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Biomedical subjects

Masaharu Nishimura

Publications and source records attributed to Masaharu Nishimura.

At least 55 records · Page 3Linked to original sources
PubMed2005

Patterns of care for COPD by Japanese physicians.

OBJECTIVE: COPD treatment guidelines are available worldwide, yet it is not known how widely they are followed. This study evaluated the clinical care of COPD patients in Japan as compared to guideline recommendations. METHODS: A sample of general and specialist physicians was selected from private outpatient clinics and public hospitals in Japan. Physicians were provided two clinical vignettes (COPD and asthma) and asked to make a diagnosis. They were next asked to define diagnostic tests and treatment recommendations specifically for a COPD patient. Responses were compared to recommendations from current COPD guidelines. RESULTS: For the COPD unknown vignette, 6.2% of physicians diagnosed COPD while 54% diagnosed chronic bronchitis or emphysema. For COPD diagnosis, 81.9% of physicians recommended a CXR, 49.1% spirometry, and 17.7% a computed tomography scan. The most frequently recommended medication for a newly diagnosed COPD patient was theophylline (37.2%) followed by expectorants (32.1%) and inhaled anticholinergics (25.9%). Inhaled beta-agonists were recommended by fewer than 20% of all physicians. CONCLUSION: Care for COPD patients by selected Japanese physicians diverges from published practice guidelines. COPD is an infrequently used diagnostic label; diagnostic evaluation is characterized by a high use of computed tomography scans, particularly by specialists; and bronchodilator use was low.

Ambulatory Care Facilities↗
PubMed2005

Small cell carcinoma of the lung exclusively localized within the left descending pulmonary artery.

We encountered a 69-year-old woman displaying a filling defect within the left descending pulmonary artery (PA) on a chest CT scan and pulmonary angiography. A subsequent 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan demonstrated focal uptake in the left hilum. A cytologic examination of transbronchial needle aspiration specimens revealed small cell carcinoma. The patient underwent concurrent radiation therapy and chemotherapy with cisplatin and etoposide, resulting in tumor shrinkage and recanalization of the involved PA. This is the first case of small cell carcinoma localized exclusively within the PA, and positive findings on FDG-PET facilitated the unexpected diagnosis.

Aged↗
PubMed2005

Transbronchial biopsy using endobronchial ultrasonography with a guide sheath and virtual bronchoscopic navigation.

STUDY OBJECTIVES: We evaluated the feasibility, safety, and efficacy of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS) and virtual bronchoscopy (VB) navigation for small peripheral pulmonary lesions < or = 30 mm in diameter. DESIGN: Pilot study. SETTING: A national university hospital. PATIENTS: We performed TBB using EBUS-GS with VB navigation for 29 patients with 30 small peripheral pulmonary lesions (average diameter, 18.6 mm) between January 1, 2004, and August 31, 2004. INTERVENTIONS: VB images were reconstructed from helical CT data. TBB was then performed using EBUS-GS with VB navigation. RESULTS: In all patients, TBB was performed safely with no complications. Bronchi seen on VB imaging were highly consistent with the actual structures confirmed using fiberoptic bronchoscopy. Following VB navigation, the endobronchial ultrasonography (EBUS) probe was inserted into third- to sixth-generation bronchi. Twenty-four lesions (80%) were visualized on EBUS images. Average durations of the initial EBUS examination of lesions, first biopsy, and the total procedure were 9.56 min, 11.99 min, and 25.72 min, respectively. Nineteen lesions (63.3%) were diagnosed from histopathologic or cytologic examination. Diagnostic sensitivities were 44.4% (8 of 18) for lesions < 20 mm in mean diameter and 91.7% (11 of 12) for lesions 20 to 30 mm in mean diameter. CONCLUSIONS: In summary, TBB using EBUS-GS with VB navigation was safely performed and was effective in diagnosing small peripheral pulmonary lesions.

Adult↗
PubMed2005

Enhanced expression of interleukin-18 receptor alpha chain by CD4+ T cells in sarcoidosis.

