Computed tomography (CT)-assessed bronchodilation induced by inhaled indacaterol and glycopyrronium/indacaterol in COPD.

BACKGROUND: Our previous studies suggested that the site of bronchodilation on CT might differ between inhaled ß2 agonists and inhaled anticholinergics in COPD. AIM: To assess and compare the bronchodilation effects of inhaled indacaterol and glycopyrronium/indacaterol by airway generation in large airways using CT. METHODS: CT scans at full inspiration and pulmonary function tests were done in 25 patients with moderate-severe COPD before and 4-5 weeks after daily inhalation of indacaterol and again another 4-5 weeks after inhalation of glycopyrronium/indacaterol. Airway inner luminal area (Ai) at the 3rd (segmental) to 6th generation of 8 selected bronchi, a total of 32 sites, in the right lung was analyzed on 3 occasions. Our proprietary software enables us to select the same airways and the same measurement sites for comparison, with simultaneous confirmation using two screens on the computer. RESULTS: The overall increase of Ai (ΔAi, %) averaged at all 32 measurement sites induced by glycopyrronium/indacaterol had a significant correlation with FEV1 improvement (r = 0.7466, p < 0.0001). Both ΔAi, % with indacaterol and ΔAi, % with additional glycopyrronium were significant at the 3rd to 6th generations. Remarkable increases in ΔAi, % were found at the 5th and 6th generations in several subjects with indacaterol or additional glycopyrronium. There were no significant site-differences in the bronchodilation pattern caused by indacaterol and by glycopyrronium/indacaterol at any of the 3rd to 6th generations. CONCLUSIONS: Additional bronchodilation with glycopyrronium was demonstrated by CT at the 3rd to 6th generations, with no site-specific differences in bronchodilation between indacaterol and glycopyrronium/indacaterol. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) system (http://www.umin.ac.jp/. ID. UMIN000012043).

Factors Affecting Time to Sputum Culture Conversion in Adults with Pulmonary Tuberculosis: A Historical Cohort Study without Censored Cases.

BACKGROUND: In patients with pulmonary tuberculosis (TB), shortening the time to sputum culture conversion is desirable to reduce the likelihood of mycobacterial transmission. A persistent positive sputum culture after 2 months of treatment is reported to be associated with the presence of cavitation and the extent of disease on chest X-ray, high colony count, diabetes mellitus, and smoking. However, little is known about factors affecting the time to sputum culture conversion. This study was conducted to evaluate factors affecting the time to sputum culture conversion throughout the course of treatment in adults with pulmonary TB. METHODS: This study was performed using a database of the medical records of patients with active pulmonary TB who were treated at Hirakata Kohsai Hospital in Hirakata City, Osaka, Japan, from October 2000 to October 2002. Cox proportional-hazards analysis was used to evaluate factors affecting the time to sputum culture conversion after adjusting for potential confounders. RESULTS: The data of 86 patients with pulmonary TB were analyzed. The median time to sputum culture conversion was 39 days, and the maximum time was 116 days. The Cox proportional-hazards analysis showed that a higher smear grading (HR, 0.40; 95%CI, 0.23-0.71) and a history of ever smoking (HR, 0.48; 95%CI, 0.25-0.94) were associated with delayed sputum culture conversion. CONCLUSION: High smear grading and smoking prolonged the time to sputum culture conversion in adults with pulmonary TB. To effectively control TB, measures to decrease the cigarette smoking rate should be implemented, in addition to early detection and timely anti-TB treatment.

Behavioral Changes in General Practitioners towards Chronic Obstructive Pulmonary Disease Over Five Years: An Observational Study.

