The role of antibiotics in asthma

There is increasing evidence that atypical respiratory pathogens such as Chlamydophila pneumoniae and Mycoplasma pneumoniae may contribute to the pathogenesis of both stable asthma and asthma exacerbations. It is postulated that these organisms may contribute to inflammation in the airways possibly by activating inflammatory mechanisms in the respiratory tract. The macrolide class of antibiotics may have a part to play in the management of asthma by exerting anti-inflammatory effects on the chronically inflamed airways in addition to their anti-infective action. The ketolide antibiotics may also have similar properties. This paper discusses the role of these antibiotics in the management of asthma.     

The role of antileukotrienes in the treatment of asthma

Cysteinyl leukotrienes (Cys-LTs) are mediators released in asthma and are both direct bronchoconstrictors and proinflammatory substances that mediated several steps in the pathophysiology of chronic asthma, including inflammatory cells recruitment, vascular leakage, and possibly airway remodelling. Available evidence from clinical trials and real world experience derived from managing patients with asthma justifies a broader role for antiLTRAs in asthma management than that recommended in the National Asthma Education and Prevention Programm (NAEPP) and National Health Lung and Blood Institute (NHLBI) treatment guidelines. Leukotriene-receptor antagonist drugs (LTRAs) seem to be effective alternatives to inhaled corticosteroids (ICS) either as monotherapy or as adjunctive therapy that reduces the need for higher doses of ICS in patients with mild-to-moderate persistent asthma. LTRAs may be used as adjunctive therapy for al levels of disease severity because they are effective in combination with ICS during long-term maintenance therapy. The agents seem especially effective in preventing aspirin-induced asthma, exercise-induced asthma (EIA) and they may provide an additional advantage of reducing nasal congestion in patients with both asthma and rhinitis.     

The beneficial effect of Vitamin C on the common cold

Summary The occurrence of common cold symptoms was recorded daily for a period of nine months by children from two male and two female boarding schools. All the children in one male and one female school received tablets containing 200 mg Vitamin C, or placebo tablets, daily on a double blind basis. Children in the other two schools received 200 or 500 mg tablets of Vitamin C. Leucocyte ascorbic acid concentrations were significantly raised in those children receiving active tablets. Comparisons of incidence, duration, severity and total intensity of cold characteristics, and of cold frequencies, were made between the different treatment groups. Cold symptoms were grouped into those characteristic of Catarrhal (C-colds), and those of Toxic (T-colds), colds. Whole (W-colds) consisted of at least one C-symptom in combination with one or more T-symptoms. 200 mg of Vitamin C had a beneficial effect on severity and total intensity of C- and W-colds, but did not affect T-colds, in girls. 500 mg produced further slight beneficial effects. With 200 mg the cold categories in boys tended to show a deterioration, and the deterioration continued in the group receiving 500 mg. Analysis of cold frequency indicated that T-colds are commoner in girls. Their C-cold frequency diminished with the smaller dose, and their T-cold frequency was reduced by the larger dose of Vitamin C. In boys C-cold frequency diminished with 500 mg of Vitamin C daily. These data suggest that there is a sexual difference in the effects of Vitamin C on the characteristics of the common cold. Evaluation of the effects of Vitamin C on toxic and catarrhal symptoms in relation to administered doses is of more importance than examination of its prophylactic or therapeutic actions. 500 mg had some beneficial effect in girls: any beneficial effect of Vitamin C on the common cold in boys will probably be associated with administration of a higher daily dose.     

白细胞介素-8在哮喘发病中的作用

目的　探讨白细胞介素 - 8(IL- 8)在支气管哮喘变态反应性炎症中具有的调节作用。方法　对 30例急性发作期支气管哮喘患者 ,30名正常对照者血浆 IL- 8浓度进行测定 ,并同时做肺功能检测一秒用力呼气容积 (FEV1 ) ,白细胞介素 - 8测定采用双抗体夹心酶联免疫吸附法 (EL ISA)。结果　支气管哮喘患者急性发作期血浆白细胞介素 - 8水平显著高于正常对照组 (P<0 .0 1)且与 FEV1 水平呈显著负相关 (r=- 0 .6 12 4,P<0 .0 0 5 )。结论　哮喘患者发作期血浆 IL - 8增多 ,它与哮喘免疫炎性细胞上的受体结合 ,趋化和激活炎性细胞 ,参与和调节炎性细胞在气道内的浸润 ,促进气道炎症的形成和气道高反应性的形成。哮喘病人血浆 IL- 8增高 ,与 FEV1 呈显著负相关 ,可作为哮喘急性发作的血清学指标之一。     

