Peribronchiolar Alveoli Research Articles

Clinicopathological diagnosis of hypersensitivity pneumonitis

To enhance the understandings of clinical, radiological and pathological features of hypersensitivity pneumonitis (HP). Six HP cases with pathological data, clinical and radiological data were retrospectively analyzed during the period from February 2009 to September 2011 at Beijing Hospital of Ministry of Health. There were 2 males and 4 females with a mean age of 51.5 years (range: 38-61). Clinically, the patients presented with chronic cough, shortness of breath and dyspnea (n = 2). The disease course was 1-8 months. Five cases had fed pigeons and other contact histories. Specimens obtained by transbronchial lung biopsy (n = 3) and open lung biopsy (n = 3) were paraffin embedded and stained by hematoxylin and eosin, special stains and immunohistochemistry. Four cases had subacute HP and 2 cases chronic HP. Three cases of subacute HP underwent transbronchial lung biopsy. One case of subacute HP and 2 cases of chronic HP were diagnosed by open lung biopsy. High-resolution computed tomography of lungs showed diffuse ground glass and patch shadow along the bronchial and centrilobular distributions. There was a predominance of upper half zone. Typical visible mosaic syndrome was present. There was poorly formed granuloma without cheesy necrosis. With an insidious medical history and complicated radiological features, chronic HP cases were characterized by pulmonary interstitial fibrosis. There were usual interstitial pneumonitis (UIP)-like fibrosis and fibrosis with an airway-centered distribution type. The lesions were distributed around bronchioles. Continuous bridge fibrosis might be present. There were bronchiolar metaplasia of peribronchiolar alveoli, poorly formed granuloma and multinucleated giant cells in interstitium. Schaumann body was identified in 1 case. Because of its diverse clinical, radiological and pathological features, HP may be easily confused with other interstitial lung diseases. Aggregate analyses yield a definite diagnosis.

Welding Fume Exposure and Associated Inflammatory and Hyperplastic Changes in the Lungs of Tumor Susceptible A/J Mice

It has been suggested that welding fume (WF) exposure increases lung cancer risk in welders. Epidemiology studies have failed to conclude that WF alone causes lung cancer and animal studies are lacking. We examined the course of inflammation, damage, and repair in the lungs of A/J mice, a lung tumor susceptible strain, caused by stainless steel WF. Mice were exposed by pharyngeal aspiration to 40 mg/kg of WF, silica, or saline. Bronchoalveolar lavage (BAL) was performed 24 hours, 1 and 16 weeks to assess lung injury and inflammation and histopathology was done 1, 8, 16, 24, and 48 weeks postexposure. Both exposures increased inflammatory cells, lactate dehydrogenase and albumin at 24 hr and 1 week. At 16 weeks, these parameters remained elevated in silica-exposed but not WF-exposed mice. Histopathologic evaluation at 1 week indicated that WF induced bronchiolar epithelial hyperplasia with associated cellular atypia, alveolar bronchiolo-alveolar hyperplasia (BAH) in peribronchiolar alveoli, and peribronchiolar lymphogranulomatous inflammation. Persistent changes included foci of histiocytic inflammation, fibrosis, atypical bronchiolar epithelial cells, and bronchiolar BAH. The principle changes in silica-exposed mice were histiocytic and suppurative inflammation, fibrosis, and alveolar BAH. Our findings that WF causes persistent bronchiolar and peribronchiolar epithelial changes, suggest a need for studies of bronchiolar changes after WF exposure.

Lifespan studies in rats exposed to 239PuO2 aerosol.

Spatial-temporal dose-distribution patterns in the lung continually change following inhalation of radionuclides. Lung clearance, microdosimetry, and radiation dose were examined in female Wistar rats exposed to high-fired 169Yb2O3-239PuO2 aerosols. Whole-body counting for 169Yb at 14 d postexposure provided an accurate (r = 0.99) estimate of 239Pu lung content. Alpha irradiation of tracheal epithelium was at least 50 times less than for bronchiolar epithelium due principally to preferential retention of 239PuO2 in peribronchiolar alveoli as compared to other alveolar regions. The formation of large aggregates (> 25 particles) increased linearly with initial lung burden starting at 0.4 kBq; mean dose rate to these focal alveolar regions was 120 Gy d-1. Concentration of 239PuO2 in pulmonary macrophages and in aggregates, along with the limited penetration of alpha particles in tissue, resulted in a highly nonhomogeneous dose distribution pattern. Alveolar clearance was best represented by a biphasic clearance curve comprised of a rapid early phase (80% initial lung burden) and a slow late phase (20% initial lung burden). Studies with intratracheally instilled 237PuO2-239PuO2 and with inhaled 239PuO2 showed that alveolar clearance was inversely proportional to initial lung burden. A single clearance function was derived from experimentally determined clearance curves for inhaled 239PuO2 that was used to accurately estimate lung dose at all initial lung burden levels. Lung doses were calculated for 2,105 exposed lifespan rats based on individually determined initial lung burden, survival time, and individually computed clearance function.

Chronic transmural bronchiolitis: a non-specific lesion of small airways.

