Treatments in respiratory medicine最新文献

Recurrent respiratory tract infections (RRTIs) in adults are the result of an imbalance between lung defense mechanisms, and bacterial burden. Antibacterial treatments can temporarily restore the equilibrium between host and bacterial load, but do not prevent recurrence of infection. An alternative approach to prevent recurrence of infection is treatment with an immunostimulant, which provides immune protection against repeated bacterial and viral infection. All immunostimulant products are bacterial in origin: lysates (first generation immunostimulants), or bacterial extracts, like bacterial ribosomes, or membrane proteoglycans. This review highlights the current state of knowledge regarding the use of immunostimulants in adults with RRTIs, taking the ribosomal immunostimulant Ribomunyl((R)) as an example. Many studies are available on the mechanism of action and clinical efficacy in prevention of RRTIs in adults treated with Ribomunyl((R)). The effect of this immunostimulant on anti-infectious responses is explained by a stimulation of both nonspecific (innate) and specific (adaptive) immunity. In order to obtain a global overview of the therapeutic efficacy of Ribomunyl((R)) the most pertinent trials were selected from the literature based on adequate patient numbers and good methodology. Results of double-blind placebo-controlled trials using Ribomunyl((R)) for the treatment of different upper or lower RRTIs have demonstrated a statistically significant reduction in the number of infectious episodes and as a consequence, a decrease in antibacterial consumption, after 3 and 6 months of treatment. The tolerance profile of Ribomunyl((R)) was good in all studies. Economic evaluations suggest that savings can be made in healthcare expenditure, in patients with recurrent episodes of infection. It is concluded that Ribomunyl((R)) is effective in preventing and reducing upper and lower respiratory tract infections in adults. The product may also have an impact on reducing the development of bacterial resistance, as a result of fewer courses of antibacterials required to treat patients with RRTIs.

Introduction: Asthma and COPD are known to have significant health and economic consequences. Little is known about the costs of the latter in the UK. In this study we report the results of a comparison of the direct medical costs associated with COPD and asthma, where diagnoses are based on a robust prevalence study of a random sample of the Northern Ireland population.

Methods: A two-stage survey was used to identify individuals with COPD and asthma. The diagnoses of asthma and COPD were based on patient history and lung function. Patients completed a detailed questionnaire covering healthcare utilization over the past 12 months, socioeconomic characteristics, impact of the disease on quality of life, and activities of daily living.

Results: Forty-nine patients were diagnosed with COPD and 57 with asthma. Three asthma patients were excluded from the main analysis because they were thought to have atypical inpatient stays or other resource use. The mean direct healthcare cost for each COPD patient was estimated at pound171.69 ($US309; year 2000 value) per annum, significantly less than the average cost of asthma among the 54 analyzed of pound544.54 ($US980) [p < 0.05]. A correlation analysis revealed that among COPD patients, disease severity, defined by lung function, was a significant predictor of costs.

Conclusion: Community-based costs for asthma are greater than those for COPD; this may relate in part to a relative under-diagnosis of COPD (73.5% COPD vs 15.8% asthma). As anticipated, the cost of COPD increases as FEV(1) decreases. Further analysis will enable modeling of the cost consequences of both increased diagnosis and better management of COPD.

