Treatments in respiratory medicine最新文献

COPD is a major cause of morbidity and mortality in Europe. The purpose of this literature review was to critically evaluate published data on COPD prevalence and the cost of COPD interventions in European countries. Selection of literature was based on article retrieval from a systematic literature search using PubMed and EMBASE. Only articles providing data in European countries published between January 1990 and March 2003 were included. European epidemiological (cross-sectional, cohort, case-control) and economic (cost-of-illness-, cost-minimization-, cost-effectiveness-, cost-benefit-, cost-utility-analysis) studies were included. Of 74 retrieved epidemiologic studies, only seven (9%) fulfilled the inclusion criteria. In the selected literature, COPD prevalence ranged from 3% among Finnish women to 57% among Italian men and women, 45 years and older. Of 56 economic studies, 24 satisfied entry criteria. Results from the final cost-of-illness studies indicated that hospital care and medication represented the major portion of costs associated with COPD. In a survey conducted in 1998/99, annual direct expenditures for COPD treatment per patient in Europe ranged from Euro 530 in France to Euro 3238 in Spain. There was a differential increase in COPD prevalence predominantly related to an aging patient population, with a high incidence of exposure to cigarette smoke. Data also showed differences in the economic impact of COPD in Europe based on the proportion of patients with severe COPD, frequency of exacerbations, and number of hospitalizations. Overall, results of this review demonstrated the need for global epidemiologic and economic studies to allow for more uniform guidelines for the prevention and cost-effective treatment of patients with COPD.

Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive, complete or partial closure of the upper airway during sleep, resulting in sleep fragmentation and oxygen desaturation. The disorder causes significant morbidity, particularly in terms of impairment of daytime functioning and the impact this has on quality of life. There is also evidence that links OSA to long-term cardiovascular morbidity, including hypertension, myocardial infarction, and stroke, and increased risk of motor vehicle accidents. There is clear evidence that effective treatment of OSA provides major benefit to patients. Nasal continuous positive airway pressure (CPAP) is the current treatment of choice, but its cumbersome nature makes tolerance and compliance less than optimal. This gives rise to the need for other alternatives that are equally effective, but more tolerable. There is growing interest in the use of oral appliances to treat snoring and OSA. The rationale is that advancement of the mandible and tongue impacts positively on upper airway caliber and function. There are many such types of appliances, and they have potential advantages over CPAP in that they are unobtrusive, make no noise, do not need a power source, and are potentially less costly. There is a growing evidence base to support the use of oral appliances in the management of OSA. Recent evidence from randomized controlled trials indicates that oral appliance therapy is effective in controlling OSA in up to 50% of patients, including some patients with more severe forms of OSA. This is associated with a significant improvement in symptoms, including snoring and daytime sleepiness. This evidence is strong for short term, and emerging for long-term treatment of OSA with oral appliances. Whilst direct comparisons with CPAP indicate the superiority of CPAP overall, similar outcomes between the two treatments appear to be achieved in a substantial subgroup of patients. Patient acceptance has, in general, been in favor of oral appliances. Notwithstanding the expanding role of oral appliance therapy, there are a number of limitations that are yet to be overcome. Key issues include the inability to reliably predict treatment outcome, the apparent need for an acclimatization period to attain maximal efficacy of treatment, uncertainty about selection of the appropriate 'dosage' of mandibular advancement required to control OSA in the individual patient, uncertainty about the influence of appliance design on treatment outcome and adverse effects, adherence to treatment, and potential long-term complications of therapy. These issues require resolution before oral appliance therapy can surpass CPAP as first-line treatment for OSA.

Despite increasing penicillin and macrolide resistance worldwide, the clinical relevance of this phenomenon is still unknown. Debate continues as to whether increasing resistance among pneumococci to beta-lactam agents, macrolides, and fluoroquinolones has been accompanied by an increase in the rate of treatment failure. In vitro findings do not appear to be predictive of in vivo outcomes. Studies have failed to demonstrate significantly higher mortality for patients infected with penicillin-resistant rather than penicillin susceptible pneumococcal strains. Treatment failures are associated solely with the highest levels of resistance. Antimicrobial resistance appears to affect other markers of morbidity, but only statistically nonsignificant trends toward increased mortality have been demonstrated. Whether macrolide resistance among invasive pneumococcal isolates is clinically relevant or a matter of limited influence remains to be determined.

