Treatments in respiratory medicine最新文献

Increased levels of antibacterial resistance among community-acquired pathogens have been influenced by various factors. Among the antibacterial-related drivers of resistance, the inappropriate and excessive use of antibacterials has been identified. A large number of antibacterial prescriptions can be attributed to syndromes of viral etiology; given that antibacterials provide no clinical benefit, this represents an important target for decreasing unnecessary antibacterial use. Notably, therapeutic exposure of bacteria to antibacterials exerts a continuous selection pressure on pathogens as well as on normal flora. This selection pressure may favor and/or enable resistance development through various mechanisms. The development of resistance may be reduced by avoiding subtherapeutic antibacterial exposure and prolonged treatment durations. Potency, or the product of in vitro antibacterial activity and the ability of an antibacterial to achieve adequate concentrations at the site of infection, is also a critical consideration. In general, the more potent an antibacterial, the less likely it is to propagate resistant isolates. Antibacterial resistance is unavoidable. However, consideration of the drivers of resistance and concerted efforts to avoid these effects will help to better control the development of resistance.

International guidelines on the management of asthma support the early introduction of corticosteroids to control symptoms and to improve lung function by reducing airway inflammation. However, not all individuals respond to corticosteroids to the same extent and it would be an advantage to be able to predict the response to corticosteroid treatment. Several biomarkers have been assessed following treatment with corticosteroids including measures of lung function, peripheral blood and sputum indices of inflammation, exhaled gases and breath condensates. The most widely examined measures in predicting a response to corticosteroids are airway hyperresponsiveness, exhaled nitric oxide (eNO) and induced sputum. Of these, sputum eosinophilia has been demonstrated to be the best predictor of a short-term response to corticosteroids. More importantly, directing treatment at normalizing the sputum eosinophil count can substantially reduce severe exacerbations. The widespread utilization of sputum induction is hampered because the procedure is relatively labor intensive. The measurement of eNO is simpler, but incorporating the assessment of NO in an asthma management strategy has not led to a reduction in exacerbation rates. The challenge now is to either simplify the measurement of a sputum eosinophilia or to identify another inflammatory marker with a similar efficacy as the sputum eosinophil count in predicting both the short- and long-term responses to corticosteroids.

Background: Allergic rhinitis is the most common allergic disease in the US. The predominant symptom of this condition is nasal congestion, which has a significant impact on quality of life and work productivity. This large survey was conducted to determine the impact of nasal congestion on the above parameters in individuals with allergic rhinitis, and treatment patterns for this symptom.

Methods: Participants were recruited voluntarily via telephone surveys and internet advertisements. Respondents with nasal congestion as a symptom of their allergic rhinitis (or who were primary caregivers to a child with nasal congestion associated with allergic rhinitis) were eligible for participation and completed a 52-question internet survey. Data were normalized to the US adult population using a weighting algorithm.

Results: Of the 2355 individuals with allergic rhinitis screened for participation in the survey, 2002 (85%) had nasal congestion. This was considered severe by 40% of respondents, compared with fewer than 30% who considered any other individual allergy symptom to be severe. Nasal congestion was the symptom that most adults and children wished to prevent, and it affected most respondents at work or school, had a notable emotional impact, and interfered with their ability to perform daily activities. Only 13% of participants receiving allergic rhinitis medication of any type, including over-the-counter medications, claimed to be very satisfied with treatment, and only 20% adhered completely to prescribing instructions. Although intranasal corticosteroids are recommended as first-line therapy for nasal congestion, only 30% of respondents with severe nasal congestion received treatment with intranasal corticosteroids.

Conclusions: Nasal congestion affects most individuals with allergic rhinitis, and has a notable impact on quality of life, emotional function, productivity, and the ability to perform daily activities. Patients need to be better educated on the appropriate use of medications, particularly intranasal corticosteroids, to manage their nasal congestion.

Lucinactant, formerly known as KL(4) surfactant, is a novel synthetic lung surfactant containing phospholipids and an engineered peptide, sinapultide, which is designed to mimic the actions of human surfactant protein B. It has been developed for use in the prevention or treatment of respiratory distress syndrome (RDS), a common problem in premature infants, which results from a deficiency or degradation of pulmonary surfactant. Lucinactant is administered intratracheally soon after birth as a replacement surfactant. In the pivotal randomized, double-blind, prophylaxis trial in premature infants, the incidence of RDS at 24 hours after birth was significantly lower in lucinactant recipients than in recipients of colfosceril palmitate, a synthetic non-protein-containing surfactant. RDS-related mortality at 14 days was significantly lower in lucinactant recipients than in recipients of colfosceril palmitate or beractant, a bovine-derived surfactant. In another randomized, double-blind, prophylaxis trial in premature infants, the rate of survival without bronchopulmonary dysplasia at 28 days of age in lucinactant recipients was not inferior to that in recipients of poractant alfa, a porcine-derived surfactant. Lucinactant was generally well tolerated. Adverse events were transient and related to the administration procedure. There were no differences in the incidences of complications of prematurity between lucinactant and the other surfactants.

