American journal of respiratory medicine : drugs, devices, and other interventions最新文献

Respiratory tract infection with eventual respiratory failure is the major cause of morbidity and mortality in cystic fibrosis (CF). Infective exacerbations need to be treated promptly and effectively to minimize potentially accelerated attrition of lung function. The choice of antibiotic depends on in vitro sensitivity patterns. However, physicians treating patients with CF are increasingly faced with infection with multidrug-resistant isolates of Pseudomonas aeruginosa. In addition, innately resistant organisms such as Burkholderia cepacia complex, Stenotrophomonas maltophilia and Achromobacter (Alcaligenes) xylosoxidans are becoming more prevalent. Infection with methicillin-resistant Staphylococcus aureus (MRSA) is also a problem. These changing patterns probably result from greater patient longevity and increased antibiotic use for acute exacerbations and maintenance care. Multidrug-resistant P. aeruginosa infection may be treated successfully by using two antibiotics with different mechanisms of action. In practice antibiotic choices have usually been made on a best-guess basis, but recent research suggests that more directed therapy can be achieved through the application of multiple-combination bactericidal testing (MCBT). Aerosol delivery of tobramycin for inhalation solution achieves high endobronchial concentrations that may overcome bacterial resistance as defined by standard laboratory protocols. Resistance to colistin is rare and this antibiotic should be seen as a valuable second-line drug to be reserved for multidrug-resistant P. aeruginosa. The efficacy of new antibiotic groups such as the macrolides needs to be evaluated.CF units should adopt strict segregation policies to interrupt person-to-person spread of B. cepacia complex. Treatment of panresistant strains is difficult and often arbitrary. Combination antibiotic therapy is recommended, usually tobramycin and high-dose meropenem and/or ceftazidime, but the choice of treatment regimen should always be guided by the clinical response.The clinical significance of S. maltophilia, A. xylosoxidans and MRSA infection in CF lung disease remains uncertain. If patients show clinical decline and are chronically colonized/infected with either of the former two pathogens, treatment is recommended but efficacy data are lacking. There are defined microbiological reasons for attempting eradication of MRSA but there are no proven deleterious effects of this infection on lung function in patients with CF. Various treatment protocols exist but none has been subject to a randomized, controlled trial. Multidrug-resistant microorganisms are an important and growing issue in the care of patients with CF. Each patient infected with such strains should be assessed individually and antibiotic treatment planned according to in vitro sensitivity, patient drug tolerance, and results of in vitro studies which may direct the physician to antibiotic combinations most likely to succeed.

Introduction: In patients with COPD who have recently been hospitalized for their disease, we examined whether treatment with inhaled corticosteroids without or with long-acting beta-adrenoceptor agonists (beta-agonists) reduced rehospitalization and mortality.

Study design: Retrospective cohort analysis in the UK General Practice Research Database.

Methods: We compared rehospitalization for a COPD-related medical condition or death within 1 year after first hospitalization, in 3636 COPD patients receiving prescriptions for inhaled corticosteroids or long-acting beta-agonists compared with 627 reference patients with COPD who were prescribed short-acting bronchodilators only.

Results: Rehospitalization within a year occurred in 13.2% of the reference COPD patients, 14.0% of users of long-acting beta-agonists only, 12.3% of users of inhaled corticosteroids only, and 10.4% of users of inhaled corticosteroids and long-acting beta-agonists. Death within a year occurred in 24.3% of the reference COPD patients, 17.3% of users of long-acting beta-agonists only, 17.1% of users of inhaled corticosteroids only, and in 10.5% of users of inhaled corticosteroids and long-acting beta-agonists. In multivariate analyses the risk of rehospitalization or death was reduced by 10% in users of long-acting beta-agonists only (NS), by 16% in users of inhaled corticosteroids only, and by 41% in users of combined inhaled corticosteroids and long-acting beta-agonists (both p < 0.05).

Conclusion: Use of inhaled corticosteroids with/without long-acting beta-agonists was associated with a reduction of rehospitalization or death in COPD patients.

