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Biomedical subjects

R F Lemanske

Publications and source records attributed to R F Lemanske.

At least 37 records · Page 2Linked to original sources
PubMed1998

Hypothesis: decreased use of pediatric aspirin has contributed to the increasing prevalence of childhood asthma.

BACKGROUND: The prevalence of asthma, atopic eczema, and allergic rhinitis has increased over the last three decades in Western countries. Speculation on the causes of this trend have focused on changes in environmental factors. We hypothesize that the decreased use of aspirin in favor of acetaminophen, due to the association of aspirin with Reye's syndrome during febrile respiratory infections, may be contributing to these trends in the United States. DATA SOURCES: A detailed literature search was conducted utilizing Medline. Studies considered relevant and important involving both humans and animals in English language were used. HYPOTHESIS: In the United States, the documented prevalence of childhood asthma has increased since 1970, but the rate of this increase accelerated upward beginning in the early 1980s when the use of pediatric aspirin decreased. During the resolution of common respiratory viral infections, prostaglandin E2 (PGE2) is produced through the actions of cyclooxygenase-2 (COX-2). Aspirin, but not acetaminophen, inhibits COX-2 activity. As PGE2 promotes TH2 and inhibits THI type cytokine generation, we hypothesize that the decreased use of aspirin may be a factor in facilitating allergic sensitization and asthma by augmenting the relative TH1/TH2 cytokine imbalance in genetically predisposed children. CONCLUSION: We have presented an hypothesis based upon epidemiologic trends, known biologic effects of cytokines and PGE2 on allergic sensitization, and a potentially relevant pharmacologic effect of aspirin to explain a component of the increasing prevalence of childhood asthma in the United States. We suggest this theory be examined further in animal models as well as in other countries where the prevalence of childhood asthma is increasing.

Animals↗
PubMed1998

Attenuation of virus-induced airway dysfunction in rats treated with imiquimod.

Viral respiratory infections cause acute airway abnormalities consisting of inflammation and physiological dysfunction in both animals and humans. It is likely that inflammatory cell products, such as cytokines, contribute substantially to viral-induced airway dysfunction. We hypothesized that imiquimod, an immune response enhancing agent that induces interferon-alpha, would attenuate the development of airway dysfunction during acute viral illness in rats. Adult Brown Norway rats were inoculated with parainfluenza type 1 (Sendai) virus or sterile vehicle, and treated with either imiquimod or water. Respiratory system resistance (Rrs), arterial oxygen tension (Pa,O2), lung viral titres and bronchoalveolar lavage (BAL) leucocyte counts were measured in anaesthetized, paralysed, ventilated rats. Virus-infected, water-treated rats had a significant decrease in Pa,O2 and had significant increases in leucocyte count and Rrs when compared to both the virus-infected, imiquimod-treated, (Pa,O2, p = 0.03; leucocyte count, p = 0.02; and Rrs, p = 0.009) and noninfected, water-treated rats (Pa,O2, p = 0.007; leucocyte count, p = 0.001; and Rrs, p = 0.01). In addition, imiquimod suppressed BAL eosinophils in both virus-infected (p = 0.02) and noninfected (p = 0.001) groups, and lowered overall virus titres (p = 0.03). Thus, both virus-induced airway inflammation and physiological dysfunction were attenuated significantly by imiquimod treatment in this animal model. By further delineating mechanisms by which infections induce airway dysfunction in animal models, more specific pharmacological interventions can be developed for the treatment of virus-induced asthma.

Adjuvants, Immunologic↗
PubMed1998

Asthma in non-inner city Head Start children.

OBJECTIVE: Asthma is a significant cause of morbidity and mortality in children. The objective of this study was to determine whether the federal program Head Start in Dane County, Wisconsin, could be used as a mechanism to identify preschool-aged children with asthma. DESIGN: Five-year, cross-sectional survey of parents with children enrolled in Head Start. METHODS: Investigator-administered asthma screening questionnaire to parents of enrolling Head Start children in Dane County, Wisconsin. MEASUREMENTS: Asthma prevalence and asthma-related health care use, including emergency department visits, hospitalizations, and medication usage, were measured using an asthma screening questionnaire developed by investigators. RESULTS: Information was gathered on 2215 children. The prevalence of physician-diagnosed asthma in the screened children was 15.8%. Parental reports of physician-diagnosed asthma were validated in a subset of 133 children, with a 98.5% confirmation rate. Independent risk factors for asthma included male gender (relative risk, 1.4) and African-American ethnicity (relative risk, 1.4). Asthma-related morbidity was substantial with 26.7% of identified children hospitalized for asthma and 54.5% with an emergency department visit during their lifetime. The majority of children (46.4%) were treated with intermittent, quick relief medications (beta-agonists) alone, whereas only 6.1% were on daily, long-term controller medications. CONCLUSIONS: Asthma screening through a Head Start program provides an effective means of targeting preschool-aged children from socioeconomic groups at high risk for asthma. Identification of children early in the disease course and those at high risk for asthma provides an ideal opportunity for the implementation of preventive and therapeutic interventions.

