Bronchiolar Inflammation Research Articles

Chronic postbronchiolitis airway instability induced with anti-IFN-gamma antibody in F344 rats.

Analogous to childhood-onset asthma in humans, rats may develop a chronic asthmalike phenotype, depending on their genetic background and the age at which they experience a viral airway injury. Brown Norway rats develop a postbronchiolitis asthmalike phenotype that may be prevented with supplements of interferon-gamma (IFN-gamma); we hypothesized that the normally resistant F344 rat strain would develop the asthmalike phenotype if the IFN-gamma response were suppressed during viral illness. Weanling F344 rats were pretreated with anti-IFN-gamma or control antibody, and inoculated with Sendai virus or vehicle. Anti-IFN-gamma treatment reduced lung IFN-gamma and increased IL-4 mRNA during the infection. Physiologic studies performed 8 wk later revealed premature airway closure (p = 0.03) and elevated specific pulmonary resistance (p < 0.01) in the postbronchiolitis anti-IFN-gamma group compared with noninfected controls and untreated postbronchiolitis rats. However, unlike the postbronchiolitis asthmalike phenotype in Brown Norway rats, bronchiolar inflammation and fibrosis were absent in the F344 rats. Lung elastic recoil and alveolar surface density also were unchanged compared with noninfected control rats. We conclude that there is an interactive effect of a weak IFN-gamma response and viral bronchiolitis at an early age that may result in persistent postbronchiolitis airway dysfunction. The presence of premature airway closure that is independent of airway wall inflammation or changes in lung elastic recoil suggests peripheral airway instability as a mechanism for the airway obstruction.

Obliterative bronchiolitis: varying presentations and clinicopathological correlation.

In obliterative bronchiolitis, inflammation and fibrosis lead to narrowing or occlusion of bronchiolar lumina. To determine how bronchiolar structural alterations relate to lung physiology, 19 patients with a pathological diagnosis of obliterative bronchiolitis were studied. The bronchiolar inflammatory and fibrotic features were correlated to the clinical presentation, and lung function tests. Eleven patients demonstrated airflow limitation, one had a restrictive pattern and one had a mixed pattern, two had isolated gas trapping, but four had normal spirometry. Mild-to-moderate bronchiolar inflammation was invariably present. It involved 60% of bronchioles subepithelially and 54% in the adventitia. Subepithelial fibrosis was observed in 15 patients and adventitial in 12. Adventitial bronchiolar inflammation correlated with forced expiratory volume in one second and forced vital capacity and inversely correlated with residual volume. Subepithelial fibrosis inversely correlated with subepithelial and adventitial inflammation. High-resolution computed tomography in 10 patients revealed inspiratory (five out of 10) and expiratory air trapping (five out of five), ground glass opacities (seven out of 10), bronchial wall thickening (five out of 10), bronchiectasis (two out of 10) and centrilobular nodules (two out of 10). The present study suggests that inflammation and fibrosis occurs in bronchioles at different time points in the disease process, or that there is no transition between these types of pathology in the same patient. No correlation was observed between the degree of bronchiolar fibrosis and the degree of airflow limitation.

Anti-inflammatory properties of ebselen in a model of sephadex-induced lung inflammation.

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), is a seleno-organic compound which protects tissues against oxidative stress. Furthermore, recent data has suggested that this compound possesses a range of anti-inflammatory properties. In this study the authors have investigated the effects of ebselen on Sephadex-induced lung oedema and bronchoalveolar lavage (BAL) tumour necrosis factor (TNF)-alpha and endothelin(ET)-1 levels in rats. Sephadex administration induced lung oedema which was accompanied by an increase in BAL TNF-alpha and ET-1 levels. Ebselen administration (1-30 mg x kg(-1), i.p. at 0, 4 and 12 h post Sephadex) significantly inhibited lung oedema (dose that produced 50% of the maximum inhibition of lung oedema 4.6 mg x kg(-1)) and BAL TNF-alpha levels in a dose-related manner with no effect on ET-1 levels. These data suggest that ebselen may be a useful therapy in lung pathologies in which bronchiolar inflammation is a feature.

Prevention of chronic postbronchiolitis airway sequelae with IFN-gamma treatment in rats.

