Relationships of serum CC16 levels with smoking status and lung function in COPD.

BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown. METHODS: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation. RESULTS: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on FEV1/FVC ratio was demonstrated among subjects with COPD (N = 245, p = 0.01). There was a positive correlation among former smokers and negative correlation among current or never smokers with COPD. Among former smokers with COPD, CC16 levels were also positively correlated with years since smoking cessation, and inversely related with pack-years smoked. Increasing CC16 levels were associated with lower odds of COPD (ORadj = 0.36, 95% CI 0.22-0.57, Padj < 0.0001). CONCLUSIONS: Smoking status is an important effect modifier of CC16 relationships with lung function. Increasing serum CC16 corresponded to increases in FEV1/FVC ratio in former smokers with COPD versus opposite relationships in current or never smokers. Additional longitudinal studies may be warranted to assess relationship of CC16 with smoking cessation on lung function among subjects with COPD.

Methods in Lung Microbiome Research.

The lung microbiome is associated with host immune response and health outcomes in experimental models and patient cohorts. Lung microbiome research is increasing in volume and scope; however, there are no established guidelines for study design, conduct, and reporting of lung microbiome studies. Standardized approaches to yield reliable and reproducible data that can be synthesized across studies will ultimately improve the scientific rigor and impact of published work and greatly benefit microbiome research. In this review, we identify and address several key elements of microbiome research: conceptual modeling and hypothesis framing; study design; experimental methodology and pitfalls; data analysis; and reporting considerations. Finally, we explore possible future directions and research opportunities. Our goal is to aid investigators who are interested in this burgeoning research area and hopefully provide the foundation for formulating consensus approaches in lung microbiome research.

Association Between Weight Loss and Glycemic Outcomes: A Post Hoc Analysis of a Remote Patient Monitoring Program for Diabetes Management.

Background: Evidence-based guidelines for the management of type 2 diabetes (T2D) consist of blood glucose monitoring, medication adherence, and lifestyle modifications that may particularly benefit from reminders, consultation, education, and behavioral reinforcements through remote patient monitoring (RPM). Objectives: To identify predictors of weight loss and to examine the association between weight loss and hemoglobin A1C (HbA1C) outcomes for T2D patients who were enrolled in an RPM program for diabetes management. Materials and Methods: The study applied logistic and ordinary least-squares regression models to examine the relationship between baseline characteristics and the likelihood of weight loss during the RPM, and how the magnitude of weight loss was related to changes in HbA1C outcomes for 1,103 T2D patients who went through 3 months of RPM from 2014 to 2017. Results: Older patients were 3% more likely to have weight loss (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.05), whereas patients with higher baseline HbA1C had 9% reduced odds (OR, 0.91; 95% CI, 0.85-0.97) of experiencing weight loss. For every pound of weight lost, there was a 0.02-point (95% CI, 0.01-0.03) reduction on the HbA1C measured at the end of the RPM. Moreover, compared with those who had weight loss of ≤3%, participants who had lost 5-7%, or >7% of their baseline weight had a 0.37- and 0.58-point reduction in HbA1C, respectively. Conclusions: This study revealed a notable relationship between weight loss and positive HbA1C outcomes for T2D patients in an RPM-facilitated diabetes management program, which pointed to the potential of integrating evidence-based lifestyle modification programs into future telemedicine programs to improve diabetes management outcomes.

Estrogen Metabolism in African-American Women with and without Breast Cancer: A Pilot Study.

