(Chest. 2005;128:876-880.)
© 2005
American College of Chest Physicians
Subepithelial Microvasculature in Large Airways Observed by High-Magnification Bronchovideoscope*
Gen Yamada, MD;
Hiroki Takahashi, MD;
Noriharu Shijubo, MD;
Takayuki Itoh, MD and
Shosaku Abe, MD
* From the Third Department of Internal Medicine (Drs. Yamada, Takahashi, and Abe), Sapporo Medical University School of Medicine, Sapporo, Japan; and the Department of Respiratory Medicine (Drs. Shijubo and Itoh), Sapporo Hospital of Hokkaido Railway Company, Sapporo, Japan.
Correspondence to: Gen Yamada, Third Department of Internal Medicine, Sapporo Medical University, School of Medicine, Chuo-ku South 1 West 16, Sapporo, 060-8543 Japan; e-mail: gyamada{at}sapmed.ac.jp
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Abstract
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Background: The bronchial vasculature serves important functions and is modified in a variety of pulmonary and airway diseases. The remarkable ability of the bronchial vasculature to undergo remodeling has implications for disease pathogenesis. However, there is very little information on normal bronchial circulation.
Objectives: The aim of this study was to obtain information on bronchial microvessels in large airways using a high-magnification bronchovideoscope.
Methods and patients: Recently, we developed a high-magnification bronchovideoscope (XBF-200HM3 [side-viewing type]) in cooperation with Olympus Medical Systems. This bronchovideoscope can provide information on the bronchial mucosa with a maximum magnification of 110 times. Between August 2000 and July 2004, 26 patients without abnormalities in the large airways were enrolled into this study. Patients underwent conventional bronchoscopy and subsequent bronchoscopy with the high-magnification bronchovideoscope. After the bronchoscopic examination, we calculated the vessel area ratios and hemoglobin indexes of images made with the high-magnification bronchovideoscope by using appropriate software. In addition, we compared the findings obtained with the high-magnification bronchovideoscope of the 26 subjects with microscopic findings of autopsied tracheas of two patients without abnormalities.
Results: Many ramifying subepithelial microvessels of large airways were mainly observed in intercartilage and membranous portions, whereas only a few microvessels were seen in cartilage portions. Histologically, these subepithelial microvessels were thought to be distributed within approximately 800 and 500 µm beneath the surface of the intercartilage portions and membranous portions, respectively. Vessel area ratios of the intercartilage portions were significantly higher than those of the cartilage and membranous portions. The hemoglobin indexes of the intercartilage portions were significantly higher than those of the cartilage and membranous portions, and these indexes were also significantly higher in the membranous portion than in the cartilage portion.
Conclusions: A dense concentration of subepithelial microvessels was mainly observed in the intercartilage portion, indicating an increase in submucosal circulation. This high-magnification bronchovideoscope is a useful tool for observing and evaluating the subepithelial microvessels in large airways.
Key Words: bronchial circulation • extrapulmonary bronchus • subepithelial vasculature • high-magnification bronchovideoscope
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Introduction
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The bronchial vasculature serves important functions and is modified by a variety of pulmonary and airway diseases. Congestion of the bronchial vasculature may narrow the airway lumen in inflammatory airway diseases, and the formation of new bronchial vessels (ie, angiogenesis) is implicated in the pathology of a variety of chronic inflammatory, infectious, or ischemic pulmonary diseases. The remarkable ability of the bronchial vasculature to undergo remodeling has implications for disease pathogenesis.1 The bronchial microvasculature provides nutrient blood flow to the airway epithelium and blood flow changes in neural and humoral stimuli, and plays a role in the conditioning of inspired air.123 However, observation of the bronchial microvasculature by a conventional bronchoscope provides us with little information.
Recently, we developed a prototype of a high-magnification bronchovideoscope (XBF-200HM3) in cooperation with Olympus Medical Systems (Tokyo, Japan). This side-viewing bronchovideoscope provides information on the bronchial mucosa with a maximum magnification of 110 times on a 14-inch video monitor, showing the subepithelial bronchial microvasculature in large airways.
In this study, we used the high-magnification bronchovideoscope to observe the subepithelial microvasculature of tracheas and extrapulmonary bronchi with no pathologic findings on conventional bronchoscopy. Next, we evaluated the subepithelial vascular circulation in each high-magnification image by calculating the vessel area ratio and hemoglobin index. The hemoglobin index is obtained by electron endoscopic measurement of hemoglobin volume.456
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Materials and Methods
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Patients
Using the high-magnification bronchovideoscope, we examined the bronchial vasculature in 26 patients (age range, 34 to 83 years; 18 men and 8 women) without intrabronchial abnormalities. We excluded the patients who had abnormal findings in the trachea and extrapulmonary bronchi using a conventional bronchoscope. In order to eliminate the influence of other diseases on the bronchial mucosa, we also excluded patients who had complications, including allergic diseases, granulomatous diseases (eg, sarcoidosis), collagen diseases, cardiovascular diseases, and infectious diseases. All patients were informed preoperatively and gave their consent.
