{"title":"Role of antimicrobial agents in the management of exacerbations of COPD.","authors":"Sat Sharma, Nicholas Anthonisen","doi":"10.2165/00151829-200504030-00001","DOIUrl":"10.2165/00151829-200504030-00001","url":null,"abstract":"<p><p>Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a common occurrence and characterize the natural history of the disease. Over the past decade, new knowledge has substantially enhanced our understanding of the pathogenesis, outcome and natural history of AECOPD. The exacerbations not only greatly reduce the quality of life of these patients, but also result in hospitalization, respiratory failure, and death. The exacerbations are the major cost drivers in consumption of healthcare resources by COPD patients. Although bacterial infections are the most common etiologic agents, the role of viruses in COPD exacerbations is being increasingly recognized. The efficacy of antimicrobial therapy in acute exacerbations has established a causative role for bacterial infections. Recent molecular typing of sputum isolates further supports the role of bacteria in AECOPD. Isolation of a new strain of Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae was associated with a considerable risk of an exacerbation. Lower airway bacterial colonization in stable patients with COPD instigates airway inflammation, which leads to a protracted self-perpetuating vicious circle of progressive lung damage and disease progression. A significant proportion of patients treated for COPD exacerbation demonstrate incomplete recovery, and frequent exacerbations contribute to decline in lung function. The predictors of poor outcome include advanced age, significant impairment of lung function, poor performance status, comorbid conditions and history of previous frequent exacerbations requiring antibacterials or systemic corticosteroids. These high-risk patients, who are likely to harbor organisms resistant to commonly used antimicrobials, should be identified and treated with antimicrobials with a low potential for failure. An aggressive management approach in complicated exacerbations may reduce costs by reducing healthcare utilization and hospitalization.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 3","pages":"153-67"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25163276","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}
Jaro Ankerst, Jan Lötvall, Sarah Cassidy, Nicola Byrne
{"title":"Comparison of the bronchodilating effects of formoterol and albuterol delivered by hydrofluoroalkane pressurized metered-dose inhaler.","authors":"Jaro Ankerst, Jan Lötvall, Sarah Cassidy, Nicola Byrne","doi":"10.2165/00151829-200504020-00006","DOIUrl":"https://doi.org/10.2165/00151829-200504020-00006","url":null,"abstract":"<p><strong>Objective: </strong>To compare the onset of bronchodilation with a new formoterol hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) with albuterol (salbutamol) HFA pMDI.</p><p><strong>Patients and methods: </strong>Thirty patients with stable mild or moderate asthma (23 using inhaled corticosteroids, mean FEV(1) 82% of predicted, >or=15% reversibility to terbutaline 1mg after 30 minutes) received formoterol HFA (Oxis) 2 x 4.5microg, albuterol HFA (Ventoline) Evohaler) 2 x 100microg, or placebo at three separate visits in this randomized, double-blind, double-dummy, three-way crossover study. FEV(1) was measured before and 3, 10, 20, 30 and 60 minutes after inhalation. Change in FEV(1) at 3 minutes after inhalation was the primary variable.</p><p><strong>Results: </strong>Mean baseline FEV(1) was stable on all study days (range 2.92-2.94L). FEV(1) values at 3 minutes were: formoterol 3.22L (8% increase), albuterol 3.23L (9% increase) and placebo 2.99L (both p < 0.001 vs placebo). Maximum FEV(1) increased similarly with formoterol and albuterol, with no differences observed between the active treatments at any time point. Patients rated treatment effective at 3 minutes in 15 of 30, 19 of 30 and 7 of 30 cases with formoterol, albuterol and placebo, respectively. All treatments were well tolerated.</p><p><strong>Conclusion: </strong>In stable, mild, or moderate asthma, formoterol 9microg and albuterol 200microg, both by HFA pMDI, provided equally rapid and effective bronchodilation.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 2","pages":"123-7"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200504020-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25043026","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":"Ipratropium bromide HFA.","authors":"Keri Wellington","doi":"10.2165/00151829-200504030-00006","DOIUrl":"https://doi.org/10.2165/00151829-200504030-00006","url":null,"abstract":"<p><p>Ipratropium bromide is a nonselective antagonist of the muscarinic receptors located on airway smooth muscle, and is delivered via a metered-dose inhaler (MDI). Because of the requirement to phase out chlorofluorocarbon (CFC)-propelled MDIs, the ipratropium bromide inhalation aerosol MDI has been redesigned with a hydrofluoroalkane as the propellant (ipratropium