Chlamydia pneumoniae is an intracellular pathogen that has been suggested to play a role in the pathology of asthma. However, so far none of the studies have provided clear evidence for a causative role of C. pneumoniae infections in asthma, although there is little doubt that chronic C. pneumoniae infection does aggravate asthma and should be treated. The diagnosis of C. pneumoniae infection is still a matter of concern for it is dependent on trained skilled personnel and can vary significantly between different diagnostic laboratories. This fact is also one of the major problems encountered when comparing epidemiological studies investigating the possible role of C. pneumoniae infections and their impact on the pathogenesis of other diseases. With regard to therapy, long-term treatment with macrolides is the best available method to eradicate C. pneumoniae. Successful therapy for C. pneumoniae, however, can also be complicated by the high possibility of de novo infection as epidemiological studies have shown that the prevalence of antibodies to C. pneumoniae increases with age in all populations studied. In the northern hemisphere the prevalence of C. pneumoniae is also affected by seasonal conditions. It is too early to draw any conclusions from the equatorial belt countries. The available data on C. pneumoniae in tropical countries indicate a much faster infection rate during early adulthood with 100% serological prevalence at an age greater than 25 years. This data, if confirmed, would argue against C. pneumoniae causing asthma since the asthma prevalence in those countries does not increase in a parallel pattern. An alternative interpretation of most studies could be that the increased rate of C. pneumoniae infections in patients with asthma results from a modified susceptibility towards the microorganism, due to yet unknown changes of the host cell's physiology. It should be kept in mind that increased prevalence of C. pneumoniae infection is not restricted to asthma. Further studies are needed to understand the role of C. pneumoniae, especially of chronic infection, in the pathogenesis of inflammatory diseases with a specific focus on the effect that the microorganism triggers in the infected host cell. Only when we understand what C. pneumoniae does to its host cell will we be able to judge its impact on the overall status of an affected patient, and this knowledge will help us to develop a successful therapy.

Directly Observed Therapy Shortcourse (DOTS) is composed of five distinct elements: political commitment; microscopy services; drug supplies; surveillance and monitoring systems and use of highly efficacious regimens; and direct observation of treatment. The difference in the way the term 'DOTS' as defined by WHO and interpreted by many observers has led to some misunderstanding. WHO generally uses the term to mean the five components of DOTS. But the word 'DOTS' is an acronym for Directly Observed Therapy Shortcourse. Many workers therefore interpret DOTS purely as direct supervision of therapy. DOTS is not an end in itself but a means to an end. In fact it has two purposes, to ensure that the patient with tuberculosis (TB) completes therapy to cure and to prevent drug resistance from developing in the community. The main criticism of DOTS rightly derives from the fact that some properly conducted randomized, controlled trials of directly observed therapy with or without the other components have shown no benefit from it. The problem is that it is impossible to design a study of modern directly observed therapy against the previous self-administered, poorly-resourced programs. As soon as a study is implemented, the attention to patients in the control (non-directly observed therapy) arm inevitably improves from the previous non-trial service situation. What is of concern is that in some trials less than 70% cure rates were achieved even in the direct observation arm. With no new drugs or adjuvant treatment available to bring the length of treatment down to substantially less than 6 months, DOTS offers the best means we have at our disposal for TB control.

There exists a complex, dynamic interaction between mechanical ventilation and the splanchnic vasculature that contributes to a myriad of gastrointestinal tract complications that arise during critical illness. Positive pressure-induced splanchnic hypoperfusion appears to play a pivotal role in the pathogenesis of these complications, the most prevalent of which are stress-related mucosal damage, gastrointestinal hypomotility and diarrhea. Furthermore, characteristics of the splanchnic vasculature make the gastrointestinal tract vulnerable to adverse effects related to positive pressure ventilation. While most of these complications seen in mechanically ventilated patients are reflections of altered gastrointestinal physiology, some may be attributed to medical interventions instituted to treat critical illness. Since maintenance of normal hemodynamics cannot always be achieved, pharmacologic prophylactic therapy has become a mainstay in the prevention of gastrointestinal complications in the intensive care unit. Improved understanding of the systemic effects of mechanical ventilation and greater application of lung-protective ventilatory strategies may potentially minimize positive pressure-induced reductions in splanchnic perfusion, systemic cytokine release and, consequently, reduce the incidence of gastrointestinal complications associated with mechanical ventilation. Herein, we discuss the pathophysiology of gastrointestinal complications associated with mechanical ventilation, summarize the most prevalent complications and focus on preventive strategies and available treatment options for these complications. The most common causes of gastrointestinal hemorrhage in mechanically ventilated patients are bleeding from stress-related mucosal damage and erosive esophagitis. In general, histamine H(2) receptor antagonists and proton pump inhibitors prevent stress-related mucosal disease by raising the gastric fluid pH. Proton pump inhibitors tend to provide more consistent pH control than histamine H(2) receptor antagonists. There is no consensus on the drug of choice for stress ulcer prophylaxis with several meta-analyses providing conflicting results on the superiority of any medication. Prevention of erosive esophagitis include careful use of nasogastric tubes and institution of strategies that improve gastric emptying. Many mechanically ventilated patients have gastrointestinal hypomotility and diarrhea. Treatment options for gastrointestinal motility are limited, thus, preventive measures such as correction of electrolyte abnormalities and avoidance of medications that impair gastrointestinal motility are crucial. Treatment of diarrhea depends on the underlying cause. When associated with Clostridium difficile infection antibacterial therapy should be discontinued, if possible, and treatment with oral metronidazole should be initiated.More studies are warranted to better understand the systemic effects of mechanical ventilation on the

