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Pulmonary retransplantation for obliterative bronchiolitis. Intermediate-term results of a North American-European series.

An international series of pulmonary retransplantation was updated to identify the predictors of survival in the intermediate-term after reoperation for obliterative bronchiolitis. The study cohort included 32 patients with end-stage obliterative bronchiolitis who underwent retransplantation in 15 North American and European centers between 1988 and 1992. Five types of retransplantation procedures were done, including repeat ipsilateral single lung transplantation (7 patients), repeat contralateral single lung transplantation (8 patients), repeat double lung transplantation (3 patients), double lung transplantation after a previous single lung transplantation (3 patients), and single lung transplantation after a previous double lung or heart-lung transplantation (11 patients). The mean interval between transplants was 564 +/- 51 days (range 187 to 1589 days). Postoperative follow-up was 100% complete and the average follow-up in surviving patients was 678 +/- 63 days. Actuarial survival was 72%, 53%, 50%, 41%, and 33% at 1, 3, 6, 12, and 24 months, respectively. Survival did not differ according to the age, preoperative diagnosis, ambulatory or ventilator status, or cytomegalovirus serologic status of the recipient before reoperation. Life-table and Cox proportional hazards analysis identified the type of retransplantation procedure and the year of reoperation as significant (p < 0.05) predictors of postoperative survival. Actuarial survival was significantly better in patients without an old, retained contralateral graft after retransplantation and in patients who underwent reoperation between 1990 and 1992, as opposed to between 1988 and 1989. Infection was the most common cause of death at all time intervals after retransplantation, although all deaths beyond 2 years resulted from obliterative bronchiolitis of the second graft. Most surviving patients are in a satisfactory clinical condition, with a mean forced expired volume in 1 second of 59% +/- 13% of predicted (repeat double lung transplant recipients) or 41% +/- 6% of predicted (repeat single lung transplant recipients). We conclude that pulmonary retransplantation for obliterative bronchiolitis is associated with significantly worse survival than after primary lung transplantation. The absence of an old contralateral graft after retransplantation and reoperation after 1989 are important predictors of survival. Additional data and follow-up are required to determine the merit of pulmonary retransplantation for obliterative bronchiolitis.

Actuarial Analysis↗

Production of acute bronchiolitis in guinea-pigs by human respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the most important cause of acute bronchiolitis in young children, and is implicated in the pathogenesis of paediatric asthma. The present studies were designed to develop a model of acute RSV bronchiolitis in young guinea-pigs, that could be used to study the mechanisms of the acute bronchiolitis and its sequelae. Anaesthetized, one month old guinea-pigs received either 4 x 10(3) plaque forming units of Long strain human RSV or uninfected cell culture medium intranasally. Bronchiolar inflammation was assessed 6 days (n = 10 RSV-inoculated; n = 10 controls) and 14 days (n = 10 RSV-inoculated; n = 9 controls) postinoculation using a semiquantitative histological scoring system. Viral replication within the lung was evaluated by culture, and the intrapulmonary distribution of viral antigens was evaluated by immunohistochemistry. The RSV-inoculated group showed histological evidence of acute bronchiolitis 6 days after inoculation, which subsided by Day 14. Replicating virus was cultured from the lungs of 9 out of 10 RSV-inoculated animals on Day 6, and 2 out of 10 animals on Day 14, with no growth from control animals. Viral antigens were identified primarily within airway epithelial cells on Day 6, and within alveolar macrophages on Day 14. Intranasal inoculation of human RSV into guinea-pigs provides a model of acute RSV bronchiolitis that may facilitate the study of both the pathogenesis of acute infection and the possible role of RSV in the subsequent development of nonspecific bronchial hyperresponsiveness in children.

Acute Disease↗

Respiratory bronchiolitis-associated interstitial lung disease.

