Comparison of airway remodelling assessed by computed tomography in asthma and COPD

Background: Few studies have directly compared airway remodelling assessed by computed tomography (CT) between asthma and chronic obstructive pulmonary disease (COPD). The present study was conducted to determine whether there are any differences between the two diseases with similar levels of airflow limitation under clinically stable conditions. Methods: Subjects included older male asthmatic patients (n = 19) showing FEV1/FVC <70% with smoking history less than 5-pack/year. Age- and sex-matched COPD patients (n = 28) who demonstrated similar airflow limitation as asthmatic patients and age-matched healthy non-smokers (n = 13) were recruited. Using proprietary software, eight airways were selected in the right lung, and wall area percent (WA%) and airway luminal area (Ai) were measured at the mid-portion of the 3rd to 6th generation of each airway. For comparison, the average of eight measurements per generation was recorded. Results: FEV1% predicted and FEV1/FVC was similar between asthma and COPD (82.3 ± 3.3% vs. 77.6 ± 1.8% and 57.7 ± 1.6% vs. 57.9 ± 1.4%). At any generation, WA% was larger and Ai was smaller in asthma, both followed by COPD and then controls. Significant differences were observed between asthma and controls in WA% of the 3rd to 5th generation and Ai of any generation airway, while no differences were seen between COPD and controls. There were significant differences in Ai of any generation between asthma and COPD. Conclusions: Airway remodelling assessed by CT is more prominent in asthma compared with age- and sex-matched COPD subjects in the 3rd- to 6th-generation airways when airflow limitations were similar under stable clinical conditions

Time trend of injection drug errors before and after implementation of bar-code verification system

BACKGROUND: Bar-code technology, used for verification of patients and their medication, could prevent medication errors in clinical practice. OBJECTIVE: Retrospective analysis of electronically stored medical error reports was conducted in a university hospital. METHODS: The number of reported medication errors of injected drugs, including wrong drug administration and administration to the wrong patient, was compared before and after implementation of the bar-code verification system for inpatient care. RESULTS: A total of 2867 error reports associated with injection drugs were extracted. Wrong patient errors decreased significantly after implementation of the bar-code verification system (17.4/year vs. 4.5/year, p < 0.05), although wrong drug errors did not decrease sufficiently (24.2/year vs. 20.3/year). The source of medication errors due to wrong drugs was drug preparation in hospital wards. CONCLUSION: Bar-code medication administration is effective for prevention of wrong patient errors. However, ordinary bar-code verification systems are limited in their ability to prevent incorrect drug preparation in hospital wards

Chemokines in bronchiolar epithelium in the development of chronic obstructive pulmonary disease.

The inflammatory chemokines interleukin-8, macrophage inflammatory protein-1, and monocyte chemoattractant protein-1, are reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although bronchiolar epithelial cells and macrophages are known to be the cellular sources, the relative contribution of each cell type remains to be elucidated. In the present study, we first quantified cytokine mRNA in human bronchiolar epithelial cells and macrophages obtained using laser-capture microdissection and explored the relationship with early-stage COPD. Only in bronchiolar epithelial cells were interleukin-8, macrophage inflammatory protein-1, and monocyte chemoattractant protein-1 mRNA levels higher in smokers with airflow limitation and/or emphysema than those in never-smokers or smokers without either airflow limitation or emphysema. No difference was observed in macrophages. Complementary DNA (cDNA) array further revealed the overexpression of CC chemokine receptor 2 in bronchiolar epithelial cells from smokers with airflow limitation and/or emphysema. This study supports the role of bronchiolar epithelium as the source of increased inflammatory chemokine levels in the early development of COPD and also demonstrates the potential use of laser-capture microdissection, combined with reverse transcriptase–polymerase chain reaction and cDNA microarrays, to investigate functional profiles of individual structural and inflammatory cells in human lungs

Airflow limitation and airway dimensions assessed per bronchial generation in older asthmatics

Background: Computed tomography (CT) has been used for non-invasive quantitative assessment of airway dimensions, potentially showing airway remodeling, in asthma. However, most studies have examined either only one airway or only airways in anatomically unidentified cross-sections. Using software capable of precisely identifying the generation of airways and measuring airway dimensions perpendicular to the long axis of airways, we examined, in older patients with stable asthma, how inter-subject variation in airway dimensions correlated among the 3rd to 6th generation of airways, and then examined relationships between airway dimensions of each generation and indices of airflow limitation. Methods: Subjects aged ≥ 55 years old comprised 59 asthmatic patients who underwent CT and pulmonary function tests on the same day. We measured airway wall area (WA%) and inner luminal area (Ai) from the 3rd to the 6th generation of eight bronchi in the right lung. Results: Excellent correlations were identified for both WA% and Ai among the generations (r = 0.744-0.930 for WA%) when we took the average of all measured bronchi per generation as a personal representative value. Significant correlations of airflow limitation indices with both WA% and Ai/BSA were found at each of the 3rd to 6th generations with similar correlation coefficients (WA% for FEV1%predicted, r = -0.410 to -0.556). Conclusions: In older patients with stable asthma, airway wall thickening and narrowing might occur in a parallel manner through 3rd to 6th generation airways. Airway dimensions at these areas of airways may thus have significant and similar correlations with indices of airflow limitation

Extracellular matrix metalloproteinase inducer is increased in smokers' bronchoalveolar lavage fluid.