Studies in Caucasian women have shown that the formation of estrogen-DNA adducts is greater in women at high risk for breast cancer or already diagnosed with the disease. To begin investigating whether the role of estrogens in the etiology of breast cancer is similar in African-American (AA) women, a saliva sample and a spot urine sample were collected from 19 AA women with breast cancer and 23 AA women not diagnosed with breast cancer. In the urine samples, 20 estrogen metabolites, conjugates, and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry, and then the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and estrogen conjugates was significantly greater in cases compared to controls (92.4 ± 46.4 vs 38.5 ± 18.9, p < 0.0001). From the saliva samples, genomic DNA was purified and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes, catechol- O-methyltransferase (rs4680) and cytochrome P450 1B1 (rs1056836). There was no association between rs4680 and rs1056836 genotypes and adduct ratios or breast cancer status. This pilot study found higher DNA adduct ratios in women with breast cancer, which suggests that estrogen metabolism is out of balance, and the formation of estrogen-DNA adducts may exert a critical role in breast cancer initiation in AA women.

Aging leads to dysfunctional innate immune responses to TLR2 and TLR4 agonists.

BACKGROUND: Sepsis is more common in the elderly. TNF⍺ is recognized as an important mediator in sepsis and Toll-like receptors (TLRs) play an important role in initiating signaling cascades to produce TNF⍺. Little is known about how innate immunity is altered in healthy human aging that predisposes to sepsis. AIMS AND METHODS: We tested the hypothesis that aging dysregulates the innate immune response to TLR 2 and 4 ligands. We performed whole blood assays on 554 healthy subjects aged 40-80 years. TNFα production was measured at baseline and after stimulation with the TLR2 agonists: peptidoglycan, lipoteichoic acid, Pam3CysK, Zymosan A and the TLR4 agonist lipopolysaccharide (LPS). In a subset of subjects (n = 250), we measured Toll-like receptor (TLR) 2, 4 and MyD88 expression using real-time PCR. RESULTS AND DISCUSSION: We measured a 2.5% increase per year in basal secretion of TNFα with aging (n = 554 p = 0.02). Likewise, TNFα secretion was increased with aging after stimulation with peptidoglycan (1.3% increase/year; p = 0.0005) and zymosan A (1.1% increase/year p = 0.03). We also examined the difference between baseline and stimulated TNFα for each individual. We found that the increase was driven by the elevated baseline levels. In fact, there was a diminished stimulated response to LPS (1.9% decrease/year; p = 0.05), lipoteichoic acid (2.1% decrease/year p = 0.03), and Pam3CysK (2.6% decrease/year p = 0.0007). There were no differences in TLR or MyD88 mRNA expression with aging, however, there was an inverse relationship between TLR expression and stimulated TNFα production. CONCLUSIONS: With aging, circulating leukocytes produce high levels of TNFα at baseline and have inadequate responses to TLR2 and TLR4 agonists. These defects likely contribute to the increased susceptibility to sepsis in older adults.

Genetic Variants in Circadian Rhythm Genes and Self-Reported Sleep Quality in Women with Breast Cancer.

INTRODUCTION: Women diagnosed with breast cancer (BC) are at increased risk of sleep deficiency. Approximately 30-60% of these women report poor sleep during and following surgery, chemotherapy, radiation therapy, and anti-estrogen therapy. The purpose of this study was to examine the relationship between genetic variation in circadian rhythm genes and self-reported sleep quality in women with BC. METHODS: This cross-sectional study recruited women with a first diagnosis of breast cancer at five sites in Nebraska and South Dakota. Sixty women were included in the study. Twenty-six circadian genes were selected for exome sequencing using the Nextera Rapid Capture Expanded Exome kit. 414 variants had a minor allele frequency of ≥5% and were included in the exploratory analysis. The association between Pittsburgh Sleep Quality Index (PSQI) score and genetic variants was determined by two-sample t-test or ANOVA. RESULTS: Twenty-five variants were associated with the PSQI score at p < 0.10, of which 19 were significant at p<0.05, although the associations did not reach statistical significance after adjustment for multiple comparisons. Variants associated with PSQI were from genes CSNK1D & E, SKP1, BHLHE40 & 41, NPAS2, ARNTL, MYRIP, KLHL30, TIMELESS, FBXL3, CUL1, PER1&2, RORB. Two genetic variants were synonymous or missense variants in the BHLHE40 and TIMELESS genes, respectively. CONCLUSIONS: These exploratory results demonstrate an association of genetic variants in circadian rhythm pathways with self-reported sleep in women with BC. Testing this association is warranted in a larger replication population.

