摘要:

Children and adolescents experiencing acute exacerbations of asthma benefit from the use of β2-adrenoceptor agonists (β2-agonists) and systemic corticosteroids. However, there have been conflicting reports regarding the efficacy of inhaled anticholinergic agents.This article summarizes the evidence provided by randomized controlled trials studying the efficacy of adding inhaled anticholinergic agents to β2-agonists in nonhospitalized children and adolescents with acute exacerbations of asthma. This systematic review of randomized controlled trials suggests that the addition of inhaled anticholinergic agents to β2-agonists is beneficial in children and adolescents, particularly those with severe exacerbations of asthma. When given in repeated doses, the addition of inhaled anticholinergic agents to β2-agonists improves lung function and reduces the risk of hospital admission by 25%. Several treatment regimens, namely ipratropium bromide (250 or 500μg per dose) every 20–60 minutes for two to three doses have been tested with similar beneficial effects. The addition of a single dose of an inhaled anticholinergic agent to β2-agonists improves lung function but does not prevent hospital admission. The review did not identify any beneficial effects of anticholinergic agents in children with nonsevere asthma. Use of anticholinergic agents was not associated with increase in the incidence of nausea, vomiting or tremor.In conclusion, the addition of repeated doses of an inhaled anticholinergic agent to inhaled β2-agonist is indicated in the emergency room management of children and adolescents with acute asthma, particularly those with severe exacerbations.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The intimate anatomical and physiologic relationship between the upper airway and esophagus consists of complex interactions between various muscles and nerves with both voluntary and involuntary patterns of control. Alterations in this harmonic relationship can lead to swallowing abnormalities ranging from dysphagia to gross aspiration, gastroesophageal reflux disease (GERD) and chronic cough. There is a paucity of data regarding pathologic alterations in the upper airway-esophageal relationship in patients with COPD.The association between GERD and respiratory symptoms is well recognized in the setting of asthma; however, the nature of this relationship remains controversial. The association of GERD and COPD is even less clear. A review of the limited data on GERD and swallowing abnormalities in patients with COPD indicate that prevalence of GERD and esophageal disorders in patients with COPD is higher than in the normal population. However, its contribution to respiratory symptoms, bronchodilator use and pulmonary function in patients with COPD remains unknown. Although dysphagia and swallowing dysfunction on videofluoroscopic swallow evaluation are common in patients with COPD, their role as exacerbators of COPD remains to be elucidated. Further clinical research is necessary to evaluate the role of GERD and swallowing dysfunction in both stable and acute exacerbation of COPD.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Pulmonary arterial hypertension (PAH) is a severe condition that markedly reduces exercise capacity and survival in the affected patient population. PAH includes primary pulmonary hypertension (PPH) and pulmonary hypertension associated with collagen vascular diseases, congenital systemic-to-pulmonary shunts, portal hypertension and HIV infection. All these conditions share virtually identical obstructive pathologic changes of the pulmonary microcirculation and probably similar pathobiologic processes. The pathophysiology is characterized by a progressive increase in pulmonary vascular resistance, leading to right ventricular failure and death. Prostacyclin is an endogenous substance that is produced by vascular endothelial cells and induces vasodilatation, inhibition of platelet activity, and antiproliferative effects. A dysregulation of prostacyclin metabolic pathways has been shown in patients with PAH and this represents the rationale for the exogenous therapeutic administration of this substance.The clinical use of prostacyclin in patients with PAH has been made possible by the synthesis of stable analogs that possess different pharmacokinetic properties but share similar pharmacodynamic effects. Experience in humans has been initially collected with epoprostenol, which is a synthetic salt of prostacyclin. Epoprostenol has a short half-life in the circulation and requires continuous administration by the intravenous route by means of infusion pumps and permanent tunnelized catheters. In addition, epoprostenol is unstable at room temperature, and the complex delivery system required is associated with several adverse effects and potentially serious complications. For these reasons, alternatives to intravenous epoprostenol have been sought and this has led to the development of analogs that can be administered subcutaneously (treprostinil), orally (beraprost sodium) or by inhalation (iloprost).Three unblinded clinical trials and several uncontrolled trials have shown that treatment with epoprostenol improved symptoms and exercise capacity in New York Heart Association (NYHA) class III and IV PAH patients and also survival in patients