Byron Thomashow

Comorbidities, Patient Knowledge, and Disease Management in a National Sample of Patients with COPD

OBJECTIVE Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States but is often undertreated. COPD often overlaps with other conditions such as hypertension and osteoporosis, which are less morbid but may be treated more aggressively. We evaluated the prevalence of these comorbid conditions and compared testing, patient knowledge, and management in a national sample of patients with COPD. METHODS A survey was administered by telephone in 2006 to 1003 patients with COPD to evaluate the prevalence of comorbid conditions, diagnostic testing, knowledge, and management using standardized instruments. The completion rate was 87%. RESULTS Among 1003 patients with COPD, 61% reported moderate or severe dyspnea and 41% reported a prior hospitalization for COPD. The most prevalent comorbid diagnoses were hypertension (55%), hypercholesterolemia (52%), depression (37%), cataracts (31%), and osteoporosis (28%). Only 10% of respondents knew their forced expiratory volume in 1 second (95% confidence interval [CI], 8-12) compared with 79% who knew their blood pressure (95% CI, 76-83). Seventy-two percent (95% CI, 69-75) reported taking any medication for COPD, usually a short-acting bronchodilator, whereas 87% (95% CI, 84-90) of patients with COPD and hypertension were taking an antihypertensive medication and 72% (95% CI, 68-75) of patients with COPD and hypercholesterolemia were taking a statin. CONCLUSION Although most patients with COPD in this national sample were symptomatic and many had been hospitalized for COPD, COPD self-knowledge was low and COPD was undertreated compared with generally asymptomatic, less morbid conditions such as hypertension.

Pilot Study of Extracorporeal Carbon Dioxide Removal to Facilitate Extubation and Ambulation in Exacerbations of Chronic Obstructive Pulmonary Disease

RATIONALE Acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring invasive mechanical ventilation (IMV) are associated with significant morbidity and mortality. Extracorporeal carbon dioxide removal (ECCO₂R) may facilitate extubation and ambulation in these patients and potentially improve outcomes. OBJECTIVES We assessed the feasibility of achieving early extubation and ambulation in subjects requiring IMV for exacerbations of COPD using single-site ECCO₂R. METHODS Five subjects with exacerbations of COPD with uncompensated hypercapnia requiring IMV were enrolled in this single-center, prospective, feasibility trial using a protocol of ECCO₂R, extubation, and physical rehabilitation. The primary endpoint was extubation within 72 hours of starting ECCO₂R. MEASUREMENTS AND MAIN RESULTS Mean preintubation pH and PaCO₂ were 7.23 ± 0.05 and 81.6 ± 15.9 mm Hg, respectively. All subjects met the primary endpoint (median duration, 4 h; range, 1.5-21.5 h). Mean duration of extracorporeal support was 193.0 ± 76.5 hours. Mean time to ambulation after extracorporeal initiation was 29.4 ± 12.6 hours. Mean maximal ambulation on extracorporeal support was 302 feet (range, 70-600). Four subjects were discharged home, and one underwent planned lung transplantation. Two minor bleeding complications occurred. There were no complications from mobilization on extracorporeal support. CONCLUSIONS ECCO₂R facilitates early extubation and ambulation in exacerbations of COPD requiring IMV and has the potential to serve as a new paradigm for the management of a select group of patients. Rigorous clinical trials are needed to corroborate these results and to investigate the effect on long-term outcomes and cost effectiveness over conventional management.

Barriers to adherence to chronic obstructive pulmonary disease guidelines by primary care physicians

Purpose: Even with the dissemination of several clinical guidelines, chronic obstructive pulmonary disease (COPD) remains underdiagnosed and mismanaged by many primary care physicians (PCPs). The objective of this study was to elucidate barriers to consistent implementation of COPD guidelines. Patients and methods: A cross-sectional study implemented in July 2008 was designed to assess attitudes and barriers to COPD guideline usage. Results: Five hundred US PCPs (309 family medicine physicians, 191 internists) were included in the analysis. Overall, 23.6% of the surveyed PCPs reported adherence to spirometry guidelines over 90% of the time; 25.8% reported adherence to guidelines related to long-acting bronchodilator (LABD) use in COPD patients. In general, physicians were only somewhat familiar with COPD guidelines, and internal medicine physicians were significantly more familiar than family physicians (P < 0.05). In a multivariate model controlling for demographics and barriers to guideline adherence, we found significant associations with two tested guideline components. Adherence to spirometry guidelines was associated with agreement with guidelines, confidence in interpreting data, ambivalence to outcome expectancy, and ability to incorporate spirometry into patient flow. Adherence to LABD therapy guidelines was associated with agreement with guidelines and confidence in gauging pharmacologic response. Conclusions: Adherence to guideline recommendations of spirometry use was predicted by agreement with the recommendations, self-efficacy, perceived outcome expectancy if recommendations were adhered to, and resource availability. Adherence to recommendations of LABD use was predicted by agreement with guideline recommendations and self-efficacy. Increasing guideline familiarity alone may have limited patient outcomes, as other barriers, such as low confidence and outcome expectancy, are more likely to impact guideline adherence.

