Pulmonary Rehabilitation and the BODE index in COPD; C. G. Cote, B. R. Celli (Eur Respir J 2005; 26:630–636).
The BODE index, which integrates body mass index, airflow limitation (forced expiratory volume in one second), dyspnoea and 6-min walk distance, predicts mortality in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves some components of BODE. It was hypothesised that changes in BODE may reflect the effects of PR. To test this, participation in PR was offered to 246 patients (BODE quartiles 2–4). The patients were divided as follows: no PR (130 who declined rehabilitation or who dropped out from PR), and PR (116 who completed PR). BODE was determined at entry, after PR, and at 1 and 2 yrs. Other outcomes were: length of stay (LOS) for respiratory-related hospitalisations and mortality. At entry, the two groups had similar age and comorbidity but different BODE. After PR, the BODE improved by 19% and returned to baseline after 2 yrs. The BODE worsened in the no PR group by 4% at 12 months and 18% at 2 yrs. Respiratory mortality at 2 yrs for PR was 7%, compared with 39% for no PR. LOS at 1 yr for COPD decreased 20% in PR, while it increased 25% in no PR. In conclusion, pulmonary rehabilitation participation improves BODE and is associated with better outcomes. The BODE index change after pulmonary rehabilitation provides valuable prognostic information.
Comments: In this observational study the authors demonstrate that the BODE index is a useful outcome measure to assess response to rehab therapy and subsequent prognosis for a group of male VA patients with a mean FEV1 of approximately 30% predicted (very severe range). The pulmonary rehab program consisted of 24, 2 hour sessions over 8 weeks and a significant response was considered to occur if patients noted a –1 change in the BODE index. Active smokers had to graduate from a smoking cessation program before being allowed to participate in PR. Analysis was completed by using an, “intent to treat” design. There were a number of features about the “no pulmonary rehab group” that may have influenced their poorer outcome. The no PR group consisted of patients who refused rehab or dropped out instead of being randomly assigned. A higher proportion of the no PR group were smokers, were on home oxygen and used oral corticosteroids. They also had a statistically significant lower baseline FEV1. There were 57 respiratory deaths in the no PR group and 8 respiratory related deaths in the PR group. Hence this was likely a sicker group who refused rehab because of how debilitated they were. Hence the improvement in the PR group versus the no PR group may be biased and largely a reflection of self-selection. Nonetheless the BODE should be considered a useful assessment tool for outcomes following various intervention strategies for COPD subjects.
Prevention of Exacerbation of Chronic Obstructive Pulmonary Disease with Tiotropium, a Once Daily Inhaled Anticholinergic Bronchodilator; D. E. Niewochner, K. Rice, C. Cote, D. Paulson, J. A. Jr. Cooper, L. Korducki, C. Cassino, S. Kesten (Ann Intern Med 2005; 143:317–326).
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(1), 36% predicted).
Intervention: Once-daily tiotropium (18 microg) 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.
Comments: This multicenter study demonstrates that Tiotropium treated subjects had a relatively modest reduction in exacerbation events and hospitalizations due to COPD exacerbations in this cohort of predominantly white (90%), male (99%) subjects from the VA system. Exacerbations were defined as an increase or new onset of cough, sputum, wheezing dyspnea or chest tightness with duration of at least 3 days requiring antibiotics or systemic steroids, hospitalization, or both. Data were analyzed by using an intention to treat principle. Patients were severe to very severe COPD patients. Over 55% of subjects in each group used inhaled corticosteroids with no significant difference between the two. Over 10% were on oral steroids regularly. Primary care providers treated exacerbations with antibiotics and steroids as they saw fit without restriction. An interesting caveat to this study was that it demonstrated that subjects using home oxygen had a particularly higher exacerbation rate than subjects not on home oxygen regardless of treatment group. This may actually be an important group to examine when studying exacerbations whereas in the past they have been excluded from such studies. The differences seen between tiotropium and placebo may have been even more impressive if follow up was for longer than 6 months. The more relevant study would have been with ipratropium used 4 times per day in the control group or as a third study group. The authors note that previous studies comparing tiotropium and ipratropium demonstrated a reduced exacerbation rate in the tiotropium group but exacerbations were only part of the secondary analysis and not the primary outcome. Sustained bronchodilation is proposed as the explanation for reduced exacerbations in this group but the actual explanation for this observation remains unknown.
Trends in Diagnosis of Symptomatic Patients with α1-Antitrypsin Deficiency Between 1968 and 2003; M. A. Campos, A. Wanner, G. Zhang, R. A. Sandhaus (Chest 2005; 128:1179–1186).
Background: Alphal-antitrypsin deficiency (AATD) is usually underrecognized, with only 5% of cases being diagnosed in the estimated 100,000 affected individuals in the United States. To support current guidelines recommending AATD testing of all individuals with COPD, we analyzed the diagnostic experience of a large cohort of symptomatic patients with AATD.
