The role of vitamin A in relation to childhood asthma with hypertension: a cross-sectional study of the NHANES database

Introduction

As one of the most common non-communicable diseases of childhood, asthma has a rising prevalence, affecting approximately 14% of children and young people worldwide (1). Childhood asthma is responsible for significant morbidity and mortality (2). Studies have found that asthma may result in an increased risk of subsequent hypertension development (3,4). Also, the increased blood pressure/hypertension in children is closely associated with hypertension and cardiovascular disease (CVD) risk in adulthood (5). Similar to adults, hypertension in childhood can result in irreversible end-organ and blood vessel damage (6). Therefore, clarifying the association between childhood asthma and hypertension, and identifying modifiable risk factors influencing this association are essential for the prevention of hypertension as well as the reduction of disease burdens.

Nutrition, as an important controllable factor, has received extensive attention in the prevention and control of both asthma and hypertension. Vitamin A (VA) is the first discovered fat-soluble vitamin, which widely presents in the human diet and is an essential nutrient for maintaining normal functions of the human body (7). VA is suggested to play an important role in inflammation, endothelial function, and oxidative stress (OS) (8). Chronic airway inflammation caused by asthma can lead to systemic inflammation, and chronic systemic inflammation causes vascular endothelial cell dysfunction, and may further lead to the occurrence and development of hypertension and CVDs (9-11). A recent study has found that higher levels of dietary VA intake are related to better pulmonary function as well as a lower risk of developing asthma (12). An animal experiment has also shown that VA supplementation can control severity through reducing inflammation levels in asthma models (13). Besides, a cohort study has suggested that VA intake levels are negatively linked to new onset risk of adult hypertension (14).

Recently, researchers have shown that diet can modulate the associations between risk factors and childhood/adulthood metabolic diseases (15,16). Therefore, it could be speculated that a higher dietary intake level of VA may help improve asthma related hypertension in children and adolescents. This study aimed to provide some new ideas on dietary aspect of asthma related hypertension prevention in youngers. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-641/rc).

Methods

Study design and study population

This was a cross-sectional study, and data of participants were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The NHANES is a survey research program to assess health and nutritional status of representative populations in the United States. Since 1999, NHANES collects information of about 5,000 individuals regularly from 15 areas and examines in every two-year period. More details on the NHANES survey conductions are shown here: https://wwwn.cdc.gov/nchs/nhanes/.

Children and adolescents who aged 8–19 years old were initially included. The exclusion criteria were (I) without information on assessment of asthma, dietary intake, or blood pressure; and (II) without data on body mass index (BMI) or cotinine. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The NHANES survey has obtained ethical approval from the Institutional Review Board (IRB) of the National Center for Health Statistics (NCHS) of the United States Centers for Disease Control and Prevention (CDC). Since this database is publicly available, ethical approval for this study has been waived by the IRB of Nanjing Medical University Affiliated Taizhou People’s Hospital.

Definition of hypertension and asthma

According to a previous study of the NHANES database, hypertension was diagnosed when children and adolescents conformed to each of the following conditions (17): (I) self-reported a diagnosis of hypertension; (II) self-reported antihypertensive medication usage; and (III) the measurement values of blood pressures (among individuals aged ≥8 years old), with the classification according to the 2017 American Academy of Pediatrics (AAP) Clinical Practice Guideline (18).

Self-reported information on asthma was collected via the NHANES questionnaires. According to a European birth cohort study’s recommendation, definition of asthma was through positive responses by respondents to the following question: “Has a doctor or other health professional ever told you that you have asthma?” (19).

Measurement of dietary VA intake

In the NHANES, collection of dietary VA data was through two 24-hour dietary recalls. Among dietary recalls, persons reported single foods/drinks consumption during midnight-to-midnight 24-hour period prior to in-person interviews. Those who <16 years of age were interviewed by a proxy interviewee, which were typically their parents. The first interview was conducted in-person in the mobile examination center (MEC), whereas the second is via telephone later in 3–10 days. Codes of interview data were converted into total nutrient intakes by the NHANES on the basis of the USDA Food and Nutrient Database for Dietary Studies (FNDDS), 5.0. More details can be found here: http://www.ars.usda.gov/ba/bhnrc/fsrg.