After viral bronchiolitis at an early age, Brown Norway (BN) rats develop chronic airway dysfunction consisting of inflammation, remodeling, episodic reversible obstruction, and hyperresponsiveness. We hypothesized that supplementation of interferon gamma (IFN-gamma) during viral illness would alter the inflammatory response and attenuate the postviral sequelae. Weanling rats were treated daily with aerosolized interferon gamma (IFN-gamma), from 2 d prior through 7 d after inoculation, and compared with saline-treated infected rats and with noninfected control rats. The IFN-gamma treatment had no significant effect on viral titers, growth retardation, or total bronchoalveolar leukocytes, but there was a slight decrease in lung interleukin-4 (IL-4) mRNA (p = 0.015) during the first week. Despite having minimal effects on the acute illness, the IFN-gamma had marked effects on postviral sequelae, the IFN-gamma group having less bronchiolar inflammation (p = 0.025) and fibrosis (p = 0.01), and lacking abnormalities in pulmonary resistance (p = 0.028) and dynamic compliance (p = 0.006) compared with the untreated postviral group. We conclude that IFN-gamma modulated the inflammatory response to viral illness, such that acute airway injury did not evolve into chronic airway dysfunction. If similar processes contribute to the development of human asthma, it may be possible to interrupt the progression of airway dysfunction with an early immunomodulatory intervention.

A new model rat with acute bronchiolitis and its application to research on the toxicology of inhaled particulate matter.

The aim of the present study was to establish a useful animal model that simulates humans sensitive to inhaled particulate matter (PM). We have developed a new rat model of acute bronchiolitis (Br) by exposing animals to NiCl2 (Ni) aerosols for five days. Three days following the Ni exposure, the animals developed signs of tachypnea, mucous hypersecretion, and bronchiolar inflammation which seemed to progress quickly during the fourth to fifth day. They recovered from lesions after four weeks in clean air. To assess the sensitivity of the Br rats to inhaled particles, two kinds of PM of respirable size were tested with doses similar to or a little higher to the recommended threshold limit values (TLVs) for the working environment in Japan. Titanium dioxide (TiO2 = Ti) was chosen as an inert and insoluble particles and vanadium pentoxide (V2O5 = V), as a representative soluble and toxic airborne material. The Br rats exposed to either Ti or V were compared the pathological changes in the lungs and the clearance of particles to those in normal control or Br rats kept in clean air. The following significant differences were observed in Br rats: 1. delayed recovery from pre-existing lesions or exacerbated inflammation, 2. reductions in deposition and clearance rate of inhaled particles with the progress of lesions. The present results suggest that Br rats are more susceptible to inhaled particles than control rats. Therefore, concentrations of particulate matter lower than the TLVs for Japan, which have no harmful effects on normal lungs, may not always be safe in the case of pre-existing lung inflammation.

Asthma and respiratory syncytial virus infection in infancy: is there a link?

Asthma and respiratory syncytial virus infection in infancy: is there a link?

Bronchiolitis in adults: pathology and imaging.

The most common high resolution CT (HRCT) findings of bronchiolitis are centrilobular nodules and branching linear structures in the secondary pulmonary lobules or areas of air trapping. These findings can be helpful in suggesting the presence of bronchiolitis. However, they are nonspecific because there are overlapping features among various kinds of bronchiolitis. Bronchiolar or peribronchiolar inflammation appears as centrilobular nodule, while bronchiolectasis filled with secretions manifests with branching linear structure on HRCT. Air trapping is secondary to bronchiolitis. Proliferative bronchiolitis with the findings of patchy areas of consolidation or ground-glass opacity can be distinguished from other bronchiolitis. Mineral dust-induced bronchiolitis and peribronchiolar lesions in sarcoidosis present with perilymphatic (centrilobular plus perilobular) micronodules in the secondary pulmonary lobule. Bronchiolitis in hypersensitivity pneumonia appears with poorly defined centrilobular nodules, associated with ground-glass opacity and air trapping.

Immunohistochemical characterization of inflammatory and proliferative events during chronic rejection in rat lung allografts.