The role of cytokines in atopic asthma

Atopic asthma results from airway inflammation triggered by an environmental allergen. Symptoms include wheezing, dyspnea and cough, airway narrowing and/or hyperresponsiveness to several inhaled stimuli. Inflammation develops in a two-phase fashion. The first phase after exposure to the allergen consists of degranulation and release of both histamine and other stored preformed inflammatory mediators as well as newly synthesized ones, including cytokines, all of which increase mucus secretion and smooth muscle contraction. The second phase occurs later and lasts longer; it is due to different molecules: several cytokines and chemokines, arachidonic acid derivatives, enzymes such as metalloproteinases and cell adhesion molecules. Cytokines are key players in the chronic inflammation in asthma patients, but details on their role and interactions still remain undetermined. Recent evidence suggests that allergic asthma is a multifaceted condition actively controlled by effector as well as regulatory T cells (Tregs). T helper (Th) 2 cells and Th17 cells increase airway inflammation, while Tregs are anti- inflammatory. Cytokines are involved in the development and activation of all T cell subpopulations. They are also involved directly or indirectly in most approaches to asthma treatment. Several cytokines have been tested as therapeutic targets and some of the currently used therapies like corticosteroids, beta agonists and allergen immunotherapy affect cytokine production. The increased knowledge on cytokine interplay and lymphocyte subsets should generate new therapeutic strategies in the near future.     

The role of environmental factors in asthma

Although the everyday experience of asthmatic patients provides ample anecdotal evidence that environmental exposures provoke bronchospasm, it has proved more difficult to assess the impact of air quality on the timing of asthma attacks and the prevalence of asthma in populations. Spectacular 'asthma epidemic days' are sometimes attributable to exceptional outdoor aero-allergen exposures. By comparison, effects of inorganic particles and gaseous pollutants in outdoor air on the incidence of asthma attacks are subtle and poorly quantified. Environmental tobacco smoke and mould growth are the indoor factors most consistently associated with respiratory morbidity, but their roles in initiating allergic asthma remain uncertain. Evidence relating asthma risk to fumes from gas cooking, and to allergens from dust mites and household pets remains confused and controversial. It is unlikely that trends in either outdoor or indoor air pollution have contributed substantially to the rise in prevalence of asthma and allergic disease in recent decades.     

The eosinophil and its role in asthma

• 1.1. The eosinophil is part of the host defence mechanism to parasitic infection, but is also a key cell in many inflammatory disorders.
• 2.2. Eosinophils synthesise a range of pro-inflammatory and cytotoxic mediators, such as basic proteins, hydrolytic enzymes, lipid mediators, cytokines, oxygen metabolites and neuropeptides.
• 3.3. Eosinophils are recruited to the lung during episodes of asthma. They migrate from the blood vessels into the tissue via a series of interactions between their surface adhesion molecules and endothelial cells or the extracellular matrix.
• 4.4. Activation and prolonged survival of eosinophils occurs upon exposure to mediators released from other tissue resident leukocytes, including eosinophils themselves, and from respiratory tract epithelial cells. Release of eosinophilic mediators causes tissue damage and persistent inflammation of the lung.
• 5.5. Currently the most effective therapy for asthma lies with anti-inflammatory drugs, of which the main choices are inhaled corticosteroids or cromolyn sodium and nedocromil sodium.

     

The metabolism of supplementary vitamin C during the common cold.

Ascorbic acid concentrations have been measured in leukocytes and plasma following oral administration of 2000 mg vitamin C in the same subjects while they had cold symptoms and after recovery from their colds. Plasma and leukocyte concentrations rose significantly in females, but only plasma concentrations rose in males, after the loading dose during colds. In the postcold tests, only plasma concentrations rose in both sexes. There was a significant difference in plasma leukocyte regression coefficients between the cold and postcold tests in females. Ascorbic acid passes into the plasma for metabolic purposes, and its storage is less in the leukocytes, during colds. Males had worse colds than females because their catarrhal symptoms were more severe. Higher tissue concentrations of ascorbic acid tended to be associated with low total, toxic, and catarrhal symptom values. A rise in tissue ascorbic acid was associated with less severe catarrhal symptoms in females. Ascorbic acid concentrations in the plasma and tongue were significantly higher after the subjects had recovered from their cold symptoms. Increasing the loading dose of vitamin C from 500 to 2000 mg more than doubled the leukocyte concentration of ascorbic acid in females. The higher dose enabled uptake of the vitamin into the leukocytes to take place over a 4-hour period. It did not give rise to increased uptake into male leukocytes. Administration of supplementary vitamin C elevated plasma ascorbic acid. The ascorbic acid then passed into the tissues depleted of vitamin C during the cold syndrome. A single supplementary dose of 2000 mg vitamin C can replete leukocyte ascorbic acid during a 4-hour period in females, but a larger dose may be necessary in males.     