Functional comparison of unilateral versus bilateral lung volume reduction surgery

BACKGROUND Lung volume reduction surgery (LVRS) has shown early promise as a palliative therapy in severe emphysema. A number of patients, however, are not candidates for a bilateral operation, or exhibit a predominantly unilateral disease distribution. METHODS Over 20 months, we performed LVRS in 92 patients selected on the basis of severe hyperinflation with air trapping, diaphragmatic dysfunction, and disease heterogeneity. Twenty-eight patients underwent unilateral LVRS on the basis of asymmetric disease distribution, prior thoracic operation, or concomitant tumor resection. RESULTS Unilateral LVRS resulted in comparable improvements in exercise capacity and dyspnea as the bilateral procedure, with a similar perioperative mortality and actuarial survival to 24 months. Improvements in spirometric indices of pulmonary function, however, were less in patients undergoing unilateral than bilateral LVRS. CONCLUSIONS In properly selected patients, unilateral LVRS provides functional and subjective benefits of comparable magnitude to those associated with a bilateral operation. Unilateral LVRS is therefore an option in the therapy of end-stage emphysema in patients with asymmetric disease distribution, a prior thoracic operation, or contraindications to sternotomy, and may have a role as a bridge to transplantation in selected cases.

Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial.

Abstract Rationale: Pulmonary hypertension with exercise is common in chronic obstructive pulmonary disease (COPD) and may contribute to exercise limitation in this disease. We aimed to determine the effects of treatment with sildenafil on exercise capacity in patients with COPD and emphysema. Methods: We performed a randomized, double-blind, placebo-controlled 2-period crossover trial of sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without pulmonary hypertension. We randomized study participants to 4 weeks of sildenafil (or placebo) followed by a 1-week washout and then 4 weeks of placebo (or sildenafil). The 2 primary outcomes were the 6-minute walk distance and oxygen consumption at peak exercise. Results: Sildenafil had no effect on 6-minute walk distance (placebo-corrected difference = -7.8 m, 95% confidence interval, -23.2 to 7.5 m, p = 0.35) or oxygen consumption at peak exercise (placebo-corrected difference = -0.1 ml/kg/min, 95% confidence interval -2.1 to 1.8 ml/kg/min, p = 0.89). Sildenafil increased the alveolar-arterial oxygen gradient (p = 0.02), worsened symptoms (p = 0.04), and decreased quality-of-life (p = 0.03). Adverse events were more frequent while receiving sildenafil (p = 0.005). Conclusions: Routine sildenafil administration did not have a beneficial effect on exercise capacity in patients with COPD and emphysema without pulmonary hypertension. Sildenafil significantly worsened gas exchange at rest and quality of life. (clinicaltrials.gov NCT00104637).

Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry

Objectives We sought to describe the characteristics of adult patients with bronchiectasis enrolled in the US Bronchiectasis Research Registry (BRR). Methods The BRR is a database of patients with non‐cystic‐fibrosis bronchiectasis (NCFB) enrolled at 13 sites in the United States. Baseline demographic, spirometric, imaging, microbiological, and therapeutic data were entered into a central Internet‐based database. Patients were subsequently analyzed by the presence of NTM. Results We enrolled 1,826 patients between 2008 and 2014. Patients were predominantly women (79%), white (89%), and never smokers (60%), with a mean age of 64 ± 14 years. Sixty‐three percent of the patients had a history of NTM disease or NTM isolated at baseline evaluation for entry into the BRR. Patients with NTM were older, predominantly women, and had bronchiectasis diagnosed at a later age than those without NTM. Gastroesophageal reflux disease (GERD) was more common in those with NTM, whereas asthma, primary immunodeficiency, and primary ciliary dyskinesia were more common in those without NTM. Fifty‐one percent of patients had spirometric evidence of airflow obstruction. Patients with NTM were more likely to have diffusely dilated airways and tree‐in‐bud abnormalities. Pseudomonas and Staphylococcus aureus isolates were cultured less commonly in patients with NTM. Bronchial hygiene measures were used more often in those with NTM, whereas antibiotics used for exacerbations, rotating oral antibiotics, steroid use, and inhaled bronchodilators were more commonly used in those without NTM. Conclusions Adult patients with bronchiectasis enrolled in the US BRR are described, with differences noted in demographic, radiographic, microbiological, and treatment variables based on stratification of the presence of NTM.

Expression of Egr-1 in Late Stage Emphysema

The transcription factor early growth response (Egr)-1 is an immediate-early gene product rapidly and transiently expressed after acute tissue injury. In contrast, in this report we demonstrate that lung tissue from patients undergoing lung reduction surgery for advanced emphysema, without clinical or anatomical evidence of acute infection, displays a selective and apparently sustained increase in Egr-1 transcripts and antigen, compared with a broad survey of other genes, including the transcription factor Sp1, whose levels were not significantly altered. Enhanced Egr-1 expression was especially evident in smooth muscle cells of bronchial and vascular walls, in alveolar macrophages, and some vascular endothelium. Gel shift analysis with (32)P-labeled Egr probe showed a band with nuclear extracts from emphysematous lung which was supershifted with antibody to Egr-1. Egr-1 has the capacity to regulate genes relevant to the pathophysiology of emphysema, namely those related to extracellular matrix formation and remodeling, thrombogenesis, and those encoding cytokines/chemokines and growth factors. Thus, we propose that further analysis of Egr-1, which appears to be up-regulated in a sustained fashion in patients with late stage emphysema, may provide insights into the pathogenesis of this destructive pulmonary disease, as well as a new facet in the biology of Egr-1.