In this study, we extracted information on dietary VA intake from the records of the first dietary recall. Dietary VA were categorized into two levels (deficient intake and sufficient intake) based on the Recommended Dietary Allowance (RDA) for United States adults released by the Dietary Guidelines for Americans 2015–2020 (20).

Variables collection

We also extracted other variables as potential confounding factors, including age, race, gender, poverty-to-income ratio (PIR), the highest parents’ education level, BMI, birth weight, ideal physical activity, cotinine, inhaled corticosteroids, total energy intake, carbohydrate intake, protein intake, total fat intake, vitamin E (VE), vitamin C (VC), zinc (Zn), selenium (Se), sodium (Na), potassium (K), fasting blood glucose (FBG), total cholesterol (TC), low density lipoprotein (LDL), triglyceride (TG), high density lipoprotein (HDL), and homeostasis model assessment of insulin resistance (HOMA-IR).

According to the recommended CDC percentiles, BMI was converted into the BMI z-score, which accounts for age and gender. Overweight status refers to 85^th percentile ≥ BMI z-score <95^th percentile, and obesity refers to BMI z-score ≥95^th percentile (21). Tobacco exposure was estimated through serum cotinine level: <0.05 ng/mL indicates non-tobacco exposure, and that ≥0.05 ng/mL indicates tobacco exposure (22). The physical activity in adolescents at 12–19 years of age was converted into energy expenditure. The calculation of energy expenditure based on records of the NHANES physical activity questionnaire (PAQ) with the formula: energy expenditure (MET·min) = recommended MET × exercise time of corresponding activity (min). Physical activity levels of children (8–11 years old) were defined using the PAQ with the question: Days physically active at least 60 min. In addition, ideal physical activity level means ≥180 MET·min/day (12–19 years old) or ≥60 MET·min/day (8–11 years old), otherwise was non-ideal. Sedentary time was self-reported time spent sitting watching TV or videos. Information on birth weight was obtained also through the questionnaire, and the low-birth-weight infant was defined as birth weight <5.5 lbs (2,500 g). Basing on the National Cholesterol Education Program guidelines, abnormal serum HDL-C, TC, LDL-C, FBG, or HOMA-IR score were defined as follows: HDL-C ≤35 mg/dL, TC ≥200 mg/dL, LDL-C ≥130 mg/dL, FBG ≥100 mg/dL and HOMA-IR ≥4.39 (23).

Statistical analyses

Continuous data were expressed as mean ± standard error (mean ± SE). Weighted two-sample t-test was utilized to compare characteristics between hypertension group and non-hypertension group. Categorical data were represented by frequency and constituent ratio [N (%)]. Rao-Scott Chi-squared test (χ²) was used for comparison. NHANES full sample 2 years MEC exam weight (WTMEC2YR) was used for analyses.

Covariates related to hypertension were screened by weighted univariate logistic regression analysis. We used weighted univariate and multivariate logistic regression analyses to investigate associations of dietary VA and asthma with hypertension in children and adolescents. Model 1 was unadjusted. Model 2 adjusted for demographic characteristics (age, race, gender, PIR, and the highest parents’ education level). Model 3 adjusted for all covariates, including age, race, gender, PIR, the highest parents’ education level, BMI, birth weight, cotinine, total energy intake, protein intake, total fat intake, VC, Na, FBG, TG, LDL, HDL, and HOMA-IR. In addition, we performed subgroup analyses of the age, gender, and BMI for further exploration on the effect of VA intake on the association between asthma and hypertension.

Evaluation indexes included odds ratios (ORs) and 95% confidence intervals (CIs). Two-sided P<0.05 indicated significantly different. Statistical analysis was performed using R version 4.2.3 (Institute for Statistics and Mathematics, Vienna, Austria).

Results

Characteristics of children and adolescents

Figure 1 shows flowchart of study process. Initially, we included 12,885 individuals at 8–19 years of age from the database. Then individuals with missing information on asthma (n=13), dietary intake (n=1,580), blood pressure (n=480), BMI (n=85) or cotinine (n=1,279) were excluded. Ultimately, 9,448 participants were included in the analyses.

Figure 1 Flowchart of children and adolescents screening. NHANES, National Health and Nutrition Examination Survey; BMI, body mass index.