Virus-induced wheezing is a relatively benign entity that is usually transient in early childhood but is responsible for much health care utilization. The condition, seen traditionally as a subset of those children diagnosed as having frequent episodic asthma, is often treated with inhaled corticosteroids, despite their lack of efficacy. However, there remains some confusion differentiating atopic asthma from virus-induced wheezing in young children and their respective treatment strategies.The demonstration of cysteinyl leukotrienes in the nasopharyngeal secretions of infants and young children who wheeze prompted investigation of the role of leukotriene receptor antagonists in the treatment of virus-induced wheezing for young children with bronchiolitis and virus-induced wheezing.Montelukast, the only leukotriene receptor antagonist studied in young children, has been proven useful in increasing the number of symptom-free days and delaying the recurrence of wheeze in the month following a diagnosis of respiratory syncytial virus-induced wheezing in children aged 3-36 months. Subsequently, in children aged 2-5 years with frequent episodic asthma, primarily involving viral induced attacks in this age group, regular therapy with daily montelukast for 12 months reduced the rate of asthma exacerbations by 31% over placebo, delayed the time to the first exacerbation by 2 months, and lowered the need to prescribe inhaled corticosteroids as preventative therapy. Additionally, montelukast has been demonstrated to be efficacious as an acute episode modifier in children aged 2-14 years (85% children <6 years) with virus-induced wheezing where it was prescribed at the onset of a viral infection in children with an established pattern of viral induced episodes of wheeze in the preceding year. In this study, emergency department visits were reduced by 45%, visits to all health care practitioners were reduced by 23%, and time of preschool/school and parental time off work was reduced by 33% for children who took montelukast for a median of 10 days.At present, there is good evidence to support the use of bronchodilators in the acute treatment of virus- induced wheezing, and increasing evidence to support the use of leukotriene receptor antagonists, in particular montelukast, in the management of children with virus-induced wheezing.

Objective: To determine whether the use of inhaled corticosteroids or leukotriene receptor antagonists (LTRAs) has had an impact on asthma mortality in Portugal during the period 1991-2001.

Methods: A population-based ecological study was conducted for the period 1991-2001. Yearly asthma death rates were computed for all ages. Data on sales of inhaled corticosteroids and LTRAs were obtained and expressed in defined daily doses (DDDs)/year. The association between the yearly rate of asthma deaths and consumption of these medications was estimated using Poisson regression.

Results: The rate of asthma death decreased steadily from 39.4 per million inhabitants in 1991 to 14.2 in 2001. At the same time, the use of inhaled corticosteroids in the population increased from 5.8 to 22.2 million DDDs per year. The adjusted rate ratio of asthma death was 0.85 (95% CI 0.78, 0.92) for every additional 5 million DDDs of inhaled corticosteroids per year and 0.84 (95% CI 0.70, 1.02) for every additional 5 million DDDs of LTRAs per year.

Conclusion: The increasing use of inhaled corticosteroids and leukotriene receptor antagonists during the 1990s in Portugal appears to have contributed to the reduction in asthma mortality in that country.

Objectives: The aim of this in vitro study was to determine the delivered dose of budesonide 200mug via a chlorofluorocarbon-free pressurized metered dose inhaler (pMDI) when administered through different spacers in tidal breathing patterns of young children.

Methods: Tidal breathing was simulated for toddlers and children. Spacers tested were Babyhaler((R)), AeroChamber((R)) Plus small and medium; the pMDI was Budiair((R)) 200microg. Output was measured after one actuation and five inhalations in primed and unprimed spacers. Cumulated output was evaluated after each of five simulated inhalations. Aerosol characteristics - i.e. particle size distribution of the output - were determined in primed spacers with a cascade impactor using high-performance liquid chromatography and UV detection.

Results: Total output from primed spacers after five inhalations was determined between 37.9microg and 40.9microg with little differences between spacers and breathing patterns. About 58-79% of this total output was inhaled with the first breath from the AeroChamber((R)) Plus and about 26% from the Babyhaler((R)). The fine particles <5mum ranged between 87% and 92% of the delivered dose for all three spacers.

Discussion and conclusion: The nominal dose (200microg) of the Budiair((R)) 200microg inhaler is reduced to 40microg delivered dose or less by using Babyhaler((R)) and AeroChamber((R)) Plus spacers taking five breaths. With a single breath the delivered dose can be reduced further to a minimum of 10microg using the Babyhaler((R)). Clinical studies are warranted in the future for decisions on 'clinical efficacy', safety, and exact dose adjustment.