Relationship of systemic IL-10 levels with proinflammatory cytokine responsiveness and lung function in agriculture workers.

BACKGROUND: Agriculture workers are exposed to microbial component- and particulate matter-enriched organic dust aerosols. Whereas it is clear that exposure to these aerosols can lead to lung inflammation, it is not known how inflammatory responses are resolved in some individuals while others develop chronic lung disease. Interleukin (IL)-10 is an immunomodulatory cytokine that is recognized as a potent anti-inflammatory and pro-resolving factor. The objective of this study was to determine whether there is a relationship of systemic IL-10 and proinflammatory responses and/or respiratory health effects in humans with prior agriculture exposure. METHODS: This is a cross sectional study of 625 veterans with > 2 years of farming experience. Whole blood was stimulated with or without organic dust and measured for IL-6, TNFα and IL-10. Participants underwent spirometry and respiratory symptoms were assessed by questionnaire. RESULTS: We found that baseline IL-10 concentration from the whole blood assay was inversely associated with ΔTNF-α (r = - 0.63) and ΔIL-6 (r = - 0.37) levels. Results remained highly significant in the linear regression model after adjusting for age, sex, BMI, race, education, smoking status, and white blood cell count (ΔTNF-α, p < 0.0001; ΔIL-6, p < 0.0001). We found no association between chronic cough (p = 0.18), chronic phlegm (p = 0.31) and chronic bronchitis (p = 0.06) and baseline IL-10 levels using univariate logistic regression models. However, we did find that higher FEV1/FVC was significantly associated with increased baseline IL-10 concentration. CONCLUSIONS: Collectively, these studies support a potential role for IL-10 in modulating an inflammatory response and lung function in agriculture-exposed persons.

Interaction of CD14 haplotypes and soluble CD14 on pulmonary function in agricultural workers.

BACKGROUND: Agricultural environments are contaminated with organic dusts containing bacterial components. Chronic inhalation of organic dusts is implicated in respiratory diseases. CD14 is a critical receptor for gram-negative lipopolysaccharide; however, its association with respiratory disease among agricultural workers is unknown. The objective of this study was to determine if serum soluble CD14 (sCD14) levels are associated with lung function among agricultural workers and if this association is modified by genetic variants in CD14. METHODS: This cross-sectional study included 584 veterans with >2 years of farming experience and that were between the ages of 40 and 80 years. Participants underwent spirometry and were genotyped for four tagging CD14 polymorphisms (CD14/-2838, rs2569193; CD14/-1720, rs2915863; CD14/-651, rs5744455; and CD14/-260, rs2569190). Serum sCD14 was assayed by ELISA. RESULTS: Subjects were 98% white males with a mean age 64.5 years. High soluble CD14 levels (> median sCD14) were associated decreased lung function (FEV1/FVC, p = 0.011; % predicted FEV1, p = 0.03). When stratified by COPD (yes/no) and smoking status (ever/never), high sCD14 levels (> median sCD14) were associated with low lung function among ever smokers with COPD (% predicted FEV1, padj = 0.0008; FEV1/FVC, padj = 0.0002). A similar trend was observed for never smokers with COPD; however, results did not reach statistical significance due to small sample size. There was a significant sCD14 x COPD/smoking interaction with lung function (% predicted FEV1, pinter = 0.0498; FEV1/FVC, pinter = 0.011). Regression models were adjusted for age, body mass index, education, sex, race and years worked on a farm. No association was found between CD14 polymorphisms/haplotypes (CD14/-2838; CD14/-1720; CD14/-651; CD14/-260) and sCD14 levels. The final model included the variables sCD14 and haplotypes and a haplotype x sCD14 interaction term. Individuals with the GTTG haplotype (CD14/-2838 → CD14/-260) and high sCD14 levels (> median sCD14) had on average 6.94 lower % predicted FEV1 than individuals with the GCCA haplotype and low sCD14 levels (≤ median sCD14, padj = 0.03). CONCLUSION: CD14 haplotypes and sCD14 are important mediators of lung function among those with COPD in this occupationally-exposed population.