Chronic rejection is assumed to be the principle cause of airway injury leading to obliterative bronchiolitis (OB) after lung transplantation (Tx). To better understand the contribution of chronic rejection in the development of OB in allografted lungs, we examined the histopathological changes and cytokine expression in inadequately immunosuppressed rat lung allografts. Three groups of rats were studied: group I, control nontransplanted Lewis (Lew) rats (n=5); group II, syngeneic Lew-to-Lew isografts (n=25); and group III, Brown Norway-to-Lew allografts (n=25). Groups II and III received two single doses of cyclosporine on postoperative days 2-3. Transplanted animals were killed (n=5) at monthly intervals from 2 months to 6 months after Tx. Resected lungs were stained with hematoxylin and eosin, Masson's trichrome, and Van Gieson's elastin, and immunostained with antisera to interleukin (IL)-1beta, IL-8, and basic fibroblast growth factor (bFGF). The intensity of immunostaining was graded from 0 to 4 (0=no staining, 4=strong staining). In groups I and II, normal airways and vessels were observed. Minimal intensity and distribution of immunostaining for all markers were detected in groups I and II. Group III allografts demonstrated acute grade II-III vascular rejection with mild bronchiolar injury and inflammation at 2 months after Tx. At 6 months after Tx, all allografts demonstrated severe and diffuse chronic vascular rejection. Late airway changes consistent with OB were detected in four of five allografts, however, these lesions were expressed infrequently. Immunohistochemical findings revealed moderate to strong expression for IL-8 and bFGF over the airway epithelium, acute and chronic inflammatory cells, and fibroblasts in allografts at 2 months after Tx. Despite focal development of OB at 6 months, intensity and distribution of immunostaining significantly decreased for all three cytokine markers. Inadequate immunosuppression of rat lung allografts leads primarily to chronic vascular rejection but fails to induce severe and diffuse development of OB. In this animal model, cytokines IL-1beta, IL-8, and bFGF are likely to play an important role in the early inflammatory phase but not during the late proliferative events of chronic rejection.

Histopathological study of Sauropus androgynus-associated constrictive bronchiolitis obliterans: a new cause of constrictive bronchiolitis obliterans.

The development of constrictive bronchiolitis obliterans in patients who have ingested Sauropus androgynus juice has not been previously reported. We describe four patients with S. androgynus-associated constrictive bronchiolitis obliterans who underwent open lung biopsies for histopathological analysis. This article aims to recognize the possible pathogenesis of the disease. The spectrum of histologic changes ranged from slight bronchiolar inflammation and fibrosis to marked submucosal fibrosis causing complete cicatricial obliteration of the lumen. A dense eosinophil infiltrate was noted in the bronchiolar submucosa or fibrotic tissue of the completely obliterated bronchioles in two patients. Immunohistochemical studies revealed that lymphocytic infiltrate consisted mainly of T lymphocytes in all patients. Immunofluorescent stains for immunoglobulin (Ig)G, IgA, IgM, C1q, C3, and C4 were negative. Electron microscopy disclosed no immune complex deposition in the specimens examined. Although the role of antibody- and complement-mediated reaction is not supported by the negative results of immunofluorescent and electron microscopic studies, the common finding of the predominant T-lymphocytic infiltrate suggests that a T-cell mediated immune response is involved in the pathogenesis of the disease. Furthermore, the finding of a heavy lymphocytic infiltrate in many bronchioles without significant collagen deposition suggests that the lymphocytic infiltrate may precede the tissue fibrosis. In addition, the presence of a dense eosinophil infiltrate may combine with lymphocytes and other immunologic and mesenchymal cells to promote antigen-specific stimulation of lymphocytes and induction of fibrosis.

Experimental lung mycotoxicosis in mice induced by Stachybotrys atra.

Stachybotrys atra is often isolated from building materials in houses with moisture problems. Spores of S. atra can contain mycotoxins which may lead to various symptoms in exposed residents in damp houses. The pathogenesis of S. atra-induced lung diseases has not been elucidated. The purpose of the present study was to investigate lung mycotoxicosis experimentally in mice after an intranasal exposure to spores of S. atra-fungus. One group of mice received one intranasal injection of spores of a toxic strain of S. atra (1 x 10(6) spores) and the other group spores of a less toxic strain. Spores of both strains contained spirolactones and spirolactams while the highly toxic strain contained also trichothecene mycotoxins, satratoxins. The spores containing satratoxins caused severe intra-alveolar, bronchiolar and interstitial inflammation with haemorrhagic exudative processes in the alveolar and bronchiolar lumen. A significant difference was observed in the severity of the lung damage caused by the two strains of S. atra. The spores without satratoxins induced a milder inflammation, so that the toxic compounds of S. atra-spores are most likely responsible for the severity of the lung injury.