Asthma↗
PubMed1998

Respiratory viruses and asthma: can the effects be prevented?

Although viral respiratory tract infections (RTIs) frequently cause exacerbations of asthma, the relationship between RTIs and the initiation and maintenance of asthma in childhood is unclear. This is in part because of the difficulty of defining asthma in young children. Current evidence supports two hypotheses: 1) that predisposed children are susceptible to both severe RTIs and asthma; and 2) that severe viral infections may have long-lasting influences on the subsequent development of asthma, and perhaps even atopy. These two proposals are not mutually exclusive. This review summarizes our current state of knowledge of the pathogenic interactions between viruses and asthma (in both human and animal models). Possible interventions that might modify the effects of viral disease in asthmatics are discussed.

Animals↗
PubMed1997

Asthma.

For unknown reasons, the morbidity and mortality from asthma are increasing in many parts of the world, making it a global health concern. The heterogeneous nature of the clinical manifestations and therapeutic responses of asthma in both adult and pediatric patients indicate that it may be more of a syndrome rather than a specific disease entity. Numerous factors, including viral infections, allergen and irritant exposure, and exercise, among others, complicate both the short- and long-term management of asthma. Therapeutic intervention has focused on the appreciation that airway obstruction in asthma consists of bronchial smooth muscle spasm and variable degrees of airway inflammation characterized by edema, mucous secretion, and the influx of a variety of inflammatory cells. Choosing appropriate medications depends on the disease severity (intermittent, mild persistent, moderate persistent, severe persistent), patterns of disease activity (exacerbations related to viruses, allergens, exercise, etc), and the age at onset (infancy, childhood, adulthood).

Asthma↗
PubMed1997

Chronic, episodic, reversible airway obstruction after viral bronchiolitis in rats.

Viral bronchiolitis in human infants has been associated with persistent airway abnormalities, but not proven as a cause. Previously we observed some adult rats had airway obstruction and hyperresponsiveness following bronchiolitis at an early age. The purpose of this study was to determine, via serial measurements of lung mechanics, whether the postbronchiolitis airway obstruction was episodic or continuous, and to determine the magnitude and duration of glucocorticoid effects. Rats were either virus- (n = 14) or sham-inoculated (n = 8) at 3 wks of age. Lung mechanics were measured 6 times in each rat at postinoculation Weeks 11-18. Half the rats in each group were treated with dexamethasone for 3 d at Week 15. The virus group had higher lung resistance (p = 0.03) and lower dynamic compliance (p = 0.005) than control rats, with airway obstruction occurring in an episodic pattern. Dexamethasone treatment had a transient effect in postbronchiolitis rats; lung resistance normalized in Week 15 (p = 0.006), then returned to pretreatment levels by Weeks 16-18. We conclude that viral bronchiolitis in rats can result in a chronic syndrome of intermittent, reversible airway obstruction which has multiple parallels with human asthma over a prolonged time period.

Airway Resistance↗
PubMed1997

An evaluation of colchicine as an alternative to inhaled corticosteriods in moderate asthma. National Heart, Lung, and Blood Institute's Asthma Clinical Research Network.

Colchicine demonstrates an array of anti-inflammatory properties of potential relevance to asthma. However, the efficacy of colchicine as an alternative to inhaled corticosteroid therapy for asthma is unknown. Five centers participated in a controlled trial testing the hypothesis that in patients with moderate asthma needing inhaled corticosteroids for control, colchicine provides therapeutic benefit as measured by maintenance of control when inhaled steroids are discontinued. Subjects were stabilized on triamcinolane acetonide (800 microg daily) and then enrolled in a 2-wk run-in during which all subjects took both colchicine (0.6 mg/twice a day) and triamcinolone. At the end of the run-in, all subjects discontinued triamcinolone and were randomized to continued colchicine (n = 35) or placebo (n = 36) for a 6-wk double-blind treatment period. The treatment groups were similar in terms of disease severity. After corticosteroid withdrawal, 60% of colchicine-treated and 56% of placebo-treated subjects were considered treatment failures as defined by preset criteria. No significant difference in survival curves was found between treatment groups (log rank = 0.38). Other measures, including changes in FEV1, peak expiratory flow, symptoms, rescue albuterol use, and quality of life scores, also did not differ between groups. Of note, subjects failing treatment had significantly greater methacholine responsiveness at baseline than did survivors (PC20, 0.81+/-1.38 versus 2.11+/-2.74 mg/ml; p = 0.01). An analysis of treatment failures suggested that the criteria selected for failure reflected a clinically meaningful but safe level of deterioration. We conclude that colchicine is no better than placebo as an alternative to inhaled corticosteroids in patients with moderate asthma. Additionally, we conclude that the use of treatment failure as the primary outcome variable in an asthma clinical trial where treatment is withdrawn is feasible and safe under carefully monitored conditions.