Maresin-1 reduces the pro-inflammatory response of bronchial epithelial cells to organic dust.

BACKGROUND: Exposure to organic dust causes detrimental airway inflammation. Current preventative and therapeutic measures do not adequately treat resulting disease, necessitating novel therapeutic interventions. Recently identified mediators derived from polyunsaturated fatty acids exhibit anti-inflammatory and pro-resolving actions. We tested the potential of one of these mediators, maresin-1 (MaR1), in reducing organic dust-associated airway inflammation. METHODS: As bronchial epithelial cells (BECs) are pivotal in initiating organic dust-induced inflammation, we investigated the in vitro effects of MaR1 on a human BEC cell line (BEAS-2B). Cells were pretreated for 1 hour with 0-200 nM MaR1, followed by 1-24 hour treatment with 5% hog confinement facility-derived organic dust extract (HDE). Alternatively, a mouse lung slice model was utilized in supportive cytokine studies. Supernatants were harvested and cytokine levels determined via enzyme-linked immunosorbent assays. Epithelial cell protein kinase C (PKC) isoforms α and ϵ, and PKA activities were assessed via radioactivity assays, and NFκB and MAPK-related signaling mechanisms were investigated using luciferase vector reporters. RESULTS: MaR1 dose-dependently reduced IL-6 and IL-8 production following HDE treatment of BECs. MaR1 also reduced HDE-stimulated cytokine release including TNF-α in a mouse lung slice model when given before or following HDE treatment. Previous studies have established that HDE sequentially activates epithelial PKCα and PKCϵ at 1 and 6 hours, respectively that regulated TNF-α, IL-6, and IL-8 release. MaR1 pretreatment abrogated these HDE-induced PKC activities. Furthermore, HDE treatment over a 24-hour period revealed temporal increases in NFκB, AP-1, SP-1, and SRE DNA binding activities, using luciferase reporter assays. MaR1 pretreatment did not alter the activation of NFκB, AP-1, or SP-1, but did reduce the activation of DNA binding at SRE. CONCLUSIONS: These observations indicate a role for MaR1 in attenuating the pro-inflammatory responses of BECs to organic dust extract, through a mechanism that does not appear to rely on reduced NFκB, AP-1, or SP-1-related signaling, but may be mediated partly through SRE-related signaling. These data offer insights for a novel mechanistic action of MaR1 in bronchial epithelial cells, and support future in vivo studies to test MaR1's utility in reducing the deleterious inflammatory effects of environmental dust exposures.

Non-typeable Haemophilus influenzae decreases cilia beating via protein kinase Cε.

BACKGROUND: Haemophilus influenzae infection of the nasal epithelium has long been associated with observations of decreased nasal ciliary beat frequency (CBF) and injury to the ciliated epithelium. Previously, we have reported that several agents that slow CBF also have the effect of activating protein kinase C epsilon (PKCε) activity in bronchial epithelial cells. The subsequent auto-downregulation of PKCε or the direct inhibition of PKCε leads to the specific detachment of the ciliated cells. METHODS: Primary cultures of ciliated bovine bronchial epithelial cells were exposed to filtered conditioned media supernatants from non-typeable H. influenzae (NTHi) cultures. CBF and motile points were measured and PKCε activity assayed. RESULTS: NTHi supernatant exposure significantly and rapidly decreased CBF in a dose-dependent manner within 10 minutes of exposure. After 3 hours of exposure, the number of motile ciliated cells significantly decreased. Direct measurement of PKCε activity revealed a dose-dependent activation of PKCε in response to NTHi supernatant exposure. Both CBF and PKCε activity changes were only observed in fresh NTHi culture supernatant and not observed in exposures to heat-inactivated or frozen supernatants. CONCLUSIONS: Our results suggest that CBF slowing observed in response to NTHi is consistent with the stimulated activation of PKCε. Ciliated cell detachment is associated with PKCε autodownregulation.