OBJECTIVE: Early detection of chronic obstructive pulmonary disease (COPD) is critical for preventing progression; however, the disease is rarely detected in the early stages. One reason for this is that COPD is not generally recognized and diagnosed by general practitioners (GPs). The objective of this study was to observe changes in the knowledge and behavior of GPs regarding the diagnosis and treatment of COPD over a five-year period. METHODS: The surveys were performed using identical and anonymous questionnaires in 2005, 2006 and 2010. During this period, various educational campaigns were conducted. MATERIALS: All members of the Shiga Medical Association working as GPs in Shiga Prefecture. RESULTS: The number of questionnaires collected was 216 of 711, 269 of 731 and 326 of 856, respectively. Throughout the study period, the number of doctors who prescribed inhaled long-acting muscarinic antagonists (LAMAs) significantly increased (p<0.001). However, there were no significant changes in the rate of possession of spirometers or recognition of COPD guidelines. When we focused on the data for internists, the rate of recognition of the guidelines increased significantly (p<0.01), despite a lack of change in the rate of possession of spirometers. Furthermore, the results of the multivariate analysis revealed that increased knowledge concerning COPD was associated with the doctor's specialty, ownership of a spirometer, number of COPD patients attending their clinic and their level of recognition of the guidelines. CONCLUSION: During the study period, the GPs prescribed more inhaled LAMAs. The rate of recognition of COPD guidelines was also increased among internists. Educational campaigns may be more effective if the backgrounds of the GPs are taken into consideration.

A mixed phenotype of airway wall thickening and emphysema is associated with dyspnea and hospitalization for chronic obstructive pulmonary disease.

RATIONALE: Quantitative computed tomography (CT) has been used to phenotype patients with chronic obstructive pulmonary disease (COPD). A mixed phenotype is defined as the presence of both airway wall thickening and emphysema on quantitative CT. Little is known about patients with COPD with the mixed phenotype. OBJECTIVES: To propose a method of phenotyping COPD based on quantitative CT and to compare clinically relevant outcomes between patients with COPD with the mixed phenotype and those with other CT-based phenotypes. METHODS: Each of 427 male smokers (187 without COPD, 240 with COPD) underwent a complete medical interview, pulmonary function testing, and whole-lung CT on the same day. The percentage of low-attenuation volume at the threshold of -950 Hounsfield units (%LAV) and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10) were measured. Patients with COPD were classified into four distinct phenotypes based on the upper limits of normal for %LAV and Pi10, which were derived from the data of smokers without COPD by using quantile regression. MEASUREMENTS AND MAIN RESULTS: Of 240 patients with COPD, 52 (21.7%) were classified as CT-normal phenotype, 39 (16.3%) as airway-dominant phenotype, 103 (42.9%) as emphysema-dominant phenotype, and 46 (19.2%) as mixed phenotype. Patients with COPD with the mixed phenotype were associated with more severe dyspnea than those with each of the remaining CT-based phenotypes (P < 0.01 for all comparisons). The number of hospitalizations for COPD exacerbations during the preceding year was 2.0 to 3.6 times higher in patients with the mixed phenotype than in those with each of the remaining CT-based phenotypes (P < 0.05 for all comparisons). Findings persisted after adjustment for age, pack-years of smoking, smoking status, body mass index, and FEV1. CONCLUSIONS: Patients with COPD with the mixed phenotype are associated with more severe dyspnea and more frequent hospitalizations than those with each of the remaining CT-based phenotypes. Thus, patients with COPD with the mixed phenotype may need more attention and interventions.

Relative contributions of emphysema and airway remodelling to airflow limitation in COPD: Consistent results from two cohorts.