STUDY OBJECTIVES: To investigate the expression of interleukin-18 receptor alpha chain (IL-18Ralpha) in BAL and peripheral blood (PB) T cells in patients with sarcoidosis compared with control subjects, to evaluate the relationship between the expression and clinical manifestations, and to clarify the mechanisms of altered expression. SUBJECTS AND METHODS: The study subjects consisted of 21 patients with sarcoidosis and 8 normal control subjects. The expression of IL-18Ralpha was examined by flow cytometry. RESULTS: The proportions of BAL CD4+ and PB CD4+ T cells expressing IL-18Ralpha were significantly increased in patients with sarcoidosis compared to control subjects. BAL CD4+ T cells expressed IL-18Ralpha in a higher proportion than did paired CD8+ T cells in patients with sarcoidosis but not in control subjects. Greater proportions of BAL CD4+ T cells and BAL CD8+ T cells than of their PB counterparts expressed IL-18Ralpha in both patients and control subjects. CD4+ T cells were more sensitive to the induction of IL-18Ralpha by cytokines in vitro, such as interleukin (IL)-2, IL-12, and tumor necrosis factor-alpha than were CD8+ T cells. Increased expression of IL-18Ralpha by BAL T cells commonly observed in patients and control subjects was associated with the expansion of CD45RO+ cells in BAL T cells. However, there were no significant correlations between the expression of IL-18Ralpha by any cell populations and BAL findings, serum angiotensin-converting enzyme activities, radiograph stages, or clinical courses. CONCLUSION: The overexpression of IL-18Ralpha predominantly by CD4+ T cells in sarcoidosis emphasizes crucial roles played by T-helper type 1 cells in the IL-18/IL-18Ralpha system in sarcoidosis.

Bronchoalveolar Lavage Fluid↗
PubMed2005

Clinical efficacy and safety of transdermal tulobuterol in the treatment of stable COPD: an open-label comparison with inhaled salmeterol.

BACKGROUND: Long-acting bronchodilators are recommended for the management of stable COPD to relieve symptoms and improve quality of life. The tulobuterol patch (Hokunalin) is a transdermal patch preparation of the beta2-adrenoceptor agonist (beta2-agonist) tulobuterol designed to yield sustained beta(2)-agonistic effects for 24 hours when applied once daily. OBJECTIVE: To compare the effectiveness of tulobuterol patch and inhaled salmeterol (Serevent Diskus) in the treatment of stable COPD. STUDY DESIGN: Clinically stable COPD patients (age > or = 40 years, postbronchodilator FEV1/FVC <70%, and postbronchodilator FEV1 <80% predicted) were enrolled in a multicenter, open-label randomized study. After a 2-week run-in period, patients were administered either tulobuterol (2mg once-daily applied as a patch) or salmeterol (50 microg per inhalation, twice a day) for 12 weeks. RESULTS: Data for 92 patients (46 each for each treatment group) were analyzed. There were no significant differences in baseline characteristics in the tulobuterol versus salmeterol groups: age, 69.2 +/- 7.4 vs 71.6 +/- 7.3 years; male, 91% versus 96%; and patients with stage II (III) COPD, 32.6% (67.4%) versus 50% (50%). FEV1, FVC, and PEF improved during treatment in both groups compared with baseline, with no significant between group differences. The total St George's Respiratory Questionnaire (SGRQ) score was significantly improved relative to baseline in the tulobuterol group at 8 weeks (-4.7 units [U]), but not in the salmeterol group at all timepoints. Domain analysis of the SGRQ scores revealed significant improvement in the symptom score relative to baseline in the tulobuterol group at weeks 4 (-6.9U), 8 (-12.0U), and 12 (-11.7U), but not in the salmeterol group in any of the domains tested. Medical Research Council dyspnea scale score improved during treatment in both groups, with no significant differences between groups. Compliance with the treatment regimen was significantly better in the tulobuterol than in the salmeterol group (98.5% vs 94.1%; p < 0.05). CONCLUSION: These findings indicate that once-daily transdermal sustained-release tulobuterol is as effective or better than the inhaled long-acting beta2-agonist salmeterol in the management of stable COPD, with significant effects on quality of life.

Administration, Cutaneous↗
PubMed2005

Pleural involvement of dialysis-related amyloidosis.

Two cases of pleural involvement of dialysis-related amyloidosis (DRA) with pleural effusion are presented. DRA is one of the most important complications in long-term dialysis patients and beta2-microglobulin is the principal protein component of DRA, but pleural deposition of beta2-microglobulin amyloid has not yet been reported. To the best of the authors' knowledge, this is the first case report of pleural involvement of DRA presenting with pleural effusion. This case study suggests that pleural involvement of DRA should be considered when exudative pleural effusion is observed in patients undergoing long-term dialysis.

