Masamichi Mineshita

Narrow Band Imaging Applied to Pleuroscopy for the Assessment of Vascular Patterns of the Pleura

Background: Narrow band imaging (NBI), which enhances blood vessels, is a new endoscopic technology for diagnosing malignancies, but it has not been investigated for pleuroscopy. Objectives: To evaluate the efficacy of NBI applied to pleuroscopy for detecting malignant lesions by assessing vascular patterns of the pleura. Methods: From May 2006 to September 2008, 45 patients with undiagnosed pleural ef-fusion underwent pleuroscopy using a pleura-videoscope with white light (WL) and NBI under local anesthesia. For this prospective study, 73 biopsy specimens were obtained from sites where images under both WL and NBI were recorded and classified regarding vascular patterns. Results: Of the 73 lesions, WL showed blood vessels in 32 lesions, and NBI in 52 lesions (WL vs. NBI; p = 0.0014). The accuracy, sensitivity and specificity in the detection of irregular vascular patterns, e.g. blood vessels with irregular caliber or punctate vessels indicating malignant lesions, were 60.3, 76.5 and 55.4% in WL, and 80.8, 85.3 and 76.9% in NBI, respectively, resulting in a significant increase in NBI (p = 0.0106 for accuracy and p = 0.0494 for specificity). For flat lesions, NBI revealed a higher accuracy rate (90.6%) in the detection of irregular vascular patterns indicating malignant lesions. Conclusion: Our study demonstrated that NBI applied to pleuroscopy displayed blood vessels significantly better than WL. NBI was useful to detect irregular vascular patterns suggesting malignant lesions, especially for flat lesions. Therefore, NBI was considered useful in the selection of optimal biopsy sites by assessing vascular patterns.

Exhaled Breath Analysis for Lung Cancer Detection Using Ion Mobility Spectrometry

Background Conventional methods for lung cancer detection including computed tomography (CT) and bronchoscopy are expensive and invasive. Thus, there is still a need for an optimal lung cancer detection technique. Methods The exhaled breath of 50 patients with lung cancer histologically proven by bronchoscopic biopsy samples (32 adenocarcinomas, 10 squamous cell carcinomas, 8 small cell carcinomas), were analyzed using ion mobility spectrometry (IMS) and compared with 39 healthy volunteers. As a secondary assessment, we compared adenocarcinoma patients with and without epidermal growth factor receptor (EGFR) mutation. Results A decision tree algorithm could separate patients with lung cancer including adenocarcinoma, squamous cell carcinoma and small cell carcinoma. One hundred-fifteen separated volatile organic compound (VOC) peaks were analyzed. Peak-2 noted as n-Dodecane using the IMS database was able to separate values with a sensitivity of 70.0% and a specificity of 89.7%. Incorporating a decision tree algorithm starting with n-Dodecane, a sensitivity of 76% and specificity of 100% was achieved. Comparing VOC peaks between adenocarcinoma and healthy subjects, n-Dodecane was able to separate values with a sensitivity of 81.3% and a specificity of 89.7%. Fourteen patients positive for EGFR mutation displayed a significantly higher n-Dodecane than for the 14 patients negative for EGFR (p<0.01), with a sensitivity of 85.7% and a specificity of 78.6%. Conclusion In this prospective study, VOC peak patterns using a decision tree algorithm were useful in the detection of lung cancer. Moreover, n-Dodecane analysis from adenocarcinoma patients might be useful to discriminate the EGFR mutation.