Asthma is a significant and increasing health problem. Airway inflammation and hyperresponsiveness are key pathophysiological mechanisms underlying asthma. Currently, effective treatments target these two processes and can lead to clinically important improvements in disease control. At present, decisions to initiate or modify therapy are based on symptoms and measures of airway caliber, with no direct assessment of airway inflammation or hyperresponsiveness. It is now possible to measure airway inflammation using noninvasive markers such as exhaled gases, induced sputum and serum measurements. Exhaled nitric oxide (eNO) and induced sputum eosinophils show the greatest promise as clinically useful markers of airway inflammation in asthma. Induced sputum can now be applied to the diagnosis of airway diseases, based on its ability to detect eosinophilic bronchitis in cough, and to differentiate between eosinophilic and non-eosinophilic asthma. The place of induced sputum and eNO in the ongoing monitoring of patients with asthma are now being investigated in controlled trials.

Objective: To examine the relationship between changes in quality of life and measures of lung function and bronchial hyper-responsiveness (BHR) during treatment with high-dose inhaled corticosteroids in patients with uncontrolled asthma.

Methods: Thirty patients with uncontrolled asthma currently receiving inhaled corticosteroids (median dose 550 microg/day) were treated with beclomethasone dipropionate (BDP) dry powder 2000 microg/day for 4 weeks. Patients completed the Asthma Quality of Life Questionnaire (AQLQ), underwent bronchial challenge with methacholine and spirometry, and made entries in asthma diary cards at baseline and after treatment with beclomethasone dipropionate.

Results: The mean change in overall AQLQ score improved significantly (p < 0.05) during the 4-week period by 0.57 (95% CI 0.29-0.84, p < 0.05), representing a minimal important difference, with similar improvements in individual domains. Change in overall AQLQ score correlated significantly with FEV(1) (p < 0.001), forced mid-expiratory flow between 25-75% of vital capacity (FEF(25-75)) [p < 0.05] and morning PEF (p < 0.05), but not with methacholine PD(20) i.e. the provocative dose of methacholine causing a 20% fall in FEV(1).

Conclusions: Quality-of-life scores related to changes in lung function but not BHR during short-term high-dose inhaled corticosteroid therapy for uncontrolled asthma.

Management of recurrent malignant pleural effusion, a common complication of malignancy, poses a challenge to clinicians. Although almost one century has elapsed since the introduction of the pleurodesis procedure, the ideal approach and best agent are still to be defined. Optimally, pleurodesis should be done at the bedside with a minimally invasive procedure, and suitable agents to achieve pleural symphysis should be inexpensive, available worldwide and free of adverse effects. To date, no substance completely fulfills these requirements. Silver nitrate should be considered for pleurodesis because of its low cost and ease of handling. Although talc has been used most frequently to induce pleurodesis, reports of death due to acute respiratory failure have raised concerns about the safety of this agent. Tetracycline, an effective alternative used in the past, is no longer commercially available. This agent has been substituted with derivatives of tetracycline, such as minocycline and doxycycline with success rates similar to those with tetracycline. Several antineoplastic agents have been injected into the pleural space with the aim of producing pleural symphysis, the most representative of this group being bleomycin. Recent knowledge of the molecular mechanisms involved in pleural inflammation has brought into focus new substances, such as transforming growth factor beta and vascular endothelial growth factor, which may be used as pleurodesis agents in the future. Nevertheless, more studies are necessary to better define the potential of these substances in the induction of pleural symphysis.Ideally, a sclerosing agent should be cost-effective, available worldwide and easily administered. Talc will probably stand as the preferred agent to be used for pleurodesis in malignant pleural effusion because of its efficacy, easy manipulation and handling. However, further investigation is necessary to minimize adverse effects related to talc.

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.

Occupational rhinitis is a common heterogeneous group of inflammatory conditions in the nose, caused by exposure to airborne irritants and sensitizers in the occupational environment. The mechanism can be allergic, neurogenic or toxic. Data from several epidemiologic studies indicate that animal dander, organic dusts, latex and chemicals can cause occupational rhinitis, but because of methodological problems as well as weaknesses in the definition of occupational rhinitis, occupational exposure is probably an underestimated cause of rhinitis. The effect of rhinitis on the mental aspects of quality of life and substantial costs due to loss of productivity make it important to diagnose and treat occupational rhinitis. Diagnosis relies on a history of exposure, skin prick testing and, if possible, nasal provoacation. Avoidance of exposure, protective measures at the workplace and medical treatment, with agents such as second generation antihistamines and nasal corticosteroids, can make it possible to avoid progress of the disease from rhinitis to asthma. The efficacies of montelukast, a leukotrienne receptor antagonist, and omalizumab, an anti-immunoglobulin E monoclonal antibody in the treatment of occupational rhinitis are yet to be evaluated