Pesticide use and thyroid disease among women in the Agricultural Health Study.

Thyroid disease is common, and evidence of an association between organochlorine exposure and thyroid disease is increasing. The authors examined the cross-sectional association between ever use of organochlorines and risk of hypothyroidism and hyperthyroidism among female spouses (n = 16,529) in Iowa and North Carolina enrolled in the Agricultural Health Study in 1993-1997. They also assessed risk of thyroid disease in relation to ever use of herbicides, insecticides, fungicides, and fumigants. Prevalence of self-reported clinically diagnosed thyroid disease was 12.5%, and prevalence of hypothyroidism and hyperthyroidism was 6.9% and 2.1%, respectively. There was an increased odds of hypothyroidism with ever use of organochlorine insecticides (adjusted odds ratio (OR(adj)) = 1.2 (95% confidence interval (CI): 1.0, 1.6) and fungicides (OR(adj) = 1.4 (95% CI: 1.1, 1.8) but no association with ever use of herbicides, fumigants, organophosphates, pyrethroids, or carbamates. Specifically, ever use of the organochlorine chlordane (OR(adj) = 1.3 (95% CI: 0.99, 1.7), the fungicides benomyl (OR(adj) = 3.1 (95% CI: 1.9, 5.1) and maneb/mancozeb (OR(adj) = 2.2 (95% CI: 1.5, 3.3), and the herbicide paraquat (OR(adj) = 1.8 (95% CI: 1.1, 2.8) was significantly associated with hypothyroidism. Maneb/mancozeb was the only pesticide associated with both hyperthyroidism (OR(adj) = 2.3 (95% CI: 1.2, 4.4) and hypothyroidism. These data support a role of organochlorines, in addition to fungicides, in the etiology of thyroid disease among female spouses enrolled in the Agricultural Health Study.

Rhinitis associated with pesticide use among private pesticide applicators in the agricultural health study.

Farmers commonly experience rhinitis but the risk factors are not well characterized. The aim of this study was to analyze cross-sectional data on rhinitis in the past year and pesticide use from 21,958 Iowa and North Carolina farmers in the Agricultural Health Study, enrolled 1993-1997, to evaluate pesticide predictors of rhinitis. Polytomous and logistic regression models were used to assess association between pesticide use and rhinitis while controlling for demographics and farm-related exposures. Sixty-seven percent of farmers reported current rhinitis and 39% reported 3 or more rhinitis episodes. The herbicides glyphosate [odds ratio (OR) = 1.09, 95% confidence interval (95% CI) = 1.05-1.13] and petroleum oil (OR = 1.12, 95% CI = 1.05-1.19) were associated with current rhinitis and increased rhinitis episodes. Of the insecticides, four organophosphates (chlorpyrifos, diazinon, dichlorvos, and malathion), carbaryl, and use of permethrin on animals were predictors of current rhinitis. Diazinon was significant in the overall polytomous model and was associated with an elevated OR of 13+ rhinitis episodes (13+ episodes OR = 1.23, 95% CI = 1.09-1.38). The fungicide captan was also a significant predictor of rhinitis. Use of petroleum oil, use of malathion, use of permethrin, and use of the herbicide metolachlor were significant in exposure-response polytomous models. Specific pesticides may contribute to rhinitis in farmers; agricultural activities did not explain these findings.

Development of an Integer-based Risk Score to Predict 90-Day Mortality After Hepatectomy in Patients With Hepatocellular Carcinoma.