Bronchiolitis in Chronic Pigeon Breeder's Disease: Morphologic Evidence of a Spectrum of Small Airway Lesions in Hypersensitivity Pneumonitis Induced by Avian Antigens

We analyzed 36 open lung biopsy specimens from patients with chronic pigeon breeder's disease (PBD) to assess bronchiolar involvement and its relationship to the parenchymal pathologic abnormalities. Likewise, 21 biopsy specimens obtained from patients with usual interstitial pneumonia (UIP) were also examined. The bronchiolar abnormalities were scored by the method of Wright et al using a panel of photographs. In addition, the severity of lung fibrosis was evaluated in all samples and expressed as percentage in multiples of ten. A variable degree of epithelial cell metaplasia, bronchiolar inflammation and fibrosis, smooth muscle hypertrophy, extrinsic small airways narrowing, and intraluminal macrophages was observed in both diseases. Occasionally, hyperplasia of lymphoid follicles was also present. Bronchiolar changes were proportional in type and severity to the parenchymal damage. Spearman's nonparametric correlation between fibrosis in parenchyma and fibrosis in membranous bronchiole for the complete group (including patients with UIP and with PBD) showed a moderate but significant association (R=0.51; p<0.01). A significant association was also demonstrated when the score for bronchiolar fibrosis and inflammation was evaluated in relation to lung fibrosis divided in high degree (>50%) and low degree (<50%), respectively. In the case of patients with PBD, the correlation between bronchiolar and parenchymatous fibrosis was of 0.33 (p<0.05). In general, bronchiolar fibrosis was less severe and inflammation more severe in PBD lungs compared with patients with UIP. Fibrosis in membranous bronchioles correlated with increased mortality in the complete group of patients, but the impact on mortality disappeared after correcting for overall fibrosis in the biopsy sample. Our findings demonstrate that a spectrum of bronchiolar lesions is usually observed in chronic PBD lungs, although the predominant pattern is similar to that found in the surrounding parenchyma, suggesting that the damage occurs in parallel.

Acute, subacute, and chronic histologic effects of simulated aspiration of a 0.7% sucralfate suspension in rats.

To assess the acute (4-hr), subacute (7-day), and chronic (21-day) effects of simulated aspiration of a 0.7% sucralfate suspension in rats. Prospective, multigroup trial in which rats were randomized to various simulated aspiration groups. Experimental animal laboratory. Forty-five Sprague-Dawley rats. Simulated aspiration was induced by single, direct, tracheal instillation of 2 mL/kg of either room air, sucralfate, or normal saline. Lung histologic changes were assessed using a quantitative numerical scoring scale. There was an increase in bronchiolar inflammation in rats undergoing acute, simulated sucralfate aspiration compared with controls. There were no significant differences (p > .05) in any other features at any time interval studied (two-way analysis of variance). Even though significant inflammatory airway lesions were produced in this acute model, these abnormalities resolved without evidence of subacute or chronic histologic progression. It remains to be determined if this pattern is unique to this specific experimental model or if it can be extrapolated to critically ill patients.

Persistence of Respiratory Syncytial Virus Genome and Protein After Acute Bronchiolitis in Guinea Pigs

Children with acute respiratory syncytial virus (RSV) bronchiolitis often develop sequelae of recurrent wheezing and asthma. To determine whether RSV persists within the lung after resolution of acute bronchiolitis, we examined the lungs of guinea pigs 60 days after intranasal inoculation with either human RSV (n = 10) or uninfected cell culture supernatant (n = 11). Evidence of viral persistence within the lung was determined by viral culture to test for replicating virus, immunohistochemistry to test for viral protein, and the reverse transcriptase-polymerase chain reaction (RT-PCR) to test for viral genomic RNA. Lungs were also examined histologically for evidence of bronchiolar inflammation or increased numbers of mast cells in the airway walls. All viral cultures were negative; however, there was positive immunohistochemical staining of occasional alveolar macrophages in six of ten RSV-inoculated guinea pigs while RT-PCR was positive in seven of ten RSV-inoculated animals. The six guinea pigs with evidence of RSV by immunohistochemistry and RT-PCR showed excess bronchiolar polymorphonuclear cell infiltrates (p < 0.005) but no increase in the number of airway wall mast cells. These results show that RSV protein and genomic RNA can persist in the lungs of experimentally inoculated guinea pigs for at least 60 days after infection and that persistence of the virus within alveolar macrophages might contribute to the pathogenesis of chronic bronchiolar inflammation.