bromide HFA). Ipratropium bromide HFA has recently been approved in the US for the maintenance treatment of bronchospasm associated with COPD. Ipratropium bromide HFA 42 microg four times daily (one dose [42 microg] is delivered via two puffs of the inhaler) demonstrated comparable efficacy to that of ipratropium bromide CFC 42 microg four times daily, as measured by spirometric testing, in a large, randomized, double-blind, placebo-controlled, 12-week trial in patients with stable COPD. Similarly, four-times-daily ipratropium bromide HFA 42 microg and ipratropium bromide CFC 42 microg provided a comparable degree of bronchodilation in patients with stable COPD during a 1-year, open-label study primarily designed to assess safety. In both studies, the tolerability profiles of ipratropium bromide HFA and ipratropium bromide CFC were comparable. The most common adverse events were related to respiratory system disorders. During the 1-year study, dry mouth was reported by 1.3% and 0.7% of patients in the ipratropium bromide HFA or ipratropium bromide CFC groups.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 3","pages":"215-20; discussion 221-2"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200504030-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25163187","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 susceptibility breakpoints: PK-PD and susceptibility breakpoints.","authors":"Paul G Ambrose","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Since the early 1960s, considerable advancements have been made to standardize and provide quality assurance for clinical susceptibility testing procedures of antimicrobial agents. Controversy, however, remains as to the interpretation of clinical laboratory susceptibility test results. While some feel susceptibility breakpoints should only detect resistance mechanisms, others believe they should predict a high probability of clinical response. This has resulted in confusion among clinicians, as it has been apparent for some time that there can be discordance between interpretive test results and clinical response to therapy (generally cures of infections caused by resistant pathogens). Nearly simultaneous with the beginning of the standardization process for clinical susceptibility testing procedures, the first penicillin-resistant Streptococcus pneumoniae isolates were detected. During the ensuing decades, penicillin-resistant pneumococci became a greater clinical concern, resulting in macrolides emerging as safe therapeutic alternatives to beta-lactam agents for the treatment of community-acquired respiratory tract infections. During the last 10 years, the incidence of pneumococcal isolates with elevated macrolide minimum inhibitory concentration (MIC) values has also increased, yet the debate over the clinical meaning of these statistics persists. The youthful science of pharmacokinetics-pharmacodynamics provides a useful platform to determine which pneumococcal strains with elevated MIC values can be treated with contemporary dosing regimens and also facilitates the proper selection of antimicrobial breakpoints for all antimicrobial classes, including the newer macrolides.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 Suppl 1 ","pages":"5-11"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25071557","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":"A rational approach to the management of severe refractory asthma.","authors":"Elisabeth Bel, Anneke ten Brinke","doi":"10.2165/00151829-200504060-00002","DOIUrl":"https://doi.org/10.2165/00151829-200504060-00002","url":null,"abstract":"<p><p>Severe refractory asthma is a heterogeneous condition with different patterns of severity and different reasons for loss of asthma control. The three main patterns include asthma with frequent exacerbations, asthma with irreversible airway obstruction, and asthma with reduced sensitivity or resistance to corticosteroids. Each of these patterns has distinct risk factors. The assessment of patients with severe asthma requires a systematic, diagnostic and management protocol. The majority of patients will benefit from thorough analysis and treatment of aggravating factors. In some patients with severe refractory asthma, in particular those with concomitant chronic rhinosinusitis, long-term administration of systemic corticosteroids may be necessary. In these patients all efforts should be directed towards reducing the dose of corticosteroids as much as possible. Although several corticosteroid-sparing agents and immunosuppressants have been proposed in the literature, none of these has gained complete acceptance in clinical practice, either because of limited efficacy or unacceptable adverse effects. Novel potent anti-inflammatory therapies aimed at reducing the need for systemic corticosteroids in patients with severe, refractory asthma are urgently needed.