Aged↗
PubMed2005

Clinical significance of the expression of tumor-associated antigen, RCAS1, and its soluble protein in pleural fluid in malignant mesothelioma.

RCAS1 is a type II membrane protein which is also secreted as a soluble protein. RCAS1 may play a role in evading immune surveillance by tumor cells and be responsible for the aggressive behavior of tumors. We examined the usefulness of RCAS1 in the follow-up of malignant mesothelioma. In addition, we examined the usefulness of its soluble protein (sRCAS1) in pleural effusion for the diagnosis of malignant mesothelioma. We studied 38 patients with pleural malignant mesothelioma and examined the correlation between RCAS1 expression, clinicopathologic variables and overall survival. We also determined the pleural fluid sRCAS1 concentration with an enzyme-linked immunosorbent assay (ELISA). We found that 34 out of 38 (89.5%) malignant mesothelioma cells stained for RCAS1. The positive rate was 90.9% in biphasic type, 78.6% in epithelioid type, and 100% in sarcomatoid type. No statistically significant correlation was observed between RCAS1 expression and gender, age, histology or clinical stage. Interestingly, survival of the malignant mesothelioma patients with RCAS1 expression was significantly increased compared with those without (median survival time: 13.0 vs. 4.3 months, p=0.011). Multivariate analysis of prognostic factors, using the Cox proportional hazards model, revealed that RCAS1 expression had a significantly positive effect on survival. sRCAS1 concentrations in pleural fluid in malignant mesothelioma were lower than those in lung cancer (2.18+/-2.20 vs. 46.3+/-129 U/ml; p=0.019). RCAS1 expression is informative for the follow-up of malignant mesothelioma patients. In addition, sRCAS1 in pleural fluid may be useful for the diagnosis of malignant mesothelioma.

Adult↗
PubMed2005

Roles of functional polymorphisms in the interleukin-18 gene promoter in sarcoidosis.

BACKGROUND AND AIM OF THE WORK: Interleukin (IL)-18 plays important roles in sarcoidosis by inducing interferon-gamma in synergy with IL-12. Results of case-control studies on the association between sarcoidosis and single nucleotide polymorphisms (SNPs) in the IL-18 gene promoter are conflicting. We reexamined the association and evaluated the clinical significance of the SNPs in sarcoidosis. METHODS: Genotyping of three SNPs, -137 G/C, -607 C/A, and -656 G/T, in the IL-18 gene promoter was performed in 161 patients with sarcoidosis and 176 healthy controls using the amplification refractory mutation system. Promoter activities were examined by a dual luciferase assay system in a cell line, THP-1. RESULTS: There was no significant difference in the genotype distribution or allele frequency of all three SNPs between controls and patients with sarcoidosis. However, -607 C/A and -656 G/T were significantly associated with serum levels of IL-18 in patients with sarcoidosis, but not in controls. The promoter activity of the haplotype -137G/-607C/-656G, one of the most common haplotypes, was significantly higher than that of the other common haplotype, -137G/-607A/-656T, accounting for the association between serum IL-18 levels and the SNPs. Meanwhile, there was no strong association between the three SNPs and the clinical phenotypes, such as patient characteristics and clinical courses. CONCLUSIONS: Our results indicate that the differences in the promoter activity according to promoter haplotypes of the IL-18 gene result in an altered protein expression in sarcoidosis. However, it is unlikely that the three SNPs examined confer susceptibility to sarcoidosis.

Adolescent↗
PubMed2005

[A case of Clostridium difficile colitis associated with paclitaxel and carboplatin chemotherapy for lung cancer].

