Bronchial Area Research Articles

In vivo collagenase-2 (MMP-8) expression by human bronchial epithelial cells and monocytes/macrophages in bronchiectasis.

The purpose of this study was to determine whether other cellular sources than neutrophils can express matrix metalloproteinase (MMP)-8 protein and mRNA in bronchiectatic (BE) lung. The molecular forms of MMP-8 in the BE bronchoalveolar lavage fluid (BALF) and healthy control BALF were analysed by western immunoblotting. MMP-8 expression was demonstrated by immunohistochemistry and in situ hybridization in BE lung tissue and by immunohistochemistry in control lung tissue. In the BE BALF, different MMP-8 species were detected: 70-80 kD MMP-8 apparently of polymorphonuclear leukocyte (PMN) origin and also 40-60 kD MMP-8 from non-PMN cellular sources, such as bronchial epithelial cells, glandular cells or monocytes/macrophages. Both of these MMP-8 species were elevated and converted to a significant extent to activated forms in BE BALF compared with healthy control BALF. The levels of high molecular weight (>80 kD) MMP-8 complexes, evidently representing MMP-8 trapped by endogenous MMP inhibitors and/or MMP-8 dimers, were significantly elevated in BE BALF compared with healthy control BALF. In BE lung tissue, the MMP-8 protein and mRNA expression was found in bronchial ciliated epithelial cells, glandular cells, neutrophils, and monocytes/macrophages infiltrating the bronchial epithelial area. Minimal MMP-8 expression was observed in neutrophils, monocytes/macrophages, and epithelial cells in control lung tissues. In this study, new potential cellular sources have been demonstrated for MMP-8 in the inflamed lung. MMP-8 from multiple cellular sources, including inflamed lung epithelium, was activated to a significant extent in the BE BALF, indicating a major role for MMP-8 in the destruction of lung and bronchial tissues.

A computed tomographic scan assessment of endotracheal suctioning-induced bronchoconstriction in ventilated sheep.

This study was directed at assessing changes in bronchial cross-sectional surface areas (BCSA) and in respiratory resistance induced by endotracheal suctioning in nine anesthetized sheep. Cardiorespiratory parameters (Swan-Ganz catheter), respiratory resistance (inspiratory occlusion technique), BCSA, and lung aeration (computed tomography) were studied at baseline, during endotracheal suctioning, and after 20 consecutive hyperinflations. Measurements performed initially at an inspired oxygen fraction (FI(O(2))) of 0.3 were repeated at an FI(O(2)) of 1.0. At an FI(O(2)) of 0.3, endotracheal suctioning resulted in atelectasis, a reduction in BCSA of 29 +/- 23% (mean +/- SD), a decrease in arterial oxygen saturation from 95 +/- 3% to 87 +/- 12% (p = 0.02), an increase in venous admixture from 19 +/- 10% to 31 +/- 19% (p = 0. 006), and an increase in lung tissue resistance (DR(rs)) (p = 0. 0003). At an FI(O(2)) of 1.0, despite an extension of atelectasis and an increase in pulmonary shunt from 19 +/- 5% to 36 +/- 2% (p < 0.0001), arterial O(2) desaturation was prevented and BCSA decreased by only 7 +/- 32%. A recruitment maneuver after endotracheal suctioning entirely reversed the suctioning-induced increase in DR(rs) and atelectasis. In three lidocaine-pretreated sheep, the endotracheal suctioning-induced reduction of BCSA was entirely prevented. These data suggest that the endotracheal suctioning-induced decrease in BCSA is related to atelectasis and bronchoconstriction. Both effects can be reversed by hyperoxygenation maneuver before suctioning in combination with recruitment maneuver after suctioning.