Children and adolescents were divided into non-hypertension group (n=8,902) and hypertension group (n=546), and we compared characteristics of participants between these two groups (Table 1). The average age of individuals in hypertension group was older than those in non-hypertension group (15.11 vs. 13.68 years). Although 6,571 (68.67%) children and adolescents had deficient dietary VA intake, the average dietary VA intake level in hypertension group was significantly lower than that in non-hypertension group (543.75 vs. 593.45 mcg). In addition, the number of individuals who had asthma was respectively 137 (27.43%) and 1,714 (19.42%).

Dietary VA in the association of asthma with hypertension

To investigate the role of dietary VA in relation to childhood asthma with hypertension, we firstly screened the covariates linked to hypertension (Table S1). Age, gender, race, PIR, the highest parents’ education level, BMI, birth weight, cotinine, total energy intake, protein intake, total fat intake, VC, Na, FBG, TG, LDL, HDL, and HOMA-IR were all significantly linked to hypertension. Secondly, associations of dietary VA and asthma with hypertension were explored (Table 2). Children and adolescents with asthma had higher odds of hypertension comparing to non-asthma ones after covariates adjustment (OR =1.35, 95% CI: 1.03–1.78, P=0.03).

Additionally, influencing of dietary VA intake on the association between asthma and hypertension was assessed (Table 3). When individuals have deficient dietary VA intakes, having asthma was significantly associated with higher odds of hypertension comparing to non-asthma (OR =1.46, 95% CI: 1.07–1.99, P=0.02). Besides, the relationship between asthma and hypertension was not significant in those who having sufficient dietary VA intakes (P=0.73). These findings indicated that a sufficient dietary VA intake may benefit to reduce asthma related hypertension risk in youngsters.

Dietary VA intake in association between asthma and hypertension in different subgroups

We further performed the subgroup analyses on the associations of dietary VA intake and asthma with hypertension among participants with different age, gender, or BMI conditions (Table 4). Having asthma was linked to higher odds of hypertension in children and adolescents who had deficient VA intakes, especially in aged ≥13 years old (OR =1.65, 95% CI: 1.21–2.26, P=0.002), male (OR =1.59, 95% CI: 1.09–2.33, P=0.02), and underweight/normal weight (OR =1.97, 95% CI: 1.14–3.43, P=0.02) subgroups.

Discussion

The present study investigated the associations of dietary VA intake and asthma with hypertension among children and adolescents. The results suggested that having asthma in children and adolescents was linked to higher odds of hypertension, comparing to those without asthma. When they had sufficient dietary VA intakes, the relationship between asthma and hypertension became not significant (P=0.73). Besides, this potential beneficial effect of sufficient dietary VA intakes on hypertension related asthma was found in aged ≥13 years old, male, and underweight/normal weight subgroups.

According to our results, asthma was associated with higher odds of hypertension comparing to non-asthma after adjusting for covariates in children and adolescents. Although no research has reported the relationship between asthma and hypertension among the younger population directly, some evidences have indicated that asthma is linked to CVDs. Based on data of the Korean Genome and Epidemiology Study-Health Examinees, Wee et al. (24) found that asthma was related to ischemic heart disease, especially in older patients and untreated asthma patients. A single-center cross-sectional study in central India suggested that children with asthma, particularly early-onset wheezers are at increased risk of developing pulmonary arterial hypertension (PAH) and right ventricle diastolic dysfunction (25). Differently, our study population were the representative populations in the United States, which relatively supplemented the literature blank in childhood asthma association with a high hypertension risk. Inflammatory is a main component in the development and progression of many lung diseases, including asthma and PAH (26). Chronic inflammation has been demonstrated to be involved in hypertension pathogenesis, and immunoreaction promotes blood pressure elevation through triggering vascular inflammation and microvascular remodeling (27,28). For example, activated T lymphocytes produces interferon-gamma (IFN-γ) and interleukin (IL)-17, and contribute to hypertension via inducing OS injury and endothelial dysfunction (29). Also, Li et al. (30) found that plasma microRNA-206, IL-13, INF-γ, and IL-4 levels in asthma induced PAH patients were significantly higher than that in healthy people. We speculated that in children and adolescents, asthma activates inflammatory response, stimulates immune factor, and further results in hypertension through inducing OS as well as endothelial dysfunction. Children and adolescents with high-risk of asthma should take care of daily blood pressure monitoring to take preventive measures on hypertension in time. Nevertheless, the true relationships and specific mechanisms between asthma and hypertension in this population need further clarification.

