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Background: Chronic obstructive pulmonary disease (COPD) is a common and disabling condition in adults. Information about therapeutic effectiveness and adverse effects of common treatment options and how clinical and spirometric characteristics affect outcomes is not well known but is important for clinicians caring for patients with stable COPD. Purpose: To evaluate the effectiveness of COPD management strategies. Data Sources: English-language publications in MEDLINE and the Cochrane Library through March 2007. Study Selection: Randomized, controlled trials (RCTs) and previous systematic reviews of inhaled therapies, pulmonary rehabilitation, disease management, and supplemental oxygen in adults with COPD. Data Extraction: Participant, study, and intervention characteristics; exacerbations; deaths; respiratory health status; exercise capacity; hospitalizations; and adverse effects. Data Synthesis: Eight meta-analyses and 42 RCTs examined inhaled therapies: short-acting anticholinergics (n = 7), long-acting anticholinergics (n = 10), long-acting [[beta].sub.2]-agonists (n = 22), corticosteroids (n = 14), dual [D.sub.2] dopamine receptor-[[beta].sub.2]-agonist (n = 3), or short-acting [[beta].sub.2]-agonist plus ipratropium (n = 3). Evidence for nonpharmacologic therapies included 3 reviews of 39 RCTs plus 6 additional RCTs of pulmonary rehabilitation, 2 reviews of 13 RCTs plus 2 additional RCTs of disease management, and 8 RCTs of oxygen. Overall, long-acting inhaled therapies, used alone or in combination, reduced exacerbations more than placebo by 13% to 25% and had similar effectiveness to each other. Average improvements in health status scores were less than what is considered to be clinically noticeable. Inhaled monotherapy did not reduce mortality rates. Inhaled corticosteroids plus long-acting [[beta].sub.2]-agonists reduced deaths in relative terms compared with placebo (relative risk, 0.82 [95% CI, 0.69 to 0.98]) and inhaled corticosteroids alone (relative risk, 0.79 [CI, 0.67 to 0.94]) but not compared with long-acting [[beta].sub.2]-agonists alone (relative risk, 0.82 [CI, 0.52 to 1.28]). Absolute reductions were 1% or less and were not statistically significant. Pulmonary rehabilitation improved health status and dyspnea but not walking distance. Neither disease management nor ambulatory oxygen improved measured outcomes. Supplemental oxygen reduced mortality rates among symptomatic patients with resting hypoxia (relative risk, 0.61 [CI, 0.46 to 0.82]). Insufficient evidence supports using spirometry to guide therapy. Limitations: Articles were limited to those in the English language. Treatment adherence, adverse effects, and effectiveness may differ among clinical settings. Short-acting inhalers for 'rescue therapy' were not evaluated. Conclusion: Long-acting inhaled therapies, supplemental oxygen, and pulmonary rehabilitation are beneficial in adults who have bothersome respiratory symptoms, especially dyspnea, and [FEV.sub.1] less than 60% predicted.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.08.006 Byline: Dennis E. Niewoehner Keywords: Chronic obstructive pulmonary disease; Exacerbation; Quality of life Abstract: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are morbid events with slow recovery periods. They consume substantial healthcare resources, and they may cause a more rapid reduction in lung function over time. Quality of life (QOL) deteriorates in patients who experience exacerbations, and the more frequent the exacerbations, the more rapid the decline in QOL. Hospitalizations due to exacerbations account for up to 70% of the cost of medical care for patients with COPD. Patients with more severe COPD have more hospitalizations compared with those with less severe disease. A number of therapeutic interventions reduce the number of exacerbations and hospitalizations due to respiratory disease. The long-acting anticholinergic bronchodilator tiotropium, influenza vaccination, and possibly case management appear to reduce need for hospitalization substantially. COPD management should include drugs and other interventions that reduce the frequency of exacerbations and minimize their negative impact on the clinical course of the disease. Author Affiliation: University of Minnesota, Minneapolis, Minnesota, USA; and Pulmonary Section, Department of Veterans Affairs Medical Center, Minneapolis, Minnesota, USA