Clinically Relevant Information Obtained by Performing Autofluorescence Bronchoscopy

The purpose of the study was to examine the clinically relevant findings that were obtained only by autofluorescence bronchoscopy and not by white-light bronchoscopy. Data from patients at risk for lung cancer who underwent both white-light bronchoscopy and autofluorescence bronchoscopy were analyzed on a per-patient and on a per-bronchoscopy base. Clinically relevant findings were defined as follows: (1) histologic examination of bronchial biopsy specimen showing moderate dysplasia, severe dysplasia, or carcinoma in situ; (2) assessment by the bronchoscopist that the bronchial area to be treated endoscopically was better visualized by autofluorescence bronchoscopy, which was of influence on the treatment. A total of 224 bronchoscopies were performed in 114 patients. Endobronchial therapy was performed during 26 of these bronchoscopies. Clinical relevant findings resulted from 28 autofluorescence bronchoscopies in 18 patients. Twenty-five of 101 intraepithelial neoplastic lesions were detected by autofluorescence bronchoscopy alone during 18 bronchoscopies in 14 patients. During 10 bronchoscopies in 9 patients, autofluorescence bronchoscopy resulted in a better visualization of the extent of endobronchial spread of tumor, which subsequently was treated with endobronchial therapy. We concluded that by adding autofluorescence bronchoscopy to white-light bronchoscopy, clinically relevant information was obtained in 13% (28 of 223) of the bronchoscopies and in 16% (18 of 114) of the patients. Journal of Bronchology7:118-121, 2000.

P53 immunohistochemistry can identify bronchial dysplastic lesions proceeding to lung cancer: a prospective study.

Dysplasia is an important step in bronchial carcinogenesis and smokers present more dysplastic lesions than nonsmokers. These lesions not always lead to malignancy, so there is a need for additional, preferentially objective, diagnostic markers. To verify whether immunohistochemical overexpression of p53 protein in dysplastic areas could be a predictive marker of the development of lung cancer, we investigated p53 overexpression in 22 bronchial dysplastic lesions obtained by fibrebronchoscopy from heavy smokers who were not diagnosed as having lung cancer and were followed for a 4-yr period. Nine (41%) lesions showed p53-positivity. Seven lung cancers (78%), mostly squamous cell carcinomas, were detected within the follow-up in these patients and 3 in 13 (23%) patients with p53-negative lesions. Lung cancer occurred in all seven patients with dysplastic lesions showing >10% p53 positive nuclei. The positive predictive value of p53 immunostaining for lung cancer was 78%. The negative predictive value of p53 was 77%. p53 staining was not detected in squamous metaplasia lesions without atypia and in normal bronchial epithelium. Our findings provide evidence that p53-overexpression in bronchial dysplastic areas may be a clinically useful marker for identifying patients proceeding to, at least, squamous cell carcinoma and, in addition, may facilitate the detection of occult tumours.

High-resolution computed tomography in pediatric patients with postinfectious bronchiolitis obliterans.

The authors performed a prospective cohort study to define the high-resolution computed tomography features of 31 pediatric patients with postinfectious bronchiolitis obliterans. All patients underwent chest radiographs and lung perfusion scans, and 27 of the 31 patients underwent high-resolution computed tomography of the lung. The most common abnormal features shown on computed tomography included bronchial wall thickening, bronchiectasis, and areas of increased and decreased attenuation. High-resolution computed tomography showed a higher sensitivity than both chest radiography and lung perfusion scanning in detecting pulmonary abnormalities in these patients.

Morphometric analysis of bronchial cartilage in chronic obstructive pulmonary disease and bronchial asthma.

