Treatments in respiratory medicine最新文献

Scleroderma, also known as progressive systemic sclerosis (SSc), is a multisystem autoimmune disorder characterized by inflammation and fibrosis involving the skin as well as internal organs such as the vasculature, esophagus, and the respiratory tract. Pulmonary involvement consists most often of interstitial fibrosis and pulmonary vascular disease leading to pulmonary arterial hypertension (PAH). Bronchiectasis is an uncommon pulmonary manifestation of systemic sclerosis. Pulmonary hemorrhage with acute renal failure and diffuse alveolar hemorrhage in the absence of a history of renal involvement or penicillamine intake have rarely been reported in patients with systemic sclerosis.On high resolution CT, evidence of interstitial disease is seen in approximately 90% of patients, the main findings being a fine reticular pattern involving the subpleural regions of the lower lobe. Other common findings include ground-glass opacities, honeycombing, and parenchymal micronodules. The most distinctive pulmonary histologic findings in patients with scleroderma are the vascular changes found in PAH in the absence of significant interstitial fibrosis.There is no strong evidence that any drug alters the course of the two main types of lung disease in systemic sclerosis. This apparent failure of therapy may reflect the fact that pulmonary involvement is usually identified at an established or late stage. It has been suggested that, for fibrosing alveolitis, corticosteroids are most effective if given in combination with cyclophosphamide. In some patients with SSc, PAH has been considered as a major cause of morbidity and mortality. Centrally infused prostacyclin (epoprostenol) and its subcutaneously infused analog treprostinil improve hemodynamics, as well as the quality of life and survival in these patients. Iloprost has also shown a positive effect on PAH in SSc patients. More recently, bosentan, an endothelin receptor antagonist, has proved effective in controlling PAH after 6 months' treatment. Sildenafil has been used as a selective pulmonary vasodilator in SSc patients with isolated PAH. This drug decreased mean pulmonary artery pressure and pulmonary vascular resistance, and increased cardiac output, with much improvement of the physical condition of the patients. Lung transplant can be considered as a last option.Clinicians must be aware of the possibility of lung disease in patients with SSc so that it can be treated as early as possible.

Pregnancy does not appear to have a consistent effect on the frequency or severity of asthma. The most common cause of worsening asthma in pregnancy is likely to be noncompliance with medication. Emphasizing to the patient in advance that fetal well-being is dependent on maternal well-being may help prevent this.In general, well controlled asthma is not associated with a higher risk of adverse pregnancy outcomes. Essential to successful asthma management is patient education that helps to ensure effective medication use, avoidance of triggers, and prompt treatment. This education should include measurement of peak expiratory flow rate and a written asthma action plan. Most of the medications that are used to control asthma in the general population can be safely used in pregnant women. Inhaled beta-adrenoceptor agonists (beta-agonists), cromolyn sodium (sodium cromoglycate), and inhaled and systemic corticosteroids all appear to be very well tolerated by the fetus. Budesonide and beclomethasone should be considered as the preferred inhaled corticosteroids for the treatment of asthma in pregnancy. Use of the leukotriene receptor antagonists zafirlukast and montelukast in pregnancy is probably safe but should be limited to special circumstances, where they are viewed essential for asthma control. Zileuton should not be used in pregnancy.Acute asthma exacerbations in pregnant women should be treated in a similar manner to that in non-pregnant patients. Maternal blood glucose levels should be monitored periodically in pregnant women receiving systemic corticosteroids because of the deleterious effects of hyperglycemia upon embryos and fetuses. During pregnancy, maternal arterial oxygen saturations should be kept above 95% if possible for fetal well-being. Ambulatory oxygenation should be checked prior to discharge to ensure that women do not desaturate with their daily activities.Acute exacerbations of asthma during labor and delivery are rare. Dinoprost, ergometrine, and other ergot derivatives can cause severe bronchospasm, especially when used in combination with general anesthesia, and should be avoided in asthmatic patients. Pregnant women who have been treated with corticosteroids in the past year may require stress-dose corticosteroids during labor and delivery. Most asthma medications, including oral prednisone, are considered compatible with breast-feeding.