BACKGROUND: The incidence of liver cancer has more than tripled since 1980. Hepatectomy represents the major curative treatment for liver cancer. The risk factors associated with 90-day mortality after hepatectomy are not well understood and there are currently no good prediction models for this outcome. The objectives of the current study were to identify risk factors of 90-day mortality after hepatectomy in patients with hepatocellular carcinoma and to develop an integer-based risk score using the National Cancer Database. METHODS: Hepatectomies recorded in the National Cancer Database during 2004-2012 were reviewed for 90-day mortality. Risk factors were identified by multivariate logistic regression models. An integer-based risk score was developed using the ß coefficients derived from the logistic regression model and tested for discriminatory ability. According to the total risk score, patients were grouped into 4 risk groups. RESULTS: The overall 90-day mortality was 10.2%. Ten risk factors were identified, which included sex, age, race/ethnicity, insurance status, education, annual hospital volume, stage, tumor grade, Charlson-Deyo Score, and surgical procedure. The risk of 90-day mortality was stratified into 4 groups. The calculated 90-day mortality rates were 2.47%, 5.88%, 12.58%, and 24.67% for low-risk, medium-risk, high-risk, and excessive-risk groups, respectively. An area under the receiver operating characteristic curve of 0.69 was obtained for model discrimination. CONCLUSIONS: The integer-based risk score we developed could easily quantify each patient's risk level and predict 90-day mortality after hepatectomy. The stratified risk score could be a useful addition to perioperative risk management and a tool to improve 90-day mortality after hepatectomy.

Symptom Clusters and Quality of Life over 1 Year in Breast Cancer Patients Receiving Adjuvant Chemotherapy.

OBJECTIVE: Evidence is scant regarding symptom clusters and quality of life (QOL) over 1 year in women who receive adjuvant breast cancer chemotherapy (CTX). Our purpose was to identify the prevalence and severity of individual symptoms, symptom clusters, and QOL in women receiving adjuvant breast cancer CTX from baseline over 1 year. METHODS: Symptoms were identified in a sample (n = 219) at three times: baseline (prior to the first adjuvant CTX treatment), 1 month after the last CTX (approximately 6 months after baseline), and 1 year after baseline. The Hospital Anxiety and Depression Scale and Symptom Experience Scale measured symptoms. The Medical Outcomes Study, Short-Form Survey, measured QOL. Exploratory factor analysis identified symptom clusters at each time and core symptoms in clusters over time. RESULTS: The prevalence and severity of 10 symptoms decreased over time (P < 0.05). Fatigue, sleep disturbance, and pain were most prevalent; all were of mild severity. Two symptom clusters were identified at baseline and one met internal consistency reliability criteria at the later times. Core symptoms were identified. Both the physical and mental component scores of QOL improved over time (P < 0.01), but physical was below the general population norms 1 year after baseline. CONCLUSIONS: The symptom experience was dynamic, and symptom clusters changed over 1 year. Despite mild severity, core symptoms and clusters persisted over 1 year, and physical health was below the general population norms. Breast cancer survivors with persistent single and co-occurring symptoms need to be taught to manage the patterns of symptoms over time because they may not resolve by 1 year.

Association of Dietary Fiber on Asthma, Respiratory Symptoms, and Inflammation in the Adult National Health and Nutrition Examination Survey Population.