A 41-year-old man admitted complaining of dyspnea was found to have lung adenocarcinoma (T4N3M1, stage IV) originating from S1+2. He underwent chemotherapy with carboplatin (CBDCA) and paclitaxel (PTX) and partial remission was obtained. However, on the 11th day of the fourth course of chemotherapy, he developed lower abdominal pain, grade 3 bloody diarrhea and grade 2 vomiting. The stool contained Clostridium difficile (CD) toxin and stool culture revealed C. difficile growth. We diagnosed CD colitis. Fortunately his symptoms recovered by fasting and fluid replacement until the next day. It has been reported that CD colitis occurrs in approximately 2% of patients with gynecological cancers receiving PTX-including chemotherapy. We thus speculate that the CD colitis of the present case was due to PTX. Although the mechanism of CD colitis by chemotherapeutical agents remains undetermined, direct damage to intestinal mucosa or changes in intestinal bacterial flora are possible. As severe CD colitis can be life threatening, we have to be aware of the possibility of it occurring in patients undergoing chemotherapy.

Adenocarcinoma↗
PubMed2004

B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression.

PURPOSE: B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs. EXPERIMENTAL DESIGN: The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically. RESULTS: Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P = 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P = 0.02). CONCLUSIONS: The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.

Adult↗
PubMed2004

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

The inflammatory chemokines interleukin-8, macrophage inflammatory protein-1alpha, 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-1alpha, 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.

Adult↗
PubMed2004

Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and atopy.

Macrophage migration inhibitory factor (MIF) is a pleiotrophic lymphocyte and macrophage cytokine; it is likely to play an important role in innate immunity. Genome-wide search for atopy susceptibility genes recently identified human chromosome 22q11, where the gene encoding MIF resides, as a region of interest for atopic traits. Both the -173G/C and -794 [CATT]5-8 repeat polymorphisms in the MIF promoter region are associated with altered levels of MIF gene transcription in vitro. We, therefore, hypothesized that these potentially functional polymorphisms may influence susceptibility to atopy and asthma. A case-control analysis examined the genetic influence of these promoter polymorphisms on the development of atopy and asthma in a Japanese population (n = 584). Evidence for significant association between the -173G/C and -794 [CATT]5-8 repeat polymorphisms and atopy was found; odds ratio for homozygotes of -173C allele was 3.67 (compared with homozygotes of -173G allele, 95% confidence interval = 1.43-9.46, p < 0.01), and odds ratio for noncarriers of the -794 [5-CATT] allele was 3.51 (compared with 5-CATT repeat homozygotes, 95% confidence interval = 1.82-6.78, p < 0.0005). No associations with asthma were detected. These results indicate that promoter polymorphisms in the MIF promoter region are risk factors for atopy and implicate MIF in the pathogenesis of atopy in a Japanese population.

Adolescent↗
PubMed2004

Improvement of endothelium-dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia.

The purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium-dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol-lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler-wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium-dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 microg/min), and endothelium-independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3-hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 +/- 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 microg/min of acetylcholine increased significantly compared to the pre-apheresis values (from -19.7 +/- 4.8 to -2.9 +/- 3.0% [P < 0.01] and from 80.7 +/- 27.6 to 155.3 +/- 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol.

Acetylcholine↗
PubMed2004

The characteristics of human NKT cells in lung cancer--CD1d independent cytotoxicity against lung cancer cells by NKT cells and decreased human NKT cell response in lung cancer patients.

The activation of human Valpha24+Vbeta11+natural killer T cells (NKT) cells (Valpha24 NKT cells) induces effective antitumor responses with secondary immune effects through activation of conventional T cells and natural killer cells. In this study, we attempted to analyze the characteristics of human NKT cells in lung cancer patients. Valpha24 NKT cells stimulated with alpha-GalCer from healthy volunteers exhibited direct cytotoxic activity against two (RERF-LC-OK and PC-3) of seven human lung cancer cell lines studied. Cytotoxicity by Valpha24 NKT cells against human lung cancer cells was dependent on the perforin pathway and independent of Fas/FasL pathway. Intracellular adhesion molecule (ICAM)-1 expression on tumor cells was clearly associated with the cytotoxicity of Valpha24 NKT cells. On the other hand, the proportion of Valpha24 NKT cells in the patients with lung cancer was lower than that in the healthy volunteers. Furthermore, the proliferative response of Valpha24 NKT cells to alpha-GalCer was significantly lower in the peripheral blood mononuclear cells in the patients with lung cancer. Addition of granulocyte colony-stimulating factor moderately restored the low proliferative response of Valpha24 NKT cells in the patients with lung cancer, however the percentage by which the response was restored in these patients was still lower than the natural response in healthy volunteers. These results suggest that Valpha24 NKT cells may play a pivotal role or the antitumor response in lung cancer.

