Treatments in respiratory medicine最新文献

{"title":"New strategies for the treatment of pulmonary hypertension in sickle cell disease : the rationale for arginine therapy.","authors":"Claudia R Morris","doi":"10.2165/00151829-200605010-00003","DOIUrl":"https://doi.org/10.2165/00151829-200605010-00003","url":null,"abstract":"<p><p>Nitric oxide (NO) is inactivated in sickle cell disease (SCD), while bioavailability of arginine, the substrate for NO synthesis, is diminished. Impaired NO bioavailability represents the central feature of endothelial dysfunction, and is a key factor in the pathophysiology of SCD. Inactivation of NO correlates with the hemolytic rate and is associated with erythrocyte release of cell-free hemoglobin and arginase during hemolysis. Accelerated consumption of NO is enhanced further by the inflammatory environment of oxidative stress that exists in SCD. Based upon its critical role in mediating vasodilation and cell growth, decreased NO bioavailability has also been implicated in the pathogenesis of pulmonary arterial hypertension (PHT). Secondary PHT is a common life-threatening complication of SCD that also occurs in most hereditary and chronic hemolytic disorders. Aberrant arginine metabolism contributes to endothelial dysfunction and PHT in SCD, and is strongly associated with prospective patient mortality. The central mechanism responsible for this metabolic disorder is enhanced arginine turnover, occurring secondary to enhanced plasma arginase activity. This is consistent with a growing appreciation of the role of excessive arginase activity in human diseases, including asthma and PHT. Decompartmentalization of hemoglobin into plasma consumes endothelial NO and thus drives a metabolic requirement for arginine, whose bioavailability is further limited by arginase activity. New treatments aimed at maximizing both arginine and NO bioavailability through arginase inhibition, suppression of hemolytic rate, or oral arginine supplementation may represent novel therapeutic strategies.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 1","pages":"31-45"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605010-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25797579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary arterial hypertension : a comprehensive review of pharmacological treatment.","authors":"Erika Berman Rosenzweig,&nbsp;Robyn J Barst","doi":"10.2165/00151829-200605020-00005","DOIUrl":"https://doi.org/10.2165/00151829-200605020-00005","url":null,"abstract":"<p><p>The treatment of pediatric pulmonary arterial hypertension (PAH) is challenging due to the serious nature of the disease, its rapid progression, and the limited treatment options available. While oral calcium channel antagonists and continuous intravenous epoprostenol have been used successfully for over a decade, novel treatment options - including prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors - may change the course of this disease for many children in the future.Prostacyclin analogs offer the benefit over continuous intravenous epoprostenol of an alternative delivery system. However, the efficacy of these medications compared with intravenous epoprostenol and the risk/benefits of each analog need to be weighed in future trials, which need to include larger numbers of pediatric patients to optimize therapy and outcome for individual children with PAH.For patients who do not have an acute response to vasodilator testing or have failed treatment with oral calcium channel antagonists, endothelin receptor antagonists may offer a viable treatment option. Furthermore, in the future, the addition of endothelin receptor antagonists to long-term therapy with calcium channel antagonists or to epoprostenol or a prostacyclin analog may increase the overall efficacy of treatment of PAH. Large multi-institutional randomized trials to determine whether sildenafil is effective and safe for the long-term treatment of PAH in children are in progress.A comprehensive review of these newer agents with an emphasis on the pathobiology/pathophysiology of PAH provides insight into the future management of pediatric PAH patients.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 2","pages":"117-27"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605020-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25885297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Diagnosis and Treatment Patterns of COPD in Primary Care.","authors":"Vijay N Joish,&nbsp;Ellen Brady,&nbsp;William Stockdale,&nbsp;Diana I Brixner,&nbsp;Riad Dirani","doi":"10.2165/00151829-200605040-00006","DOIUrl":"https://doi.org/10.2165/00151829-200605040-00006","url":null,"abstract":"<p><strong>Objective: </strong>Many patients with COPD are misdiagnosed or under-treated. The characteristics of COPD patients and the patterns of treatment have not been well characterized in primary care settings. The objective of this study was to identify patterns of COPD onset, diagnosis and treatment with the goal of facilitating appropriate treatment at earlier stages.