Rationale: High intake of dietary fiber may have antiinflammatory properties and be protective against respiratory morbidity.Objectives: We examined the relationship between dietary fiber intake and asthma, respiratory symptoms, and inflammation among adults who participated in the 2007 to 2012 NHANES (National Health and Nutrition Examination Survey).Methods: We analyzed data from adults 20 to 79 years of age (n = 13,147) with complete information on fiber intake, total calorie intake, body mass index, smoking status, and poverty level. Fiber intake was categorized into quartiles, with Q1 being lowest quartile of intake and Q4 being the highest quartile. Respiratory morbidities included asthma, wheeze, cough, and phlegm. Self-report questionnaires were used to define asthma, wheeze, cough, and phlegm production. Serum C-reactive protein (CRP) was used as a biomarker of inflammation. Exclusion criteria included current pregnancy and implausible intake of total calories.Results: A total of 69.5% of participants were non-Hispanic white; 54.5% were nonsmokers, and 7.8% had current asthma. After adjusting for covariates, fiber intake was associated with asthma (P = 0.01), with an increased odds of asthma with lower fiber intake (Q1 vs. Q4: odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0-1.8; P = 0.027). There were significant interactions between fiber and sex and fiber and race/ethnicity; stronger associations were seen for women and for non-Hispanic white adults. Low fiber intake (Q1) was associated with increased odds of wheeze (OR, 1.3; 95% CI, 1.0-1.6; P = 0.018), cough (OR, 1.7; 95% CI, 1.2-2.3; P = 0.002), and phlegm (OR, 1.4; 95% CI, 1.1-2.0; P = 0.021) compared with high fiber intake. The odds of having high CRP versus nondetectable CRP were 1.6 times higher in the low-fiber group (Q1) compared with high-fiber group (Q4; OR, 1.6; 95% CI, 1.0-2.5).Conclusions: High-fiber diet may mediate an inflammatory response and decrease odds of having asthma, especially for women and specific racial groups, cough, wheeze, and phlegm production when compared with low-fiber diet.

Association between CD14 polymorphisms and serum soluble CD14 levels: effect of atopy and endotoxin inhalation.

BACKGROUND: A prerequisite for activation of the innate immune response by endotoxin is its binding to CD14. OBJECTIVE: The aim of this study was to evaluate the role of CD14 polymorphisms, atopy, and inhaled endotoxin in modulating serum CD14 levels. METHODS: Healthy volunteers (n = 88) were genotyped for CD14 polymorphisms at the -1619, -1359, and -159 loci, relative to the transcription start site. Subjects inhaled 20 mug of endotoxin, and white blood cell, C-reactive protein, LPS-binding protein, and soluble CD14 (sCD14) levels were measured before and after exposure. RESULTS: Homozygotes for the -1619G, -1359G, and -159T alleles had higher baseline levels of sCD14 than carriers of the CD14/-1619AA (P = .015), -1359GT/TT (P = .015), or -159CC (P = 0.017) genotypes. sCD14 levels increased within 24 hours of endotoxin inhalation (P < .0001 for all biomarkers); however, the association between CD14 polymorphisms and sCD14 levels was no longer present after exposure. The atopic status of an individual did not alter these associations. CD14 polymorphisms were not associated with levels of white blood cells, C-reactive protein, and LPS-binding protein before or after endotoxin challenge. CONCLUSION: These data suggest that CD14 promoter polymorphisms and inhaled endotoxin modulate sCD14 levels.

Saturated Fat Intake Is Associated with Lung Function in Individuals with Airflow Obstruction: Results from NHANES 2007⁻2012.

Nutritional status is a well-recognized prognostic indicator in chronic obstructive pulmonary disease (COPD); however, very little is known about the relationship between lung function and saturated fat intake. We used data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES) to assess the relationship between saturated fatty acid (SFA) intake and lung function in the general US adult population. Adults in NHANES (2007⁻2012) with pre-bronchodilator spirometry measurements and dietary SFA intake were included. Primary outcomes were lung function including forced expiratory volume in one second (FEV1), FEV1, forced vital capacity (FVC), FEV1/FVC ratio, percent predicted FEV1 and percent predicted FVC. Multivariable regression models in the general population as well as those with spirometry-defined airflow obstruction were used to assess the relationship between lung function measurements and dietary SFA intake after adjustment for confounders. 11,180 eligible participants were included in this study. Univariate analysis revealed a statistically significant positive association between total SFA intake and lung function outcomes; however, these relationships were attenuated after adjustment for covariates. A secondary analysis of individuals with spirometry-defined airflow obstruction (FEV1/FVC < 0.7) revealed that a lower intake of SFA was associated with reduced FEV1 (ß = -126.4, p = 0.04 for quartile 1 vs. quartile 4), FVC (ß = -165.8. p = 0.01 for quartile 1 vs. quartile 4), and percent predicted FVC (ß = -3.3. p = 0.04 for quartile 1 vs. quartile 4), after adjustment for relevant confounders. No associations were observed for the FEV1/FVC ratio and percent predicted FEV1. It is possible that characteristics such as food source and fatty acid chain length may influence associations between saturated fatty acid intake and health outcomes.

