Effect of PPAR γ agonist(rosiglitazone) on the secretion of Th2 cytokine in asthma mice

Objective: To explore the effect of PPAR γ agonist(rosiglitazone) on the secretion of Th2 cytokines and the proportion of immune cell subsets in asthma mice,Methods: Ovalbumin(OVA)-sensitized mice were used to build asthma models,Those mice were divided into the normal control group,model group and rosiglitazone group,Differences of the changes in lung histopathology of mice in the three group were observed through hematoxylin and eosin(HE) strain,and the numbers of the total cells,eosinophils and neutrophils in BALF of mice in the three groups were compared,ELISA and real-time PCR were employed to detect the protein levels of interleukin(IL)-5,IL-13,IL-4 and IL-10 and m RNA level,respectively,Flow cytometry number was implied to analyze the proportion of immune cell subsets in peripheral blood of mice,Results: Compared with the mice in the control group,and mice of the model group,the infiltration of inflammatory cells in BALF increased,bronchial smooth muscle became thickened,a large amount of collagen deposited,the secretion of Th2 cytokine increased significantly,the ratio of regulatory T cells(Treg) decreased,the ratio of T17 cells rose distinctly; while in mice of the rosiglitazone group,the changes of their lung histopathology were improved obviously,the number of infiltration of inflammatory cells declined,the thickened smooth muscle relieved,the deposition of collagen decreased,the secretion of Th2 cytokine was inhibited,the ratio of Treg went up,and the increased of the ratio of T17 cells was inhibited but still not return to normal level,Conclusions: Rosiglitazone can regulate the proportion of Treg and Th17 cells and inhibit the secretion of Th2 cytokines,which inhibit the airway inflammatory response for asthma mice effectively.     

The effect of biomass fuel exposure on the prevalence of asthma in adults in India – review of current evidence

Introduction: The combustion of biomass fuels is a major source of respiratory disease among individuals in the developing world. Over two million people world-wide rely on biomass fuels to supply their household energy needs with an estimated 1.6 million deaths annually being attributable to biomass smoke exposure. As a developing country, India relies heavily on the use of solid fuels as a source of energy. These materials supply 75% of the country’s domestic energy need and are attributed as the cause of over 600?000 deaths annually. Diseases such as chronic bronchitis and acute lower respiratory tract infections are strongly correlated to biomass smoke exposure. While not as strongly correlated, accumulating evidence suggests that asthma prevalence may be related to solid fuel smoke. Methods: This review examines the current literature linking biomass smoke exposure to the reporting of asthma symptoms. A PubMed search was performed using key terms biomass, asthma, India and respiratory disease. Preference was given to recent articles that surveyed the adult population within India. Results: The reviewed articles showed an increased odds ratio for reporting a diagnosis of asthma or symptoms consistent with asthma following biomass smoke exposure. While the literature supports a strong association between household air pollution and the development of chronic bronchitis and acute lower respiratory tract infections in India, this review establishes a more firm relationship between reported asthma symptoms and biomass smoke exposure. Conclusion: The exposure to biomass fuel smoke results in respiratory diseases in developing countries. Among these diseases, asthma appears to be a preventable pulmonary pathology that is associated with household air pollution. Measures to reduce exposure may decrease the burden of disease which could help advance social and economic progress in these nations. Further research and out-reach efforts are needed to reduce the total burden of lung diseases, including asthma, across the developing world. This reduction could save millions of dollars annually and lower morbidity and mortality in the affected populations.     

Is the diagnosis of asthma different in elderly?

Asthma is mis-diagnosed, under-diagnosed and under-treated in older populations but has a high mortality rate. The physiological changes due to aging of lung, the co-morbid situations and poly pharmacy may change the typical presentation of asthma in older people and cause diagnostic difficulties. But it therefore should be diagnosed properly by taking of all differential situations especially chronic obstructive pulmonary disease into consideration since the appropriate management of the disease will alter the morbidity and mortality.     

Evaluating the effects of asthma therapy on childhood growth: what can be learnt from the published literature?