Assessing the Site of Maximal Obstruction in the Trachea Using Lateral Pressure Measurement during Bronchoscopy

RATIONALE Lateral airway pressure can provide valuable physiological information during bronchoscopy. OBJECTIVES To evaluate tracheal obstruction during intervention. METHODS To prospectively measure lateral airway pressure during bronchoscopy using a double-lumen catheter in 15 healthy subjects and 30 patients with tracheal obstruction. Pressure difference was used to evaluate the site of maximal obstruction. The angle between pressure recordings on either side of the stenosis was measured simultaneously (pressure-pressure curves) to assess the degree of tracheal obstruction. MEASUREMENTS AND MAIN RESULTS In the experimental study, the angle of the pressure-pressure curve was unaffected by breathing maneuvers whereas the pressure difference was affected. In healthy subjects, no pressure difference between the carina and trachea was observed during tidal breathing, and the angle was close to 45°. In patients with tracheal obstruction, the dyspnea scale, pressure difference, and angle changed significantly beyond 50% obstruction (P<0.0001). After stenting, the pressure difference disappeared and the angle was close to 45°. The degree of tracheal obstruction was significantly correlated with the pressure difference (r=0.83, P<0.0001) and angle (r=-0.84, P<0.0001). The cross-sectional area, dyspnea scale, pulmonary function tests, pressure difference, and the angle significantly improved after procedures (P<0.0001). Responder rates on the modified Medical Research Council Scale were 84.6% for obstructions above 80%, and 58.8% for obstructions between 50 and 80%. CONCLUSIONS The direct measurement of pressure difference and the angle of the pressure-pressure curve represent a new assessment modality for the success of interventional bronchoscopy. Measuring lateral airway pressure could estimate the need for additional procedures better than bronchoscopy alone.

Bronchoscopic interventions for chronic obstructive pulmonary disease

Over the past decade, several non‐surgical and minimally invasive bronchoscopic lung volume reduction (BLVR) techniques have been developed to treat patients with severe chronic obstructive pulmonary disease (COPD). BLVR can be significantly efficacious, suitable for a broad cohort of patients, and associated with a solid safety profile at a reasonable expense. The introduction of BLVR is also expected to accelerate the further development of interventional pulmonology worldwide. Recently, results from clinical studies on BLVR techniques have been published, providing valuable information about the procedures indications, contraindications, patient‐selection criterion and outcomes. BLVR utilizing one‐way endobronchial valves is gaining momentum as an accepted treatment in regular medical practice because of the identification of best responders. Patients with a heterogeneous emphysema distribution and without inter‐lobar collateral ventilation show encouraging results. Furthermore, for patients with collateral ventilation, who are not considered candidates for valve treatment, and for patients with homogeneous emphysema, the introduction of lung volume reduction coil treatment is a promising solution. Moreover, with the development of newer treatment modalities, that is, biochemical sealant and thermal water vapor, the potential to treat emphysema irrespective of collateral flow, may be further increased. Nevertheless, patient selection for BLVR treatment will be crucial for the procedures success and should be performed using a multidisciplinary team approach. Consequently, BLVR needs to be concentrated in high‐volume centres that will offer better quality and experience with treatment challenges and adverse events. This review gives a general overview of BLVR from an expert and scientific perspective.

Assessment of central airway obstruction using impulse oscillometry before and after interventional bronchoscopy

