Biomedical subjects

Debra J Romberger

Publications and source records attributed to Debra J Romberger.

14 recordsLinked to original sources

PubMed2005

Alcohol intake is associated with altered pulmonary function.

Little is known about the effect of moderate alcohol intake on lung function in the general population. Because moderate alcohol intake appears to reduce cardiovascular disease risk, we hypothesized that moderate alcohol intake is associated with better pulmonary function. To test this hypothesis, we examined the association between alcohol intake and pulmonary function, measured by spirometry, in a representative sample of U.S. adults who participated in the Third National Health and Nutrition Examination Survey. A stratified multistage clustered probability design was used to select a population-based sample. Data analyzed included alcohol intake, smoking status, education, body mass, sex, age, race, diabetes status, and CHF status. The Third National Health and Nutrition Examination Survey was conducted from 1988 to 1994 by the National Center for Health Statistics of the Centers for Disease Control and Prevention, Atlanta, GA. We analyzed data from 15,294 study participants who completed extensive questionnaires in the household and a comprehensive physical examination, including pulmonary function testing, either in the household or at a specially equipped mobile examination center. Low-to-moderate alcohol intake was not associated with reduced odds of obstructive lung function. In fact, increased odds for obstructive lung pattern were observed only in former heavy drinkers. In contrast, low-to-moderate alcohol intake was associated with better forced vital capacity and forced exhaled volume in 1s in the absence of obstruction, consistent with reduced odds for lung restriction. Using a logistic regression model, we found that individuals reporting alcohol consumption had a lower risk of lung restriction both before and after adjusting for confounding factors including smoking (P< or =.001). Alcohol intake-related reduced risk for restriction was associated with lower risk of CHF, diabetes, obesity, and lower markers of inflammation (white blood cell, fibrinogen, and C-reactive protein) consistent with less lung congestion, external restriction, and/or lung inflammation. Our analyses indicate that alcohol consumption, even at very modest intake levels, is associated with less lung restriction.

Adolescent↗

PubMed2005

Tumor necrosis factor-alpha hyper-responsiveness to endotoxin in whole blood is associated with chronic bronchitis in farmers.

Many farmers experience chronic bronchitis, airflow obstruction, and asthma. It is thought that these respiratory problems may be related to workplace inhalation of organic dust containing endotoxin. The purpose of this study was to determine whether whole blood cytokine responsiveness to endotoxin is associated with airflow disorders (i.e., airflow obstruction, chronic bronchitis, and doctor-diagnosed asthma). Farmers (N = 95) were recruited from a rural cohort study and completed a respiratory symptom and history questionnaire, spirometry, and blood sampling. Blood was incubated 24 hours in the presence and absence of endotoxin and supernatants were analyzed for TNF-alpha, IL-1beta, IL-6, and IL-8. Hypo- or hyper-responsiveness to endotoxin was based on whether cytokine values were in the lower or upper 10% of the group range, respectively. A significant association existed between TNF-alpha hyper-responsiveness and chronic bronchitis. These results indicate that the whole blood cytokine assay may be useful to identify individual responsiveness to endotoxin, and may provide an additional diagnostic tool to evaluate persons potentially at risk for developing chronic bronchitis following exposure to organic dust in the workplace.

Aged↗

PubMed2004

Polymorphisms in the CD14 gene associated with pulmonary function in farmers.

RATIONALE AND OBJECTIVES: Farmers experience airway obstruction, which may be attributable in part to endotoxin inhalation. CD14 is a receptor for endotoxin. MATERIALS AND METHODS: Based on our findings of increased circulating CD14 associated with the CD14/-159 T allele, we hypothesized that carriers of this allele would have decreased lung function among endotoxin-exposed individuals. CD14/-159TT farmers (n = 19) had significantly lower lung function as measured by FEV1 (p = 0.028) and mean forced expiratory flow during the middle half of the FVC (FEF25-75) (p = 0.05) compared with farmers with the C allele (n = 78). Also, farmers with the CD14/-1619GG genotype (n =11) were associated with lower lung function (FEV1, p = 0.008; FEF25-75, p = 0.009) compared with farmers with the A allele (n = 86). RESULTS: No association between CD14/-550 and lung function was observed (FEV1, p = 0.32; FEF25-75, p = 0.11). Increased prevalence of wheezing was reported in farmers homozygous for CD14/-159T (p = 0.013) or CD14/-1619G (p = 0.019) compared with farmers with the CC or AA genotype, respectively. No association was found between TLR4/Asp299Gly and lung function or wheeze. CONCLUSION: We conclude that the CD14/-159 or CD14/-1619 loci may play a role in modulating lung function and wheeze among agricultural workers.