with PPH. Subcutaneous treprostinil improved symptoms, exercise, hemodynamics and clinical events in the largest clinical trial ever performed in PAH, but local infusion site reactions limited efficacy in a proportion of patients. Oral beraprost sodium improved exercise capacity only in patients with PPH and is the only prostacyclin analog that has also been tested in NYHA class II patients. Inhaled iloprost has improved symptoms, exercise capacity and clinical events in patients with PAH and inoperable chronic thromboembolic pulmonary hypertension. The favorable effects of prostanoids observed in all studies coupled with different profiles of adverse events and tolerability for each prostacyclin analog allow the unique opportunity to select the most appropriate compound for the individual patient with PAH.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Asthma is a chronic inflammatory disease of the airways that affects approximately 100 million people worldwide. In order to reduce symptoms, improve pulmonary function, and decrease morbidity, current treatment guidelines emphasize the importance of controlling the underlying inflammation in patients with asthma. Leukotrienes are leukocyte-generated lipid mediators that promote airway inflammation. Recognition of the importance of leukotrienes in the pathogenesis of asthma has led to the development of leukotriene modifiers, the first new class of drugs for the treatment of asthma to become available in 25 years.Controlled clinical trials with the four currently used leukotriene modifiers (montelukast, zafirlukast, and zileuton in the US and pranlukast in Japan) have established their efficacy in improving pulmonary function, reducing symptoms, decreasing night-time awakenings, and decreasing the need for rescue medications. They exert anti-inflammatory effects that attenuate cellular infiltration and bronchial hyperresponsiveness and complement the anti-inflammatory properties of inhaled corticosteroids. In patients with moderate and severe asthma, they permit tapering of the corticosteroid dose.In patients with exercise-induced asthma, leukotriene modifiers limit the decline in and quicken the recovery of pulmonary functions without the tolerance issues seen with chronic long-acting β2-adrenoceptor agonist use. In patients with aspirin (acetylsalicylic acid)-induced asthma, they improve pulmonary function and shift the dose response curve to the right, reducing the patient’s response to aspirin. In patients with seasonal allergic rhinitis, with or without concomitant asthma, they improve nasal, eye, and throat symptoms as well as quality of life.Leukotriene modifiers are generally safe and well tolerated with adverse effect profiles similar to that of placebo. The one safety issue raised with leukotriene modifiers, Churg-Strauss Syndrome, appears to be the unmasking of an already present syndrome that is manifested when the leukotriene modifiers permit corticosteroid doses to be reduced. Although current treatment guidelines recommend their use in patients with mild persistent asthma, these guidelines were developed just as leukotriene modifiers were coming to the market, before much of the clinical efficacy data were published. Because asthma is a heterogeneous disease, the different asthma phenotypes respond differently to therapies; consequently asthma therapy needs to be individualized. Leukotriene modifiers increase the therapeutic options for patients with asthma and, based on recent data, it is expected that future guidelines will describe expanded uses for these agents in clinical circumstances where these drugs are effective.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Modern sleep medicine has been in existence for only 20 years and therefore has to be regarded as a comparatively recent field of specialization. For this reason it is not surprising that there are numerous new trends and developments concerning the treatment of sleep-related breathing disorders. This review focuses on developments in the treatment of obstructive sleep apnea (OSA) over the last 5 years.The review is based on a Medline bibliographic search using the key words ‘treatment’, ‘obstructive sleep apnea’ and ‘sleep-related breathing disorders’ and covers papers published since 1997, including references in these articles.In respect to conservative treatments the following important developments were found. Oral devices were shown to be effective in about 50–70% of patients with OSA, but at this stage it is not possible to predict in which patients successful treatment can be expected. As subjective compliance averages only about 50%, thermoplastic devices used as trial devices provide a reasonable alternative to reduce costs. Automatic continuous positive airway pressure (CPAP) units have been shown to cut costs when used for pressure titration in severe sleep apneics during the day or when used in so-called split-night procedures in appropriate cases. Nasal CPAP has proven to be effective in children, showing higher compliance rates than in adults. The development of mouth-pieces provides the possibility of using CPAP orally, e.g. after nasal surgery. Electrical stimulation of the tongue muscles shows promising preliminary results. Nevertheless, further research in this field is necessary.In the field of surgery, the most valuable development has been tissue reduction using radiofrequency energy, which has been shown to be effective and minimally invasive. Other fundamentally new surgical techniques have not been attempted within the last 5 years; instead, development in this area appears to be defined by a combination of previously known methods (so-called multilevel surgery) and optimized methods of patient selection. Such combined surgical procedures has achieved success rates of about 70%.Taking all these developments into account, CPAP therapy remains the gold standard for treatment of patients with OSA; yet the low long-term compliance rates of 60–70% have to be regarded as a major challenge warranting further effort.