</p><p><strong>Methods: </strong>A national electronic medical record database was used to identify patients with at least a 6-month history prior to a diagnosis of COPD (ICD-9 codes 491.xx, 492.xx, and 496). Pulmonary function test (PFT) results closest to the first diagnosis of COPD were evaluated to characterize disease severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Prescription data were evaluated at the time of diagnosis. All descriptive statistics were conducted using STATA statistical software.</p><p><strong>Results: </strong>A total of 14 691 patients met the study criteria. Prescription data were available for 9354 (64%) of these patients. Of this group, only slightly over 50% (n = 5264) had a respiratory-related prescription on the date of diagnosis. For those not having a respiratory drug at the time of diagnosis, the average time between diagnosis and the first respiratory-related prescription was 106 (SD +/- 256.4) days. Only 389 (<3%) patients had any PFT data recorded on or prior to the day of their first diagnosis of COPD, and only 273 (2%) had sufficient PFT data available to determine their GOLD severity class. The average time between diagnosis and first COPD prescription was greatest for patients in the lowest severity category (Class 0/I; 163 +/- 288.2 days), and smallest for patients in the highest severity category (Class IV; 124 +/- 152.3 days).</p><p><strong>Conclusion: </strong>COPD is often not diagnosed or treated until the later stages of disease, and spirometry is not used routinely to diagnose, stage or guide treatment decisions.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 4","pages":"283-93"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605040-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26115660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Health-Related Quality of Life in Patients with Obstructive Sleep Apnea : What are the Available Options?","authors":"Neomi Shah,&nbsp;Francoise Roux,&nbsp;Vahid Mohsenin","doi":"10.2165/00151829-200605040-00002","DOIUrl":"https://doi.org/10.2165/00151829-200605040-00002","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) syndrome is a common and often life-altering sleep-related breathing disorder. It not only adversely affects cardiovascular health, but the quality of life of these patients is also often significantly compromised. They experience excessive daytime sleepiness and poor cognitive, social and exercise performance. Furthermore, they often have marital problems with increased divorce rates, depression, and poor job performance.Our purpose in writing this review is to highlight the various neuropsychiatric domains that are affected in OSA patients and to emphasize that identifying and treating this condition can significantly improve the quality of life of these individuals. In recent years there has been ample evidence supporting the role of treatment for OSA to improve cardiovascular outcomes. We provide similar evidence supporting the treatment of OSA to improve health-related quality of life outcomes for these patients. Surgical, non-surgical and pharmacologic modalities are currently available as effective options for the treatment of OSA, with continuous positive airway pressure therapy appearing to be the most promising.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 4","pages":"235-44"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605040-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26115656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial therapy in childhood asthma and wheezing.","authors":"Arne Simon, Oliver Schildgen","doi":"10.2165/00151829-200605040-00004","DOIUrl":"10.2165/00151829-200605040-00004","url":null,"abstract":"<p><p>There is an increasing number of viral and bacterial pathogens suspected of contributing to asthma pathogenesis in childhood, making it more difficult for the practitioner to make specific therapy decisions. This review discusses the role of viruses, e.g. respiratory syncytial virus, human metapneumovirus, influenza viruses and rhinoviruses, as well as the role of the atypical bacteria Chlamydophila pneumoniae and Mycoplasma pneumoniae, as contributors to childhood asthma. Diagnosis, prevention, and therapy are discussed, including a summary of drugs, i.e. macrolide antibacterials, antivirals, and vaccine regimens already available, or at least in clinical trials. For the practitioner dealing with patients every day, drug regimens are assigned to the individual pathogens and an algorithm for the management of atypical infections in patients with asthma or recurrent wheezing is presented.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 4","pages":"255-69"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26115659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monotherapy versus Combination Therapy in Patients Hospitalized with Community-Acquired Pneumonia.","authors":"Martin Kolditz,&nbsp;Michael Halank,&nbsp;Gert Höffken","doi":"10.2165/00151829-200605060-00002","DOIUrl":"https://doi.org/10.2165/00151829-200605060-00002","url":null,"abstract":"<p><p>Current international guidelines for the management of community acquired pneumonia (CAP) recommend therapy with a beta-lactam plus a macrolide or a 'respiratory' fluoroquinolone alone in patients hospitalized in a medical ward, and combination therapy with a beta-lactam plus a macrolide or a fluoroquinolone in patients hospitalized in the intensive care unit. However, which of the available options should be preferred remains a matter of debate, and there are