The difficulties of assessing the effects of asthma therapy on childhood growth were explored in the first part of this review. In this part of the review growth studies with inhaled corticosteroids were selected that included a control group, measured height by stadiometry and were of > or = 1 yr duration. The studies were classified as type 1 (placebo control), type 2 (nonsteroidal therapy control), type 3 (comparator inhaled corticosteroid control) or type 4 ("real-life" studies with dose adjustment). The design attributes of these studies were then compared with the recommendations described in the first part of this review. Of the 18 studies identified, 17 were susceptible to one or more important confounding factors. Nevertheless, the outcomes of all 18 studies were mostly consistent. At recommended doses, beclomethasone dipropionate and budesonide demonstrated a small degree of growth suppression over 1-2 yrs (study types 1 and 2), but there was little evidence of such an effect with fluticasone propionate. Studies comparing different inhaled corticosteroids at recommended doses indicated more rapid growth with fluticasone propionate than with beclomethasone dipropionate or budesonide. However, none of the inhaled corticosteroids appeared to affect final height. In conclusion, the results from the majority of published growth studies with inhaled corticosteroids must be interpreted with a degree of caution owing to their potential susceptibility to important confounding factors. Further well-designed studies are needed to establish whether different inhaled corticosteroids have different effects on growth in the long term.     

Beta2-agonist eutomers: a rational option for the treatment of asthma?

Beta2-adrenoceptor agonists (beta2-agonists) such as albuterol (salbutamol) and terbutaline and their long-acting analogs salmeterol and formoterol are widely used as bronchodilators in the treatment of asthma. They are chiral drugs historically marketed as racemic mixtures of an active (eutomer) and essentially inactive (distomer) stereoisomer. Despite their obvious therapeutic value and widespread use, beta2-agonists have been implicated, somewhat controversially, in causing an increase in asthma mortality and a deterioration of asthma control by a mechanism that remains elusive. Inherent toxicity of the distomers has been widely touted as an explanation and has given rise to pressure for the replacement of the racemates with pure eutomer formulations (the so-called chiral or racemic switch). This has culminated in the recent introduction into clinical practice of the single active stereoisomer of albuterol (levalbuterol) and the promise of other pure beta2-agonist eutomer formulations to follow. This article examines the evidence on which these chiral switches are based. Clinical studies designed to reveal negative effects of beta2-agonists have searched for reductions in lung function, increases in airway responsiveness to bronchoconstrictor mediators and worsening of asthma control. Crossover studies administering the pure stereoisomers and racemate of albuterol have not shown a clear superiority of the pure eutomer formulation over the racemate in terms of either bronchial hyperresponsiveness, tachyphylaxis to bronchoprotective effects or improvements in lung function. Clinical toxicity of beta2-agonist distomers on any aspect of asthmatic lung function has also not been demonstrated in the relatively short-term inhalational studies (single dose or repeated dose studies <1 week) that have been carried out. In animal studies, the administration of beta2-agonist racemates and distomers has been shown to enhance bronchial hyperresponsiveness but only in ovalbumin-sensitized animals where the relevance to humans is questionable. The pharmacokinetics and metabolism of beta(2)-agonist stereoisomers appear to be essentially similar whether administered as single stereoisomers or as racemates. Levalbuterol may be slightly more potent than an equivalent dose given as racemate, but there is some evidence that it forms a small amount of the distomer in vivo which detracts somewhat from its purported benefits over use of the racemate. Whilst there remains a clear need for studies of longer duration with sensitive clinical endpoints to evaluate the benefits of beta2-agonist eutomers and to investigate distomer toxicity, the chiral switch for beta2-agonists in general, and for albuterol in particular, does not appear to be justified on the basis of the evidence available to date.     

Does the medical diagnosis of occupational asthma coincide with the legal diagnosis?

Objective: The incidence of occupational asthma (OA) is increasing worldwide. In this study, we first aimed to document the rate of diagnosis of OA among patients who were referred to our clinic from the Social Security Institution and the factors that affected diagnosis; secondly, we aimed to assess the consistency of the medical and legal diagnoses. Methods: The study involved 132 consecutive patients who were referred to our clinic for the evaluation of OA between 2010 and 2015. Detailed workplace history, the tools used in the diagnosis such as peak expiratory flow (PEF) monitoring and bronchial provocation tests, and the final medical diagnosis were recorded from case files. Results: Asthma was diagnosed in 75% (n = 99) of the patients. Among them, 22.2% were diagnosed as having OA. The diagnosis was confirmed by serial PEF measurements, non-specific bronchial hyperreactivity assessment or both of the tests both at work and off-work periods. OA diagnosis was mostly established in active workers (72.7%). The legal diagnosis period was completed in 54.5% of these 22 patients, and 50% (n = 11) were officially diagnosed as having OA with a 91.6% concordance with medical diagnosis. Conclusion: This study verifies the importance of diagnosing asthma correctly as a first step in the evaluation of OA. Diagnostic tests other than specific provocation tests could be preferential in patients who still work in the same field. We believe that cooperation with the patient's occupational physician and adequate recognition of the work environment will improve the consistency of legal and medical diagnoses.     