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Eosinophilic bronchitis is a common and treatable cause of chronic cough. The major pathological feature is eosinophilic airway inflammation, similar to that seen in asthma. However, the associated airway dysfunction is quite different, with evidence of heightened cough reflex sensitivity, but no variable airflow obstruction or airway hyperresponsiveness. Recent evidence suggests that the differences in functional association are related to differences in localization of mast cells in airway wall, with airway smooth muscle infiltration occurring in asthma and epithelial infiltration in eosinophilic bronchitis.Diagnosis is usually made with induced sputum analysis after exclusion of other causes for chronic cough on clinical, radiological and lung function assessment. The cough responds well to inhaled corticosteroids but dose and duration of treatment remain unclear. Little is known about the natural history of this condition. However, some patients with COPD without a history of previous asthma have sputum eosinophilia, so one possibility is that some cases of eosinophilic bronchitis may develop fixed airflow obstruction. Further study of this interesting condition will increase our understanding of airway inflammation and airway responsiveness, leading to novel targets for therapeutics for both eosinophilic bronchitis and asthma.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Clarithromycin is an orally active, advanced-generation macrolide that has been reformulated as an extended-release tablet (Biaxin®XL Filmtab®) allowing convenient once-daily administration. The reformulation is intended to improve patient compliance and the tolerability of the drug.Although maximum plasma clarithromycin concentrations are lower and reached later with the extended-release tablets than with the immediate-release tablets, the two formulations are bioequivalent with respect to the area under the plasma concentration-time curve. Bioequivalence is also achieved between the formulations for the microbiologically active metabolite, 14-hydroxy-clarithromycin.Two randomized trials in patients with acute exacerbations of chronic bronchitis (AECB) showed that a 7-day course of clarithromycin extended-release 1000mg once daily produced clinical cure rates of 83% and 85% and bacteriologic cure rates of 86% and 92% at the test-of-cure study visit. Similar rates of cure were achieved with a 7-day course of twice-daily clarithromycin immediate-release and with a 10-day course of twice-daily amoxicillin/clavulanic acid.A 7-day course of clarithromycin extended-release 1000mg once daily produced clinical and bacteriologic cure rates of 88% and 86%, respectively, in patients with community-acquired pneumonia (CAP). Similar cure rates were achieved in recipients of once-daily levofloxacin in the same trial.In patients with acute maxillary sinusitis, a 14-day course of either once-daily clarithromycin extended-release or twice-daily clarithromycin immediate-release produced statistically equivalent clinical cure rates of 85% and 79%, respectively. Both treatment groups achieved similar rates of radiographic success and resolution of sinusitis. Recent results indicate that clarithromycin extended-release 500mg once daily for 5 days is also effective in the treatment of patients with streptococcal pharyngitis/tonsillitis and in the treatment of AECB.The most frequently reported drug-related events with clarithromycin extended-release were abnormal taste (7% incidence), diarrhea (6%) and nausea (3%). Most adverse drug reactions were of a mild and transient nature. In comparative clinical trials, clarithromycin extended-release had an improved gastrointestinal tolerability profile compared with the immediate-release formulation. In addition, clarithromycin extended-release was better tolerated than amoxicillin/clavulanic acid and as well tolerated as levofloxacin. Further studies are required to assess the cost-effectiveness ratio of clarithromycin relative to comparator antibacterial agents.ConclusionClarithromycin extended-release is an effective treatment for AECB, CAP, acute maxillary sinusitis, and pharyngitis (although not approved for the latter in the US), and is administered in a convenient dosage regimen that has the potential to encourage good compliance. The reformulation modulates clarithromycin absorption kinetics thereby improving tolerability. Therefore, clarithromycin extended-release provides a useful option for the treatment of specific respiratory tract infections.

ISSN:1175-6365    

出版商:ADIS    

年代:2003

数据来源: ADIS