Respiratory bronchiolitis-associated interstitial lung disease is a distinct clinical syndrome found in current or former cigarette smokers. The disease often is confused with other interstitial lung diseases, especially idiopathic pulmonary fibrosis. The clinical presentation resembles those of patients with other interstitial lung diseases--cough and dyspnea, with coarse rales on physical examination. Diffuse fine reticulonodular interstitial opacities are found on chest radiograph, usually with normal-appearing lung volumes. Bronchial wall thickening, prominence of peribronchovascular interstitium, small regular and irregular opacities, and small peripheral ring shadows are distinctive features. Pulmonary function testing may be normal but usually demonstrates mild to moderate restriction and normal or slightly reduced diffusing capacity. A mixed obstructive-restrictive pattern is common. Respiratory bronchiolitis-associated interstitial lung disease is characterized histologically by an inflammatory process involving the membranous and respiratory bronchioles. The pathologic findings are dominated by the finding of tan-brown pigmented macrophages within respiratory bronchioles and neighboring alveolar ducts and alveoli. The pulmonary parenchyma away from the airway usually is normal or may demonstrate mild hyperinflation. The clinical course and prognosis of respiratory bronchiolitis-associated interstitial lung disease are unknown. Most patients respond favorably to corticosteroids, with documented improvement in lung function and chest radiographs. Smoking appears to play a role in the pathogenesis, so smoking cessation is important in the resolution of this syndrome.

Bronchiolitis↗

Reproduction of the obliterative bronchiolitis lesion after heterotopic transplantation of mouse airways.

Obliterative bronchiolitis, characterized histopathologically by airway inflammation and occlusion of small airways by vascularized fibrous tissue, constitutes an important threat to the long-term survival of lung and heart-lung transplant recipients. The pathogenesis of obliterative bronchiolitis is poorly understood, and successful preventative or treatment strategies are not available. We sought to develop a preclinical model system of obliterative bronchiolitis by transplanting murine airway grafts, consisting of tracheas and main bronchi, into the subcutaneous tissue of allogeneically mismatched recipient animals. By 10 days after transplantation, allografts demonstrated subepithelial and/or peritracheal inflammation, epithelial necrosis, and early fibroproliferation. Grafts harvested 21 days after transplantation demonstrated fibroproliferation in the airway wall or lumen in nine of 10 allografts versus 0 of 10 isografts (P = 0.0001). In addition, abnormal epithelium (ie, nonciliated cuboidal, squamous, or absent) was seen in all allografts, while nine of nine isografts demonstrated normal respiratory epithelium (P = 0.0003). Although differences exist between this model and the chronic rejection process in human lung transplant recipients, these findings reproduce the characteristic features of obliterative bronchiolitis and demonstrate that this lesion can result from allograft rejection. This model will be useful for studying the pathogenesis, prevention, and treatment of obliterative bronchiolitis after lung transplantation.

Animals↗

Respiratory syncytial virus bronchiolitis: clinical aspects and epidemiology.

Sixty to ninety percent of the clinical syndrome of bronchiolitis is caused by respiratory syncytial virus (RSV) infection. RSV epidemiology has several unusual characteristics. RSV infects nearly all infants in the first year of life, with a peak incidence of hospitalized infants with bronchiolitis between 2-6 months of age. It is the only virus that causes most severe disease during the first month of life, i.e. at a time when maternal antibodies are present. Lower respiratory tract infections caused by RSV are limited to children younger than 3 yrs but symptomatic infection with RSV occurs throughout life. Infants with cardiac disease as well as infants with bronchopulmonary dysplasia are especially prone to develop severe RSV bronchiolitis. Apnoea is a complication that occurs in infants younger than 3 months and after a history of apnoea of prematurity. Nosocomial infection is a major health problem. Hospital staff may spread the infection by becoming infected and shedding the virus, or by carrying contaminated secretions between patients. Classical teaching has been that the prevalence of wheeze is high after acute viral bronchiolitis in infancy, but recent data suggest that infants with already lower maximal expiratory flows at functional residual capacity are more prone to develop wheeze at the time of RSV bronchiolitis.