To clarify the changes in bronchial cartilage in diseased airways, we performed morphometric analysis of airways in autopsied lungs of 16 patients with chronic bronchitis (Group CB), pulmonary emphysema (Group PE), and bronchial asthma (Group BA), and in control patients without respiratory diseases (Group CN). Although degeneration of bronchial cartilage was clearly observed in airways from all groups except Group CN, the most extreme change was seen in Group CB. Increased perichondrial fibrosis was observed in both Groups CB and BA, and the more extreme change was seen in Group BA. Both the area proportions of degenerated cartilage (Deg%) and perichondrial fibrosis (Fib%) to total cartilage in bronchi (3 to 8 mm in diameter), cut vertically in the cross-section profile, were measured with a digitizing tablet coupled to a computer. No significant differences in the area proportion of cartilage to bronchial wall were observed among the four study groups. The Deg% values of Groups CB (mean: 15.4%), BA (mean: 12.9%), and PE (mean: 9.6%) were significantly higher than those of Group CN (mean: 1.0%) (p < 0.01 in each case). The Deg% values correlated significantly with the number of neutrophils in the bronchial walls (r = 0.63, p < 0. 01). Both Group CB (mean: 28.5%) and Group BA (mean: 33.6%) showed significantly higher values of Fib% than did Group CN (mean: 18.5%) (p < 0.01, each), and the value for Group PE (mean: 21.8%) was slightly increased (p < 0.05). The values of Fib% correlated significantly with the number of eosinophils in the bronchial walls (r = 0.51, p < 0.05), thickness of basement membrane (r = 0.77, p < 0.0002), bronchial gland area (r = 0.56, p < 0.02), and goblet-cell area (r = 0.55, p < 0.02). Further, the values of Deg% correlated significantly with those of Fib% (r = 0.64, p < 0.01). These findings indicate that airways in chronic obstructive pulmonary disease and bronchial asthma have both degenerative changes in the cartilage (chondrocytes) and increased perichondrial fibrosis, and that these alterations in bronchial cartilage may differ in chronic bronchitis and bronchial asthma.

Airway hyperreactivity: assessment with helical thin-section CT.

To determine the accuracy of helical computed tomography (CT) for assessing reversible changes in bronchial size and air trapping due to airway hyperreactivity. Spirometry and helical CT were performed in 15 patients with mild asthma and six healthy control subjects before and after bronchial provocation with methacholine chloride and after reversal of provocation with albuterol. CT was performed at suspended functional residual capacity and at residual volume in two lung regions (above and below the carina). Bronchial area and lung attenuation measurements were compared. At baseline, lung attenuation frequency distribution curves were similar between the control and asthma groups. After methacholine, control subjects showed a decrease of less than 10% in the forced expiratory volume at 1 second (FEV1) and no significant differences in lung attenuation curves. Patients with asthma showed a 20%-36% decrease in FEV1, with significant decreases in the median and lowest 10th percentile regions of the attenuation curves and in the cross-sectional area of small (< 5-mm2) airways (P < .001 for all comparisons). After albuterol, control subjects showed no change in spirometric measurements, lung attenuation, or bronchial size, whereas all such parameters returned to baseline levels in patients with asthma. Functional helical CT can accurately demonstrate reversible airflow obstruction resulting from airway hyperreactivity.

Silica induced Expression of IL-1beta, IL-6, TNF-beta, TGF-alpha, in the Experimental Murine Lung Fibrosis

Background: Silica-induced lung diseases is characterized by the accumulation of inflammatory cells at early stage and fibrosis in pulmonary parenchyma and interstitium at late stage. As a consequence of inflammation, silicosis is accompanied with the expansion of interstitial collagen and the formation of fibrotic nodule. In this process, several kinds of lung cells produce cytokines which can amplify and modulate pulmonary fibrosis. The alveolar macrophage is a potent source of proflammatory cytokines and growth factor. But in the process of silicotic inflammation and fibrosis, there are many changes of the kinetics in cytokine network. And the sources of cytokines in each phase are not well known. Method: 2.5 mg of silica was instillated into the lung of C57BL/6J mice. After intratracheal instillation of silica, the lungs were removed for imunohistochemical stain at 1, 2, 7 day, 2, 4, 8, 12 week, respectively. We investigated the expression of IL-1, IL-6, TNF- and TGF- in lung tissue. Results: 1) The expression of IL-6 increased from 1 day after exposure to 8 weeks in vascular endothelium. Also peribronchial area were stained for IL-6 from 7 days and reached the peak level for 4 weeks. 2) The IL-1 was expressed weakly at the alveolar and peribronchial area through 12 weeks. 3) The TNF- expressed strongly at alveolar and bronchial epithelia during early stage and maintained for 12 weeks. 4) TGF- was expressed strongly at bronchial epithelia and peribronchial area after 1 week and the strongest at 8 weeks. Conclusion: The results above suggests IL-6, TNF- appear to be a early inflammatory response in silica induced lung fibrosis and TGF- play a major role in the maintenance and modulation of fibrosis in lung tissue. And the regulation of TNF- production will be a key role in modultion of silica-induced fibrosis.