Lung involvement in malaria has been recognized for more than 200 hundred years, yet our knowledge of its pathogenesis and management is limited. Pulmonary edema is the most severe form of lung involvement. Increased alveolar capillary permeability leading to intravascular fluid loss into the lungs is the main pathophysiologic mechanism. This defines malaria as another cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).Pulmonary edema has been described most often in non-immune individuals with Plasmodium falciparum infections as part of a severe systemic illness or as the main feature of acute malaria. P.vivax and P.ovale have also rarely caused pulmonary edema.Clinically, patients usually present with acute breathlessness that can rapidly progress to respiratory failure either at disease presentation or, interestingly, after treatment when clinical improvement is taking place and the parasitemia is falling. Pregnant women are particularly prone to developing pulmonary edema. Optimal management of malaria-induced ALI/ARDS includes early recognition and diagnosis. Malaria must always be suspected in a returning traveler or a visitor from a malaria-endemic country with an acute febrile illness. Slide microscopy and/or the use of rapid antigen tests are standard diagnostic tools. Malaria must be treated with effective drugs, but current choices are few: e.g. parenteral artemisinins, intravenous quinine or quinidine (in the US only). A recent trial in adults has shown that intravenous artesunate reduces severe malaria mortality by a third compared with adults treated with intravenous quinine. Respiratory compromise should be managed on its merits and may require mechanical ventilation.Patients should be managed in an intensive care unit and particular attention should be paid to the energetic management of other severe malaria complications, notably coma and acute renal failure. ALI/ARDS may also be related to a coincidental bacterial sepsis that may not be clinically obvious. Clinicians should employ a low threshold for starting broad spectrum antibacterials in such patients, after taking pertinent microbiologic specimens. Despite optimal management, the prognosis of severe malaria with ARDS is poor.ALI/ARDS in pediatric malaria appears to be rare. However, falciparum malaria with severe metabolic acidosis or acute pulmonary edema may present with a clinical picture of pneumonia, i.e. with tachypnea, intercostal recession, wheeze or inspiratory crepitations. This results in diagnostic confusion and suboptimal treatment. Whilst this is increasingly being recognized in malaria-endemic countries, clinicians in temperate zones should be aware that malaria may be a possible cause of 'pneumonia' in a visiting or returning child.

Ventilator-associated pneumonia (VAP) is the most frequently occurring nosocomial infection, accounting for considerable morbidity and mortality. Diagnosis can be difficult, creating important therapeutic challenges for intensivists. Early therapy is important in maximizing outcomes, but inappropriate antibacterial treatment has its own risks. A balance needs to be struck between the necessary therapeutic benefits and the negative effects (selection of resistant pathogens, costs, and adverse effects) of antibacterials. Several studies have indicated, in various groups of critically ill patients including those with VAP, that starting treatment with an ineffective antibacterial can increase hospital and intensive care unit length of stay and mortality. When the responsible microorganisms cannot be defined, it may be better to start treatment with a broad-spectrum antibacterial regimen, taking into account individual patient factors and local bacteriology patterns, including antibacterial resistance. As soon as the nature of the pathogen has been defined, the antibacterial agent(s) should be modified accordingly, with the primary aim to reduce the antibacterial spectrum. The optimal duration of therapy is controversial and probably best tailored to the individual patient depending on clinical response and resolution of the factors used to diagnose VAP in that patient. Consultation with an infectious disease specialist may facilitate these therapeutic decisions. With the high morbidity and mortality associated with VAP, prevention is an important issue. General measures include adequate hand hygiene. Physicians must be aware of the risk factors for VAP and of accepted and effective strategies of prevention.