Bronchiolitis, Viral↗

Efficacy of bronchodilators in the treatment of bronchiolitis.

UNLABELLED: Bronchiolitis is a common respiratory infection affecting young children. Much controversy revolves around the efficacy of bronchodilators in the treatment of bronchiolitis. This study was conducted to address this issue. AIM: To determine the efficacy of bronchodilators in the treatment of bronchiolitis. METHOD: All children less than 2 years old with bronchiolitis were randomly assigned to receive nebulisations of Salbutamol, Ipratropium bromide or normal saline. A fourth group given only humidified oxygen without nebulisation were used as a control. RESULTS: Data were obtained for 120 patients. Fifty-one (42%) had respiratory syncytial virus (RSV) isolated from their nasopharyngeal aspirates. The demographic characteristics of the 4 groups were similar. There was no significant difference between the groups in terms of severity score, number of nebulisations required in the nebulised groups and the outcome as measured by the length of hospitalisation. CONCLUSION: The use of bronchodilators did not alter the course of the disease and is therefore not effective in the treatment of bronchiolitis.

Albuterol↗

Expression of inducible nitric oxide synthase and formation of peroxynitrite in posttransplant obliterative bronchiolitis.

BACKGROUND: Obliterative bronchiolitis is characterized histologically by inflammation, epithelial cell damage and loss, fibrosis, and eventual obliteration of airways. Production of high levels of the potential cytotoxin nitric oxide by inducible nitric oxide synthase has been implicated in several inflammatory diseases. The damaging effects of nitric oxide are mediated by peroxynitrite, are formed from nitric oxide and superoxide, and can be demonstrated by the detection of nitrotyrosine. Our previous finding of high inducible nitric oxide synthase expression in inflamed airway epithelium led us to hypothesize that release of nitric oxide in obliterative bronchiolitis mediates the characteristic epithelial damage. METHODS: Immunocytochemistry was carried out to seek expression of inducible nitric oxide synthase and nitrotyrosine in transplant samples from patients with obliterative bronchiolitis (n=10) and, as controls, unused donor lungs (n=5). RESULTS: Inducible nitric oxide synthase was strongly expressed in the damaged airway epithelium in obliterative bronchiolitis and in inflammatory cells, where its distribution was matched by that of nitrotyrosine. Normal controls showed little or no immunoreactivity for any of the antigens studied. CONCLUSIONS: Our findings suggest that nitric oxide may play a role in the pathogenesis of obliterative bronchiolitis and indicate that further work is essential to fully understand the processes and mechanisms involved.

Bronchiolitis Obliterans↗

Bronchiolization of the alveoli in lung cancer: pathology, patterns of differentiation and oncogene expression.

We examined the incidence and association of bronchiolization of the alveoli with non-small cell lung cancer in lung resection specimens from 2 patient groups: those with non-small cell lung cancer and those diagnosed with a variety of non-neoplastic lung conditions. We observed marked variation in bronchiolization of the alveoli morphology ranging from normal to severely atypical and developed a classification scheme based on growth pattern, cell number and cytologic criteria. Patterns of differentiation, proliferation and growth factor receptor and oncogene expression were studied using immuno-histochemical and in situ hybridization techniques. While low-grade (0-I) bronchiolization of the alveoli lesions demonstrated markers similar to normal bronchiolar epithelium, a significant decrease in the Clara cell 10 kDa protein and tubulin and an increase in surfactant protein-A expression were observed in high-grade (II-III) lesions. Focal p53 expression was detected in 2 high-grade lesions, while c-myc mRNA and cJun protein were observed in all grades. No correlation was observed between bronchiolization of the alveoli incidence and histologic tumor type. A comparison of marker expression in lesions and tumors from the same case revealed a negative correlation between cytokeratin-14 and c-erbB-2 immuno-reactivity. Only one bronchialization of the alveoli lesion was found in the non-neoplastic patient group. We conclude that up to 12% of non-small cell lung cancer resection specimens contain bronchiolization of the alveoli lesions which exhibit altered morphology and patterns of differentiation.