Interventions to Reduce Rehospitalizations after Chronic Obstructive Pulmonary Disease Exacerbations. A Systematic Review

RATIONALE Approximately 20% of patients hospitalized for COPD exacerbations in the United States will be readmitted within 30 days. The Centers for Medicare and Medicaid Services has recently proposed to revise the Hospital Readmissions Reduction Program to financially penalize hospitals with high all-cause 30-day rehospitalization rates after a hospitalization for COPD exacerbation on or after October 1, 2014. OBJECTIVES To report the results of a systematic review of randomized clinical trials evaluating interventions to reduce the rehospitalizations after COPD exacerbations. METHODS Multiple electronic databases were systematically searched to identify relevant studies published between January 1966 and June 2013. Titles, abstracts, and, subsequently, full-text articles were assessed for eligibility. Each study was appraised using predefined criteria. MEASUREMENTS AND MAIN RESULTS Among 913 titles and abstracts screened, 5 studies (1,393 participants) met eligibility criteria. All studies had a primary outcome of rehospitalization at 6 or 12 months. No study examined 30-day rehospitalization as the primary outcome. Each study tested a different set of interventions. Two studies (one conducted in Canada and one conducted in Spain and Belgium) showed a decrease in all-cause rehospitalization over 12 months in the intervention group versus comparator group (mean number of hospitalizations per patient, 1.0 vs. 1.8; P = 0.01; percent hospitalized, 45 vs. 67%; P = 0.028; respectively). The only study conducted in the United States found a greater than twofold higher risk of mortality in the intervention group (17 vs. 7%, P = 0.003) but no significant difference in rehospitalizations. It was unclear which set of interventions was effective or harmful. CONCLUSIONS The evidence base is inadequate to recommend specific interventions to reduce rehospitalizations in this population and does not justify penalizing hospitals for high 30-day rehospitalization rates after COPD exacerbations.

Adult Bronchiectasis Patients: A First Look at the United States Bronchiectasis Research Registry.

Objectives We sought to describe the characteristics of adult patients with bronchiectasis enrolled in the US Bronchiectasis Research Registry (BRR). Methods The BRR is a database of patients with non‐cystic‐fibrosis bronchiectasis (NCFB) enrolled at 13 sites in the United States. Baseline demographic, spirometric, imaging, microbiological, and therapeutic data were entered into a central Internet‐based database. Patients were subsequently analyzed by the presence of NTM. Results We enrolled 1,826 patients between 2008 and 2014. Patients were predominantly women (79%), white (89%), and never smokers (60%), with a mean age of 64 ± 14 years. Sixty‐three percent of the patients had a history of NTM disease or NTM isolated at baseline evaluation for entry into the BRR. Patients with NTM were older, predominantly women, and had bronchiectasis diagnosed at a later age than those without NTM. Gastroesophageal reflux disease (GERD) was more common in those with NTM, whereas asthma, primary immunodeficiency, and primary ciliary dyskinesia were more common in those without NTM. Fifty‐one percent of patients had spirometric evidence of airflow obstruction. Patients with NTM were more likely to have diffusely dilated airways and tree‐in‐bud abnormalities. Pseudomonas and Staphylococcus aureus isolates were cultured less commonly in patients with NTM. Bronchial hygiene measures were used more often in those with NTM, whereas antibiotics used for exacerbations, rotating oral antibiotics, steroid use, and inhaled bronchodilators were more commonly used in those without NTM. Conclusions Adult patients with bronchiectasis enrolled in the US BRR are described, with differences noted in demographic, radiographic, microbiological, and treatment variables based on stratification of the presence of NTM.

Sarcoidosis-Associated Fibrosing Mediastinitis with Resultant Pulmonary Hypertension: A Case Report and Review of the Literature

Pulmonary hypertension, a common manifestation of advanced sarcoidosis, is thought to result from fibrosis with chronic hypoxia and destruction of small vessels, extrinsic compression of pulmonary arteries, or granulomatous vasculitis. We report a case of sarcoidosis-associated pulmonary hypertension due to fibrosing mediastinitis. Our patient presented with cough and dyspnea on exertion and was found to have pulmonary artery enlargement, pulmonary venous compression, and mediastinal soft tissue enhancement on magnetic resonance imaging. Pulmonary hypertension was confirmed by right heart catheterization and sarcoidosis was diagnosed by histologic examination of tissue obtained at mediastinoscopy. Treatment with steroids resulted in decreased pulmonary artery pressures as well as symptomatic improvement. While pulmonary hypertension is a common complication of sarcoidosis, fibrosing mediastinitis is an unusual etiology that should be considered by clinicians.