Administration, Inhalation↗
PubMed1997

Effects of dexamethasone on acute virus-induced airway dysfunction in adult rats.

Respiratory viral infections have been associated with airway obstruction and hyperresponsiveness, and exacerbations of asthma. Although virus-induced asthma is thought to be precipitated by airway inflammation, the clinical efficacy and rationale for using antiinflammatory treatment during such exacerbations remains controversial. The purpose of this study was to use a well characterized animal model of respiratory viral illness to test the hypothesis that the inflammatory response to viral infection is responsible for the development of airway dysfunction. Adult rats were inoculated with either Sendai virus or sterile vehicle and treated with daily injections of dexamethasone or saline. At postinoculation d 4, 5, or 6, rats were evaluated for airway obstruction, hyperresponsivenes, inflammation, and lung viral titers. Saline-treated infected rats had significant airway obstruction (increased resistance, decreased dynamic compliance), hyperresponsiveness (i.v. methacholine), and inflammation (increased bronchoalveolar lavage leukocytes) compared with noninfected controls. In contrast, dexamethasone-treated infected rats had no increase in bronchoalveolar lavage leukocytes and significantly smaller changes in airway physiology, but had increased lung viral titers compared with saline-treated infected rats. We conclude that glucocorticoid suppression of the inflammatory response to respiratory viral infection largely prevents virus-associated airway dysfunction.

Animals↗
PubMed1996

Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. Asthma Clinical Research Network.

BACKGROUND: Inhaled beta-agonists are the most commonly used treatment for asthma, but data suggest that regularly scheduled use of these agents may have deleterious effect on the control of asthma. We compared the effects of regularly scheduled use of inhaled albuterol with those of albuterol used only as needed in patients with mild chronic, stable asthma. METHODS: In a multicenter, double-blind study, we randomly assigned 255 patients with mild asthma to inhale albuterol either on a regular schedule (126 patients) or only as needed (129 patients). The patients were followed for 16 weeks. RESULTS: The primary outcome indicator, peak expiratory air flow measured in the morning, did not change significantly during the treatment period in the scheduled (416 liters per minute after the run-in period and 414 liters per minute after the treatment period) or the as-needed (424 liters per minute at both times) treatment groups (P=0.71). There were no significant differences between the two groups in peak flow variability, forced expiratory volume in one second, the number of puffs of supplemental albuterol needed, asthma symptoms, asthma quality-of-life score, or airway responsiveness to methacholine. The statistically significant differences between the groups in evening peak flow and in the short-term bronchodilator response to inhaled albuterol were small and judged to be clinically unimportant. CONCLUSIONS: In patients with mild asthma, neither deleterious nor beneficial effects derived from the regular use of inhaled albuterol beyond those derived from use of the drug as needed. Inhaled albuterol should be prescribed for patients with mild asthma on an as-needed basis.

Administration, Inhalation↗
PubMed1996

Rat eosinophils: isolation and characterization of superoxide production.

Studies with isolated cells are important to the understanding of mechanisms by which eosinophils participate in allergic inflammation. Due to species variability, isolation techniques and cell biology need to be defined for each source. We developed methods to obtain rat eosinophils with purity and viability exceeding 90%, characterized the superoxide anion production of these cells in response to standard activators, and compared these results with those previously obtained in our laboratories with the use of human eosinophils. Rat eosinophils responded vigorously to phorbol myristate acetate and poorly to platelet-activating factor and to N-formyl-methionyl-leucyl-phenylalanine, parallel to the responses of human eosinophils. In contrast, rat eosinophils responded unlike human eosinophils to other activators, having a larger response to calcium ionophore A23187, a smaller response to serum-treated or serum-opsonized zymosan, and a negative rather than positive modulatory effect of cytochalasin B. We conclude that rat eosinophils can be obtained in high purity and with intact responsiveness to a number of different activators.

Animals↗
PubMed1996

Attenuation of airway hyperresponsiveness during acute viral infection using the 21-aminosteroid U-83836E in rats.