Tracheobronchial Constriction in Asthmatics Induced by Isocapnic Hyperventilation With Dry Cold Air

Although it is well known that isocapnic hyperventilation (IHV) with dry cold air produces airway constriction in asthmatic subjects, the site of airway narrowing is nuclear. To address this issue, we have quantified the tracheal and bronchial response to IHV with dry cold air in 15 patients with mild asthma and 7 healthy control subjects. We employed the acoustic reflection technique to evaluate changes in airway cross-sectional areas caused by IHV with dry cold air. Airway areas were measured during tidal breathing before and 5 to 10, 30, 60, and 90 min following cold air challenge. For analysis purposes, airway areas were divided into three anatomic segments: extrathoracic tracheal segment, intrathoracic tracheal segment, and main bronchial segment. These segments were assessed at a fixed volume below total lung capacity. Maximal and partial expiratory flow-volume curves were also obtained before each set of area measurements. In normal subjects, IHV with dry cold air caused no significant changes in FEV1, flow at 30% of the vital capacity in the partial curve (V30p), or airway areas. In asthmatics, at 5 to 10 min after challenge, we found that FEV1 decreased by 22 +/- 5% (mean +/- SEM) (p < 0.0001), V30p by 33 +/- 8% (p < 0.003), intrathoracic tracheal area by 10.7% +/- 2% (p < 0.03), and main bronchial area by 14 +/- 3% (p < 0.003). At 30 min, tracheal and main bronchial areas were returned to baseline levels; however, FEV1 and V30p were still significantly decreased, by 13 +/- 3% and 16 +/- 4%, respectively. We conclude that in asthmatics, IHV with dry cold air causes both tracheal and bronchial constriction, and that recovery seems to occur first in the central airways.

Evidence of cumulative gene losses with progression of premalignant epithelial lesions to carcinoma of the bronchus

Human bronchial carcinoma is thought to develop through progressive stages from basal cell hyperplasia to squamous metaplasia, dysplasia, carcinoma in situ, and finally invasive cancer. In this study, we used tissue microdissection to examine loss of heterozygosity of chromosomes 3p21, 5q21, and 9p21 at each stage of the epithelial progression to invasive cancers. Forty-eight premalignant/malignant bronchial sites were biopsied from 13 patients (including 9 subjects without cancer) using fluorescence bronchoscopy. Eighteen sites with moderate/severe dysplasia in 6 patients were subjected to bronchoscopic and molecular follow-up during a 3-month to 2-year period. Seven separate cases of advanced non-small cell bronchial cancers were also analyzed. From the baseline biopsies, the prevalence of 3p and 9p deletions increased significantly from no deletion in the hyperplasia/metaplasia samples (n = 9) to 37 and 31% of the informative cases, respectively, in the dysplasia samples (n = 29), to 100 and 83%, respectively, for the carcinomas in situ (n = 6), and 100% in the invasive cancers (n = 11). Chromosome 5q deletion was significantly more frequent in invasive cancers (70% of the informative cases) as compared to carcinoma in situ (40%), dysplasias (33%), and hyperplasia/metaplasia samples (11%). The number of chromosome alterations also increased significantly from the lowest to the highest grade lesions, showing evidence of accumulation of genetic damage from one group to another. The molecular follow-up analysis showed that the same genomic alteration can persist in a given dysplastic bronchial area for several months or years, and that the persistence or the regression of the molecular abnormality is well correlated with the evolution of the disease on follow-up. Our results suggest that molecular analysis of bronchial biopsies obtained by fluorescence bronchoscopy may be a very useful means to study the natural history of preinvasive bronchial lesions and the outcome of interventions, such as with chemopreventive treatment.