The differentiation of bacterial biofilms in the airway environment, the pathogenesis of airway biofilm, and possible therapeutic methods are discussed. Biofilm diseases that characteristically involve the respiratory system include cystic fibrosis (CF), diffuse panbronchiolitis (DPB), and bronchiectasia with Pseudomonas aeruginosa (P. aeruginosa) infection. There is evidence to suggest that almost all strains of P. aeruginosa have the genetic capacity to synthesize alginate, a main matrix of biofilms, when ecological conditions are unfavorable for their survival. The bacteria inside the mature biofilm show increased resistance to both antibacterials and phagocytic cells, express fewer virulence factors because of their stationary state of growth, and are less stimulatory to the mucosa because of the 'sandwich binding'. These factors facilitate both the colonization of bacteria and their extended survival even under unfavorable conditions. Since the biofilm limits colonization to a latent form, the clinical symptoms in this situation are unremarkable. However, the clinical progression of both CF and DPB proceeds in two characteristic directions. The first is an acute exacerbation caused by planktonic bacteria that have germinated from the biofilm. The second is a slow progression of disease that is induced by harmful immune reactions. The harmful reactions are mediated by alginate, which induces antigen antibody reactions around the airways, as well as formation of circulating immune complexes that are deposited on lung tissue. Furthermore, the highest titer of bacterial permeability increasing anti-neutrophil cytoplasmic autoantibodies (BPI-ANCA) is observed in association with highly impaired pulmonary function in patients with CF and DPB, as well as in patients with a lengthy period of colonization with P. aeruginosa. BPI-ANCA subsequently makes chronic airway infection even more intractable. The long-term use of 14- or 15-ring membered macrolides results in a favorable clinical outcome for patients with DPB and in some patients with CF. In the last 10 years, an increasing number of studies have reported secondary actions of macrolides that include effects on both airway and phagocytic cells, as well as an anti-biofilm activity. The 14- or 15-ring membered macrolides inhibit: (i) the alginate production from P. aeruginosa; (ii) the antibody reaction to alginate, which leads to a decrease in the immune complex formation; and (iii) the activation of the autoinducer 3-O-C12-homoserine lactone and subsequent expression of lasI and rhlI in quorum sensing systems in P. aeruginosa. These anti-biofilm actions of macrolides may represent their basic mechanisms of action on airway biofilm disease.

Objective: Data on intranasal corticosteroids suggest that individual product attributes may influence patient preference for therapy in allergic rhinitis. The study objective was to compare product sensory attributes and their impact upon patient preference for scent-free mometasone furoate nasal spray (MFNS) versus fluticasone propionate nasal spray (FPNS) in patients with symptomatic allergic rhinitis.

Methods: In a double-blind, crossover study, 100 patients were randomized to MFNS microg followed by FPNS 200 microg, or vice versa. Patients rated the study drugs by completing an individual product sensory attributes questionnaire at the end of each period of drug administration. An overall sensory preference questionnaire was completed following crossover.

Results: A significantly greater number of patients preferred MFNS to FPNS (p < 0.05). MFNS was superior for a number of individual sensory attributes based on mean patient ratings: significantly fewer patients perceived scent/odor (immediately and 2 minutes after drug administration; p < 0.001), taste (immediately after drug administration; p = 0.002), and after-taste (2 minutes after drug administration; p = 0.007) with MFNS compared with FPNS. Similarly, product sensory attribute preference data demonstrated that twice the number of patients preferred MFNS to FPNS for scent/odor (p = 0.0005), immediate taste (p = 0.005), and after-taste (p = 0.005). Fifty-four percent of patients said they would choose a prescription for MFNS compared with 33% for FPNS (p = 0.03). In addition, 47% of patients would be more likely to comply (use daily as directed) with MFNS compared with 25% with FPNS (p = 0.03).

Conclusion: Several individual sensory attributes of MFNS were rated significantly superior to FPNS. Overall, based on the tested sensory attributes, patients preferred MFNS to FPNS therapy for the treatment of allergic rhinitis.

Inflammation of the distal lung, which consists of the small airways (internal diameter <2 mm) and alveolar tissue, is an important feature of the asthma clinical syndrome comprising airway inflammation, airway hyperresponsiveness and bronchodilator-responsive expiratory airflow limitation. Support for this assertion is derived from histologic studies which have demonstrated evidence of inflammation in this anatomic compartment, along with additional studies, which have elucidated the radiologic and physiologic correlates of distal lung inflammation. Delivering inhaled drugs to this area is challenging and is dependent on a number of drug- and delivery device-related factors, as well as on a patient's inhaler technique and bronchial anatomy. Newer chlorofluorocarbon-free formulations of inhaled corticosteroids such as hydrofluoroalkane propelled metered-dose inhalers and dry powder inhalers appear to have certain advantages with regard to drug delivery that facilitate improved drug delivery to the distal lung. Mounting evidence indicates that recognition and treatment of distal lung inflammation may be key components of appropriate asthma pharmacotherapy.

