Novel relationship of serum cholesterol with asthma and wheeze in the United States

Department of Health and Human Services, Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 10/2009; 124(5):967-74.e1-15. DOI: 10.1016/j.jaci.2009.08.005
Source: PubMed


Cholesterol exerts complex effects on inflammation. There has been little investigation of whether serum cholesterol is associated with asthma, an inflammatory airways disease with great public health impact.
To determine relationships between levels of 3 serum cholesterol measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and non-HDL-C) and asthma/wheeze in a sample representative of the US population.
Cross-sectional study of 7005 participants age >or=6 years from the 2005 to 2006 National Health and Nutrition Examination Survey.
Serum TC and non-HDL-C were lower in patients with current asthma than in subjects without current asthma in the overall population (TC, 188.5 vs 192.2 mg/dL; non-HDL-C, 133.9 vs 137.7 mg/dL; P < .05 for both), whereas HDL-C was not different. Adjusted odds ratios (ORs) from multivariate logistic regression per 1-SD increase of TC and non-HDL-C for current asthma were 0.92 (95% CI, 0.86-0.98) and 0.91 (95% CI, 0.85-0.98), respectively. On racial/ethnic stratification, these relationships reflect marked reductions unique to Mexican Americans (MAs; TC, 171.4 vs 189.3 mg/dL; P < .001; OR, 0.62; 95% CI, 0.48-0.80; non-HDL-C, 119.8 vs 137.9 mg/dL; P < .001; OR, 0.62; 95% CI, 0.48-0.79). Among MAs, the adjusted OR for wheeze requiring medical attention was 0.57 (95% CI, 0.43-0.75) for TC and 0.53 (95% CI, 0.33-0.85) for non-HDL-C. Relationships between cholesterol and asthma/wheeze were independent of body mass index and serum C-reactive protein, and similar between atopic and nonatopic participants.
Serum TC and non-HDL-C are inversely related to asthma in the US population, chiefly reflecting a relationship among MAs.