Leukocyte infiltration of the lung is a characteristic feature of allergic asthma and it is thought that these cells are selectively recruited by chemokines. Extensive research has confirmed that chemokine receptors are expressed on the main cell types involved in asthma, including eosinophils, T helper type 2 cells, mast cells and even neutrophils. Moreover, animal experiments have outlined a functional role for these receptors and their ligands. Chemokines signal via seven-transmembrane spanning G-protein coupled receptors, which are favored targets of the pharmaceutical industry due to the possibility of designing small-molecule inhibitors. In fact, this family represents the first group of cytokines where small-molecule inhibitors have been designed. However, the search for efficient antagonists of chemokine/chemokine receptors has not been easy; a particular feature of the chemokine system is the number of molecules with overlapping functions and binding specificities, as well as the difficulty in reconciling the in vivo biologic functional validation of chemokines in rodent models with the development of antagonists which bind the human receptor, because of the lack of species cross-reactivity. The chemokines and their receptors that are active during allergic reactions are reviewed. Possible points of interaction that may be a target for development of new therapies, as well as the progress to date in developing inhibitors of key chemokine receptors for asthma therapy, are also discussed.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal pulmonary disease for which there are no proven drug therapies. Anti-inflammatory and immunosuppressive agents have been largely ineffective. The precise relationship of IPF to other idiopathic interstitial pneumonias (IIPs) is not known, despite the observation that different histopathologic patterns of IIP may coexist in the same patient. We propose that these different histopathologic 'reaction' patterns may be determined by complex interactions between host and environmental factors that alter the local alveolar milieu. Recent paradigms in IPF pathogenesis have focused on dysregulated epithelial-mesenchymal interactions, an imbalance in T(H)1/T(H)2 cytokine profile and potential roles for aberrant angiogenesis. In this review, we discuss these evolving concepts in disease pathogenesis and emerging therapies designed to target pro-fibrogenic pathways in IPF.

Nosocomial pneumonia or hospital-acquired pneumonia (HAP) causes considerable morbidity and mortality. It is the second most common nosocomial infection and the leading cause of death from hospital-acquired infections. In 1996 the American Thoracic Society (ATS) published guidelines for empirical therapy of HAP. This review focuses on the literature that has appeared since the ATS statement. Early diagnosis of HAP and its etiology is crucial in guiding empirical therapy. Since 1996, it has become clear that differentiating mere colonization from etiologic pathogens infecting the lower respiratory tract is best achieved by employing bronchoalveolar lavage (BAL) or protected specimen brush (PSB) in combination with quantitative culture and detection of intracellular microorganisms. Endotracheal aspirate and non-bronchoscopic BAL/PSB in combination with quantitative culture provide a good alternative in patients suspected of ventilator-associated pneumonia. Since culture results take 2-3 days, initial therapy of HAP is by definition empirical. Epidemiologic studies have identified the most frequently involved pathogens: Enterobacteriaceae, Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus ('core pathogens'). Empirical therapy covering only the 'core pathogens' will suffice in patients without risk factors for resistant microorganisms. Studies that have appeared since the ATS statement issued in 1996, demonstrate several new risk factors for HAP with multiresistant pathogens. In patients with risk factors, empirical therapy should consist of antibacterials with a broader spectrum. The most important risk factors for resistant microorganisms are late onset of HAP (>/=5 days after admission), recent use of antibacterial therapy, and mechanical ventilation. Multiresistant bacteria of specific interest are methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter calcoaceticus-baumannii, Stenotrophomonas maltophilia and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Each of these organisms has its specific susceptibility pattern, demanding appropriate antibacterial treatment. To further improve outcomes, specific therapeutic options for multiresistant pathogens and pharmacological factors are discussed. Antibacterials developed since 1996 or antibacterials with renewed interest (linezolid, quinupristin/dalfopristin, teicoplanin, meropenem, new fluoroquinolones, and fourth-generation cephalosporins) are discussed in the light of developing resistance.Since the ATS statement, many reports have shown increasing incidences of resistant microorganisms. Therefore, one of the most important conclusions from this review is that empirical therapy for HAP should not be based on general guidelines alone, but that local epidemiology should be taken into account and used in the formulation of local guidelines.