The role of neurotrophins in bronchial asthma.

Allergic bronchial asthma is characterized by chronic inflammation of the airways, development of airway hyperreactivity and recurrent reversible airway obstruction. Target and effector cells responsible for airway hyperresponsiveness and airway obstruction include sensory and motor neurons as well as epithelial and smooth muscle cells. Although it is well established that the inflammatory process is controlled by T-helper (Th) 2 cells and the Th2-derived cytokines interleukin-4, airway hyperresponsiveness-5 and interleukin-13, the mechanisms by which immune cells interact with neurons, epithelial cells or smooth muscle cells still remain uncertain. Since there is growing evidence for extensive communication between neurons and immune cells, the mechanisms of this neuro-immune crosstalk in lung and airways of asthmatic patients are recently becoming the focus of asthma research. Neurotrophins represent candidate molecules regulating and controlling this crosstalk between the immune and peripheral nervous system. They are constitutively expressed by resident lung cells and produced in increasing concentrations by immune cells invading the airways under pathological conditions. They modify the functional activity of sensory and motor neurons, leading to enhanced and altered neuropeptide and tachykinin production. These effects are defined as "neuronal plasticity". The consequences are the development of "neurogenic inflammation" due to neuropeptide and tachykinin activities.     

Vitamin C metabolism and the common cold

Summary Male and female university students at the commencement of common cold symptoms were given a single dose of 500 mg of vitamin C. Plasma and leucocyte ascorbic acid concentrations were then measured for six hours. Symptom severity was recorded. The test was repeated twenty-three days after the last symptom had disappeared. The ascorbic acid blood response curve had then returned to normal. Significant and similar elevations of plasma ascorbic acid occurred in both sexes in the cold and post-cold tests. The leucocyte response was significantly reduced in the males but was unaffected in the females in the cold test. The regression coefficients between leucocyte and plasma values (P/L regressions) confirmed that ascorbic acid metabolism was less deranged in females than males during the cold test. Administration of ascorbic acid was associated with increases in blood ascorbic acid concentrations during the post-cold period but not during colds. A single dose of 1000 mg raised blood ascorbic acid concentrations in both sexes during their colds. The elevation was higher, and maintained for two hours longer in the females.In vitro incubation of leucocytes in ascorbic acid confirmed that their ascorbic acid load could be increased by approximately 100% while cold symptoms were present. A significant association between cold symptoms and the state of ascorbic acid metabolism was demonstrated by correlating the ratio of toxic to catarrhal symptoms with P/L regressions during colds. When catarrhal symptoms are severe, ascorbic acid passes from the leucocytes into the plasma, and thence into the inflamed respiratory membranes. When toxic symptoms are relatively more severe, ascorbic acid is retained in the cells. The beneficial effect of vitamin C on the common cold is associated with its influence on ascorbic acid metabolism. A sex-linked difference in ascorbic acid metabolism is manifested during the common cold which affects assessment of the effects of vitamin C on the common cold.     

Evaluation of echinacea for treatment of the common cold

Considered to have immunostimulating activity, echinacea is a widely used phytomedicinal for treatment of the common cold and upper respiratory tract infections (URTIs). We reviewed the literature from the MEDLINE database (January 1966-July 1999), International Pharmaceutical Abstracts (IPA) online database, Cambridge Scientific Abstracts Biological Sciences online database, Alt-Health Watch online database, EMBase CD-ROM database, and references from published articles, reviews, and letters to evaluate evidence from clinical trials of echinacea's purported efficacy for treating or preventing URTIs. Twelve clinical studies published from 1961-1997 concluded that echinacea was efficacious for treating the common cold, but the results are unclear due to inherent flaws in study design. Five trials were published since 1997; two showed that echinacea lacked efficacy for treating and preventing URTI symptoms, and three concluded that it was effective in reducing the frequency, duration, and severity of common cold symptoms. Again, these results are unclear because of methodologic uncertainties, such as small populations and use of noncommercially available, nonstandardized dosage forms. Although evidence for echinacea's efficacy is inconclusive, it appears to be safe. Patients without contraindications to it may not be dissuaded from using an appropriate preparation to treat the common cold.