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    • "Despite of encouraging results from fundamental research in support of the hypothetical link between serum cholesterol and asthma, clinical studies have yielded divergent results. While some studies have denied[2122] any relationship between asthma and serum cholesterol, few others have shown positive[23] as well as negative[2425] correlations. This has led to unclear knowledge about the subject of interest. "
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    ABSTRACT: Proinflammatory role of serum cholesterol in asthma has been recently explored with contradicting results. Clarity on the link between serum cholesterol and asthma may lead to new evolutions in planning management strategies. The objective of our study was to examine the relationship between the serum cholesterol, asthma and its characteristics. A total of 40 asthmatics and 40 normal subjects were examined cross-sectionally and their serum fasting cholesterol and serum high sensitivity C reactive protein (hsCRP) levels were measured along with other baseline investigations. All subjects were non-smokers. Serum total cholesterol (mean ± SD) among asthmatics was 176.45 ± 30.77 mgs/dL as compared to 163.33 ± 26.38 mgs/dL among normal subjects (P < 0.05). This higher serum cholesterol level was found to be associated with asthma independent of age, gender, body mass index (BMI), socio-economic status and serum hsCRP levels. However, the association was only modest (adjusted odds ratio 1.033; 95% confidence interval [CI] 1.008-1.059). There was no association between the serum cholesterol and asthma characteristics such as duration of illness, intake of inhaled steroids and frequency of emergency department visits. Other risk factors identified were poor ventilation (adjusted odds ratio 9.27; 95%CI 1.83-46.99) and overcrowding (adjusted odds ratio 41.9; 95% CI 3.15-557.46) at home. Our study found a modest but significant association between higher levels of serum cholesterol and asthma, which is independent of age, gender, BMI, socio-economic status and serum hsCRP. Future research is required in a larger population to substantiate above association and its clinical implications. Poor ventilation and overcrowding at home are risk factors for asthma possibly facilitating increased exposure to indoor allergens.
    No preview · Article · Oct 2013 · Lung India
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    • "Significant racial and ethnic differences have been observed in the prevalence of asthma27 and dyslipidemia28 and the relationship between these two diseases. Total serum cholesterol and non-high density lipoprotein (non-HDL) cholesterol were found to be inversely related to the prevalence of asthma in a US population, with the effect observed chiefly among Mexican-Americans.29 In Korean subjects, however, we found no association between asthma and the profiles of any lipids, including LDL-cholesterol, triglycerides, HDL-cholesterol, and total cholesterol (data not shown). "
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    ABSTRACT: Asthma is prevalent in many countries. Few studies have investigated the association between asthma and concomitant diseases. We retrospectively analyzed the fourth Korean National Health and Nutrition Survey database, performed in 2008 using nationwide stratified random sampling to obtain a representative cohort of the Korean population. We evaluated the association between both self-reported ever-asthmatics and wheezers and concomitant diseases such as arthritis, hypertension, gastrointestinal (GI) ulcers, dyslipidemia, diabetes mellitus, rhinitis, depression, stroke, and obesity in subjects aged ≥40 years. A multivariate analysis was performed to identify concomitant diseases independently associated with asthma, after adjustment for age, gender, income, cigarette smoking, and other chronic diseases. Of the total of 4,445 subjects, 2,596 (58.4%) were female and the mean age was 58.3 years. Of the 4,445 subjects, 195 (4.4%) had been diagnosed with asthma at some point, and 444 (10%) were wheezers. Multivariate analysis showed that arthritis (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.26-2.42), rhinitis (OR 1.78, 95% CI 1.14-2.78), depression (OR 1.45, 95% CI 1.05-2.07), and obesity (OR 1.61, 95% CI 1.08-2.40) were significantly associated with self-reported ever-asthma, and arthritis (OR 1.50, 95% CI 1.19-1.909), hypertension (OR 1.34, 95% CI 1.07-1.67), GI ulcers (OR 1.48, 95% CI 1.05-2.08), rhinitis (OR 1.60, 95% CI 1.16-2.19), depression (OR 1.94, 95% CI 1.51-2.48), and obesity (OR 1.56, 95% CI 1.17-2.09) were significantly associated with wheezers. These findings indicate that arthritis, rhinitis, depression, and obesity may be associated with both self-reported ever asthma and wheezers in the Korean population.
    Full-text · Article · Jan 2013 · Allergy, asthma & immunology research
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    • "The electrophoretic mobility shift assay was carried out as described by Shiraga et al. [37]. Nuclear extracts were prepared from untransfected, siRNA-transfected (60 nM, 48 h/72 h) and scrambled siRNA transfected NCI-H460 cells by using NE-PER Nuclear and Cytoplasmic Extraction Reagent Kit (Pierce) according to the manufacturer's protocol. "
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    ABSTRACT: STAT6 transcription factor has become a potential molecule for therapeutic intervention because it regulates broad range of cellular processes in a large variety of cell types. Although some target genes and interacting partners of STAT6 have been identified, its exact mechanism of action needs to be elucidated. In this study, we sought to further characterize the molecular interactions, networks, and functions of STAT6 by profiling the mRNA expression of STAT6 silenced human lung cells (NCI-H460) using microarrays. Our analysis revealed 273 differentially expressed genes after STAT6 silencing. Analysis of the gene expression data with Ingenuity Pathway Analysis (IPA) software revealed Gene expression, Cell death, Lipid metabolism as the functions associated with highest rated network. Cholesterol biosynthesis was among the most enriched pathways in IPA as well as in PANTHER analysis. These results have been validated by real-time PCR and cholesterol assay using scrambled siRNA as a negative control. Similar findings were also observed with human type II pulmonary alveolar epithelial cells, A549. In the present study we have, for the first time, shown the inverse relationship of STAT6 with the cholesterol biosynthesis in lung cancer cells. The present findings are potentially significant to advance the understanding and design of therapeutics for the pathological conditions where both STAT6 and cholesterol biosynthesis are implicated viz. asthma, atherosclerosis etc.
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