BACKGROUND: Spirometry is used to physiologically assess patients with central airway obstruction (CAO) before and after interventional bronchoscopy, but is not always feasible in these patients, does not localize the anatomic site of obstruction, and may not correlate with the patients functional impairment. Impulse oscillometry may overcome these limitations. We assessed the correlations between impulse oscillometry measurements, symptoms, and type of airway narrowing, before and after interventional bronchoscopy, and whether impulse oscillometry parameters can discriminate between fixed and dynamic CAO. METHODS: Twenty consecutive patients with CAO underwent spirometry, impulse oscillometry, computed tomography, dyspnea assessment, and bronchoscopy, before and after interventional bronchoscopy. The collapsibility index (the percent difference in airway lumen diameter during expiration versus during inspiration) was calculated using morphometric bronchoscopic images during quiet breathing. Variable CAO was defined as a collapsibility index of > 50%. Fixed CAO was defined as a collapsibility index of < 50%. The degree of obstruction was analyzed with computed tomography measurements. RESULTS: After interventional bronchoscopy, all impulse oscillometry measurements significantly improved, especially resistance at 5 Hz, which decreased from 0.67 ± 0.29kPa/L/s to 0.38 ± 0.17kPa/L/s (P < .001), and reactance at 20 Hz, which increased from –0.09 ± 0.11 to 0.03 ± 0.08 (P < .001). Changes in dyspnea score correlated with resistance at 5 Hz, the difference between the resistance at 5 Hz and the resistance at 20 Hz, and the reactance at 5 Hz, but not with spirometry measurements. The type of obstruction also correlated with dyspnea score, and showed distinct impulse oscillometry measurements. CONCLUSIONS: Impulse oscillometry measurements correlate with symptom improvements after interventional bronchoscopy. Impulse oscillometry might be useful to discriminate variable from fixed central airway obstruction. (University Hospital Medical Information Network, http://www.umin.ac.jp/english, ID000005322).

Cell therapy with adipose tissue-derived stem/stromal cells for elastase-induced pulmonary emphysema in rats

AIMS The purpose of this study was to elucidate the mechanism underlying the effects of adipose tissue-derived stem/stromal cell (ASC) transplantation on porcine pancreatic elastase-induced emphysema. MATERIALS & METHODS ASCs (2.5 × 10(6)) were transplanted into pancreatic elastase (250 U/kg)-treated rats, after which gas exchange and growth factor/cytokine levels in lung tissue were determined. RESULTS ASC transplantation restored pulmonary function (arterial oxygen tension and alveolar-arterial oxygen tension difference) almost to that of normal animals. Enlargement of the alveolar airspaces was inhibited. HGF and CINC-1 levels were significantly higher in the ASC group even at 2 weeks after transplantation. Sponge implantation with CINC-1 induced neovascular formation with increased HGF. In vitro secretion of HGF and CINC-1 from ASCs was promoted in the presence of IL-1β. CONCLUSION Not only HGF, but also CINC-1, secreted from transplanted and viable ASCs presumably contributed to lung repair through angiogenesis.

Effects of Bronchodilators on Regional Lung Sound Distribution in Patients with Chronic Obstructive Pulmonary Disease

Background: Bronchodilators have been reported to influence regional lung ventilation in patients with chronic obstructive pulmonary disease (COPD), which may change regional lung sound distribution. Vibration response imaging (VRI) is a lung imaging system for the assessment of breath sounds. Objective: To evaluate the effects of a short-acting β2-agonist (SABA) on the regional distribution of lung sounds in COPD patients. Methods: A double-blind crossover trial was performed to compare the treatment of COPD patients with an SABA (20 µg of inhaled procaterol) versus a placebo. The percentage of regional lung sound energy [quantitative lung data (QLD)] was evaluated with VRI. VRI, spirometry, and impulse oscillometry (IOS) were performed immediately before and 30 min after SABA administration. Results: Ten male patients (69.6 ± 14.2 years of age, percentage predicted forced expiratory volume in 1 s: 43.8 ± 16.9%) were evaluated. The use of an SABA produced significant functional improvements in the spirometric and IOS measurements. Among the homogeneous emphysema patients (n = 7), the upper-lung QLD decreased (from 24.2 ± 5.8 to 18.8 ± 6.1%, p < 0.05) and the lower-lung QLD increased (from 37.9 ± 12.7 to 46.1 ± 14.3%, p < 0.05) following SABA inhalation. However, the significant redistribution of the regional lung QLD to the lower-lung field was not observed in 2 of the 3 inhomogeneous emphysema patients. Conclusion: The additional use of an SABA by COPD patients improved their pulmonary function, which was accompanied by changes in regional lung air flow. The distribution of emphysematous lesions and the bronchial reactivity to SABA appeared to affect the redistribution of the lung sounds following bronchodilator administration.

