Endobronchial biopsy: a guide for asthma therapy selection in the era of bronchial thermoplasty.

OBJECTIVE: Bronchial thermoplasty (BT) reduces airway smooth muscle in patients with severe asthma. We developed a novel standardized histologic grading system assessing inflammation and structural remodeling on endobronchial biopsy (EBBx) in severe persistent asthma and evaluated airway structure before and after BT. In addition, we correlated invasive and non-invasive inflammatory markers in severe persistent asthma. METHODS: Thirty-three patients with severe persistent asthma underwent bronchoscopy, including bronchoalveolar lavage (BAL) and diagnostic EBBx. The control group (N = 41) underwent EBBx for other clinical indications. Biopsies were graded for airway inflammation and epithelial and submucosal structural features. We also evaluated airway histology in three patients before and after BT. RESULTS: Compared to the control group, patients with severe persistent asthma more often had intraepithelial eosinophils and lymphocytes (67% vs. 17% and 61% vs. 27%; p < .001 and p = .005, respectively) and prominent smooth muscle and goblet cell hyperplasia (88% vs. 29% and 47% vs. 22%, p < .001 and p = .004, respectively). Other features including epithelial denudation and basement membrane thickening were not significantly different. Following BT, airway smooth muscle was no longer prominent due to partial replacement by fibrosis. Increased submucosal eosinophilic inflammation and BAL eosinophilia correlated with exhaled nitric oxide (eNO, p = .05 for both). CONCLUSIONS: We developed a clinically applicable standardized histologic grading system which identified structural but not inflammatory changes before and after BT in severe persistent asthmatics. Additionally, we demonstrated that eNO is representative of submucosal eosinophilia in this population. This semi-quantitative assessment will be useful for practicing pathologists assessing EBBx from severe persistent asthma patients for diagnostic and clinical research purposes.

Teaching the use of respiratory inhalers to hospitalized patients with asthma or COPD: a randomized trial.

BACKGROUND: Hospitalized patients frequently misuse their respiratory inhalers, yet it is unclear what the most effective hospital-based educational intervention is for this population. OBJECTIVE: To compare two strategies for teaching inhaler use to hospitalized patients with asthma or chronic obstructive pulmonary disease (COPD). DESIGN: A Phase-II randomized controlled clinical trial enrolled hospitalized adults with physician diagnosed asthma or COPD. PARTICIPANTS: Hospitalized adults (age 18 years or older) with asthma or COPD. INTERVENTIONS: Participants were randomized to brief intervention [BI]: single-set of verbal and written step-by-step instructions, or, teach-to-goal [TTG]: BI plus repeated demonstrations of inhaler use and participant comprehension assessments (teach-back). MAIN MEASURES: The primary outcome was metered-dose inhaler (MDI) misuse post-intervention (<75% steps correct). Secondary outcomes included Diskus® misuse, self-reported inhaler technique confidence and prevalence of 30-day health-related events. KEY RESULTS: Of 80 eligible participants, fifty (63%) were enrolled (BI n=26, TTG n=24). While the majority of participants reported being confident with their inhaler technique (MDI 70%, Diskus® 94%), most misused their inhalers pre-intervention (MDI 62%, Diskus® 78%). Post-intervention MDI misuse was significantly lower after TTG vs. BI (12.5 vs. 46%, p=0.01). The results for Diskus® were similar and approached significance (25 vs. 80%, p=0.05). Participants with 30-day acute health-related events were less common in the group receiving TTG vs. BI (1 vs. 8, p=0.02). CONCLUSIONS: TTG appears to be more effective compared with BI. Patients over-estimate their inhaler technique, emphasizing the need for hospital-based interventions to correct inhaler misuse. Although TTG was associated with fewer post-hospitalization health-related events, larger, multi-centered studies are needed to evaluate the durability and clinical outcomes associated with this hospital-based education.

The validity of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for identifying patients hospitalized for COPD exacerbations.

BACKGROUND: Acute exacerbations of COPD (AE-COPD) are a leading cause of hospitalizations in the United States. To estimate the burden of disease (eg, prevalence and cost), identify opportunities to improve care quality (eg, performance measures), and conduct observational comparative effectiveness research studies, various algorithms based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes have been used to identify patients with COPD. However, the validity of these algorithms remains unclear. METHODS: We compared the test characteristics (sensitivity, specificity, positive predictive value, and negative predictive value) of four different coding algorithms for identifying patients hospitalized for an exacerbation of COPD with chart review (reference standard) using a stratified probability sample of 200 hospitalizations at two urban academic medical centers. Sampling weights were used when calculating prevalence and test characteristics. RESULTS: The prevalence of COPD exacerbations (based on the reference standard) was 7.9% of all hospitalizations. The sensitivity of all ICD-9-CM algorithms was very low and varied by algorithm (12%-25%), but the negative predictive value was similarly high across algorithms (93%-94%). The specificity was > 99% for all algorithms, but the positive predictive value varied by algorithm (81%-97%). CONCLUSIONS: Algorithms based on ICD-9-CM codes will undercount hospitalizations for AE-COPD, and as many as one in five patients identified by these algorithms may be misidentified as having a COPD exacerbation. These findings suggest that relying on ICD-9-CM codes alone to identify patients hospitalized for AE-COPD may be problematic.