Background: Patients with chronic obstructive pulmonary disease (COPD) frequently develop exacerbations, leading to major clinical and health resource use ramifications. Objective: To prospectively evaluate the effectiveness of a long-acting inhaled anticholinergic bronchodilator, tiotropium, in reducing COPD exacerbations and exacerbation-related health care utilization. Design: Randomized, double-blind study. Setting: 26 Veterans Affairs medical centers. Patients: 1829 patients with moderate to severe COPD (mean baseline [FEV.sub.1], 36% predicted). Intervention: Once-daily tiotropium (18 [micro]g) or placebo for 6 months. Patients otherwise received usual care, except for other anticholinergic bronchodilators. Measurements: The coprimary end points were the percentage of patients with a COPD exacerbation and the percentage of patients with a COPD-related hospitalization. Results: Tiotropium significantly reduced the percentage of patients experiencing 1 or more exacerbations compared with placebo (27.9% vs. 32.3%, respectively; difference, -5.7 percentage points [95% CI, -10.4 to -1.0 percentage points]; P = 0.037). Fewer tiotropium patients were hospitalized because of COPD exacerbation (7.0% vs. 9.5%, respectively; difference, -3.0 percentage points [CI, -5.9 to -0.1 percentage points]; P = 0.056), although this difference was of borderline statistical significance. Analysis of secondary outcomes indicates that tiotropium may lengthen the time to first COPD exacerbation (P = 0.028) and reduce health care utilization for exacerbations, including the frequency of hospitalizations (P = 0.047), unscheduled clinic visits (P = 0.019), and days of antibiotic treatment (P = 0.015). Tiotropium did not statistically significantly reduce all-cause hospitalization rates. Limitations: Trial participants were enrolled from 1 health care system, and 99% were men. The follow-up period extended for only 6 months. Conclusions: Tiotropium reduces COPD exacerbations and may reduce related health care utilization in patients with moderate to severe COPD.

Study objective: Measures of health-related quality of life (HRQL) correlate with disease stage in persons with COPD. However, as their predictive capacity for mortality or medical utilization is less well [...]

Although virtually all individuals with advanced lung cancer succumb to the disease, a substantial portion of individuals diagnosed at an earlier stage can be cured. This dichotomy has provoked interest [...]

Byline: Jeffrey B. Rubins, Jordan Dunitz, Hanna B. Rubins, Michael A. Maddaus, Dennis E. Niewoehner Abstract: Objective: To determine whether measurement of preoperative serum carcinoembryonic antigen concentrations adds useful prognostic data to current preoperative staging of lung cancer by computed tomography, bronchoscopy, and mediastinoscopy. Methods: A prospective cohort study of 130 consecutive patients was evaluated for suspected lung cancer from July 1991 through December 1992 at a university-affiliated Veterans Affairs Medical Center. Serum concentrations of carcinoembryonic antigen were measured before diagnosis, staging, or resection of cancer. Results: Malignant disease was diagnosed by bronchoscopy, needle biopsy, mediastinoscopy, or resection in 111 of 130 patients. In the 50 patients undergoing resection with curative intent, multivariate analysis indicated that carcinoembryonic antigen was a significant predictor of survival independent of patient age, pathologic stage, histologic type, and tumor size (P = .0357). Conclusions: Elevated preoperative serum concentrations of carcinoembryonic antigen predict a poor prognosis for lung cancer independent of other conventional staging parameters and have an adjunctive role in the staging of lung cancer. (J Thorac Cardiovasc Surg 1998;116:412-6) Article History: Received 24 November 1997; Revised 30 January 1998; Revised 14 May 1998; Accepted 3 June 1998 Article Note: (footnote) [star] From the Pulmonary Diseasea and General Internal Medicine Divisions,b Department of Medicine, and Department of Thoracic Surgery,c Veterans Affairs Medical Center and University of Minnesota School of Medicine, Minneapolis, Minn., [star][star] Supported by the Veterans Affairs Department of Research., a Address for reprints: Jeffrey B. Rubins, MD, Pulmonary (111N), VA Medical Center, One Veterans Dr, Minneapolis, MN 55417., aa 12/1/92144

Inhaled and systemic corticosteroids are commonly prescribed for the treatment of COPD. Despite their frequent use, there is insufficient evidence regarding efficacy of steroid therapy in COPD. While awaiting the results of more definitive prospective trials, the clinician must evaluate whether the benefits of such therapy outweigh the potential for adverse events. This is particularly pertinent in the population of patients with COPD who generally are older, less active, and have significant tobacco use histories, all of which may place them at greater risk for adverse effects. In this review, we examine the current scientific evidence supporting the many purported adverse systemic effects associated with the use of corticosteroids in the treatment of COPD. (CHEST 1997; 111:732-43) Key words: adverse effects; chronic obstructive pulmonary disease; corticosteroids Abbreviations: ACTH=corticotropin; HPA=hypothalamic-pituitary-adrenal; PSC=posterior subcapsular cataract, COPD remains one of the leading causes of disability and death in developed countries. In addition to bronchodilators, oxygen, and antibiotics, many physicians prescribe inhaled and systemic corticosteroids. Large doses [...]

