

Table 2.

Dietary habits in the study children

Diet characteristic		AC group (n = 105)	Control group (n = 105)	χ 2	P-value
Fish oil supplements (n, %)	Absent	76(72.38)	59(56.19)	2.45	0.01*
	Present	29(27.62)	46(43.81)
Vit A supplements (n, %)	Absent	72(68.57)	72(68.57)	0.00	1.00
	Present	33(31.42)	33(31.42)
Sweet food (days/week)	1	12(11.43)	17(16.19)	6.70	0.08
	2–4	44(41.9)	57(54.29)
	5–7	33(31.43)	22(20.95)
	never	16(15.24)	9(8.57)
Fast food (days/week)	1	30(28.57)	35(33.33)	3.74	0.29
	2–4	47(44.76)	53(50.48)
	5–7	21(20)	14(13.33)
	never	7(6.67)	3(2.86)
Beverages (days/week)	1	21(20)	23(21.9)	1.17	0.76
	2–4	57(54.29)	61(58.1)
	5–7	22(20.95)	16(15.24)
	never	5(4.76)	5(4.76)
Seafood and fish (days/week)	1	45(42.86)	29(27.62)	6.15	0.10
	2–4	44(41.9)	53(50.48)
	5–7	14(13.33)	18(17.14)
	never	2(1.9)	5(4.76)
Snacking before sleep (days/week)	1	31(29.52)	36(34.29)	2.23	0.53
	2–4	46(43.81)	49(46.67)
	5–7	17(16.19)	14(13.33)
	never	11(10.48)	6(5.71)

*P<0.05 **P<0.01 ***P<0.001

Body mass index (BMI)

Of all the children in the study, 63.33% had a normal BMI. The incidence of overweight and obesity in the AC group (39.05%) was significantly higher than that in the control group (16.19%) (P < 0.05). The BMI of the two groups is presented in Table 3. The trend chi-square test showed that the risk of occurrence of AC increased with increasing BMI (χ² = 3.47; P _trend < 0.01).

Table 3.

Comparison of children’s body mass index between two groups

Body mass index	Case group (n = 105)	Control group (n = 105)	Total	χ2	P trend
Under weight	7(6.67)	12(11.43)	19(9.05)	3.47	< 0.001***
Healthy weight	57(54.29)	76(72.38)	133(63.33)
Overweight and Obesity	41(39.05)	17(16.19)	58(27.62)

*P<0.05 **P<0.01 ***P<0.001

Physical activity and sleep time

More than half of the children slept for 8–10 h in both groups. In the AC group, 16.19% of children slept for more than 10 h, which was less than those in the control group. More children (27.62%) in the AC group slept less than 8 h than in the control group (19.05%). Nevertheless, there was no significant difference in sleep duration between the two groups (χ² = 5.39; P = 0.07). The mean physical exercise duration was 1.2 h per day in the AC group and 1.6 h per day in the control group. There were significant differences in physical activity between the two groups (χ² = 12.64; P < 0.01). Compared with those in the control group, more children (55.24%) in the AC group had less than 1 h of physical activity per day, and fewer children had 2–3 h (17.14%) or more than 3 h (4.76%) per day (Table 4).

Table 4.

Physical activity and sleep time in the study children

Characteristics		Case group (n = 105)	Control group (n = 105)	χ2	P trend
Sleeping time (hours/day)	< 8	29(27.62)	20(19.05)	5.39	0.07
	8 ~ 10	59(56.19)	55(52.38)
	> 10	17(16.19)	30(28.57)
Physical Exercise (hours/day)	0	24(22.86)	15(14.29)	12.64	< 0.01**
	≤ 1	58(55.24)	43(40.95)
	2–3	18(17.14)	35(33.33)
	> 3	5(4.76)	12(11.43)

*P<0.05 **P<0.01 ***P<0.001

Risk factors

Multivariate analysis of the association of AC with risk factors, including AR, allergic dermatitis, having been breastfed, consumption of fish oil supplements and high BMI (overweight and obesity), was conducted (Table 5). The multivariate-adjusted ORs for AC were 3.05 for high BMI (overweight and obesity) (95% CI, 1.30–7.20, P = 0.01), 0.34 for having been breastfed (95% CI, 0.16–0.72; P = 0.005) and 0.38 for consumption of fish oil supplements (95% CI, 0.17–0.81; P = 0.01).

Table 5.

Multivariate analysis of dietary habits and physical activity

Variable	B-value	P-value	OR(95% CI)
Breastfeeding	-1.08	0.0045**	0.34 (0.16–0.72)
Fish oil supplements	-0.98	0.0124*	0.38 (0.17–0.81)
Physical exercise (≤ 1)	1.6123	0.0570	5.01 (0.95–26.38)
Physical exercise (2–3)	1.6792	0.0253*	5.36 (1.23–23.36)
Physical exercise (> 3)	0.6281	0.4229	1.87 (0.40–8.71)
Under weight	-0.27	0.6671	0.76 (0.22–0.63)
Overweight and Obesity	1.1155	0.0108*	3.05 (1.30–7.20)

*P<0.05 **P<0.01 ***P<0.001

Discussion

AC is a growing public health problem that degrades the quality of life [23]. PAC and SAC account for 86% of AC cases [7]. With the improvement of living standards and changes in lifestyle, the prevalence of AC and obesity is gradually increasing [24]. In recent years, studies have confirmed obesity as a probable risk factor for the development of allergic diseases [14, 15]. The current study investigated the association of lifestyle, dietary habits and nutritional status with AC in children. Our results showed that BMI was higher in children with AC than in healthy children. The multivariate analysis revealed that overweight and obesity increased the risk of AC. In addition, having been breastfed and consuming fish oil supplements were protective factors against AC in children.