Adult↗

PubMed2004

Alcohol consumption and smoking status: the role of smoking cessation.

Cigarette smoking is common among persons with alcohol dependence or abuse with as many as 80% of persons who are alcohol dependent also being smokers. Not only is smoking common in persons with heavy alcohol consumption, but also nicotine dependence appears more severe in smokers with a history of alcohol dependence. This combined exposure to both tobacco smoke and alcohol results in major health consequences including additive risks for some diseases such as head and neck cancers. Although modest alcohol consumption has some positive health benefits, smoking typically negates these benefits. The cellular mechanisms impacted by combined smoking and alcohol exposure are poorly understood, but molecular epidemiology approaches are providing insights regarding the importance of effects on oxidant/antioxidant pathways and on metabolic pathways involving the cytochrome P450 system. Given the prevalence of smoking in the alcohol dependent population, smoking cessation in this group has the potential for tremendous impact. In recent years, smoking cessation approaches have been initiated in this population, but much work remains in order to define the optimal smoking cessation strategies for persons in alcohol treatment programs.

Alcohol Drinking↗

PubMed2003

Glucocorticoids modulate TGF-beta production by human fetal lung fibroblasts.

TGF-beta1 is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGF-beta isoforms affect TGF-beta production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFLF) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TGF-beta1, -beta2, or -beta3. Post-culture media were collected for ELISA assays of TGF-beta1, -beta2, and -beta3. TGF-beta mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TFG-beta2 and -beta3 stimulated TGF-beta1 production significantly (p < 0.01 relative to control). TGF-beta1 stimulated TGF-beta2 production (p < 0.01 relative to control). TGF-beta3 was undetectable. Glucocorticoids significantly inhibited TGF-beta1 and TGF-beta2 production and reduced expression of the up-regulated TGF-beta1 and TGF-beta2 mRNA induced by exogenous TGF-beta1, -beta2, or -beta3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF-beta-stimulated cells, it was reduced by glucocorticoids. Thus, TGF-beta isoforms may stimulate production of various TGF-beta isoforms in the lung. Glucocorticoids then may block TGF-beta production by modulating mRNA levels and c-Jun.

Cells, Cultured↗

PubMed2003

Ultrafine carbon black particles inhibit human lung fibroblast-mediated collagen gel contraction.

Both acute and chronic exposure to particulates have been associated with increased mortality and morbidity from a number of causes, including chronic obstructive pulmonary disease and other chronic lung diseases. The current study evaluated the hypothesis that ultrafine carbon particles, a component of ambient particulates, could affect tissue repair. To assess this, the three-dimensional collagen gel contraction model was used. Ultrafine carbon black particles, but not fine carbon black, inhibited fibroblast-mediated collagen gel contraction. Although previous research has indicated that inflammatory effects of ultrafine carbon black particles are mediated by oxidant mechanisms, the current study suggests that ultrafine carbon black's inhibition of fibroblast gel contraction is mediated by the binding of both fibronectin and transforming growth factor (TGF)-beta to the ultrafine particles. Binding of TGF-beta was associated with a reduction in nuclear localization of Smads, indicative of inhibition of TGF-beta signal transduction. There was also a decrease in fibronectin mRNA, consistent with a decrease in TGF-beta-mediated response. Taken together, these results demonstrate the ability of ultrafine particles to contribute to altered tissue repair and extend the known mechanisms by which these biologically active particles exert their effects.

Base Sequence↗

PubMed2002

Effect of cigarette smoke on fibroblast-mediated gel contraction is dependent on cell density.

Cigarette smoke exposure has been associated with a variety of diseases, including emphysema. The current study evaluated the interaction of cell density and cigarette smoke extract (CSE) on fibroblast contraction of collagen gels. Protein levels of transforming growth factor (TGF)-beta1, fibronectin, PGE(2), and TGF-beta1 mRNA were quantified. Although both 5 and 10% CSE inhibited contraction by low-density fibroblasts (1 x 10(5) cell/ml), only 5% CSE augmented contraction in higher-density cultures (3-5 x 10(5) cells/ml). CSE also inhibited fibronectin and TGF-beta1 production in low-density cultures but stimulated fibronectin production in high-density cultures. Active TGF-beta1 was readily detectable only in higher-density cultures and was markedly augmented by 5% CSE. In contrast, although TGF-beta1 mRNA expression was inhibited in high-density cultures by 10% CSE, expression was increased in the presence of 5% CSE. These results suggest that CSE-induced inhibition of low-density fibroblast contraction is due to inhibition of fibronectin production, whereas CSE's stimulatory effect on high-density cells is the result of increased release of TGF-beta1. These effects may help explain the varied pathologies associated with exposure to cigarette smoke.