surprisingly few prospective randomized trials strictly comparing mono- versus dual therapy strategies in CAP patients. Thus, the recommendation of combining a macrolide with a beta-lactam rather than using a beta-lactam alone in hospitalized patients is derived mainly from observational data, and the suggested combination of a beta-lactam with a fluoroquinolone in severe CAP has been rarely examined in a clinical trial.As there have been sound theoretical arguments for and against combination therapy regimens, the rationale for the different options is discussed and available clinical trial data are reviewed in this article. A final conclusion about the superiority of one antibacterial regimen over another in hospitalized patients with CAP cannot be drawn on the basis of the limited data available. So far, combination therapy probably should be preferred in all patients presenting with severe pneumonia, whereas in general, combination therapy is not necessary in patients in a medical ward, and combination therapy with a beta-lactam plus a macrolide or monotherapy with a respiratory fluoroquinolone should be considered equivalent in this latter patient group. On the other hand, the available data demonstrate that empirical coverage of atypical bacteria in all patients with mild-to-moderate CAP seems unnecessary, and beta-lactam monotherapy might perform equally well when compared with respiratory fluoroquinolones in patients with non-severe CAP. Thus, the alternative use of a beta-lactam alone at adequate dosage in clinically stable patients seems justified, if CAP due to Legionella pneumophila is unlikely.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 6","pages":"371-83"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605060-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26430454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of nonsteroidal anti-inflammatory drugs in patients with aspirin hypersensitivity : safety of cyclo-oxygenase-2 inhibitors.","authors":"Marek L Kowalski,&nbsp;Joanna Makowska","doi":"10.2165/00151829-200605060-00005","DOIUrl":"https://doi.org/10.2165/00151829-200605060-00005","url":null,"abstract":"<p><p>This article provides information on the pathogenesis of aspirin hypersensitivity, cross-sensitivity, and cross-tolerance of different NSAIDs in patients with respiratory types of reactions. Hypersensitivity to aspirin may affect 5-20% of patients with chronic asthma and an unknown fraction of patients with chronic urticaria-angioedema. These patients develop cross-reactions to other, chemically non-related, NSAIDs with strong inhibitory activity towards cyclo-oxygenase (COX)-1 (e.g. indomethacin, naproxen, ketoprofen). Avoidance of aspirin and all cross-reacting NSAIDs as well as education of patients are crucial. As an alternative antipyretic or analgesic drug, aspirin-sensitive asthmatic patients may take acetaminophen (paracetamol) in low or moderate doses (<1000mg). Preferential COX-2 inhibitors (nimesulide, meloxicam) are tolerated by the majority but not all hypersensitive patients. Selective COX-2 inhibitors (celecoxib and rofecoxib [withdrawn from the market]) are well tolerated by almost all aspirin-sensitive asthmatic patients. In patients with coronary artery disease requiring treatment with aspirin, desensitization to aspirin may be an alternative approach. Thus, for the majority of patients with asthma and hypersensitivity to aspirin or other NSAIDs, an alternative anti-inflammatory drug can be found. However, in each individual case physicians must consider the choice of an alternative NSAID carefully.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 6","pages":"399-406"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605060-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26430833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticosteroid insensitivity in smokers with asthma : clinical evidence, mechanisms, and management.","authors":"Neil C Thomson,&nbsp;Malcolm Shepherd,&nbsp;Mark Spears,&nbsp;Rekha Chaudhuri","doi":"10.2165/00151829-200605060-00010","DOIUrl":"https://doi.org/10.2165/00151829-200605060-00010","url":null,"abstract":"<p><p>Corticosteroids are the most effective treatment for asthma, but the therapeutic response varies considerably between individuals. Several clinical studies have found that smokers with asthma are insensitive to the beneficial effects of short- to medium-term inhaled corticosteroid treatment compared with non-smokers with asthma. It is estimated that 25% of adults in most industrialized countries smoke cigarettes, and similar surveys amongst asthmatic individuals suggest that the prevalence of smoking in this grouping mirrors that found in the general population. Therefore, cigarette smoking is probably the most common cause of corticosteroid insensitivity in asthma. Cigarette smoking and asthma are also associated with poor symptom control and an accelerated rate of decline in lung function. The mechanism of corticosteroid insensitivity in smokers with asthma is currently unexplained but could be due to alterations in airway inflammatory cell phenotypes, changes in glucocorticoid receptor alpha/beta ratio, and/or reduced histone deacetylase activity. Smoking cessation should be encouraged in all smokers with asthma. Short-term benefits include improvements in lung function and asthma control. However, the numbers of sustained quitters is disappointingly small. Additional or alternative drugs need to be identified to treat those individuals who are unable to stop smoking or who have persistent symptoms following smoking cessation.