To investigate nine patients with histological changes at open lung biopsy compatible with so-called "small airways disease"; to define these changes and distinguish them from other types of bronchiolitis; and to correlate them with clinical features, respiratory physiology, and other laboratory investigations. The open biopsy sections and the clinical records were reviewed. There was chronic inflammation of the walls of centri-acinar respiratory bronchioles and peribronchiolar alveoli. Peripheral alveoli of affected acini were spared. Although lumens were narrowed and distorted, obstruction by granulation tissue plugs was not a feature. Clinical backgrounds included Hodgkin's disease, yellow nail syndrome, sicca syndrome, asthma and psoriasis. The main presenting symptoms were cough, dyspnoea and wheeze, often associated with basal crackles and basal shadowing. There was no consistent immunological or haematological abnormality. Sputum culture was negative in six patients, and a variety of organisms were cultured from three others. In most cases respiratory function tests revealed an irreversible obstructive defect (combined in some cases with a restrictive defect), gas trapping, and well preserved gas transfer. Lung volumes were normal. Bronchodilators, with steroids and azathioprine in more seriously affected patients, stabilised the disease process. The histological changes may be distinguished from bronchiolitis obliterans and bronchiolitis obliterans organising pneumonia by the absence of intraluminal granulation tissue plugs, and from the obliterative bronchiolitis of rheumatoid disease and diffuse peribronchiolitis on clinical grounds. Although often striking, this lesion does not represent a clinico-pathological entity, and may occur in the distal lung in association with a number of different diseases. "Small airways disease" is often used by clinicians in a functional context, and may lead to confusion. It is suggested that "chronic transmural bronchiolitis" is a more appropriate term.

Relation between small airways disease and parenchymal destruction in surgical lung specimens.

The relation between small airways disease and parenchymal destruction was investigated in lungs and lobes removed at surgery from 27 patients aged 15-70 years. Eight of the 27 patients were life-long non-smokers. The degree of small airways disease was assessed by semi-quantitative grading (SAD score) and by measuring diameter and wall thickness of membranous bronchioles. Parenchymal destruction was measured in three ways. Firstly, the number of alveolar attachments on membranous bronchioles per millimetre of circumference (AA/mm) was counted; the number of broken attachments was subtracted from the total AA/mm to give the numbers of intact attachments (normal AA/mm). Secondly, a point counting technique was used to give a destructive index (DI). Thirdly, the mean linear intercept (Lm) was determined. Total and normal AA/mm correlated negatively with the SAD score of membranous bronchioles (rs = -0.48 and -0.51) and with wall thickness (rs = -0.37 and -0.45) and DI correlated with wall thickness (rs = 0.5) and with the SAD score of respiratory bronchioles (rs = 0.53). Lm did not correlate with indices of small airway disease and total and normal AA/mm did not correlate with diameter. Multiple regression analyses showed that the correlation of total AA/mm with the SAD score of membranous and respiratory bronchioles and with wall thickness were not confounded by age or smoking. It is concluded that small airways disease is related to destruction of peribronchiolar alveoli, and it is postulated that small airways disease has a direct role in the causation of centrilobular emphysema.

Quantitative scanning electron microscopic autoradiography of inhaled 239PuO2.

We have applied the scanning electron microscope (SEM) to obtain autoradiographs of particles of 239PuO2 deposited in rat lung. The technique was used to obtain quantitative information on the clearance rates of particles from the alveoli, bronchioles and trachea up to 240 d after exposure. At all times, the concentration of particles on the surface of the bronchioles was an order of magnitude greater than on the tracheal surface. The clearance of Pu from both regions followed a biphasic pattern, similar to that obtained by radiometric analysis of the whole lung. Most of the radiation dose to the bronchiolar epithelium originated from Pu particles in peribronchiolar alveoli in which they were preferentially retained, compared to other alveolar regions. The prolonged retention of particles in the peribronchiolar alveoli may be a significant factor in the induction of lung carcinomas.

Membrane perturbations and mediation of gap junction formation in response to taurine treatment in normal and injured alveolar epithelia.

Nitrogen dioxide is an air pollutant that causes pulmonary alterations. Employing light and transmission electron microscopy, we examined plastic sections and freeze-fracture replicas of alveolar epithelium of groups of hamsters exposed to nitrogen for 24 h to determine taurine-induced changes in intercellular junctions. Prior to exposure, one group of hamsters was given 0.5% taurine in their drinking water for 2 weeks. A second group of hamsters was given taurine-free water. The taurine-treated group was divided into three subgroups. The first subgroup was exposed to nitrogen dioxide at a concentration of 7 ppm for 24 h, the second subgroup was exposed to nitrogen dioxide at a concentration of 30 ppm for 24 h, and the third subgroup was exposed to normal room air for 24 h. The nontaurine-treated animals were similarly divided into three subgroups and treated as described above. The lungs of the hamsters exposed to nitrogen dioxide without the taurine pretreatment exhibited extensive inflammatory cell infiltration in the walls of the terminal bronchioles, alveolar ducts, and peribronchiolar alveoli. The degree of infiltration was proportional to the degree of nitrogen dioxide concentration. The taurine-treated animals exposed to nitrogen dioxide and the nontaurine-treated animals exposed to room aid did not show any inflammatory infiltrate. Freeze-fracture replicas of the tight junctional regions of the type I and type II pneumocytes revealed significant fragmentation in the nitrogen dioxide-exposed lungs. It was also observed that the tight junctions between the type I pneumocytes of the taurine-treated groups, whether exposed or not, revealed gap junction-like aggregates among the tight junction fibrils. The 30-ppm nitrogen dioxide exposed group exhibited larger and more frequent gap junctions between the pneumocytes than those observed in the 7-ppm nitrogen dioxide exposed group. The evidence suggests that taurine may have an effect on plasma membranes and intercellular communications. Changes in intercellular communication may contribute to decreased susceptibility to injury and increased pneumocyte survival.