Prospective evaluation by computed tomography and pulmonary function tests of children with mediastinal masses

Our ability to predict respiratory compromise during general anesthesia in a child with an anterior mediastinal mass is limited. Two prior reports have found a correlation between adequacy of ventilation during general anesthesia and the tracheal cross-sectional area obtained from computed tomograms (computed tomography [CT] scans). These and other reports have suggested that pulmonary function tests may provide additional information regarding anesthetic risks, but no studies have evaluated the extent of respiratory compromise in children with an anterior mediastinal mass. We prospectively evaluated 31 children with mediastinal masses before 34 surgical procedures. At each evaluation the tracheal area (as a percent of the predicted area on the basis of age and gender) was determined by CT. Pulmonary function tests were performed in the sitting and supine positions. The eleven children with either a tracheal area or peak expiratory flow rate (PEFR) of less than 50% of predicted received only a local anesthetic; the majority of children above these levels (17 of 22) received a general anesthetic. Eleven of 31 patients had significant pulmonary restriction as defined by total lung capacity of less than 75% of predicted. Eight patients had a PEFR in the supine position of less than 50% of predicted. PEFR was lower in the supine than the upright position in all patients (median value of decrease, 12%). In 28 of 34 evaluations the child had a tracheal area greater than 50% of predicted, a criterion proposed for safe utilization of general anesthesia. This latter guideline, however, did not identify all patients with significant impairment of pulmonary function; five patients had a PEFR of less than 50% of predicted but tracheal areas of greater than 50% of predicted. All children were administered anesthetics uneventfully with these guidelines. Although the tracheal area can be accurately measured with the CT scan, this does not identify all children with mediastinal masses and abnormal pulmonary function. A large mass may produce significant restrictive impairment and hence reduction in PEFR by the intrathoracic volume it occupies and yet not cause tracheal compression. It may also reduce the PEFR by narrowing the bronchi distal to the carina. Currently no CT standards exist for measuring bronchial areas in children. Our study did not evaluate whether impaired pulmonary function as measured by PEFR would be predictive of respiratory collapse during general anesthesia because all were excluded and operated on under local anesthesia. General anesthesia was well tolerated in children with tracheal area and PEFR greater than 50% of predicted. Pulmonary function tests in children with anterior mediastinal masses may add valuable information to the anatomic evaluation obtained by CT scan.

Advantages of Sirius Red staining for quantitative morphometric collagen measurements in lungs.

Sirius Red staining is presented as a method for collagen determination, enabling quantitative morphometric measurements to be performed in locally defined tissue areas. The advantage of this method is especially shown for alveolar lung tissue. By excluding the bronchial areas in the tissue sections, the differences in the degree of fibrosis proved to be more discrete after different loads of quartz dust than by any other method. The difference of 12 micrograms collagen measured colorimetrically represented a 1.2-fold increase. The collagen measured in the alveolar tissue by the morphometric method rose from 9.8 to 28.6%. This is a 2.9-fold increase, underlining the vast improvement in sensitivity. Thus, this method is specifically suitable for the evaluation of very small fibrotic lesions. The quartz doses given are particularly low compared to most other investigations. Histologic lung and lymph node sections from female Wistar rats injected intratracheally with differing quantities of quartz dust (0.03, 0.1, 0.5, 1.75 mg) were stained with Sirius Red, and the collagen fibers measured with a quantitative image analysis. The results for lymph nodes using different methods (wet weight determination, quantitative measurement of quartz typical areas, colorimetric and morphometric collagen determination) showed a high correlation at the different doses. This showed that the morphometric method is suitable for the quantitative measurement of collagen. Corresponding results were also found in the comparative lung tissue measurements (colorimetric and morphometric collagen determination). However, the morphometric method has the decisive advantage that measurements can be restricted to defined tissue areas and do not destroy the section.

Inhaled particles and respiratory disease

Inhaled particles and respiratory disease

Pulmonary neuroendocrine cells in pediatric lung disease: alterations in airway structure in infants with bronchopulmonary dysplasia.