Bronchi↗

Mechanisms of relaxations of bovine isolated bronchioles by the nitric oxide donor, GEA 3175.

1. The present study was designed to investigate the effects and mechanisms of relaxation induced by the nitric oxide (NO) donor, GEA 3175 (a 3-aryl-substituted oxatriazole derivative) on bovine bronchioles (effective lumen diameter 200-800 microm) suspended in microvascular myographs for isometric tension recording. 2. In segments of bovine bronchioles contracted to 5-hydroxytryptamine, GEA 3175 (10(-8)-10(-4) M) induced concentration-dependent reproducible relaxations. These relaxations were slow in onset compared to other NO-donors such as 3-morpholinosydonimine-hydrochloride (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 3. In 5-hydroxytryptamine-contracted preparations the order of relaxant potency (pD2) was: salbutamol (7.80) > GEA 3175 (6.18) > SIN-1 (4.90) > SNAP (3.55). In segments contracted to acetylcholine, the relaxant responses were reduced and GEA 3175 relaxed the bronchioles with pD2 = 4.41 +/- 0.12 and relaxations of 66 +/- 10% (n = 4), while SNAP and salbutamol caused relaxations of 19 +/- 6% (n = 4) and 27 +/- 6% (n = 8) at the highest concentration used, respectively. 4. Oxyhaemoglobin (10(-5) M), the scavenger of nitric oxide, caused rightward shifts of the concentration-relaxation curves to GEA 3175 and NO. 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 3 x 10(-6) M) and LY 83583 (10(-6) M), the inhibitors of soluble guanylate cyclase, also reduced the relaxations induced by GEA 3175 and nitric oxide. However, ODQ did not affect salbutamol-evoked relaxation in the bovine small bronchioles. 5. GEA 3175-induced relaxations were reduced in potassium-rich (60 mmol l(-1) K+) solution. Glibenclamide (10(-6) M) markedly inhibited the relaxations induced by the opener of ATP-sensitive K+ channels, levcromakalim (3 x 10(-8)-10(-5) M), but it did not modify the relaxations induced by GEA 3175 or salbutamol. Apamin (5 x 10(-7) M), a blocker of the small Ca2+-activated K+-channels did not affect the relaxations to GEA 3175. In contrast, blockers of large Ca2+-activated K+-channels, charybdotoxin (3 x 10(-8)-10(-7) M) and iberiotoxin (10(-8) M), did inhibit the relaxations to GEA 3175. The combination of apamin and charybdotoxin did not induce an additional inhibitory effect on the relaxations to GEA 3175 compared to charybdotoxin alone. 6. In preparations where a concentration-response curve to GEA 3175 or NO was first obtained in the presence of LY 83583, incubation with charybdotoxin (10(-7) M) did produce an additional inhibitory effect of the relaxations. However. in the presence of ODQ (3 x 10(-6) M), iberiotoxin (10(-8) M) did not produce additional reduction of the NO- or GEA 3175-induced relaxations. 7. The present results suggest that the slow-releasing NO-donor GEA 3175 is more potent than the traditional NO donors in inducing relaxations of bovine bronchioles. GEA 3175, as for exogenously added NO, elicits relaxations through a cyclic GMP-dependent mechanism followed by opening of large conductance Ca2+-activated K+-channels.

Albuterol↗

Severity assessment in children hospitalized with bronchiolitis using the pediatric component of the Comprehensive Severity Index.