IgG4-related pleural disease presenting as a massive bilateral effusion.

A 74-year-old woman with massive bilateral pleural effusion, which was exudative in nature, and with mononuclear cell predominance underwent a pleuroscopy. Parietal pleura were thickened and partly reddish in color. Biopsy specimens taken from the parietal pleura revealed lymphoplasmacytic inflammation with fibrosis. As her performance status rapidly worsened with thoracentesis, we performed bilateral pleurodesis using talc. Pathologic evaluation of the pleural biopsy specimen with immunohistochemical staining revealed 91 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of 91%. Thus, the diagnosis of pleuritis from IgG4-related disease was established. Our case suggests that IgG4-related disease is one of the causes of pleural effusion, and it should be included in the differential diagnosis of unexplained pleuritis.

Clinical application of virtual bronchoscopic navigation system for peripheral lung lesions.

Transbronchial lung biopsy is an indispensable method for the diagnosis of peripheral lung lesions; however, the diagnostic yield still remains unsatisfactory. Endobronchial ultrasound with guide sheath (EBUS-GS) is an excellent method for the decision of biopsy points and has contributed to improvements in diagnostic yield, but the decision of choosing the proper bronchus depends on the individual ability of each bronchoscopist. To clarify the usefulness of the virtual bronchoscopic navigation system (VBN), we evaluated the diagnostic yield and time required to determine the target lesion. Fifty-seven cases using EBUS-GS with VBN (VBN/EBUS-GS group) and 55 cases using EBUS-GS (EBUS-GS group) were compared. In the VBN/EBUS-GS group, computer software detects the air density in the bronchi from the computed tomography image and imports a detailed virtual Bronchoscopic Image. After inserting the starting position and the peripheral target lesion, the software depicts the most ideal route to the target lesion during the bronchoscopic procedure. EBUS is then used to confirm the accuracy of the route. Diagnostic yield was 84.2% for the VBN/EBUS-GS group and 80.0% for EBUS-GS group. The required time to determine the biopsy position was significantly less in the VBN/EBUS-GS group (5.54±0.57 min in VBN/EBUS-GS group vs. 9.27±0.86 min in EBUS-GS group, P<0.01). In conclusion, VBN proved useful in shortening the time needed to determine the biopsy position.

Airway measurements in tracheobronchial stenosis using endobronchial ultrasonography during stenting.

Purpose To assess airway measurements, endobronchial ultrasonography (EBUS) and multidetector, row computed tomography (MDCT) images were compared in patients with tracheal stenosis. Methods Airway stenting was performed on 31 patients, 25 malignant and 6 benign. EBUS and MDCT images were compared before intervention to assess the degree of airway narrowing at 212 sites. Of these, 130 sites were considered normal and 82 abnormal. For malignant stenosis, airway measurements were taken at 160 sites including 112 normal and 48 abnormal. For benign stenosis, airway measurements were taken at 52 sites including 18 normal and 34 abnormal. This technique enables the EBUS probe to measure the distal end to the proximal end of the stenosis whereby the inflated balloon size changes according to the degree of stenosis. Results The diameter and length of the stenotic sites measured by EBUS and MDCT were nearly equal in all patients. Significant correlation was seen at all 212 sites (r=0.805, P<0.0001), 130 normal (r=0.758, P<0.0001) and 82 abnormal (r=0.654, P<0.0001). For malignant cases, there was significant correlation in a total of 160 sites (r=0.810, P<0.0001), 112 normal (r=0.782, P<0.0001) and 48 abnormal (r=0.564, P<0.0001). Benign cases showed significant correlations in total 52 sites (r=0.780, P<0.0001), 18 normal (r=0.778, P<0.0001) and 34 abnormal (r=0.731, P<0.0001). Conclusion This EBUS technique was successful in establishing accurate airway measurements for suitable airway stent sizes in interventional procedures, especially in cases with tracheobronchial malacia.