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 6","pages":"365-79"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200504060-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25729797","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":"Anti-inflammatory medications for cystic fibrosis lung disease: selecting the most appropriate agent.","authors":"James F Chmiel, Michael W Konstan","doi":"10.2165/00151829-200504040-00004","DOIUrl":"https://doi.org/10.2165/00151829-200504040-00004","url":null,"abstract":"<p><p>The lung disease of cystic fibrosis (CF) is characterized by a self-sustaining cycle of airway obstruction, infection, and inflammation. Therapies aimed at decreasing the inflammatory response represent a relatively new strategy for treatment. Attention has focused primarily upon the therapeutic potential of corticosteroids and NSAIDs. Although beneficial, the use of systemic corticosteroids is limited by their unacceptable adverse effects. It is unclear if inhaled corticosteroids are a viable alternative, although their use in CF has dramatically increased in recent years. High-dose ibuprofen has been shown to slow progression of CF lung disease, but its use has not been widely adopted despite a favorable risk-benefit profile. Thus, other anti-inflammatory approaches are under investigation. Since the inflammatory response can be triggered by many stimuli and since the pathways activated by these stimuli produce many mediators, there are a plethora of targets for anti-inflammatory therapeutics. Specific antibodies, receptor antagonists, and counter-regulatory cytokines, such as interleukin (IL)-10 and interferon-gamma, inhibit the pro-inflammatory mediators responsible for the damaging inflammation in the CF airway, including tumor necrosis factor-alpha, IL-1beta and IL-8. Studies of molecules that modulate intracellular signaling cascades that lead to the production of inflammatory mediators, are underway in CF. For patients with established disease, recent and projected advances in therapies that are directed at neutrophil products, such as DNase, antioxidants, and protease inhibitors, hold great promise for limiting the consequences of the inflammatory response. To optimize anti-inflammatory therapy, it is necessary to understand the mechanism of action of these agents in the CF lung to determine which agents will be most beneficial, and to determine which therapies should be initiated at what age and stage of lung disease. Hope remains that correction of the abnormal CF transmembrane conductance regulator protein or gene replacement therapy will be curative. However, correction of the basic defect must also correct the dysregulated inflammatory response in order to be effective. Until those therapies aimed at repairing the basic defect are realized, limiting the effects of the inflammatory process will be important in slowing the decline in lung function and thus prolonging survival in patients with CF.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 4","pages":"255-73"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200504040-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25235196","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 role of tiotropium bromide, a long-acting anticholinergic bronchodilator, in the management of COPD.","authors":"Farzad Saberi, Denis E O'Donnell","doi":"10.2165/00151829-200504040-00005","DOIUrl":"https://doi.org/10.2165/00151829-200504040-00005","url":null,"abstract":"<p><p>Bronchodilator therapy forms the mainstay of treatment for symptomatic patients with COPD. Long-acting bronchodilators, which maintain sustained airway patency over a 24-hour period, represent an advance in therapy. Tiotropium bromide is a new long-acting inhaled anticholinergic agent with superior pharmacodynamic properties compared with the short-acting anticholinergic, ipratropium bromide. Tiotropium bromide has been consistently shown to have a greater impact than ipratropium bromide on clinically important outcome measures such as health status. The mechanisms of clinical benefit with tiotropium bromide are multifactorial, but improved airway function, which enhances lung emptying and allows sustained deflation of over-inflated lungs, appears to explain improvements in dyspnea and exercise endurance in COPD. Inhaled tiotropium bromide therapy has also been associated with reduction in acute exacerbations of COPD as well as reduced hospitalizations. The safety profile of tiotropium bromide is impressive: dry mouth is the most common adverse event and rarely necessitates termination of the drug. No tachyphylaxis to tiotropium bromide has been demonstrated in clinical trials lasting up to 1 year. There is preliminary information that the combination of long-acting anticholinergics and long-acting beta2-adrenoceptor agonists provides additive physiological and clinical benefits. According to recent international guidelines, long-acting bronchodilators should be considered early in the management of symptomatic patients with COPD in order to achieve effective symptom alleviation and reduction in activity limitation. Tiotropium bromide, because of its once-daily administration and its established efficacy and tolerability profile, has emerged as an attractive therapeutic option for this condition.