Jonathan Ilowite

Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double-blind, multicenter study.

BACKGROUND For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids, addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines. OBJECTIVE To compare montelukast, a once-daily leukotriene receptor antagonist, and salmeterol, a twice-daily, long-acting beta-agonist, concomitantly administered with inhaled fluticasone, according to the percentage of patients without an asthma attack for 1 year. METHODS A randomized, double-blind, double-dummy, multicenter study was conducted. Adult patients with moderate-to-severe persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 microg/d) who remained symptomatic during a 4-week run-in period were randomized to the addition of salmeterol (84 microg/d) or montelukast (10 mg/d) for 48 weeks. RESULTS Of the 1,473 randomized patients, 743 were randomized to montelukast and 730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients in the montelukast group and 83.3% of patients in the salmeterol group remained attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts compared with salmeterol, whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second, asthma-specific quality of life, morning peak expiratory flow rate, and decreased nocturnal awakenings compared with montelukast. Differences between treatments were small, and both treatments were generally well tolerated. CONCLUSIONS Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period, but, based on noninferiority limits, the study was inconclusive with regard to a difference between treatment groups.

Bronchiectasis: new findings in the pathogenesis and treatment of this disease.

Purpose of reviewBronchiectasis is an under-appreciated cause of chronic lung disease in the USA. We highlight developments in diagnosis and treatment of this debilitating disease. Recent findingsA possible link between gastroesophageal reflux and development of nontuberculous mycobacterial lung disease was highlighted. Reflux is more common in patients with nontuberculous mycobacterial lung disease, and among those with established bronchiectasis more extensive disease was observed in those patients who also had reflux. Long-term mortality in bronchiectasis was significantly associated with age, lower body mass index, dyspnea, lack of vaccination, hypoxemia, hypercapnia, and other functional parameters. In a large, randomized clinical trial, addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas infection produced microbiologic improvement correlating with clinical outcomes but not overall improvement. A review noted that five macrolide trials reported reduced sputum volume, improved lung function, and better symptom control. Finally, articles suggested benefit from inhaled hyperosmolar agents (e.g. hypertonic saline and inhaled mannitol). SummaryThe possible link between gastroesophageal reflux and nontuberculous mycobacterial lung disease, and the microbiology and resistance patterns of bacteria observed in these patients were clarified. A large study of inhaled tobramycin for exacerbations was inconclusive, but macrolide therapy and hyperosmolar agents hold promise.

A Preliminary Quality of Life Questionnaire-Bronchiectasis: A Patient-Reported Outcome Measure for Bronchiectasis

BACKGROUND The Quality of Life Questionnaire-Bronchiectasis (QOL-B) is the first disease-specific, patient-reported outcome measure for patients with bronchiectasis. Content validity, cognitive testing, responsivity to open-label treatment, and psychometric analyses are presented. METHODS Reviews of literature, existing measures, and physician input were used to generate the initial QOL-B. Modifications following preliminary cognitive testing (N = 35 patients with bronchiectasis) generated version (V) 1.0. An open-ended patient interview study (N = 28) provided additional information and was content analyzed to derive saturation matrices, which summarized all disease-related topics mentioned by each participant. This resulted in QOL-B V2.0. Psychometric analyses were carried out using results from an open-label phase 2 trial, in which 89 patients were enrolled and treated with aztreonam for inhalation solution. Responsivity to open-label treatment was observed. Additional analyses generated QOL-B V3.0, with 37 items on eight scales: respiratory symptoms; physical, role, emotional, and social functioning; vitality; health perceptions; and treatment burden. For each scale, scores are standardized on a 0-to-100-point scale; higher scores indicate better health-related quality of life. No total score is calculated. A final cognitive testing study (N = 40) resulted in a minor change to one social functioning scale item (QOL-B V3.1). RESULTS Content validity, cognitive testing, responsivity to open-label treatment, and initial psychometric analyses supported QOL-B items and structure. CONCLUSIONS This interim QOL-B is a promising tool for evaluating the efficacy of new therapies for patients with bronchiectasis and for measuring symptoms, functioning, and quality of life in these patients on a routine basis. A final psychometric validation study is needed and is forthcoming. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00805025; URL: www.clinicaltrials.gov.