Antibodies↗

PubMed2002

Lysophosphatidic acid in airway function and disease.

Lysophosphatidic acid (LPA) is a bioactive lipid mediator and important component of serum. Studies over the past several years which have documented diverse effects of LPA on multiple types of airway cells and which suggest possible involvement of LPA in lung disease are reviewed here. LPA enhances contractility of airway smooth muscle. It also stimulates proliferation of cultured airway smooth muscle cells and exhibits a striking synergism with epidermal growth factor (EGF) for stimulating mitogenesis. Recent studies of the molecular components and signaling pathways mediating synergism are described, including LPA-induced upregulation of EGF receptors and activation of multiple transcription factors by both LPA and EGF. A model for the effects of LPA and EGF on mitogenesis that includes EGF receptor upregulation and synergism between Ras and Rho for activation of the transcription factor AP-1 is presented. LPA stimulates fibronectin secretion and filopodia extension in airway epithelial cells as well as proliferation and collagen gel contraction by lung fibroblasts. A hypothesis for LPA involvement in the airway repair and remodeling, which contribute to the pathology of asthma and other airway diseases, is presented, and future directions for research into the roles of LPA in airway function and disease are suggested.

Animals↗

PubMed2002

Agricultural lung disease.

Agricultural work is associated with high rates of injury, disability, and illness. Agricultural workers are at increased risk for a variety of illnesses including respiratory disorders, dermatologic conditions, and cancer. The recognition of ODTS led to increased understanding of acute illness in farmers and grain workers. Previously, many cases of acute illness were probably erroneously called farmer's lung. The same agents that are responsible for ODTS are responsible for the high prevalence of bronchitis in certain agricultural workers. The recent description of the innate immune system is very exciting because it will lead to increased understanding of the pathogenesis of organic dust induced disorders.

Agricultural Workers' Diseases↗

PubMed2002

Glucocorticoids modulate TGF-beta production.

TGF-beta is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGB-beta isoforms affect TGF-beta production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFL-1) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TFG-beta1, -beta2, and -beta3. TGF-beta mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TGF-beta2 and -beta3 stimulated TGF-beta1 production significantly (p < 0.01 relative to control). TGF-beta1 stimulated TGF-beta2 production (p < 0.01 relative to control). TGF-beta3 was undetectable. Glucocorticoids significantly inhibited TGF-beta1 and -beta2 production and reduced expression of the upregulated TGF-beta1 and -beta2 mRNA induced by exogenous TGF-beta1, -beta2 or -beta3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF-beta-stimulated cells, it was reduced by glucocorticoids. Thus, TGF-beta isoforms may stimulate production of various TGF-beta isoforms in the lung. Glucocorticoids then may block TGF-beta production by modulating mRNA levels and c-Jun.

Animals↗

PubMed2002

Evaluation of subclinical respiratory tract inflammation in heavy smokers who switch to a cigarette-like nicotine delivery device that primarily heats tobacco.

Cigarette smoking remains a major public health problem. For smokers who cannot or do not wish to quit, few options exist to reduce health risks. A cigarette-like nicotine delivery device that heats rather than burns tobacco might deliver nicotine with fewer toxins. The current study was designed to determine whether asymptomatic heavy smokers who did not wish to quit had improvement in lower respiratory tract inflammation after switching to Eclipse, a cigarette-like nicotine delivery device that primarily heats rather than burns tobacco. Twelve smokers of at least 40 cigarettes daily, asymptomatic and in good health, underwent paired bronchoscopies, bronchoalveolar lavages and endobronchial biopsies before and after 2 months of using Eclipse. Eight normal non-smoking individuals were evaluated on one occasion for comparison. Inflammation was assessed by direct inspection and by cytological parameters. Goblet cell metaplasia was assessed histologically. Compared to non-smokers, smokers had increased visible inflammation, increased recovery of inflammatory cells and increased percentage of goblet cells. There were significant reductions in all these parameters following a switch to Eclipse use, although the improvement did not reach the normal range. No significant differences were observed in peripheral blood measures. Nicotine levels were generally maintained, and exhaled carbon monoxide (CO) levels trended strongly upward. One individual experienced a transient twofold increase in CO and concurrently experienced transient headaches. Eclipse use may be a strategy to reduce the health risks for heavy smokers unwilling or unable to quit.

Adult↗

PubMed2002

Anesthetic-related cardiac arrest and its mortality: a report covering 72,959 anesthetics over 10 years from a US teaching hospital.