OBJECTIVE: Practice variation in the management of children hospitalized with bronchiolitis may result in significant differences in resource utilization. Determination of cost-effective care requires an objective means of adjusting for severity. We examined the correlation of the pediatric component of the Comprehensive Severity Index (CSI) with resource utilization in children hospitalized with bronchiolitis at ten children's medical centers. DESIGN: Demographics, clinical findings, laboratory results, interventions, and outcomes were retrospectively extracted from the charts of 804 consecutive children with International Classification of Disease, Ninth Revision codes for bronchiolitis from 10 children's medical centers. Comorbidities of prematurity, heart disease, and a prior history of wheezing or hospitalization, and the viral etiology of the illness were specifically examined. CSI scoring was performed at admission and maximum and correlated with patient variables and measures of resource utilization (hospital costs, length of stay, pediatric intensive care unit admission, and intubation). The performance of CSI relative to the Pediatric Risk of Mortality III was also evaluated. SETTING: Ten tertiary children's medical centers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One child died and >99% of children returned to their baseline state of health. Admission CSI was comparable to the aggregate of all patient variables in its correlation with hospital costs (r2 = 0.23 vs. r2 = 0.24, respectively) and lengths of stay (r2 = 0.23 vs. r2 = 0.24, respectively). Maximum CSI had the highest correlation coefficient with hospital costs (r2 = 0.42) and lengths of stay (r2 = 0.41), whereas the correlation of admission Pediatric Risk of Mortality III scores with costs was r2 = 0.12 and with lengths of stay was r2 = 0.07. CSI scores also correlated well with measures of resource utilization in subgroups of bronchiolitis patients with comorbidities or other risk factors for severe disease. CONCLUSIONS: CSI scores correlate well with resource use in pediatric patients hospitalized with bronchiolitis. This severity scoring system may be useful in assessing the cost-effectiveness of their care.

Journal Article↗

Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: a longitudinal birth cohort study.

Several epidemiological studies have reported recurrent wheezing and asthma in children after respiratory syncytial virus (RSV) bronchiolitis in infancy. The relationship with allergic sensitization is less clear and recent evidence suggests an interaction between atopy and RSV infection in the development of asthma. Data from a large, population-based, birth-cohort (Avon Longitudinal Study of Parents and Children) were used to compare outcomes of children according to whether or not they had been admitted to hospital in the first 12 months with RSV-proven bronchiolitis. Outcomes considered were 12-month prevalence of wheeze at two ages (between 30-42 and 69-81 months), cumulative prevalence of doctor-diagnosed asthma at 91 months and skin prick test defined atopy at 7 yr. Multivariable logistic regression models were used to calculate odds ratios for outcomes adjusted for potential confounders. A total of 150 infants (1.1% of the cohort) were admitted to hospital within 12 months of birth with RSV bronchiolitis. The prevalence of wheezing was 28.1% in the RSV group and 13.1% in controls at 30-42 months and 22.6% vs. 9.6% at 69-81 months. The cumulative prevalence of asthma was 38.4% in the RSV group and 20.1% in controls at 91 months. Atopy was found in 14.6% of the RSV group and in 20.7% of controls at 7 yr. RSV bronchiolitis was associated with subsequent wheezing between 30-42 (Odds ratio [95% CI] 2.3 [1.3, 3.9]) and 69-81 months (OR 3.5 [1.8, 6.6]) and with the cumulative prevalence of asthma at 91 months (OR 2.5 [1.4, 4.3]) but not with atopy (OR 0.7 [0.2, 1.7]). In a population-based birth cohort, RSV bronchiolitis was associated with subsequent wheezing and asthma but not with the development of atopy by age 7 yr.

Asthma↗

Regenerative growth of respiratory bronchioles in dogs.

Loss of lung units due to pneumonectomy stimulates growth of the remaining lung. It is generally believed that regenerative lung growth involves only alveoli but not airways, a dissociated response termed "dysanaptic growth." We examined the structural response of respiratory bronchioles in immature dogs raised to maturity after right pneumonectomy. In another group of adult dogs, we also examined the effect of preventing mediastinal shift after right pneumonectomy on the response of respiratory bronchioles. In immature dogs after pneumonectomy, the volume of the remaining lung increased twofold, with no change in volume density, numerical density, or mean diameter of respiratory bronchiole, compared with that in the control lung. The number of respiratory bronchiole segments and branch points increased proportionally with lung volume. In adult dogs after pneumonectomy, prevention of mediastinal shift reduced lung strain at a given airway pressure, but lung expansion and regenerative growth of respiratory bronchiole were not eliminated. We conclude that postpneumonectomy lung growth is associated with proliferation of intra-acinar airways. The proportional growth of acinar airways and alveoli should optimize gas exchange of the regenerated lung by enhancing gas conductance and mixing efficiency within the acinus.