BACKGROUND AND OBJECTIVE: The relative contributions of emphysema and airway remodelling to airflow limitation remain unclear in chronic obstructive pulmonary disease (COPD). We aimed to evaluate the relative contributions of emphysema and airway wall thickness measured by quantitative computed tomography (CT) to the prediction of airflow limitation in two separate COPD cohorts. METHODS: Pulmonary function tests and whole-lung CT were performed in 250 male smokers with COPD, including 167 from University Medical Center at Ho Chi Minh City, Vietnam, and 83 from Shiga University of Medical Science Hospital, Japan. The same CT analysis software was used to measure the percentage of low attenuation volume (%LAV) at the threshold of -950 Hounsfield units and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10). The standardized coefficients in multiple linear regressions were used to evaluate the relative contributions of %LAV and Pi10 to predictions of FEV1 /FVC and FEV1 % predicted. RESULTS: Both %LAV and Pi10 independently predicted either forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC) or FEV1 % predicted (P ≤ 0.001 for all standardized coefficients). However, the absolute values of the standardized coefficients were 2-3 times higher for %LAV than for Pi10 in all prediction models. The results were consistent in the two COPD cohorts. CONCLUSIONS: %LAV predicts both FEV1 /FVC and FEV1 better than Pi10 in patients with COPD. Thus, emphysema may make a greater contribution to airflow limitation than airway remodelling in COPD.

Airway wall area derived from 3-dimensional computed tomography analysis differs among lung lobes in male smokers.

BACKGROUND: It is time-consuming to obtain the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), a comparable index of airway dimensions in chronic obstructive pulmonary disease (COPD), from all airways of the whole lungs using 3-dimensional computed tomography (CT) analysis. We hypothesized that √Aaw at Pi10 differs among the five lung lobes and √Aaw at Pi10 derived from one certain lung lobe has a high level of agreement with that derived from the whole lungs in smokers. METHODS: Pulmonary function tests and chest volumetric CTs were performed in 157 male smokers (102 COPD, 55 non-COPD). All visible bronchial segments from the 3rd to 5th generations were segmented and measured using commercially available 3-dimensional CT analysis software. √Aaw at Pi10 of each lung lobe was estimated from all measurable bronchial segments of that lobe. RESULTS: Using a mixed-effects model, √Aaw at Pi10 differed significantly among the five lung lobes (R(2) = 0.78, P<0.0001). The Bland-Altman plots show that √Aaw at Pi10 derived from the right or left upper lobe had a high level of agreement with that derived from the whole lungs, while √Aaw at Pi10 derived from the right or left lower lobe did not. CONCLUSION: In male smokers, CT-derived airway wall area differs among the five lung lobes, and airway wall area derived from the right or left upper lobe is representative of the whole lungs.

tfdA-like genes in 2,4-dichlorophenoxyacetic acid-degrading bacteria belonging to the Bradyrhizobium-Agromonas-Nitrobacter-Afipia cluster in alpha-Proteobacteria.

The 2,4-dichlorophenoxyacetate (2,4-D)/alpha-ketoglutarate dioxygenase gene (tfdA) homolog designated tfdAalpha was cloned and characterized from 2,4-D-degrading bacterial strain RD5-C2. This Japanese upland soil isolate belongs to the Bradyrhizobium-Agromonas-Nitrobacter-Afipia cluster in the alpha subdivision of the class Proteobacteria on the basis of its 16S ribosomal DNA sequence. Sequence analysis showed 56 to 60% identity of tfdAalpha to representative tfdA genes. A MalE-TfdAalpha fusion protein expressed in Escherichia coli exhibited about 10 times greater activity for phenoxyacetate than 2,4-D in an alpha-ketoglutarate- and Fe(II)-dependent reaction. The deduced amino acid sequence of TfdAalpha revealed a conserved His-X-Asp-X(146)-His-X(14)-Arg motif characteristic of the active site of group II alpha-ketoglutarate-dependent dioxygenases. The tfdAalpha genes were also detected in 2,4-D-degrading alpha-Proteobacteria previously isolated from pristine environments in Hawaii and in Saskatchewan, Canada (Y. Kamagata, R. R. Fulthorpe, K. Tamura, H. Takami, L. J. Forney, and J. M. Tiedje, Appl. Environ. Microbiol. 63:2266-2272, 1997). These findings indicate that the tfdA genes in beta- and gamma-Proteobacteria and the tfdAalpha genes in alpha-Proteobacteria arose by divergent evolution from a common ancestor.