Bronchial responsiveness and acute bronchodilator response in chronic obstructive pulmonary disease and diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is characterised clinically by chronic airflow limitation and respiratory tract infection, and pathologically by chronic bronchiolar inflammation. To elucidate the functional differences between chronic obstructive pulmonary disease (COPD) and DPB the bronchial responsiveness to methacholine was compared in 64 patients with COPD and 32 patients with DPB, and the bronchodilator response was compared in 72 patients with COPD and 49 with DPB. Bronchial responsiveness to methacholine was determined by the dosimeter method and expressed as PD20FEV1, and bronchodilator response was measured as the change in percentage predicted response with 5 mg nebulised salbutamol. Baseline FEV1 was similar in the two groups of patients. Patients with COPD were more responsive to methacholine than were those with DPB (geometric mean PD20FEV1 8.87 v 48.0 cumulative units). Reversibility of air flow obstruction, expressed as the difference between the percentage predicted postbronchodilator FEV1 and prebronchodilator FEV1, was significantly larger in patients with COPD than in those with DPB (7.87 (6.52)% v 4.16 (4.43)%). The observation that patients with DPB differ substantially in bronchial responsiveness from those with COPD is thought to reflect the difference in the mechanisms of these two diseases--that is, airway disease in DPB and more parenchymal disease in the group of patients with COPD. The nature of bronchiolar inflammation in COPD and DPB is also different, possibly explaining the difference in bronchial responsiveness. More fixed airflow limitation as a result of structural bronchiolar lesions in DPB will explain the smaller reversibility of airflow obstruction.

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.

Acquired segmental emphysema: The enlarging spectrum of Swyer-James/Macleod's syndrome

Three cases of Macleod's syndrome are described, all of which required surgical resections for distressing symptoms. This provided a rare opportunity tc examine the pathologic features of a condition that is usually diagnosed on ils radiologic features, and the etiology of which remains unestablished. Three patients (2 women and 1 man), aged 20, 23, and 24 years, were referred from respiratory physicians because of unilateral hyperlucent lungs and associated symptoms. All 3 patients had unilateral hyperlucent lungs, but only 1 patient had demonstrable mediastinal shift on expiratory and inspiratory chest computed tomographic scan. Segmentectomies were performed (n = 4) in all the patients without perioperative morbidity or mortality. Patients have been followed up between 6 and 18 months, and remain asymptomatic with a return to normal lifestyle. Histologic examination of the specimens found inflammation of the bronchus in all 3 patients, but only two specimens had evidence of bronchiolar inflammation. In only 1 patient was there a reduction in bronchiole number. All 3 patients showed presence of emphysema. These cases are notable for the segmental distribution of the disease. Pathologic examination lends support to the theory that previous respiratory tract infection may play a role in the pathogenesis of this condition.

Diseases of the Small Airways

The term “bronchiolitis obliterans” has been used differently by clinicians and pathologists and encompasses two distinct morphologic entities: classic bronchiolitis obliterans with intraluminal polyps and constrictive bronchiolitis. Bronchiolitis obliterans with organizing pneumonia (BOOP pattern) is characterized by classic bronchiolitis obliterans, with intraluminal polyps affecting mainly respiratory bronchioles and alveolar ducts. This represents a nonspecific reaction to acute lung injury and can be seen in a variety of circumstances. Many patients have an idiopathic syndrome (idiopathic BOOP) with well-defined clinical and radiographic features that characterize it clinically as a form of interstitial (infiltrative) lung disease. Idiopathic BOOP is usually steroid-responsive and has a good prognosis.Constrictive bronchiolitis is characterized by bronchiolar inflammation, peribronchiolar and submucosal scarring, and progressive bronchiolar luminal narrowing. Constrictive bronchiolitis is also seen i...