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 4","pages":"275-81"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200504040-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25235197","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":"Parental smoking and childhood asthma: clinical implications.","authors":"Kai-Håkon Carlsen, Karin C Lødrup Carlsen","doi":"10.2165/00151829-200504050-00005","DOIUrl":"https://doi.org/10.2165/00151829-200504050-00005","url":null,"abstract":"<p><p>Environmental tobacco smoke and constituents are global risks for human health. Considerable evidence shows that environmental tobacco smoke exposure contributes to, and exacerbates, respiratory disorders. This review assesses the causal role of environmental tobacco smoke exposure for childhood respiratory disorders, and in particular asthma. Tobacco smoke and environmental tobacco smoke exposure during pregnancy have an effect upon lung function in newborn infants; exposure after birth also has an effect upon lung function. An effect upon bronchial responsiveness has been suggested but the evidence is not as strong as for lung function. From 1997 to 1999 a comprehensive set of systematic reviews concerning the relationship between exposure to environmental tobacco smoke and respiratory health in children summarized the results from hundreds of published papers. The evidence for a causal relationship between environmental tobacco smoke exposure and asthmatic symptoms on the one hand, and between environmental tobacco smoke exposure and reduction in lung function on the other hand, was quite strong, whereas the evidence between environmental tobacco smoke exposure and development of allergy was much weaker. Here we present an overview of the effects of environmental tobacco smoke exposure on lung health in children. A hypothesis has been put forward regarding upregulation of pulmonary neuroendocrine cells in relationship to mechanisms of tobacco smoke products (TSP)-induced pulmonary disease. It has also been reported that genetic variation makes part of the population especially vulnerable to environmental tobacco smoke exposure during pregnancy. Furthermore, there is a need for intervention to reduce environmental tobacco smoke exposure in young children, by educating parents and adolescents about the health effects of environmental tobacco smoke exposure. Studies are needed to identify possible critical periods when environmental tobacco smoke exposure is more likely to induce harmful effects on lung health in young children in order to implement effective preventive strategies.</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 5","pages":"337-46"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200504050-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25278988","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":"Spotlight on amoxicillin/clavulanic acid 2000 mg/125 mg extended release (XR) in respiratory tract infections in adults.","authors":"Paul L McCormack, Gillian M Keating","doi":"10.2165/00151829-200504050-00007","DOIUrl":"https://doi.org/10.2165/00151829-200504050-00007","url":null,"abstract":"<p><p>Amoxicillin/clavulanic acid 2000 mg/125 mg extended release (Augmentin XR), referred to herein as amoxicillin/clavulanic acid XR, is a pharmacokinetically enhanced formulation designed to provide more effective therapy in adults and adolescents than conventional formulations against community-acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with reduced susceptibility to amoxicillin.Amoxicillin/clavulanic acid XR maintains plasma amoxicillin concentrations >4 microg/mL for a mean of 49% of the dosing interval indicating that it would be highly effective against S. pneumoniae strains with minimum inhibitory concentrations (MICs) above the National Committee for Clinical Laboratory Standard's amoxicillin +/- clavulanic acid susceptibility breakpoint of < or = 2 microg/mL. Amoxicillin/clavulanic acid XR is at least as effective as conventional amoxicillin/clavulanic acid formulations, levofloxacin, and clarithromycin in treating community-acquired pneumonia, acute bacterial sinusitis, or acute exacerbations of chronic bronchitis, and has a tolerability profile comparable to that of conventional amoxicillin/clavulanic acid formulations. While the incidence of amoxicillin- or multidrug-resistant S. pneumoniae is not currently sufficient in most regions to warrant the routine empiric use of amoxicillin/clavulanic acid XR, the drug would be extremely useful in those regions with a high incidence of resistant pathogens or in selected patients (i.e. those with S. pneumoniae isolates having amoxicillin MICs > or = 2 microg/mL but < or = 4 microg/mL).</p>","PeriodicalId":87162,"journal":{"name":"Treatments in respiratory medicine","volume":"4 5","pages":"361-2"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00151829-200504050-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25278990","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}