Management of community-acquired pneumonia (CAP) remains surprisingly controversial. Optimal duration of antimicrobial therapy reflects one of the open questions due to the lack of sufficient randomized clinical trial data. Recently, there have been efforts to rationalize antimicrobial therapy of this disease. Trials addressing the issue of short-course antimicrobial therapy for CAP have revealed no adverse outcomes with a treatment duration of 5 days when compared with conventional courses of 7-10 days. There is accumulating evidence that a shorter duration of antimicrobial therapy may have benefits in patients with CAP, as it might enhance compliance, decrease the development of antimicrobial resistance, decrease the incidence and shorten the duration of adverse drug effects, reduce treatment costs and improve patient satisfaction with therapy. Nevertheless, remaining questions regarding the influence of patient selection, disease severity or choice of antimicrobial for short-course therapy indicate the need for further randomized controlled clinical trials in this area of research. This article summarizes current evidence for short-course therapy in patients with CAP and draws conclusions for clinical practice.

Neonatal chronic lung disease (CLD) is the major long-term pulmonary complication of preterm birth affecting about 20% of infants who need mechanical ventilation. CLD is the result of abnormal repair processes following inflammatory lung injury that lead to remodeling of the lung. Inflammation may be initiated by a variety of stimuli including mechanical ventilation, oxygen toxicity and infection. The resultant neutrophil chemotaxis and degranulation leads to the release of enzymes such as matrix metalloproteinases that can cause proteolysis of the lung extracellular matrix. Abnormal healing with remodeling leads to poorly compliant lungs with reduced capacity for gas exchange. Drugs can influence the normal process of lung modeling or remodeling. Fetal lung development can be influenced by glucocorticosteroids and inflammation. Both can cause abnormal lung modeling with fewer, larger alveoli and accelerated lung maturation, which confers benefits in terms of reduced morbidity and mortality from respiratory distress syndrome but potentially increases the risk of subsequent lung injury. Antioxidants, such as retinol (vitamin A), administered post-natally may reduce the effects of oxidative stress leading to a modest reduction in CLD but they require repeated intramuscular injections. Postnatal glucocorticosteroid therapy can modify the lung inflammatory response and reduce CLD but it can also have detrimental effects on the developing brain and lung, thereby creating a clinical dilemma for neonatologists. Proteinase inhibitors may be a rational therapy but more research is needed before they can be accepted as a treatment for preterm neonates.'Modeling' is defined as planning or forming that follows a set pattern. The term is used to describe the normal process of lung growth and development that culminates in mature branching alveolar air spaces surrounded by a network of capillaries. Normal lung modeling occurs under a variety of genetic and hormonal influences that can be altered, leading to abnormal patterns of growth. 'Remodeling' is defined as altering the structure of or re-making and, in the case of the lung, is used to describe the abnormal patterns of lung growth that occur after lung injury. Modeling and remodeling of the lungs occur to an extent throughout life but never more rapidly than during the fetal and early neonatal periods, and factors that influence this process may lead to development of neonatal CLD. Some of the factors involved in normal and abnormal lung modeling and inflammation and glucocorticosteroid-induced remodeling in the perinatal period, in the context of neonatal CLD, are reviewed with considerations of how various drugs may influence these processes.

Continuous oxygen therapy (COT) has become widely accepted in the last 20 years in patients with continuous hypoxemia. This review focuses on guidelines for COT, adherence to these guidelines, and the effect of COT on survival, hospitalization, and quality of life. Guidelines for COT are mainly based on three randomized studies where documentation of hypoxemia (P(a)O2 <60mm Hg) and administration of oxygen at least 15 hours/day, are essential. There is less certainty concerning the required correction for hypoxemia, the attitude against current smokers with hypoxemia, the frequency and methods of follow up, and the effect of prescribing domiciliary oxygen to patients with temporary hypoxemia due to a clinically unstable condition (i.e. short-term oxygen therapy [STOT]). The administration of COT to patients with hypoxemic conditions other than COPD rests on extrapolation of data from COPD patients in the NOTT (Nocturnal Oxygen Therapy Trial) and MRC (British Medical Research Council) studies. Adherence to these guidelines is low in general, and very low in some cases. In some countries, STOT accounts for the majority of all prescriptions of domiciliary oxygen, and because nearly half of these patients do not meet the hypoxemia criteria at 3-month follow-up, re-evaluation is mandatory. Only 35%, approximately, of the patients are followed up, and this is one of the main reasons for poor adherence to the hypoxemia criteria. In order to improve the quality of surveillance of COT, more effort has to be put into education of the patients and staff responsible for COT, centralization of the domiciliary organizations, better equipment for ambulation and traveling, and regular follow-up preferably with home visits. The role of an oxygen register on the quality of surveillance of COT has to be determined. The beneficial effect of COT on survival is well established, and some evidence suggests that COT reduces hospitalization. It appears that ambulatory oxygen from liquid source or lightweight cylinders improves disease-specific quality of life modestly in selected patients who partake in regular outdoor activity. Whether COT from oxygen concentrators improves quality of life significantly is, at present, less clear.