Adult↗
PubMed2004

Phase I trial of carboplatin and weekly paclitaxel in patients with advanced non-small-cell lung cancer.

OBJECTIVE: This study was designed to determine the maximum tolerated dose of paclitaxel administered weekly in combination with carboplatin and to assess its dose limiting toxicity and preliminary activity in patients with previously untreated, advanced non-small-cell lung cancer. METHODS: Carboplatin was administered at a fixed dose that maintained an area under the curve of 6. Paclitaxel was given over 1 h once a week for 3 weeks starting at 60 mg/m(2) and escalated in 10 mg/m(2) increments. RESULTS: Twenty-one patients were treated with six dose levels (60, 70, 80, 90, 100, 110 mg/m(2)) of paclitaxel. The dose limiting toxicity was infection and the maximum tolerated dose was 110 mg/m(2). Nine of 21 (42.9%) patients demonstrated a therapeutic response. CONCLUSION: Weekly paclitaxel and carboplatin were well tolerated. Based on our results, 100 mg/m(2) of paclitaxel for 3 weeks of a 4-week cycle, in combination with carboplatin, was recommended for a phase II study.

Adenocarcinoma↗
PubMed2004

Expression of RCAS1 in human gastric carcinoma: a potential mechanism of immune escape.

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) inhibits the in vitro growth of receptor-expressing cells and induces apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we investigated RCAS1 expression in gastric cancer and precancerous lesions by immunohistochemical means. We then analyzed the relationship between RCAS1 expression and clinicopathological variables, and examined whether RCAS1 expression is associated with infiltration of tumor-infiltrating lymphocytes (TILs) and apoptosis of TILs. Of 54 gastric cancers analyzed, RCAS1 expression was positive in 52 (96%) of them. The expression pattern of RCAS1 in gastric cancer cells could be classified as granular staining either enriched in the glandular side of the cytoplasm with polarity (P pattern) or scattered diffusely in the cytoplasm and on the cell membranes (D pattern). Nineteen of 39 intestinal-type carcinomas (49%) showed the P pattern, and all of 13 diffuse type carcinomas (100%) showed the D pattern. In contrast, all RCAS1-positive specimens of gastric adenoma and metaplastic mucosa were of the P pattern. The D pattern of gastric cancers was more frequently recognized in carcinomas with large size (P < 0.01), in those with regional lymph node metastasis (P < 0.05) and in those that had invaded beyond the submucosa (P < 0.01), compared with the P pattern. On the same sections, significantly less TILs were identified in RCAS1-positive areas than RCAS1-negative areas. Furthermore, the rate of apoptosis of TILs was significantly higher in RCAS1-positive areas than in RCAS1-negative areas. The expression and distribution of RCAS1 may be involved in malignant transformation, tumor progression, histological type and tumor escape from host immune surveillance in gastric cancer.

Aged↗
PubMed2004

Effect of low-dose theophylline on airway inflammation in COPD.

OBJECTIVE: Recent studies have shown that theophylline may exert anti-inflammatory effects on neutrophils. We undertook to assess the effect of theophylline on airway inflammation in COPD. METHODOLOGY: We performed a 4-week randomized double-blind, placebo-controlled study in 11 theophylline-naive patients with mild to moderate COPD. After a 1-week run-in period, six subjects were administered 400 mg/day theophylline (Theodur; Nikken Chemicals Co. Ltd, Tokyo, Japan) for 4 weeks, while five subjects were administered a placebo. Induced sputum was obtained before and after the run-in period and then after 2 and 4 weeks of treatment. Cell differential count and levels of interleukin-8, matrix metalloproteinase-9, neutrophil elastase (NE), myeloperoxidase (MPO), alpha1-antitrypsin (alpha1-AT), leukotriene B4 and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assessed. RESULTS: No variable was significantly different during the run-in period or with placebo treatment. In contrast, theophylline treatment significantly decreased NE and MPO levels at 4 weeks, although the cell differential count did not change appreciably as a result of treatment. CONCLUSION: These results suggest that 4 weeks of theophylline treatment attenuates neutrophil-associated inflammation in the airways of mild to moderate COPD patients. However, the clinical benefits remain to be determined.

Aged↗