Pharmacological Treatment Options for Bronchiectasis : Focus on Antimicrobial and Anti-Inflammatory Agents

Patients with bronchiectasis experience tenacious mucus, recurrent infectious exacerbations, and progressive worsening of symptoms and obstruction over time. Treatment is aimed at trying to break the cycle of infection and progressive airway destruction. Antibacterial treatment is targeted towards likely organisms or tailored to the results of sputum culture. Inhaled antibacterial therapy may offer the advantage of increased local concentration of medication, while minimizing systemic adverse effects; however, to date, studies have been equivocal in this disorder. Macrolides, in addition to their antibacterial properties, have unique anti-inflammatory properties, which may make them useful in this disorder. Other mucoactive and anti-inflammatory agents, such as inhaled corticosteroids, mannitol and hypertonic saline, may also prove useful in this disease, but further studies are needed.

Ergonomics in bronchoscopy: is there a need for better design or a change in the work environment?

The field of conventional bronchoscopy has undergone a paradigm shift over the last decade. The ability to visualize peribronchial structures in real time has increased the diagnostic and therapeutic scope of flexible bronchoscopy. Ultrasound engineering and the development of a probe with an interface capable of sound wave transmission, has led to the development of a new procedure, endobronchial ultrasound, which has been widely adapted, both throughout the USA and worldwide [1]. Similarly, techniques such as electromagnetic navigation bronchoscopy, autofluorescence bronchoscopy, optical coherence tomography and other interventional procedures, including bronchial thermoplasty, cryotherapy, brachytherapy, balloon dilatation and stent are increasingly being adopted at large academic centers [2]. Flexible bronchoscopy is an effective alternative to rigid bronchoscopy in treating distal airway lesions and less advanced malignant lesions [3]. The emphasis with all of these procedures is to reduce procedurerelated complications and improve patient comfort. However, the additional physical strain and exposure to cumulative trauma on the person actually performing the procedure is often overlooked. The prolonged nature of the procedures combined with unusual postures can result in overuse injuries, such as carpal tunnel syndrome, tendonitis, epicondilitis, neck sprain, shoulder pain and DeQuervain’s tenosynovitis. These injuries may be common in bronchoscopists performing a high number of these procedures. Minimal research has been carried out in this regard, and the available data to measure the magnitude of this problem are scarce.

Utility of Inferior Vena Cava Filters in Severe Pulmonary Embolism, Catheter-directed Therapy in Massive and Submassive Pulmonary Embolism, and HAS-BLED Score to Determine Risk of Major Hemorrhage in Pulmonary Embolism

The American College of Chest Physicians and the American Society of Hematology advocate use of an inferior vena cava (IVC) filter only when anticoagulation is contraindicated, whereas the Society of Interventional Radiology has a list of absolute, relative, and prophylactic indications (2–4). To clarify this issue further, Mismetti and colleagues performed a prospective, randomized, open-label study evaluating the efficacy and safety of retrievable IVC filters for preventing pulmonary embolism (PE) recurrence in patients presenting with acute severe PE and superficial venous thrombosis or deep venous thrombosis (DVT) (1). A total of 399 patients from 17 French centers were openly randomized to either a retrievable IVC filter plus anticoagulation group (n = 200) or an anticoagulation-only group (n = 199). Approximately 65% of patients in each group had evidence of right ventricular dysfunction. Primary outcome was recurrence of fatal or symptomatic nonfatal PE at 3 months. Secondary outcomes were fatal or nonfatal symptomatic PE at 6 months and new or recurrent symptomatic DVT at 3 and 6 months. By 3 months, PE had recurred in six patients in the filter group and three patients in the control group (relative risk with filter, 2.00; 95% confidence interval [CI], 0.51–7.89; P = 0.50). One additional PE recurrence was observed in each group between 3 and 6 months. No difference was observed between the two treatment groups with respect to DVT, major bleeding, or death from any cause at 3 and 6 months. This is a landmark clinical trial as it sheds light on outcomes after IVC filter placement in patients with non–high-risk PE and superficial venous thrombosis or DVT who are also anticoagulated. An earlier study performed by the same investigators determined that in patients with proximal DVT on anticoagulation, IVC filters reduced the risk of PE but increased that of DVT and did not affect survival (5). The strengths of this study are in its originality, the clinical relevance of the subject matter, and the multicenter and prospective nature. A major limitation is that the patient characteristics selected to determine PE severity are not the ones in current use. Standardized criteria for PE severity, such as the Pulmonary Embolism Severity Index score or the classification of patients with acute PE on the basis of early mortality risk proposed by the European Society of Cardiology, were not available while this study was being undertaken (6, 7). Thus, this study may not represent the population that best benefits from an IVC filter placement. An exceptionally high filter retrieval rate seen in this study (79%) will be very difficult to duplicate in the community, leading to increased complications such as DVT, filter migration, and IVC stenosis (8). Another minor limitation was the time (7 yr) needed to complete this study. Studies with inclusion criteria that are better validated to measure PE severity are needed to define the specific role of IVC filters. n