With the increasing incidence of obesity in China, increasing attention has been given to children with obesity over the last several decades. The increase in the number of obese children has coincided with an increase in the incidence of allergies, which clinically manifest as chronic respiratory diseases (asthma, AR, AD) [25]. Many prospective studies have verified that obesity/high BMI is a risk factor for the development of atopic allergic diseases, such as AD, AR and BA [26, 27]. However, there are few reports on the relationship between BMI and AC incidence. The current study found a positive association between high BMI (overweight and obesity) and AC. The results were similar to those for other allergic diseases (AD, AR, BA). Kusunoki and coworkers [28] showed that childhood obesity was negatively associated with AC prevalence, which is contrary to our results. The differences may be explained by different diagnostic criteria for AC. In their research, the diagnosis of AC was based on a questionnaire survey including the following questions: Has your child ever had eye symptoms? Has your child ever had itchy-watery eyes? However, in clinical practice, the incidence of AC in children is often underestimated because of poor communication, so this questionnaire survey may underestimate the incidence of AC in children. In our study, the diagnostic criteria were based on allergic history and slit-lamp examinations by an ophthalmologist, so AC was more accurately diagnosed.

Our results revealed that overweight and obesity increase the risk of AC; however, the underlying mechanisms are unclear. AC is primarily caused by type I hypersensitivity reactions. Histamine is the main proinflammatory mediator that accounts for at least half of the signs and symptoms of AC [29]. Clinical studies have found that an increased histamine reaction is associated with increased BMI [27, 30]. Furthermore, obesity may enhance inflammation in AR and BA [31, 32]. However, prospective studies are needed to determine the causal direction of the association between obesity and inflammation in AC. Further studies are needed to confirm whether obesity increases inflammation in AC.

Multivariate analysis confirmed that having been breastfed was a protective factor against AC in children. This conclusion is similar to previous studies, which have reported the protective effect of breastfeeding against other allergic diseases. A recent systematic review and meta-analysis found that breastfeeding was protective against asthma in children 5–18 years of age and was associated with a reduced risk of AR in children up to 5 years of age and eczema in children up to 2 years of age [33]. Breastfeeding for at least 6 months is recommended in World Health Organization (WHO) guidelines [34]. Breastfeeding duration had some protective effects against long-term allergic disease. Previous studies found that a shorter duration of breastfeeding was associated with a higher risk of obesity and asthma in school-age children [35]. Breastfeeding for more than 6 months was significantly protective against wheezing and repeated rhinitis [36].

Another important finding from this study was that consumption of fish oil supplements is a protective factor against AC. Fish oil is rich in n-3 long-chain polyunsaturated fatty acids (LCPUFAs), mainly eicosapentaenoic acid (EPA C20:5 n-3) and docosahexaenoic acid (DHA C22:6 n-3). Clinical studies have found that consumption of n-3 LCPUFA supplements in early infancy can reduce the incidence of eczema [37, 38], AR [39, 40], recurrent asthma [41] and the incidence of bronchitis and bronchiolitis [42]. Several studies have indicated that consumption of dietary n-3 LCPUFA supplements is associated with a lower incidence and symptoms of allergic disease [43, 44]. SAC and PAC result from IgE-mediated type I hypersensitivity reactions. Dietary n-3 LCPUFA increases the levels of EPA and DHA in blood, which could compete and replace arachidonic acid (AA) in membrane phospholipids and reduce IgE-induced prostaglandin 2 release during mast cell degranulation (prostaglandin, PGD2) [45]. In addition, EPA and DHA have been shown to inhibit the release of proinflammatory cytokines such as IL-1, IL-6, IL-8, and TNF-a from monocytes and macrophages [46, 47] and allergy-related mediator release by human mast cells [45]. In an AC mouse model, consumption of dietary n-3 LCPUFA supplements suppressed eosinophil infiltration of the conjunctiva and scratching behaviour [48]. Although the underlying molecular mechanisms by which fish oil supplements reduce the risk of AC remain unclear, our findings support recommendations for consuming fish oil supplements to reduce the risk of AC in children.

This study has some limitations. First, the study population comprised only Chinese children. Therefore, the results are not representative of children of other races and regions. Second, the data were collected through a questionnaire survey, so there is no uniform dose standard for dietary fish oil supplementation. In addition, the questionnaire records are dependent on people’s memory and may cause bias. Therefore, further studies are needed to evaluate the relationship between the protective effect of fish oil supplementation and AC. Third, the duration of breastfeeding in this study was inconsistent, ranging from 6 to 12 months. The amount of breastfeeding was not accurately measured due to on-demand feeding. The results of this study can only confirm the reduced risk of AC in children who were breastfed compared with those who were not but cannot indicate whether there is a difference in children with different breastfeeding durations and amounts. Lastly, the sample size was small and was from a single center. The risk and protective factors of AC need to be further verified by large sample or randomized controlled design trials. Future studies can focus on whether there is a difference in the protective effect of breastfeeding amount and duration against AC incidence or symptoms.

Conclusions

In summary, this research revealed that high BMI (overweight and obesity) increases the risk of AC. Having been breastfed and consuming fish oil supplements reduces the risk of AC. Breastfeeding and consuming fish oil supplements are recommended in children susceptible to AC.

Author contributions

LC conceived and designed research; XJT, QL and LC collected data; JTH analyzed the data wrote the initial paper; XJT and LC wrote the main manuscript text; LC revised the paper; All authors read and approved the final manuscript.

Funding

Not applicable.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving research study participants were approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University, Chongqing, China (NO.2022 − 486). Verbal informed consent was obtained from legal guardian of all subjects/patients. Verbal consent was witnessed and formally recorded.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.