Despite four decades of investigation, the function of pulmonary neuroendocrine cells (NEC) remains unclear. Since NEC secretory products may influence airway growth or differentiation or alter airway smooth muscle tone, increased numbers of NEC seen in bronchopulmonary dysplasia (BPD) may be partially responsible for the genesis of the structural and pathophysiological alterations seen in this disease state. Changes in airway structure were studied in six infants dying with BPD and six conceptional age-matched control infants dying of noncardiopulmonary disease. Changes in bombesin-, calcitonin-, and serotonin-immunoreactive NEC were quantified in lung specimens from three infants who died at 2 months of age with severe BPD and three conceptional age-matched controls. There were no differences in either bronchiolar or bronchial airway epithelial areas, but significant increases in bronchiolar (1.8-fold) (P < 0.001) and especially bronchial smooth muscle (2.5-fold) (P < 0.001) were documented in infants with BPD. Few bombesin-, calcitonin-, and serotonin-immunoreactive cells were identified in cartilaginous airways; however, there was a clear increase in the total number of bronchiolar immunoreactive cells in infants with severe BPD (28.5 +/- 11.2 cells/mm airway epithelium) compared to control infants (4.5 +/- 4.9) (P < 0.05). Our results confirm that airway wall composition does change in BPD, but there is either no or an inverse correlation between NEC number and airway epithelial and smooth muscle areas and cell numbers. The role of NEC secretory products in airway smooth muscle growth and function requires further investigation.

Insensitivity of maximum expiratory flow to bronchodilation in normal dogs

We examined the effects of the inhaled parasympatholytic agent atropine and the sympathomimetic agent salbutamol on partitioned frictional pressure (Pfr) losses to the site of flow limitation (choke point, CP) in dogs to see how changes brought about by these agents would affect maximum expiratory flow (Vmax) and response to breathing 80% He-20% O2 (delta Vmax) in terms of wave-speed theory of flow limitation. In open-chest dogs, a Pitot-static tube was advanced down the right lower lobe to locate CP, to determine CP lateral and end-on pressures (PE), and to partition the airway into peripheral (alveoli to sublobar) and central (sublobar to CP) segments. Measurements were obtained at approximately 50% vital capacity. After inhalation, CP locations were unchanged with both bronchodilating agents. After atropine inhalation, Pfr central was decreased by one-half compared with base line. Despite the decrease in Pfr central, however, Vmax failed to increase after atropine because of altered bronchial area pressure (BAP) behavior at the CP site. After salbutamol inhalation, Pfr peripheral was reduced by about one-half compared with base line. However, Vmax failed to increase, because this reduction was too small to significantly increase the CP pressure head (i.e., PE). delta Vmax was also insensitive to these agents. Our results show mechanisms by which small changes in Pfr, as well as the complex interaction of changes in Pfr and BAP, may limit the use of Vmax in detecting bronchodilation at different airway sites.

Effect of omental, intercostal, and internal mammary artery pedicle wraps on bronchial healing

Bronchial transection and devascularization is necessary in the course of sleeve resection or lung transplantation, leaving distal bronchial segments ischemic and subject to stricture or dehiscence. Thirty mongrel dogs underwent left lung autotransplantation. The bronnchial anastomosis was wrapped with omentum (n = 9), intercostal muscle pedicle (n = 9), or internal mammary artery pedicle grafts (n = 6). Six control animals underwent bronchial anastomosis without an external wrep. Bronchial revascurlarization by capillary ingrowth from the pedicle to the bronchial submucosal plexus was demonstrated with all three types of vascular pedicle grafts; however, more consistent and confluent vascular ingrowth was provided by internal mammary artery pedicle grafts. Additionally, the bronchial anastomotic cross-sectional area was significantly better in the internal mammary artery group (84.5 ± 3.3) as compared with that of the omental (68.4 ± 8.3), intercostal muscle (66.9 ± 10.9), or contral groups (70.2 ± 7.6). An internal mammary artery pedicle graft and the presence of dense confluent submucosal vascular ingrowth from any pedicle graft were independently predictive ( p < 0.05) of minimizing bronchial anastomotic narrowing. These data are consistent with previous findings suggesting that omental and intercostal muscle pedicle grafts promote early bronchiai revascuiarization; moreover, the data demonstrate the superiority of an internal mammary artery pedicle graft to provide submucosal vascular ingrowth and to minimize anastomotic stenosis.