Animals↗

Branching pattern of airways and air spaces of a single human terminal bronchiole.

A polyurethane-foam enlarged reconstruction was made from serial sections of a portion of young adult human lung parenchyman. Study of the progeny of a terminal bronchiole disclosed three generations of respiratory bronchioles and an irregular branching pattern of eight generations of alveolar ducts. Sacs and alveoli arose from the lateral and distal aspects of all generations of ducts. There were an average of 3.5 alveoli per sac. Considering the terminal bronchiole as the first generation branch of the acinus, over 60 per cent of the alveoli counted and predicted were members of the 10-12th generations. The acinus contained one terminal bronchiole and approximately 14 respiratory bronchioles, 1,200-1,500 ducts, 2,500-4,500 sacs, and 14,000-20,000 alveoli.

Adult↗

Smooth muscle development during postnatal growth of distal bronchioles in infant rhesus monkeys.

Development of smooth muscle in conducting airways begins early in fetal life. Whereas the pattern and regulation of smooth muscle differentiation are well-defined, the impact of airway growth on the process is not. To evaluate the transformations in organization during postnatal growth, smooth muscle bundle organization (size, abundance, and orientation) was mapped in five generations of distal airways of infant rhesus monkeys (5 days and 1, 2, 3, and 6 mo old). On the basis of direct measurement of the bronchiole proximal to the terminal bronchiole, length increased by 2-fold, diameter by 1.35-fold, and surface area by 2.8-fold between 5 days and 6 mo of age. Smooth muscle bundle size was greater in proximal bronchioles than in respiratory bronchioles and did not change with age. However, relative bundle size decreased in proportion to airway size as the airways grew. Relative bundle abundance was constant regardless of airway generation or age. The distribution of smooth muscle bundle orientation changed with age in each airway generation, and there were significant changes in the terminal and respiratory bronchioles. We conclude that smooth muscle undergoes marked organizational changes as airways grow during postnatal development.

Age Factors↗

Inert gas single-breath washout and structural alteration of respiratory bronchioles.

With the perspective of establishing a link between a respiratory function test and alterations of membranous bronchioles, respiratory bronchioles, and alveolar ducts, we performed forced expirations and four kinds of single-breath washout maneuvers on 27 men due to undergo a lobectomy for peripheral bronchial carcinoma. For the single-breath washouts, the inhaled gas mixture consisted of 90% O2, 5% He, 5% SF6. The four maneuvers were the standard vital capacity test and three successive inhalations of 0.5, 1, and 1.5 L from functional residual capacity. The slopes of N2, He, and SF6 for each maneuver were computed, as well as a new index (I2) describing the relative decrease of the difference between the SF6 and the He slopes induced by a larger inspiratory volume. The histologic analysis focused on pigmentation, inflammation, and fibrosis of membranous bronchioles, respiratory bronchioles, and alveolar ducts. There was a linear relationship with a highly significant correlation coefficient between the new index I2 and the degree of inflammatory (r = 0.73) and fibrotic (r = 0.63) changes of the respiratory bronchioles; this correlation persisted in patients with a normal FEV1/VC ratio. These preliminary data open the way to finding a test for early peripheral (intraacinar) airway dysfunction.

Adult↗

Chrysotile asbestos inhalation induces tritiated thymidine incorporation by epithelial cells of distal bronchioles.