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 6","pages":"467-81"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605060-00010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26430838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety profile of sublingual immunotherapy.","authors":"Giovanni Passalacqua,&nbsp;Laura Guerra,&nbsp;Federica Fumagalli,&nbsp;Giorgio Walter Canonica","doi":"10.2165/00151829-200605040-00001","DOIUrl":"https://doi.org/10.2165/00151829-200605040-00001","url":null,"abstract":"<p><p>Sublingual immunotherapy (SLIT) was proposed for clinical practice about 20 years ago with the main aim of improving the safety and avoiding the adverse effects of traditional treatment for allergic airways disease. To date, 32 randomized controlled trials and 6 postmarketing surveys have been published that provide a robust documentation of the safety profile of the treatment.Looking at the randomized trials it emerges that the more frequent adverse event of SLIT is oral itching or swelling, followed by gastrointestinal complaints. These adverse events are invariably described as mild and easily managed by adjusting the dose. Relevant systemic adverse events (asthma, urticaria, angioedema) occur sporadically and, with the exception of oral/gastrointestinal adverse events, the incidence of adverse events seems not to differ between the placebo and active groups. The safety profile of SLIT does not differ between adults and children.The postmarketing surveys consistently show that the incidence of adverse events associated with SLIT is less than 10%, corresponding to less than 1 adverse event per 1000 doses, and is thus quite superior to the safety profile of subcutaneous immunotherapy. Of note, the most recent data show that the rate of adverse events with SLIT is not increased in children below the age of 5 years.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 4","pages":"225-34"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605040-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26115655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of phosphodiesterase inhibitors in the management of asthma.","authors":"Neil Martin,&nbsp;Peter T Reid","doi":"10.2165/00151829-200605030-00006","DOIUrl":"https://doi.org/10.2165/00151829-200605030-00006","url":null,"abstract":"<p><p>Asthma is a chronic inflammatory condition characterised by reversible airflow obstruction and airway hyperreactivity. The course of the illness may be punctuated by exacerbations resulting in deterioration in quality of life and, in some cases, days lost from school or work. That asthma is common and increasingly prevalent magnifies the importance of any potential economic costs, and promoting asthma control represents an important public health agenda. While lifestyle changes represent a valuable contribution in some patients, the majority of asthmatic patients require therapeutic intervention. The recognition of the role of inflammation in the pathogenesis of asthma has led to an emphasis on regular anti-inflammatory therapy, of which inhaled corticosteroid treatment remains the most superior. In selected patients, further improvements in asthma control may be gained by the addition of regular inhaled long-acting beta(2)-adrenoceptor agonists or oral leukotriene receptor antagonists to inhaled corticosteroid therapy. However, a significant minority of patients with asthma remain poorly controlled despite appropriate treatment, suggesting that additional corticosteroid nonresponsive inflammatory pathways may be operative. Furthermore, some patients with asthma display an accelerated decline in lung function, suggesting that active airway re-modeling is occurring. Such observations have focused attention on the potential to develop new therapies which complement existing treatments by targeting additional inflammatory pathways. The central role of phosphodiesterase (PDE), and in particular the PDE4 enzyme, in the regulation of key inflammatory cells believed to be important in asthma - including eosinophils, lymphocytes, neutrophils and airway smooth muscle - suggests that drugs designed to target this enzyme will have the potential to deliver both bronchodilation and modulate the asthmatic inflammatory response. In vivo studies on individual inflammatory cells suggest that the effects are likely to be favorable in asthma, and animal study models have provided proof of concept; however, first-generation PDE inhibitors have been poorly tolerated due to adverse effects. The development of second-generation agents such as cilomilast and roflumilast heralds a further opportunity to test the potential of these agents, although to date only a limited amount of data from human studies has been published, making it difficult to draw firm conclusions.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"5 3","pages":"207-17"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200605030-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26021702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}