Dichotomous airway response to exercise in asthmatic patients.

The extent and location of airway narrowing in asthmatic subjects are usually inferred from measurements of maximal expiratory flow rates and airway resistance. In the present study, we used the acoustic reflection technique to measure the airway cross-sectional area in 14 asthmatic subjects and 8 normal controls before and following treadmill exercise tests. In normal subjects, exercise caused no significant change in FEV1 and bronchial area, but did cause a significant increase in the intrathoracic tracheal area from 2.0 +/- 0.7 cm2 to 3.1 +/- 0.7 cm2 (p less than 0.002). In the asthmatics, exercise was followed by a 37 +/- 15% reduction in forced expiratory volume in 1 s(FEV1), and a 36% decrease in bronchial area from 8.5 +/- 2.8 cm2 to 5.4 +/- 1.1 cm2 (p less than 0.001); however, extra- and intrathoracic tracheal areas increased significantly. These findings provide direct and quantitative evidence that the bronchi are the main site of airway narrowing in exercise-induced asthma, and draw attention to the phenomenon of tracheal dilatation that occurs concomitant with bronchoconstriction in asthmatic patients.

Relationship of ventilation inhomogeneity to morphologic variables in excised human lungs.

Ventilation inhomogeneity, as assessed by the regional distribution of 133Xe and the single breath washout (SBW) curve, is compared with the morphologic aspects in excised human lungs. Morphologic measurements include central airway diameter, bronchial gland area, peripheral airway diameter, and the alveolar surface-to-volume ratio. Lung inflation with a constant concentration of 133Xe results in relatively more 133Xe distributed to the lung base than to the apex. Neither the vertical gradient in ventilation nor other interregional inhomogeneities in 133Xe distribution are correlated with morphologic variations in the lung. Also, interregional inhomogeneities of 133Xe distribution do not correlate with phase III slope of the SBW curve. This suggests that the phase III slope is determined primarily by intraregional ventilation inhomogeneities. Within the phase IV region of the SBW curve two distinct inflections are identified: an inflection at volume V1 and another sharper inflection at volume V2. Both the phase III slope and V2 correlate significantly (p less than 0.05) with peripheral airway diameter, indicating that parameters of the SBW curve do assess peripheral airway properties.

Prediction of maximal expiratory flow in excised human lungs

The predictions of the wave-speed theory of flow limitations were tested against measured values of maximal expiratory flow (Vmax) in nine normal excised human lungs. We obtained static pressure-volume curves and deflation pressure-area (PA) curves of the first three to four airway generations. The pressure drop from the alveolus to the flow-limitation site was assumed to consist of a peripheral frictional loss (estimated from a catheter upstream from the flow-limitation site) and a convective acceleration pressure drop. Predicted Vmax was determined graphically by finding the lowest flow for which the Bernoulli PA curve was tangent to one of the bronchial PA curves. At the point of tangency, local flow speed equals local wave speed. At low lung volumes a point of tangency with the PA curves of the first few generations did not exist, and the flow-limitation site was assumed to be the minimal bronchial area at zero transpulmonary pressure. There was good agreement between measured and predicted Vmax. Measured Vmax was not different from Vmax predicted from normal living man. The wave-speed theory predicted flow over much of the vital capacity, but other mechanisms may limit flow at low lung volumes.

Lye corrosion carcinoma of the esophagus: a review of 63 cases.

Clinical material and the results of treatment of 63 esophageal lye corrosion carcinoma patients are presented below. The mean age of patients at lye ingestion was 6.2 years; the mean latent time between lye corrosion and esophageal carcinoma was 41 years. The later the lye was ingested the earlier carcinoma of the esophagus appeared. Eighty-four percent of carcinomas(all of which were of histologically squamous cell type) were found to be in the bronchial bifurcation area of the esophagus. Sixty-eight percent of lye corrosion carcinoma patients had been treated with resection or radiotherapy (over 4000 rads). Every tenth patient of whole material had surveved for over seven years. Both surgery and radiotherapy as practiced in our clinics had better survival rates than for previous esophageal carcinoma series.