Previous studies in a rat model of asbestosis have demonstrated increased incorporation of tritiated thymidine by bronchiolar and alveolar epithelial cells 19 to 72 h after a single, 5-h exposure to chrysotile asbestos. This increase in thymidine labeling occurred at the first alveolar duct bifurcations, where terminal bronchioles end and where asbestos deposition is most concentrated. To determine whether airways more proximal than the terminal bronchioles exhibit a similar type of proliferative response to asbestos, incorporation of tritiated thymidine by airway epithelial cells was determined by light microscopic autoradiography. Incorporation by the epithelium in regions of the trachea, mainstem bronchi, and bronchioles was measured in lung tissue from sham-exposed and chrysotile asbestos-exposed rats, zero and 33 h after exposure. Sham-exposed animals and those studied immediately after exposure exhibited no increases in tritiated thymidine incorporation at any airway level. Tritiated thymidine incorporation by epithelial cells of bronchioles in peripheral regions of the lungs was significantly increased, as much as 20-fold, 33 h after chrysotile exposure. In the same asbestos-exposed animals, epithelial cells of the trachea, the bronchi, and the larger bronchioles did not exhibit increased cell labeling. The fact that asbestos was deposited throughout all airway levels, yet increased thymidine incorporation is observed primarily in the peripheral bronchiolar regions, raises interesting questions regarding the mechanisms of asbestos-induced cell proliferation.

Animals↗

Oleic acid-associated bronchiolitis obliterans-organizing pneumonia in beagle dogs.

Accidental intra-airway exposure of dogs with pure oleic acid produced bronchiolitis obliterans and bronchopneumonia. Pulmonary changes included multifocal to coalescing necrosis of bronchioles and adjacent alveoli, hemorrhage, inflammation, and exudation of fibrin. Hyperplasia of bronchiolar and alveolar epithelial cells and proliferation of loose fibrovascular connective tissue formed polyps or plugs of variable size and shape. Polyps in the airways primarily consisted of fibroblasts with loose or myxoid stroma and were variably covered with attenuated epithelial cells. Some polyps had prominent vasculature, mixed inflammatory cell infiltration, and/or necrosis. Polyps or plugs variably effaced bronchioles and adjacent alveoli. The changes closely resembled human bronchiolitis obliterans-organizing pneumonia (BOOP). Controlled intra-airway delivery of oleic acid in dogs may be a potential animal model of obstructive pulmonary diseases such as BOOP or bronchiolitis obliterans.

Animals↗

[Distribution of epithelial cells in respiratory bronchioles, with special reference to influence of cigarette smoking].

Using lung lobes resected surgically for coin lesions, 5 microns-thick sections were made from normal tissues not accompanying emphysema and the proportion of various types of epithelial cells seen in respiratory bronchioles was estimated under a light microscope. The respiratory bronchioles which were cut perpendicularly to the long axis were categorized into three types; type 1 respiratory bronchioles the circumference of which had alveolar orifices in less than one third of its area; type 2, alveolar orifice were recognized in from one third to two thirds of the total area, and type 3, in more than two thirds. Taking several reports into consideration, type 1 respiratory bronchioles are likely to be located proximally, type 3, more distally and type 2, in intermediate locations. In type 1, a large part of bronchiolar walls was covered with columnar cells, whereas the area distributed by these cells was reduced and the area devoid of epithelium increased in type 2. Almost the entire surface of the bronchiolar wall was devoid of epithelium in type 3. Moreover, in smokers and ex-smokers, the proportion of the area not containing epithelium was larger than in non-smokers, which was distinct in type 1. An ultrastructural study revealed the area where no epithelium was seen by light microscopy to be covered with type 1 alveolar cells. In addition, the total pathological score introduced by semiquantitative assessment of fibrosis, muscle hypertrophy, mural inflammation, pigment and intralumenal macrophages was larger in smokers. Distribution of epithelial cells seems to be noteworthy in the assessment of structural changes of respiratory bronchioles due to smoking.

Aged↗