Surgery is generally considered to be the treatment of choice for anatomically localized non-small-cell lung cancer, but its effectiveness remains unproven. Observational studies have been of limited value because the criteria by which patients are selected for surgery create substantial differences between patients who undergo surgery and those who do not. One small randomized trial of surgery vs radiotherapy was inconclusive, but several large trials of lung cancer screening have provided indirect evidence against a benefit from surgery. Two ongoing randomized trials, one on extensive vs limited resection and the other on the effect of surgery in more extensive disease, may provide further insight into the effectiveness of surgery in the treatment of localized non-small-cell lung cancer. Development of a large randomized trial to directly assess the effectiveness of surgery in the treatment of localized non-small-cell lung cancer has been precluded by ethical concerns, but may need to be reconsidered if indicated by the findings of the two ongoing studies.

The morphologic basis for airflow obstruction in chronic obstructive pulmonary disease is extremely complex and consists of heterogeneous lesions. Emphysema seems to be the single most important lesion in this disorder. Abnormalities of the peripheral conducting airways, including inflammation, fibrosis, smooth muscle hypertrophy, and hyperplasia of mucus-secreting elements, are also of functional importance. Low-grade inflammation involving both airways and parenchyma occurs after only short-term exposure to cigarette smoke. This chronic inflammatory reaction may initiate other, largely irreversible, tissue responses that are responsible for airflow function. In the case of emphysema, tissue obstruction is thought to be due to an elastase-antielastase imbalance, leading to accelerated destruction of elastic fibers in the alveolar walls. Logical strategies for controlling the development of emphysema might include measures to prevent the influx of phagocyte-borne elastases into the lung as well as efforts to supplement the antiprotease shield of the lower airways. Anti-inflammatory drugs might also be effective in suppressing cigarette-smoke--induced reactions in the conducting airways. Other agents might be effective by preventing bronchoconstriction and the proliferation of smooth muscle elements in airway walls., Over the last two decades, the incidence of chronic obstructive pulmonary disease (COPD) has been increasing. COPD is a major cause of mortality and new methods of preventing and treating COPD are needed. Cigarette smoking is the leading known cause of COPD. The physiological changes that occur in the lungs of patients with COPD include lung tissue inflammation, destruction of the elastic fibers that allow the lungs to expand, fibrosis (the formation of dense, nonelastic tissue), excessive growth of smooth muscle cells, and excessive mucus production. Emphysema is the most serious form of COPD, which occurs when enzymes called proteases, such as elastase, destroy the lung tissue. Cigarette smoking causes emphysema by causing inflammation in the lungs, which increases the amount of proteases and tissue damage. Under normal circumstances, the lung tissue makes a substance called alpha-1 proteinase inhibitor (alpha1-PI), which inactivates proteases so that they do not damage the lung tissue. However, during chronic cigarette smoking large amounts of proteases are made and there is not enough alpha1-PI to prevent tissue damage. Emphysema can also be caused by an inherited deficiency of alpha1-PI. Infusions of alpha1-PI have been used to treat patients with alpha1-PI deficiency, but this form of treatment is very expensive. Corticosteroids reduce tissue inflammation and may be effective in slowing the progression of COPD. Clinical studies are needed to determine if drugs such as ipratropium, which that dilate the lung air passages, can help slow the progression of COPD in cigarette smokers. At the present time, the best method of preventing COPD is preventing or stopping cigarette smoking. (Consumer Summary produced by Reliance Medical Information, Inc.)

We believe that systemic corticosteroid therapy for COPD has increased substantially over the past 15 to 20 years. Most medical textbooks and therapy manuals now advise physicians to give systemic [...]

In this issue (see pages 1, 44) Drs. Lam and Newhouse have written a timely review on theophylline. Use of this drug has increased at an extraordinary rate over the [...]