Persistent light to moderate alcohol intake and lung function: A longitudinal study.

Alcohol intake has been inconsistently associated with lung function levels in cross-sectional studies. The goal of our study was to determine whether longitudinally assessed light-to-moderate alcohol intake is associated with levels and decline of lung function. We examined data from 1333 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease. Alcohol intake was assessed with four surveys between 1972 and 1992. Subjects who completed at least two surveys were classified into longitudinal drinking categories ("never", "inconsistent", or "persistent drinker"). Spirometric lung function was measured in up to 11 surveys between 1972 and 1992. Random coefficient models were used to test for differences in lung function by drinking categories. After adjustment for sex, age, height, education, BMI categories, smoking status, and pack-years, as compared to never-drinkers, persistent drinkers had higher FVC (coefficient: 157 mL, p < 0.001), but lower FEV1/FVC ratio (-2.3%, p < 0.001). Differences were due to a slower decline of FVC among persistent than among never-drinkers (p = 0.003), and these trends were present independent of smoking status. Inconsistent drinking showed similar, but weaker associations. After adjustment for potential confounders, light-to-moderate alcohol consumption was associated with a significantly decreased rate of FVC decline over adult life.

Short term dynamics of the sputum microbiome among COPD patients.

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. The complexity of the lung microbial community in COPD patients has been highlighted in recent years. Evidence suggests that transplantation, medications, age, and disease severity influence microbial community membership. However, the dynamics of the lung microbiome in stable COPD patients remain poorly understood. In this study, we completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on replicate sputum samples collected from 4 former smokers with COPD (Stage 2) within a 2-day time period. Samples from each individual over the two-day period were similar based on α-diversity, principle component analysis and taxonomy at the phyla and genera level. Sputum samples from COPD patients were also collected between 2-9 months of follow-up. Data suggest an increased variability of the sputum microbiota when comparing samples collected ≤ 3 months compared to those collected ≥ 4 months; however, no statistically significant shifts in the abundance (>2-fold) of taxa between the two time points was observed. Bacterial composition and the number of operational taxonomic units (OTUs) remained similar over time. Results from this study suggest that the sputum microbiome is relatively stable in clinically stable COPD patients (Stage 2). This study furthers our understanding of the dynamics of the lung microbiome in COPD patients.

A principal factor analysis to characterize agricultural exposures among Nebraska veterans.

Agricultural workers are at an increased risk of developing chronic respiratory disorders. Accurate estimation of long-term agricultural exposures based on questionnaires has been used to improve the validity of epidemiologic investigations and subsequent evaluation of the association between agricultural exposures and chronic diseases. Our aim was to use principal factor analysis (PFA) to distill exposure data into essential variables characterizing long-term agricultural exposures. This is a cross-sectional study of veterans between the ages of 40 and 80 years and who worked on a farm for ≥2 years. Participant characteristics were: 98.1% were white males with a mean age 65±8 (SD) years and 39.8% had chronic obstructive pulmonary disease. The final model included four factors and explained 16.6% of the variance in the exposure data. Factor 1 was a heterogeneous factor; however, Factor 2 was exclusively composed of exposure to livestock such as hogs, dairy and poultry. Factor 3 included exposures from jobs on or off the farm such as wood dust, mineral dust, asbestos and spray paint. Crop exposure loaded exclusively in Factor 4 and included lifetime hours of exposure and maximum number of acres farmed in the participants' lifetime. The factors in the final model were interpretable and consistent with farming practices.