Extracellular matrix metalloproteinase inducer (EMMPRIN), also called basigin, is present in the lung during development, but its expression in normal adult lung is minimal. Increases of EMMPRIN have been found in various forms of experimental lung injury. To determine whether EMMPRIN might be involved in alveolar injury/repair associated with smoking, we developed an ELISA for EMMPRIN and applied it to bronchoalveolar lavage fluids from never-smokers (n = 7), former smokers (n = 16), and current smokers (n = 58). The smoker groups included subjects with emphysema, as determined by high-resolution chest computed tomography. EMMPRIN levels were significantly elevated in current and former smokers (315 ± 20 and 175 ± 15 pg/ml SEM, respectively, compared with 31 ± 7 pg/ml in never-smokers), but the EMMPRIN levels of smokers with emphysema were not different from smokers without emphysema. Immunohistochemistry of smokers' lung tissue showed EMMPRIN in bronchiolar epithelium and alveolar macrophages, but EMMPRIN mRNA in alveolar macrophages was not different between current and never-smokers. Matrix metalloproteinase-1 was also detectable in the bronchoalveolar lavage fluid from some smokers but not in never-smokers. These findings indicate that smoking is associated with increased intrapulmonary EMMPRIN. Whether EMMPRIN is involved in smoking-induced lung pathology remains to be determined

A Case of Follicular Bronchiolitis Associated with Asthma, Eosinophilia, and Increased Immunoglobulin E

A 49-year-old woman, who had been diagnosed with asthma, showed a bilateral diffuse pattern of small centrilobular nodules on CT. Laboratory data revealed peripheral eosinophilia and a marked increase in total serum IgE levels. The nodules detected on CT were initially considered to be associated with bronchiolar infiltration of eosinophils. Pathological findings from thoracoscopy revealed infiltration of eosinophils into the airway lumen and walls, goblet cell hyperplasia, and thickening of the basement membrane in large bronchi, consistent with asthma. However, hyperplastic lymphoid follicles with reactive germinal centers were observed along the bronchioles. The follicles had no evidence of monoclonality suggested by immunohistological analysis, and no remarkable infiltrates of eosinophils, suggesting follicular bronchiolitis. After treatment with prednisolone, the small diffuse nodules improved markedly, and peripheral eosinophilia and total serum IgE levels also decreased. To the best of our knowledge, this is the first documented case report of follicular bronchiolitis associated with asthma, eosinophilia, and elevated IgE with a definite pathophysiological diagnosis

Levels of Transferrin in Bronchoalveolar Lavage Fluid in Sarcoidosis

There has been only one report showing high levels of transferrin (Tf) in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. The aim of this study is to assess the levels of Tf in both BALF and serum and to examine the relationship between the levels of Tf and other disease markers in sarcoidosis. Subjects were 64 sarcoidosis and 10 healthy controls. Tf in BALF and serum was measured by nephelometric assay. Median Tf levels in BALF from sarcoidosis was 0.70 mg/dl (range, 0.00-3.97), which was significantly higher when compared with controls (0.36 mg/dl; range, 0.00-1.02) (p = 0.005). In contrast, median Tf levels in serum from sarcoidosis was 258 mg/dl (range, 171-383), which was significantly lower when compared with controls (322 mg/dl; range, 234-356) (p = 0.003). Tf levels in BALF were significantly correlated with both the percentage of lymphocytes (r = 0.617, p = 0.001) and serum angiotensin-converting enzyme activity (r = 0.363, p = 0.003) and serum soluble interleukin-2 receptor (r = 0.450, p = 0.001) in sarcoidosis. Levels of Tf in BALF from patients with sarcoidosis were not influenced by smoking status. The levels of Tf in sarcoidosis are high in BALF, but low in serum. Increased levels of Tf in BALF may reflect the disease activity

Extracellular matrix metalloproteinase inducer in interstitial pneumonias.

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycosylated transmembrane protein that induces matrix metalloproteinases (MMPs), is minimally expressed in the normal adult lung. We previously reported that it is up-regulated in murine bleomycin–induced lung injury. In this study, we determined the expression of EMMPRIN and its association with MMP-2, MMP-7, and MMP-9 in interstitial pneumonias (IPs). We performed immunohistochemistry for EMMPRIN and MMPs on lung tissue from 22 subjects with various IPs. We did bronchoalveolar lavage (BAL) on 9 of these subjects and 13 others with IPs to measure the soluble EMMPRIN in BAL fluid. For comparison, immunohistochemistry or BAL was done on 14 subjects without IPs. The staining intensity for each protein was scored from 0 to 3 in various epithelial cell types. Soluble EMMPRIN in BAL fluid was measured by an enzyme-linked immunosorbent assay. Extracellular matrix metalloproteinase inducer was prominent in abnormal epithelial cells. It was more prominent in hyperplastic type II cells, compared with epithelium in alveolar bronchiolization. It was also elevated in BAL fluid from the subjects with IPs. Matrix metalloproteinases were expressed in cells expressing EMMPRIN, although the profile of MMPs varied among the different abnormal epithelial cell types with MMP-2 and MMP-7 in hyperplastic type II cells and MMP-7 and MMP-9 in cells showing squamous metaplasia and cells comprising bronchiolization. These results suggest a role of EMMPRIN in reepithelialization in IPs