Misuse of respiratory inhalers in hospitalized patients with asthma or COPD.

BACKGROUND: Patients are asked to assume greater responsibility for care, including use of medications, during transitions from hospital to home. Unfortunately, medications dispensed via respiratory inhalers to patients with asthma or chronic obstructive pulmonary disease (COPD) can be difficult to use. OBJECTIVES: To examine rates of inhaler misuse and to determine if patients with asthma or COPD differed in their ability to learn how to use inhalers correctly. DESIGN: A cross-sectional and pre/post intervention study at two urban academic hospitals. PARTICIPANTS: Hospitalized patients with asthma or COPD. INTERVENTION: A subset of participants received instruction about the correct use of respiratory inhalers. MAIN MEASURES: Use of metered dose inhaler (MDI) and Diskus devices was assessed using checklists. Misuse and mastery of each device were defined as <75% and 100% of steps correct, respectively. Insufficient vision was defined as worse than 20/50 in both eyes. Less-than adequate health literacy was defined as a score of <23/36 on The Short Test of Functional Health Literacy in Adults (S-TOFHLA). KEY RESULTS: One-hundred participants were enrolled (COPD n = 40; asthma n = 60). Overall, misuse was common (86% MDI, 71% Diskus), and rates of inhaler misuse for participants with COPD versus asthma were similar. Participants with COPD versus asthma were twice as likely to have insufficient vision (43% vs. 20%, p = 0.02) and three-times as likely to have less-than- adequate health literacy (61% vs. 19%, p = 0.001). Participants with insufficient vision were more likely to misuse Diskus devices (95% vs. 61%, p = 0.004). All participants (100%) were able to achieve mastery for both MDI and Diskus devices. CONCLUSIONS: Inhaler misuse is common, but correctable in hospitalized patients with COPD or asthma. Hospitals should implement a program to assess and teach appropriate inhaler technique that can overcome barriers to patient self-management, including insufficient vision, during transitions from hospital to home.

Hospitalizations for acute exacerbations of chronic obstructive pulmonary disease: how you count matters.

ICD-9-CM diagnosis codes are increasingly used to estimate the burden of disease, as well as to evaluate the quality of care and outcomes of various conditions. Acute exacerbations of COPD (AE-COPD) are common and associated with substantial health and financial burden in the U.S. Whether published algorithms that employ different combinations of ICD-9-CM codes to identify patients hospitalized for AE-COPD yield similar or different estimates of disease burden is unclear. In this study, the Nationwide Inpatient Sample from years 2000-2006 was used to identify and compare the number of hospitalizations, healthcare utilization, and outcomes for patients hospitalized for AE-COPD in the U.S. AE-COPD was identified using five different published ICD-9-CM algorithms. Estimates of the annual number of hospitalizations for AE-COPD in the U.S. varied more than 2-fold (e.g., 421,000 to 870,000 in 2006). Outcomes and healthcare utilization of patients hospitalized for AE-COPD varied substantially, depending on the algorithm used (e.g., in-hospital mortality 2.0% to 5.1%, total hospital days 2.0 to 5.1 million in 2006). Observed trends in the number of hospitalizations over the 7-year period varied depending on which algorithm was used. In conclusion, the estimated health burden and trends in hospitalizations for AE-COPD in the United States differ, depending on which ICD-9-CM algorithm is used. To improve our understanding of the burden of AE-COPD and to ensure that quality of care initiatives are not misdirected, a validated approach to identifying patients hospitalized for AE-COPD is needed.

Impact of burkholderia infection on lung transplantation in cystic fibrosis.

RATIONALE: Lung transplantation offers the only survival option for patients with cystic fibrosis (CF) with end-stage pulmonary disease. Infection with Burkholderia species is typically considered a contraindication to transplantation in CF. However, the risks posed by different Burkholderia species on transplantation outcomes are poorly defined. OBJECTIVES: To quantify the risks of infection with Burkholderia species on survival before and after lung transplantation in patients with CF. METHODS: Multivariate Cox survival models assessed hazard ratios of infection with Burkholderia species in 1,026 lung transplant candidates and 528 lung transplant recipients. Lung allocation scores, incorporating Burkholderia infection status, were calculated for transplant candidates. MEASUREMENTS AND MAIN RESULTS: Transplant candidates infected with different Burkholderia species did not have statistically different mortality rates. Among transplant recipients infected with B. cenocepacia, only those infected with nonepidemic strains had significantly greater post-transplant mortality compared with uninfected patients (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.04-6.12; P = 0.04). Hazards were similar between uninfected transplant recipients and those infected with B. multivorans (HR, 0.66; 95% CI, 0.27-1.56; P = 0.34). Transplant recipients infected with B. gladioli had significantly greater post-transplant mortality than uninfected patients (HR, 2.23; 95% CI, 1.05-4.74; P = 0.04). Once hazards for species/strain were included, lung allocation scores of B. multivorans-infected transplant candidates were comparable to uninfected candidate scores, whereas those of candidates infected with nonepidemic B. cenocepacia or B. gladioli were lower. CONCLUSIONS: Post-transplant mortality among patients with CF infected with Burkholderia varies by infecting species. This variability should be taken into account in evaluating lung transplantation candidates.