Methods: A total of 1,020 members of AlphaNet, a not-for-profit health management company devoted to patients with AATD, provided information regarding their AATD diagnostic experience as part of a larger survey-based outcome study.
Results: The average age at diagnosis was 45.5 ± 9.5 years, and the average interval between the onset of symptoms and diagnosis was 8.3 ± 6.9 years (±SD); 30.8% were diagnosed in patients > 50 years old. Two thirds of the diagnoses were made by the first or second physician, and 20% by the fourth or more physicians. From 1968 to 2003, there was a steady increase in age at diagnosis (p < 0.05), the number of physicians required for diagnosis (p > 0.05), and years with symptoms before diagnosis (p > 0.05), while the proportion of cases diagnosed by the first or second physician decreased (p < 0.001). Individuals with a diagnosis at < 35 years of age saw fewer physicians than other age groups (p < 0.05), and show a tendency toward a shorter diagnostic interval over time (p > 0.05). Diagnoses were made in men earlier than in women (p < 0.05), and the proportion of individuals in whom AATD was detected because of asthma or COPD has increased (p < 0.05).
Conclusion: There has not been a significant improvement in earlier disease diagnosis between 1968 and 2003. There has been improved AATD detection in older individuals. The diagnostic delay is still significant, and efforts should be directed to increase early AATD detection by health-care providers and patients.
Comments: While αl-antitrypsin deficiency may constitute 1-3% of patients with emphysema it remains under-diagnosed. Sadly there has been little improvement in early detection of the disease. This is a study based on telephone interviews as part of a larger questionnaire about outcomes of symptomatic α1-antitrypsin deficient patient's. A subset of questions asked them to recall their diagnostic experience. The explanation for the steady increase in age at diagnosis and symptoms before diagnosis likely relates to the fact that more patients with symptomatic COPD are being tested compared to before when largely individuals were screened because of family members known to have α1-Antitrypsin deficiency. The study points to there being a general under-recognition of the condition particularly in women because of the persistent gender bias in diagnosing COPD. Although the study is likely biased by several factors in terms of the patient population being symptomatic patients who are part of the AlphaNet network and have been on augmentation therapy it still highlights the need for greater awareness and testing of all COPD patients for α1-Antitrypsin deficiency as recommended by the ATS/ERS statement on diagnosis and management of individuals with α1-antitrypsin deficiency published in 2003.
Results of a Case-Detection Programme for α1-Antitrypsin Deficiency in COPD Patients; C. de la Roza, F. Rodriguez-Frias, B. Lara, R. Vidal, R. Jardi, M. Miravitlles (Eur Respir J 2005; 26:616–622).
Alpha(1)-Antitrypsin (alpha(1)-AT) deficiency is an underdiagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The present authors have conducted a nationwide case detection programme of alpha(1)-AT deficiency in unselected patients with COPD using dried blood spots. The first phase analysed samples from 971 patients by determining alpha(1)-AT concentrations and identifying the deficient Z allele by genotyping using rapid real-time PCR. The second phase analysed 1,166 samples with alpha(1)-AT concentrations and identified both the S and the Z allele, but only in samples with low alpha(1)-AT concentrations. A total of eight (0.37%) individuals with the severe deficiency PiSZ were detected. In addition, three patients were identified with the PiSZ genotype in the second phase (0.3%). The global cost of the programme was 41,512, which represents 19.42 per sample and 5,189 per PiZZ detected. A sensitivity analysis demonstrated that performing Z genotype to all samples would have resulted in increased costs of 28 per sample and 7,479.5 per PiZZ case identified. In conclusion, a case detection programme of alpha(1)-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood spots is feasible and at a reasonable cost per case detected. Diagnostic yield and cost depend largely on inclusion criteria and the protocol for processing of samples.
Comments: When considering the ATS/ERS recommendations for detection programs for α1-antitrypsin deficiency in all COPD patients, the development of rapid reliable low cost methods are critical. While no clear criteria were stated for making the diagnosis of COPD, subjects in the second phase of the study had a mean FEV1 of 48% predicted and an average pack year history of 53.8. The rationale to test for Z and S alleles in only patients with low α1-antitrypsin concentrations is reasonable and significantly reduces costs. The cutoff value of 100 mg/dL−1 was determined by studying the correlation between the different phenotypes and the concentrations obtained in the dry blood samples. One caution was that 5% of samples could not be analyzed because of insufficient quantity of sample. Proper education of physicians and ancillary staff is key to ensuring viable samples for analysis using this method. It is helpful that the authors provide the cost analysis but it would have been useful to examine the costs compared to more conventional testing methods. Further studies should examine the costs versus benefits of testing for other alleles and/or phenotypes such as PiMZ.