Bronchiolar Inflammation and Fibrosis Associated with Smoking: A Morphologic Cross-sectional Population Analysis

The lungs of 42 smokers and 13 nonsmoking males of various ages who died suddenly and unexpectedly were examined grossly using Gough-Wentworth whole-lung sections and by microscopic planimetry to assess the severity and prevalence of emphysema. The bronchioles in representative histologic sections were evaluated for inflammation and epithelial metaplasia as well as for fibrosis and muscular hypertrophy. Postmortem interviews with next of kin established a history of cigarette smoking and excluded possible occupational exposures to toxic or particulate inhalants. Emphysematous changes were not prominent in members of the study group, but they tended to be more severe in smokers (p = 0.059) and increased in severity with age (p less than 0.001). Inflammatory changes (so-called smoker's bronchiolitis) were evident in smokers of all ages, although they were significantly less prominent in the lungs of older smokers. On the other hand, respiratory and membranous bronchiolar wall fibrosis was increasingly evident in older smokers (p less than 0.05). Muscular hypertrophy in the bronchiolar walls was significantly greater in smokers, but a change with age was not observed. These findings strongly suggest that bronchiolar fibrosis is associated with chronic cigarette use. These lesions occur independently of emphysema and may account for some of the subtle physiologic alterations observed in smokers.

Neutrophilia in Bronchoalveolar Lavage Fluid of Diffuse Panbronchiolitis

The clinical and pathologic features of diffuse panbronchiolitis (DPB) have been well reported to date, although its pathogenesis remains unknown. In the present study, we performed bronchoalveolar lavage (BAL) on three patients with biopsy specimen-proven DPB and eight patients with highly probable DPB (six women and five men; one smoker and ten nonsmokers), nine patients with chronic bronchitis (all men, five smokers and four nonsmokers), and nine normal control subjects (six women and three men, all nonsmokers) to clarify the cell populations in the lower respiratory tract. Neutrophils comprised 55.3 +/- 24.4 percent of recovered cells by BAL in DPB patients but only 6.6 +/- 6.4 percent in chronic bronchitis patients, and 1.8 +/- 1.5 percent in normal control subjects (p less than 0.001, all comparisons). The DPB patients also exhibited a decreased percentage of alveolar macrophages (34.9 +/- 23.5 percent) compared with chronic bronchitis patients and normal control subjects (p less than 0.001, all comparisons). The percentage of lymphocytes of the recovered lavage cells in DPB patients did not differ from that in chronic bronchitis patients and normal control subjects. These results indicate that neutrophils play an important role in the pathogenesis of DPB. They also suggest that neutrophilia of BAL-recovered fluid is a common finding in diseases associated with bronchiolar inflammation despite some clinical and pathophysiologic differences.

Localization of Inflammation and Virions in Canine Adenovirus Type 2 Bronchiolitis

Beagle puppies develop bronchiolar inflammation and histamine hyperresponsiveness with canine adenovirus type 2 (CAV2) infections. We determined the distribution of bronchiolar lesions and correlated inflammation with virions and bronchoalveolar lavage fluid (BALF) cytology. Nineteen beagle puppies were inoculated with tissue culture fluid (control puppies, n = 8), or CAV2 (CAV2, n = 11). The puppies had clinical assessments and measurements of lung resistance (RL), and dynamic compliance (Cdyn) immediately before inoculation (Day zero) and 3 days later (Day 3). The puppies were killed on Day 3, the lungs were removed, and the right intermediate lobe was lavaged. The BALF was assessed for total and differential cell counts. Bronchiolar inflammation was quantitated by bronchiolar inflammation scores (BIS). CAV2 was localized by immunofluorescent antibody staining and electron microscopy. The control puppies remained healthy. The CAV2 puppies had positive cultures for CAV2, respiratory symptoms, and generalized necrotizing bronchiolitis. Alveolar inflammation was quantitatively less prominent than bronchiolar inflammation, and RL and Cdyn were unchanged. The BALF neutrophilia correlated with the BIS. CAV2 was present within bronchiolar epithelium, alveolar epithelial type 2 cells, neutrophils, and macrophages. CAV2 was not found in airways smooth muscles or nerves, nor in any noninflamed tissues of CAV2 puppies or in control animals. Our data suggest that acute CAV2 in beagle puppies produces an inflammation of most bronchioles. Intracellular CAV2 was found in bronchiolar epithelium, macrophages, neutrophils, and alveolar epithelial type 2 cells. Bronchiolar inflammation was reflected in BALF cytology. We conclude that bronchiolar inflammation as indicated by BIS and BALF cytology is related temporarily to histamine hyperresponsiveness in our beagle puppies.