Respiratory viral infections have been associated with exacerbations of asthma in humans, and are known to produce airway obstruction and hyperresponsiveness in rats. Virus-induced airway dysfunction may result in part from inflammatory cells and their products, and agents that target these mechanisms might therefore attenuate viral airway injury. The 21-aminosteroid class of drugs has been reported to attenuate tissue injury in a variety of models, and we hypothesized that U-83836E, an orally-active aminosteroid, would prevent the development of airway dysfunction during acute viral illness. Adult rats were inoculated with either parainfluenza type 1 (Sendai) virus or sterile vehicle, treated with either U-83836E 20 mg/kg or water by oral gavage twice daily, and studied on postinoculation day 5, 6 or 7. Anesthetized, paralysed, mechanically ventilated rats were placed in a body plethysmograph for measurements of airway obstruction (resistance, dynamic compliance, eucapneic PaO2), and responsiveness to i.v. methacholine; lungs were lavaged to obtain inflammatory cells. The water-treated virus group was significantly different from the non-infected controls for all variables. Virus-induced hyperresponsiveness was attenuated (P = 0.027) by aminosteroid treatment, although airway obstruction and inflammation were not improved by the treatment. We conclude that 21-aminosteroids may protect airways from virus-induced hyperresponsiveness.

Acute Disease↗
PubMed1996

Parainfluenza virus-induced persistence of airway inflammation, fibrosis, and dysfunction associated with TGF-beta 1 expression in brown Norway rats.

Parainfluenza type 1 (Sendai) virus infection in young rats induces airway growth abnormalities associated with persistent pulmonary dysfunction and hyperresponsiveness. The objectives of this study were to compare virus-susceptible brown Norway (BN) rats and virus-resistant F344 rats and to determine which of several virus-induced structural abnormalities, including bronchiolar hypoplasia, alveolar dysplasia, bronchiolar mural fibrosis, and increases in bronchiolar mast cells, were associated with virus-induced increases in pulmonary resistance and hyperresponsiveness to methacholine. We also determined whether bronchiolar mural thickening and fibrosis may be caused by increased bronchiolar expression of cytokines such as TGF-beta 1 into airways. BN rats infected with virus developed increases in respiratory resistance and hyperresponsiveness that persisted for 28 to 65 d after inoculation. Functional abnormalities were most strongly associated with bronchiolar mural thickening and fibrosis as well as with recruitment of inflammatory cells, including macrophages, mast cells, lymphocytes, and eosinophils, into the bronchiolar wall. F344 rats were resistant to significant virus-induced alterations in bronchiolar airway wall thickness and mast cell increases as well as to pulmonary function abnormalities. BN rats had increase pulmonary mRNA levels of TGF-beta 1 at 10 and 14 d after viral inoculation as compared with F344 rats. BN rats also had greater numbers of bronchiolar macrophages expressing TGF-beta 1 protein that were localized in bronchiolar walls at 10, 14, and 30 d after inoculation. We conclude that recruitment and persistence of airway inflammatory cells and airway wall fibrosis may be important alterations induced by viral lower respiratory disease during early life that can lead to long-term airway dysfunction and hyperresponsiveness. Virus-induced airway fibrosis may be mediated in part by increased TGF-beta 1 gene expression by bronchiolar macrophages in genetically susceptible individuals.

Airway Resistance↗
PubMed1995

Childhood asthma. Older children and adolescents.

Asthma is a very significant health problem in children and adolescents, and it is disturbing that this problem is increasing despite recent advances related to asthma pathogenesis and treatment. In this age group, treatment of asthma may be especially challenging because of the need to deal with schools as well as the patient and family, and because of concern for the effects of asthma and asthma therapy on physical and psychological development. Successful asthma therapy in children and adolescents requires close attention to these issues, as well as efforts designed to transfer the responsibility of asthma care from the parent to the adolescent in an age-appropriate fashion.

Adolescent↗
PubMed1994

Adverse reaction to lupine-fortified pasta.

A 5-year-old girl with peanut sensitivity experienced urticaria and angioedema after ingesting a spaghetti-like pasta fortified with sweet lupine seed flour. The pasta was extracted and used in immunologic studies in patients with peanut sensitivity to determine whether such individuals are at similar risk. Results of skin prick tests with the lupine pasta extract were positive in five of seven subjects; these patients also reported a history of adverse reactions to green peas. In direct RAST studies IgE binding from pooled sera from patients with peanut sensitivity to the lupine pasta extract was 7 times that of a nonallergic control serum, and individual serum samples demonstrated binding from 1 to 6 times that of the negative control. Direct RAST studies of lupine seed flour with serum samples from patients with peanut allergy demonstrated IgE binding 1 to 11 times that of the negative control. Immunoblotting studies of electrophoretically separated pasta extract and lupine seed flour proteins showed IgE-binding protein bands at approximately 21 kd and in the range of 35 to 55 kd molecular weight. We conclude that some peanut-sensitive patients may be at risk for adverse reactions to lupine.

Adult↗