In addition, the distribution of subepithelial microvessels in the tracheas of two male patients who had been autopsied (ages, 62 and 66) and who had both died of gastric cancer, was examined. Using the high-magnification bronchovideoscope, we compared the longitudinal distribution of microvessels of the formalin-fixed specimens of the tracheas obtained at autopsy.
High-Magnification Bronchovideoscope
The high-magnification bronchovideoscope is 6.3 mm in diameter. This flexible bronchovideoscope is equipped with a charge-coupled device (CCD) at its distal end (Fig 1
). By using the prism, the images of the bronchial mucosa are captured by the CCD through a magnifying objective lens. As with a conventional bronchovideoscope, optical information is converted to electric signals by the CCD and transmitted to the video processor (EVIS CV-240; Olympus Medical Systems). The signals from the high-magnification bronchovideoscope were reconstructed into visual signals by the video processor and projected onto a 14-inch video monitor.
The observation depth was 1 to 3 mm, and the images of the bronchial mucosa were visualized with a magnification power of 55 to 110 times on a video monitor according to the distance between the objective lens and the bronchial surface. The view angle was 40°, but little distortion is seen. In addition, a forward-viewing optical fiberscope was attached to act as a guide. By using this front-viewing system, we confirmed the orientation and approached the endobronchial destinations while obtaining a high-magnification view.
We observed the trachea and extrapulmonary bronchi of these patients under local anesthesia. In brief, after muscle injection of atropin sulfate, 0.5 mg, and pentazocin, 15 mg, and the nebulization of 12 mL of a 2% lidocaine solution, a conventional bronchovideoscope (BF-P200, BF-1T200, or BF-T200; Olympus Medical Systems) was orally inserted into the trachea under local anesthesia, and the endobronchial lumen was examined. After conventional bronchoscopy was performed, we inserted the high-magnification bronchovideoscope into the trachea by using the forward-viewing system. We observed the trachea and extrapulmonary bronchi enfacely under high magnification. Each bronchoscopic image obtained using the high-magnification bronchovideoscope was recorded in an electronic file.
Calculation of Vessel Area Ratio and Hemoglobin Index
Forty-nine images of the cartilage portion, 52 images of the intercartilage portion, and 44 images of membranous portion from the 26 healthy subjects were analyzed. In order to evaluate the microvessel distribution obtained by the high-magnification bronchovideoscope, the vessel area ratio and hemoglobin index were calculated using appropriate software (SolemioENDO ProStudy; Olympus Medical Systems).
In brief, these parameters were calculated and determined as follows. First, a region of interest (ROI) was selected from the original high-magnification bronchovideoscope images on a computer display, and vascular images in the ROI were obtained. The microvessels were depicted as pixels. The vessel area ratio was determined as the number of pixels in the vessel area within the ROI. Next, the hemoglobin index was calculated.
Statistical Analysis
Results were expressed as the mean ± SD. Differences in vessel area ratios and hemoglobin indexes were compared using the Mann-Whitney U test.
The correlation between vessel area ratios and hemoglobin indexes was analyzed using the Spearman signed rank test. Differences were considered to be statistically significant when the p value was < 0.05.
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Results
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Observation of Subepithelial Venous Networks of Large Airways by High-Magnification Bronchovideoscope Compared to Microscopic Findings
We compared the images of large airways obtained by a conventional bronchovideoscope with those obtained by the high-magnification bronchovideoscope (Fig 2
). The high-magnification bronchovideoscope images clearly showed the subepithelial ramifying microvessels. Many microvessels were observed in the intercartilage portion (Fig 2, top right, B) and the membranous portion (Fig 2, bottom right, D), whereas only a few microvessels were observed in the cartilage portion (Fig 2, bottom left, C). Longitudinal mucosal folds were also observed in the membranous portion.
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Figure 2.. Normal tracheal view obtained in a 30-year-old healthy female volunteer obtained with a conventional bronchovideoscope (BF-P200; Olympus Medical Systems) [top left, A] and a high-magnification view of intercartilage portion (top right, B) and the membranous portion (bottom right, D). The arrowheads in top left, A, show each observation site of the high-magnification bronchovideoscope. The upper panel of bottom left, C, is a cartilage portion.