The recent increase in bacterial resistance has been, and continues to be, unmatched by drug discovery and development. The judicious use of antibacterials must be observed so as to contain bacterial resistance and maintain the utility of agents currently on the market. Appropriate antibacterial use involves antibacterial avoidance when not indicated. When indicated, appropriate antibacterial use dictates that the optimal drug, dose and duration be utilized. Professional society guidelines facilitate drug selection as well as outline diagnostic criteria and important considerations for patient stratification. Pharmacodynamics is also key for drug selection and often guides determination of not only the optimal drug but also the optimal dose and duration. Importantly, bacterial eradication is essential, as it will reduce clinical failure, recurrence, or relapse and prevent the selection of resistance. Additional strategies to influence antibacterial prescribing and use such as formal continuing medical education, printed educational materials, better diagnostic tests, and vaccination contribute to the efforts to minimize bacterial resistance and are also addressed.

Introduction: In addition to offering favorable pharmaceutical performance, an ideal inhaler should be well accepted by patients, as this may facilitate compliance. We report a study that specifically assessed inhaler preference in patients with obstructive lung disease after treatment with ipratropium bromide/fenoterol hydrobromide (Berodual delivered via either Respimat Soft Mist Inhaler (SMI) or hydrofluoroalkane metered dose inhaler (HFA-MDI).

Methods: Patients with COPD, asthma or mixed disease were randomized to receive ipratropium bromide/fenoterol hydrobromide 20/50 microg via Respimat SMI or 40/100 microg via HFA-MDI for 7 weeks each, in a crossover design. Patients were trained in inhaler use and given < or =5 attempts to demonstrate satisfactory technique. At the end of each treatment period, patients completed a 15-item satisfaction questionnaire, and inhaler technique was re-tested. On study completion, patients were asked which inhaler they preferred and they rated their willingness to continue using each inhaler. Clinical efficacy outcomes were measured by diary card to check whether switching inhaler affected efficacy.

Results: In total, 245 patients were randomized and 224 used both inhalers within their respective treatment periods. Of 201 patients expressing a preference, 162 (81%) preferred Respimat SMI and 39 (19%) preferred HFA-MDI (p < 0.001). Patients would rather continue using Respimat SMI than HFA-MDI (p < 0.001). Mean scores for 13 of the 15 satisfaction questions were significantly higher for Respimat SMI than HFA-MDI (p < 0.05); in addition, the total score was also significantly higher for Respimat SMI (p < 0.001). Most patients (217/224; 97%) were judged to have good technique with Respimat SMI after 7 weeks' use. Differences in efficacy measures between the devices were not significant.

Conclusion: These data indicated that a large majority of patients preferred Respimat SMI to HFA-MDI.

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.

Introduction and objective: Asthma, owing to its chronic nature, is associated with a substantial economic burden. Healthcare providers need to compare the cost effectiveness of alternative asthma treatment options to ensure that they obtain the best value for money from the resources they control. The objective of the current study was to compare the cost effectiveness of salmeterol/fluticasone propionate in combination with fluticasone propionate plus montelukast in patients with symptomatic asthma uncontrolled with inhaled corticosteroid (ICS) monotherapy.

Study design and methods: Direct healthcare resource data were prospectively collected during a double-blind, randomized, 12-week clinical study of inhaled salmeterol/fluticasone propionate 50/100 microg twice daily (n = 356) and inhaled fluticasone propionate 100 microg twice daily plus oral montelukast 10mg daily (n = 369). Resources were costed in Dutch guilders (NLG) from the perspective of The Netherlands healthcare system using 1999/2000 prices, but have been presented in US dollars and euros. The primary effectiveness measure was the proportion of successfully treated weeks (based on mean morning PEF values). Secondary measures were episode-free days, symptom-free days, and symptom-free nights.

Results: Salmeterol/fluticasone propionate was more effective than fluticasone propionate plus montelukast as measured by the proportion of successfully treated weeks mean 63.3% vs 39.0%; median difference 25%; p < 0.001). Salmeterol/fluticasone propionate was also more effective than fluticasone propionate plus montelukast according to the secondary effectiveness measures. The mean total direct daily healthcare costs per patient were 16% higher with fluticasone propionate plus montelukast than with salmeterol/fluticasone propionate mainly due to higher drug costs in the former group (2.25 US dollars vs 1.94; 1.92 euro vs 1.66, respectively; the NLG was fixed against the euro at a rate of 1 euro = NLG2.2 on 31 December 1998; 1 US dollars = NLG1.883, June 2003; 1 US dollars= 0.848 euro, June 2003). Incremental cost-effectiveness analyses showed that salmeterol/fluticasone propionate was dominant over fluticasone propionate plus montelukast and sensitivity analyses showed these results to be robust.

Conclusion: Salmeterol/fluticasone propionate is a more cost-effective treatment option than fluticasone propionate plus montelukast for patients with symptomatic asthma uncontrolled by ICS.