The dry-powder inhaler (DPI) Turbuhaler((R)) has been on the market for nearly two decades. Products containing terbutaline, formoterol, budesonide, and the combination budesonide/formoterol are widely used by patients with asthma and COPD. Most patients and physicians find Turbuhaler((R)) easy to use, and local side effects are rare. This is thought to arise from the lack of additives or only small amounts in the formulation, in addition to minimal deposition of the drug in the oropharynx and on the vocal cords during inspiration.The function of Turbuhaler((R)) has frequently been questioned. This article aims to review and clarify some key issues that have been challenged in the literature (e.g. the effectiveness of Turbuhaler((R)) in patients with more restricting conditions), to discuss the importance of lung deposition, and to explain the low in vivo variability associated with Turbuhaler((R)) and the lack of correlation with the higher in vitro variability.Turbuhaler((R)), like other DPIs, is flow dependent to some degree. However, a peak inspiratory flow (PIF) through Turbuhaler((R)) of 30 L/min gives a good clinical effect. These PIF values can be obtained by patients with conditions thought to be difficult to manage with inhalational agents, such as asthmatic children and adult patients with acute severe airway obstruction and COPD. Excellent clinical results with Turbuhaler((R)) in large controlled studies in patients with COPD and acute severe airway obstruction provide indirect evidence that medication delivered via Turbuhaler((R)) reaches the target organ.Due to the large amount of small particles and the moderate inbuilt resistance in Turbuhaler((R)), which opens up the vocal cords during inhalation, Turbuhaler((R)) is associated with a high lung deposition (25-40% of the delivered dose) compared with pressurized metered-dose inhalers (pMDIs) and other DPIs. A good correlation has been found between lung deposition and clinical efficacy. A high lung deposition always results in the best ratio between clinical efficacy and risk of unwanted systemic activity. Studies with Turbuhaler((R)) also show that the in vivo variation in lung deposition is significantly lower compared with a pMDI or, for example, the Diskus((R)) inhaler, and much lower than the in vitro dose variability seen in laboratory tests. Turbuhaler((R)) appears to be a reliable DPI which can be used with confidence by patients with airway diseases, including those with clinical conditions believed to be difficult to manage with inhalational therapy.

Tracheobronchomalacia (TBM) and excessive dynamic airway collapse (EDAC) are both dynamic forms of central airway obstruction characterized by a decrease of >/=50% in the cross-sectional area of the tracheobronchial lumen. The differences between these two entities, however, are not uniformly accepted in the medical community. While TBM is characterized by a weakness of the tracheobronchial cartilaginous structures, EDAC is marked by excessive bulging of the posterior membrane into the airway lumen during exhalation. These disease entities are probably underdiagnosed because they present with a variety of nonspecific symptoms similar to patients with other obstructive ventilatory disorders such as asthma and COPD. Diagnosis is confirmed by dynamic radiologic imaging studies or bronchoscopy. Current therapeutic management depends on the extent, type, and severity of airway abnormalities noted and the clinical presentation. Proposed management alternatives include conservative medical therapy, and minimally invasive and open surgical interventions. Inhaled bronchodilators should be used only if symptoms and ventilatory function improve after use. Continuous positive airway pressure acts as a pneumatic stent and should be considered as an alternative or additional therapeutic modality. Endoluminal stent insertion can improve symptoms and pulmonary function in patients with central airway obstruction and should be considered for patients with symptoms refractory to conservative therapy. Several open surgical procedures have also been performed over the years, including tracheostomy, airway splinting, tracheal resection and, more recently, external tracheal stents. Endobronchial laser therapy, resorbable stents, application of grafting materials used to support the collapsed airway as well as the use of cartilage regeneration techniques are experimental, and their efficacy in humans remains to be determined. Future studies should compare therapeutic interventions and outcomes such as functional status, ventilatory function, and bronchoscopic and radiologic appearances in order to define the costs and benefits of individual and combined treatment modalities.

Bronchial asthma is a chronic inflammatory disease of the airways which is recognized as a highly prevalent health problem in both the developed and the developing world, with significant human and economic consequences.Allergy is acknowledged as a major risk factor for asthma. The pathogenetic aspects of allergic asthma are characterized by airway inflammation with infiltration of mast cells, basophils, eosinophils, monocytes and T helper type 2 lymphocytes, along with the isotype switching of B cells to generate immunoglobulins of the immunoglobulin E (IgE) class. Increased asthma severity is not only associated with recurrent hospitalization and increased mortality but also with higher social costs.Inhaled corticosteroids are the standard anti-inflammatory medication and are effective for most asthma patients, but there is a substantial number of asthmatics who remain symptomatic even after receiving treatment with inhaled corticosteroids and long-acting beta(2)-adrenoceptor agonists (beta(2)-agonists), and sometimes are in need of systemic corticosteroids to control the disease. These patients account for about 50% of the healthcare costs of asthma.New treatment options more specifically targeting the pathophysiologic events causing development of asthma are therefore required in these patients.A novel therapeutic approach to asthma and other allergic respiratory diseases involves interference with the action of IgE and prevention of subsequent IgE-mediated responses.Omalizumab is a humanized recombinant monoclonal anti-IgE antibody developed for the treatment of allergic diseases, with clear efficacy in adolescent and adult patients with moderate-to-severe allergic asthma. This non-anaphylactogenic anti-IgE antibody inhibits IgE functions by blocking free serum IgE and inhibiting their binding to cellular receptors. Omalizumab therapy is well tolerated and significantly improves symptoms and disease control, and reduces asthma exacerbations and the need to use high dosages of inhaled corticosteroids. Moreover, omalizumab improves quality of life of patients with severe persistent allergic asthma that is inadequately controlled by currently available asthma medications. In conclusion, omalizumab may fulfill an important need in patients with moderate-to-severe asthma inadequately controlled with inhaled corticosteroids +beta(2)-agonists.