For all we know, no study has investigated the influence of dietary VA intake on the correlation between asthma and hypertension in youngster. A previous prospective cohort study basing on the China Health and Nutrition Survey (CHNS) showed a L-shaped relationship of dietary VA with new-onset hypertension in general Chinese adults (14). Liang et al. (31) suggested that serum VA level in patients with hypertension was not significantly different from controls’, whereas the lecithin retinol acyltransferase (LRAT), an indicator of VA storage function, was lower in the hypertensive group, and LRAT was negatively associated with blood pressure. In children and adolescents, a higher intake of preformed VA was found to be linked to higher lung function as well as a lower incident asthma risk according to a population-based birth cohort (12). In comparison, the average level of VA intake was 590.72 mcg/day in our research, the estimated median intake of dietary VA intake level of participants was 429 mcg/day in Talaei et al.’s study, and besides, we used the food source VA instead of the preformed VA. However, a meta-analysis considered that serum VA levels are lower in asthma patients than in healthy persons, but there is no significant association between VA intake and asthma risk in children, nor between serum VA levels and asthma risk (32). Compared with above studies, we investigated the role of dietary VA intake in relation to asthma with hypertension in children and adolescents, that can provide some references for the formulation of dietary prevention strategies to prevent hypertension in children with asthma. Researchers pointed out that decreased levels of VA may be resulted from an increased use of the anti-oxidant during the chronic OS present in asthma (33). Chen et al. (34) observed that serum VA was positively and significantly associated with both systolic and diastolic blood pressure, indicating that it might be important in the underlying cause and prevention of hypertension. Herein, dietary VA intake may supplement the loss of VA due to the occurrence of asthma and causes an increase in blood pressure. Also, further studies in the mechanism exploration are warranted.

In addition, subgroup analyses showed that this potential beneficial effect of VA on correlation of asthma with hypertension was also significant in aged ≥13 years old, male, and underweight/normal populations. The total serum VA or serum retinol in younger children (aged 4–5 years old) was lower than older children (aged 9–11 years old) (35). VA deficiency is also most commonly found in children aged <5 years old (36). Because of the possibility that children under 5 years old may take VA supplements or intake VA-rich foods to prevent VA deficiency as per doctor’s advice, the beneficial effect of sufficient dietary VA intake on asthma related hypertension might be more significant in those who are of older age. VA deficiency affects early lung development, alveolar formation, tissue maintenance and regeneration (37). As a matter of fact, though boys’ growth rates are generally higher than that in girls before 10 years old, no gender differential in developing VA deficiency has been confirmed (38). Wei et al. (39) performed a cross-sectional study of children (7–11 years old) in Chongqing, China, suggesting that serum VA in obese group was significantly lower than that in overweight and normal weight groups. Also, in Liang et al.’s research, waist circumference was positively linked to blood pressure (31). Our findings indicated that BMI plays an important role in the mechanisms that VA regulating the risk of asthma related hypertension, especially in children without overweight or obesity. But the explanation for this potential regulation effect needs to be clarified.

This study is the first to explore the effect of VA on the correlation between asthma and hypertension in children and adolescents, which may provide some ideas for childhood hypertension prevention. We considered potential confounding factors as much as possible based on the NHANES database, in which study samples were large and representative, and therefore, the study results were relatively reliable. However, due to the across-sectional fact of this research, causal relationships were hard to be concluded. In addition, information on dietary intake was collected via dietary recalls in the NHANES, that could have the recalling bias, and that also cannot reflect the long-term intake habits of the children and adolescents. More prospective cohort studies are still needed to clarify the beneficial effect of VA intake on relationship between asthma and hypertension in children and adolescents.

Conclusions

A sufficient dietary VA intake may benefit to the prevention of asthma related hypertension in youngster. Also, patients with asthma aged ≥12 years old, male, or with underweight/normal weight should take great concern on blood pressure monitoring.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-641/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-641/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-641/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The NHANES database has obtained ethical approval from the IRB of the NCHS. Since it is publicly available, ethical approval for this study has been waived by the IRB of Nanjing Medical University Affiliated Taizhou People’s Hospital.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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