Treatment of acute severe asthma and chronic obstructive pulmonary disease in Danish hospitals. Do national recommendations improve on the quality of the treatment?

Studies have demonstrated suboptimal treatment of acute severe asthma and chronic obstructive pulmonary disease (COPD). We examined the quality of treatment in Denmark and the effect of intervention, by publication of recommendations for standardised treatment. All 70 hospitals in Denmark with emergency facilities participated in a telephone questionnaire, examining treatment behaviours among house officers. The survey was repeated 3 years later, after publication of national recommendations for treatment of acute exacerbations of asthma and COPD. The response rate in both surveys was 100%. An insufficient handling of nebulisers, a huge variation in the delivered dose of bronchodilators and a suboptimal use of corticosteroids was found. A significant trend towards more liberate use of oxygen was seen in both asthma (3.2 l min(-1) versus 4.8 l min(-1), P<0.001) and COPD (1.5 l min(-1) versus 1.9 l min(-1), P = 0.047). Further, a huge difference in treatment behaviours was revealed from this survey The knowledge among house officers of basic principles of treatment was insufficient. Treatment behaviour was only moderately affected by national publication of detailed recommendations for treatment. This study indicates a need for implementing tools for quality control.     

“Noninvasive” oral treatment of asthma in the emergency room

One hundred forty consecutive patients with acute asthmatic episodes presenting to the emergency room were studied prospectively to assess the efficacy of oral therapy. After the emergency room staff was oriented to the pharmacologic action of hydroalcoholic elixir of theophyline, oral terbutaline, and a metered-dose hand-held nebulizer (metaproterenol), use of oral therapy as Initial therapy rose from 12 percent to 76 percent (p = 0.005). More than half of these patients were discharged without receiving any of the traditional more invasive therapies of subcutaneous epinephrine, intravenous hydrating fluids with aminophylline, and machine-delivered sympathomimetic aerosols. Oral therapy did not substantially after the total time spent in the emergency room. Only 4 percent treated with oral therapy required further treatment in the emergency room within 48 hours; 2 percent vomited after treatment. Oral therapy is safe and effective for most asthmatic patients presenting to the emergency room, as they generally are undermedicated with regard to theophyllines and sympathomimetic drugs. Use of oral therapy in the emergency room is a potent tool for educating asthmatic patients in the use of medication available for home use. The patients who require emergency room treatment despite being well-medicated at home (a small minority) need a higher level of care including intermittent positive-pressure breathing, corticosterolds, and often hospitalization.     

Standing on the shoulders of giants

The cover of this well-illustrated,monochrome book has mini-portraits of eight surgical pioneers that suggest the scope of this coffee table sized hardback.Andreas Vesalius     

Brittle asthma: a separate clinical phenotype of asthma?

There is now good evidence that brittle asthma should be regarded as a separate clinical phenotype of asthma at the severe end of the spectrum. Two types of brittle asthma can be identified. Type I is characterized by wide swings in peak expiratory flow (PEF) despite maximal therapy and type II by very sudden attacks out of the blue. Type I brittle asthma is more common in females and although the exact aetio-pathogenic mechanisms are not yet known, several factors including allergen sensitization (with exposure) and psychosocial factors may be important. Peak expiratory flow monitoring is essential for recognising these patients. Treatment of type I brittle asthma is difficult and needs to be holistic, with particular attention being paid to psychosocial factors where required. Continuous subcutaneous infusion of terbutaline (or salbutamol)) and dietary exclusion of relevant foods to which the patient may be allergic may be helpful in selected patients. Type II brittle asthma is less difficult to manage and includes the use of self-administered subcutaneous adrenaline to abort the rapidly developing exacerbations.     

Clinical study on the impact of serum β_2 microglobulin level on prognosis of dilated cardiomyopathy patients

正Objective To explore the impact of the serumβ_2-microglobulin (β_2-MG) level on the prognosis of patients with dilated cardiomyopathy (DCM). Methods Data from 101 heart failure patients due to DCM,who were hospitalized in our department between June 2013 and