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Next, we examined the distribution of microvessels in the tracheas of the two autopsied patients. A longitudinal cross-section of the tracheas showed many microvessels, mainly in the intercartilarge portion (Fig 3
, top, A), and only a few were present in the cartilage portion (Fig 3, middle, B). Microvessels were observed in the intercartilage portions, and relatively large microvessels in these portions were distributed between approximately 600 and 800 µm beneath the bronchial surface. In the membranous portions, microvessels were distributed within approximately 500 µm of the bronchial surface.
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Figure 3.. Microscopic findings from the trachea of an autopsied patient. Longitudinal cross-sections of the intercartilarge portion (top, A), the cartilage portion (middle, B), and the membranous portion (bottom, C) are shown. Microvessels were highly concentrated in the intercartilage portion, whereas there were only a few microvessels in the cartilage portion. Microvessels were distributed in longitudinal folds in the membranous portion. Bar = 300 µm.
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Vessel Area Ratios and Hemoglobin Indexes
Vessel area ratios and hemoglobin indexes were calculated from the high-magnification the bronchovideoscope images of the large airways (Table 1
, Fig 4
). The vessel area ratio of the intercartilage portions was significantly higher than that of the cartilage portions (p < 0.0001) and that of the membranous portions (p = 0.0198). However, there was no significant difference between the cartilage portions and the membranous portions.
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Figure 4.. The vessel area ratios of the intercartilage portions were significantly higher than those of the cartilage portion (p < 0.0001) and those of membranous portion (p = 0.0198) [left]. The hemoglobin index of the intercartilage portions was significantly higher than that of the intercartilage portions (p < 0.0001) and that of the membranous portions (p = 0.0017). The hemoglobin index of the membranous portions was significantly higher than that of the cartilage portions (p < 0.0001) [right].
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The hemoglobin index of the intercartilage portions was significantly higher than that of the intercartilage portions (p < 0.0001) and that of the membranous portions (p = 0.0017). The hemoglobin index of the membranous portions was significantly higher than that of the cartilage portions (p < 0.0001).
There was a significant correlation between the vessel area ratios and the hemoglobin indexes (p < 0.0001) [Fig 5
]. In addition, there was no significant difference between each size of ROI.
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Discussion
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The subepithelial structure of the normal bronchial tree consists mainly of cartilage rings, longitudinal and circular muscular folds, and subepithelial vessels. These vessels were observed through the transparent epithelium, which was covered with a mucosal layer, and were thought to form a venous network in the subepithelial layer of the bronchus.23 Many ramifying microvessels were clearly observed by the high-magnification bronchovideoscope because both the side view and high magnification were achieved.
The large airway, including the trachea and extrapulmonary bronchi, is anatomically divided into the following three parts: cartilage portion; intercartilage portion; and membranous portion. As seen with a conventional bronchovideoscope, the distribution of the subepithelial venous network seems to be random. However, according to our observations with the high-magnification bronchovideoscope, subepithelial microvessels were concentrated mainly in the intercartilage portions, whereas there were few microvessels in the cartilage portions. Some microvessels were also observed in the membranous portions in addition to the longitudinal folds. Similarly, the intercartilage portions had the highest hemoglobin index values among the three areas. The value of the hemoglobin index correlated with the vessel area ratios. These findings indicate an increase of microcirculation in the intercartilage portion in the large airways.
The depth of the visible subepithelial microvessels below the epithelial surface is unclear. A longitudinally sectioned trachea showed that thick vessels were distributed more deeply than thin vessels. According to the findings in the 26 subjects and in the trachea specimens obtained by autopsy in 2 subjects that were obtained with the high-magnification bronchovideoscope, it was speculated that the vessels made visible with this bronchovideoscope were probably distributed within 800 µm below the epithelial surface. Whether or not microvessels are visible depends on their diameter and histologic condition.
The bronchial vessels are able to regenerate and form new vessels very rapidly in various conditions.12 Mucosal blood flow is thought to be influenced by vascular and airway pressures, inspired air conditions, and anatomic neurotransmitters.78 In situ observation of these bronchial changes with high-magnification devices may provide us with new information concerning various bronchial mucosal changes in patients with respiratory diseases such as bronchial asthma, chronic bronchitis, sarcoidosis, and lung cancer. Quantitative analysis of the vascular densities or microcirculation in various bronchial diseases may lead to a better understanding of the hemodynamics of these pathologic states.
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Acknowledgements
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The authors thank Yu-ichi Morizane, Toshiyuki Kubonoya, Kenji Yamazaki, and Hideki Tanaka of Olympus Medical Systems (Tokyo, Japan) for their technical support.
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Footnotes
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Abbreviations: CCD = charge-coupled device; ROI = region of interest
This investigation was supported by a grant from the Japanese Foundation for Research and Promotion of Endoscopy in 2003.
Received for publication December 20, 2004.
Accepted for publication March 1, 2005.
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References
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Abstract
Introduction