Tritiated thymidine-labeled bronchioloalveolar cells and radiation dose following inhalation of plutonium in rats.

The goal of this study is to show the relationship of inhaled Pu particle distribution and alveolar-bronchiolar target-cell response with respect to the formation of pulmonary carcinoma. The proliferation of type 2 alveolar epithelium and nonciliated bronchiolar epithelium appears critical in the induction of lung tumors associated from inhaled 239PuO2. Female, Wistar rats were either sham-exposed (40 rats) or given a single inhalation to 169Yb-239PuO2 (99 rats, ILB, 3.9 +/- 1.2 kBq) and examined at 20 time intervals from 1 day to 700 days postexposure for Pu particle distribution in airways by SEM quantitative autoradiography and for cell labeling with tritiated thymidine. Initially, deposited Pu particles were rapidly cleared from the surface of the trachea, bronchi, and bronchioles within a few days. Thereafter, about 5 times more alpha track exposure to the bronchiolar epithelium was delivered from Pu particles found in peribronchiolar alveoli than from Pu particles being cleared from bronchiolar surfaces. Exposure of bronchiolar epithelium at later times was due mostly to the formation of peribronchiolar Pu particle aggregates. A maximal increase in labeled alveolar wall cells was seen at 60 days after exposure, decreasing gradually to control levels by 400 days. Cell labeling in focal alveolar regions of Pu aggregation was about 5 fold higher. Increased bronchiolar epithelium labeling appeared in two phases. The first phase was seen 15 days after exposure, associated with initial deposition and clearance of Pu particles. The second phase slowly reached a maximum at 250 days and was associated with peribronchiolar Pu aggregate formation. The temporal-spatial dose-distribution pattern for inhaled Pu particles is an important aspect of Pu-induced pulmonary carcinogenesis.

Diffuse Bacterial Bronchiolitis With Bronchiolar Pneumonia in Adults

Three patients had diffuse reticulonodular shadowing on chest roentgenogram, dyspnea, cough, purulent sputum, airways obstruction, variable fever, and leukocytosis. Lung tissue from two showed inflammatory exudate in bronchioles and peribronchiolar alveoli; all had multiple isolates of either Haemophilus influenzae or Streptococcus pneumoniae from sputum or lung tissue. When examined in the context of similar syndromes reported by others under different labels in the past, these observations suggest that this is a specific clinical entity, which is both uncommon and serious. Despite initial misdiagnosis in all three cases, the two patients in whom the true nature of the disease was promptly recognized had complete recovery after the institution of appropriate antibacterial therapy. The most accurate and appropriate term for this entity is diffuse bacterial bronchiolitis with bronchiolar pneumonia.

Microscopic Lesions Associated with the Isolation of Haemophilus somnus from Pneumonic Bovine Lungs

Sixty-one of 68 sets of bovine lungs from which only Haemophilus somnus was isolated had microscopic lesions of purulent bronchiolitis and bronchopneumonia. In 37 of 61 lungs, the bronchiolar exudates were markedly necrotic with accompanying necrosis of the adjacent bronchiolar epithelium. Bronchiolitis obliterans was prominent in 23 of 28 lungs affected with chronic lesions with abscesses present in seven. Alveolar filling with inflammatory cells (neutrophils with fewer macrophages) was limited to peribronchiolar alveoli in 25 of 61 lungs and was multifocal to diffuse in the other 36. Lesions in the remaining lungs (7 of 68) were classified as fibrinous pneumonia with bronchiolitis (2), fibrinous pleuritis (2), suppurative interstitial pneumonia with vasculitis (2), and diffuse congestion (1).

Interalveolar pores in mouse lung. Regional distribution and alterations with age.

Quantitative analysis of the regional distribution of interalveolar pores in the lungs of BALB/c mice 1 to 28 months of age (n = 25) was performed by scanning electron microscopy. In all the age groups examined, the subpleural and peribronchiolar alveoli had significantly more pores than the midzonal region (p < 0.01). No significant changes were noted in the number of pores per alveolus between 3 and 26 months of age in the midzonal, peribronchiolar, and subpleural alveoli. We concluded that (1) intralevolar pores are regionally distributed in the lungs of BALB/c mice by 3 months of age, and (2) the number of pores do not significantly change with increasing age during the first 26 months.