BACKGROUND: A prospective and retrospective case analysis study of all perioperative cardiac arrests occurring during a 10-yr period from 1989 to 1999 was done to determine the incidence, cause, and outcome of cardiac arrests attributable to anesthesia. METHODS: One hundred forty-four cases of cardiac arrest within 24 h of surgery were identified over a 10-yr period from an anesthesia database of 72,959 anesthetics. Case abstracts were reviewed by a Study Commission composed of external and internal members in order to judge which cardiac arrests were anesthesia-attributable and which were anesthesia-contributory. The rates of anesthesia-attributable and anesthesia-contributory cardiac arrest were estimated. RESULTS: Fifteen cardiac arrests out of a total number of 144 were judged to be related to anesthesia. Five cardiac arrests were anesthesia-attributable, resulting in an anesthesia-attributable cardiac arrest rate of 0.69 per 10,000 anesthetics (95% confidence interval, 0.085-1.29). Ten cardiac arrests were found to be anesthesia-contributory, resulting in an anesthesia-contributory rate of 1.37 per 10,000 anesthetics (95% confidence interval, 0.52-2.22). Causes of the cardiac arrests included medication-related events (40%), complications associated with central venous access (20%), problems in airway management (20%), unknown or possible vagal reaction in (13%), and one perioperative myocardial infarction. The risk of death related to anesthesia-attributable perioperative cardiac arrest was 0.55 per 10,000 anesthetics (95% confidence interval, 0.011-1.09). CONCLUSIONS: Most perioperative cardiac arrests were related to medication administration, airway management, and technical problems of central venous access. Improvements focused on these three areas may result in better outcomes.

Adolescent↗

PubMed2002

Glutathione prevents inhibition of fibroblast-mediated collagen gel contraction by cigarette smoke.

Cigarette smoke, the major risk factor for the development of emphysema, contains over 4,700 chemical compounds, including free radicals and other oxidants (10(14)/puff). An imbalance between oxidants and antioxidants has been proposed in the pathogenesis of chronic obstructive pulmonary disease. Inhibition of repair processes has been suggested to be one pathway contributing to the development of emphysema. We hypothesized that cigarette smoke inhibition of repair might result from a shift of the oxidant/antioxidant balance in favor of oxidants. To evaluate this hypothesis, N-acetyl-L-cysteine (NAC), which serves as a substrate for glutathione (GSH) production, and buthionine sulfoximine (BSO), which inhibits GSH production, were incubated in the presence and absence of cigarette smoke extract (CSE) with fibroblasts in three-dimensional collagen gels. Neither agent alone altered gel contraction. CSE inhibition of gel contraction, however, was mitigated by NAC and potentiated by BSO. Parallel effects were observed on cigarette smoke inhibition of fibronectin production and mRNA expression as well as by changes in intracellular GSH content. Pretreatment of fibroblasts with NAC or BSO resulted in similar effects, suggesting that neither agent was acting directly on smoke but, rather, was altering cellular response to smoke. In conclusion, smoke inhibition of fibroblast repair, as reflected by collagen gel contraction and fibronectin production, may be modulated by intracellular GSH levels.

Acetylcysteine↗

PubMed2002

Th2 cytokine regulation of type I collagen gel contraction mediated by human lung mesenchymal cells.

Asthma is characterized by chronic inflammation of the airway wall with the presence of activated T helper 2 (Th2) lymphocytes. The current study assessed the ability of Th2 cytokines to modulate fibroblast-mediated contraction of collagen gels to determine if Th2 cytokines could contribute to tissue remodeling by altering mesenchymal cell contraction. Human fetal lung fibroblasts, human adult bronchial fibroblasts and human airway smooth muscle cells were cast into native type I collagen gels and allowed to contract in the presence or absence of IL (interleukin)-4, IL-5, IL-10, or IL-13. IL-4 and IL-13 but not IL-5 and IL-10 augmented collagen gel contraction in a concentration-dependent manner. Neither IL-4 nor IL-13 altered fibroblast production of transforming growth factor-beta or fibronectin. Both, however, decreased fibroblast prostaglandin (PG) E(2) release. Decreased PGE(2) release was associated with a decreased expression of cyclooxygenase 1 and 2 protein and mRNA. Indomethacin completely inhibited PGE(2) release and also augmented contraction. IL-4 and IL-13, however, added together with indomethacin further augmented contraction suggesting both a PGE-dependent and a PGE-independent effect. These findings suggest that IL-4 and IL-13 may modulate airway tissue remodeling and, therefore, could play a role in the altered airway connective tissue which characterizes asthma.

Animals↗