Hyperplasia Of Bronchus-associated Lymphoid Tissue Research Articles

PATHOMORPHOLOGICAL CHANGES AND BACTERIAL PATHOGENS ASSOCIATED WITH SWINE PNEUMONIAS IN SOUTHWEST NIGERIA

Pneumonia is a major economic threat to swine industry worldwide, however, there is still dearth of information on the pathology and associated pathogens in Nigeria, and these were therefore investigated. Lungs from 408 slaughtered pigs were randomly collected from abattoirs in Abeokuta, Ibadan and Lagos. The lung samples were cultured for bacterial pathogens using standard techniques, while formalin-fixed tissues were processed for histopathological examination. Grossly, the most consistent lesion was bronchopneumonia (35.3%). The main histopathological findings were lymphoid hyperplasia of bronchus-associated lymphoid tissue (BALT) (88.2%), suppurative bronchopneumonia (63.6%), suppurative bronchitis and bronchiolitis with concurrent epithelial hyperplasia (57.1%), as well as thickened alveolar septa due to cellular infiltration consisting predominantly of neutrophils (54.1%). Ten different species of bacteria were isolated from the lung samples in which two or more pathogens were isolated from each sample (82.7%). Pasteurella multocida was the most frequently isolated bacterium (54.8%). Among the bacteria isolated, there were significant (P < 0.05) differences in the frequencies of isolation of β-haemolytic Streptococci, P. multocida, Haemophilus species and Escherichia coli between the pneumonic lungs and apparently normal lungs. The results of bacterial culture, gross and histopathological changes recorded in this study are consistent with bacterial pneumonia possibly caused by most of the bacteria identified in the present study.
 

Effects of Chronic Secondhand Smoke (SHS) Exposure on Cognitive Performance and Metabolic Pathways in the Hippocampus of Wild-Type and Human Tau Mice.

Background:Exposure to secondhand smoke (SHS) is a risk factor for developing sporadic forms of sporadic dementia. A human tau (htau) mouse model is available that exhibits age-dependent tau dysregulation, neurofibrillary tangles, neuronal loss, neuroinflammation, and oxidative stress starting at an early age (3–4 months) and in which tau dysregulation and neuronal loss correlate with synaptic dysfunction and cognitive decline.Objective:The goal of this study was to assess the effects of chronic SHS exposure (10 months’ exposure to ) on behavioral and cognitive function, metabolism, and neuropathology in mice.Methods:Wild-type (WT) and htau female and male mice were exposed to SHS (90% side stream, 10% main stream) using the SCIREQ® inExpose™ system or air control for 168 min per day, for 312 d, 7 d per week. The exposures continued during the days of behavioral and cognitive testing. In addition to behavioral and cognitive performance and neuropathology, the lungs of mice were examined for pathology and alterations in gene expression.Results:Mice exposed to chronic SHS exposure showed the following genotype-dependent responses: a) lower body weights in WT, but not htau, mice; b) less spontaneous alternation in WT, but not htau, mice in the Y maze; c) faster swim speeds of WT, but not htau, mice in the water maze; d) lower activity levels of WT and htau mice in the open field; e) lower expression of brain PHF1, TTCM1, , and HSP90 protein levels in WT male, but not female, mice; and f) more profound effects on hippocampal metabolic pathways in WT male than female mice and more profound effects in WT than htau mice.Discussion:The brain of WT mice, in particular WT male mice, might be especially susceptible to the effects of chronic SHS exposure. In WT males, independent pathways involving ascorbate, flavin adenine dinucleotide, or palmitoleic acid might contribute to the hippocampal injury following chronic SHS exposure. https://doi.org/10.1289/EHP8428

A SURVEY OF PARASITE LESIONS IN WILD RED DEER ( CERVUS ELAPHUS) FROM ARGENTINA.

In Argentina there is little information about diseases that affect exotic ungulates and the health risks that they pose to native wildlife, livestock, and humans. The aim of this study was to evaluate the health status of red deer ( Cervus elaphus) in the Nahuel Huapi National Park and surrounding areas in Patagonia, Argentina. During three consecutive hunting seasons, necropsies were performed on 101 red deer, and tissues were examined histologically. The most common lesions were those associated with hepatic and pulmonary parasites. Fasciola hepatica was observed in 15 red deer and was associated with cholangiohepatitis (8%) and/or cholangitis (10%). Dictyocaulus sp. (likely Dictyocaulus eckerti) was associated with interstitial pneumonia (5%), bronchitis (5%), pulmonary emphysema (13%), and bronchus-associated lymphoid tissue hyperplasia (13%). Other findings included Sarcocystis spp. cysts in the myocardium (89%) associated with interstitial, focal, lymphoplasmacytic myocarditis (8%); periportal lymphoplasmacytic hepatitis (8%); hepatic centrilobular necrosis (6%); lymphoplasmacytic interstitial nephritis (25%); and follicular hyperplasia in mediastinal, prescapular, and prefemoral lymph nodes (86%). Our report of lesions caused by endemic parasites of livestock in free-ranging exotic red deer in Patagonia sets the foundation for a health-monitoring and -surveillance system of wildlife in this region, which is essential for the sustainable management of threatened Argentinean native fauna.

Evaluation of oxidative response and tissular damage in rat lungs exposed to silica-coated gold nanoparticles under static magnetic fields.

The purpose of our study was the evaluation of toxicological effects of silica-coated gold nanoparticles (GNPs) and static magnetic fields (SMFs; 128 mT) exposure in rat lungs. Animals received a single injection of GNPs (1,100 µg/kg, 100 nm, intraperitoneally) and were exposed to SMFs, over 14 days (1 h/day). Results showed that GNPs treatment induced a hyperplasia of bronchus-associated lymphoid tissue. Fluorescence microscopy images showed that red fluorescence signal was detected in rat lungs after 2 weeks from the single injection of GNPs. Oxidative response study showed that GNPs exposure increased malondialdehyde level and decreased CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in rat lungs. Furthermore, the histopathological study showed that combined effects of GNPs and SMFs led to more tissular damages in rat lungs in comparison with GNPs-treated rats. Interestingly, intensity of red fluorescence signal was enhanced after exposure to SMFs indicating a higher accumulation of GNPs in rat lungs under magnetic environment. Moreover, rats coexposed to GNPs and SMFs showed an increased malondialdehyde level, a fall of CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in comparison with GNPs-treated group. Hence, SMFs exposure increased the accumulation of GNPs in rat lungs and led to more toxic effects of these nanocomplexes.

Relationship Between Expression of Interleukin-5 and Interleukin-13 by Epithelial Cells and Bronchiolar Changes in Pigs Infected with Mycoplasma hyopneumoniae

Mycoplasma hyopneumoniae (Mh) is a bacterium that specifically infects the surface of bronchi and bronchioles of pigs without invading the host cells,and it is considered to be the primary agent of porcine enzootic pneumonia (PEN). The present study investigates the morphological and immunohistological changes induced in bronchiolar epithelium by Mh infection. Lungs from 20 pigs with naturally occurring Mh pneumonia were compared with those from 10 uninfected controls. Bronchiolar epithelial height, inflammatory infiltration, hyperplasia of bronchus-associated lymphoid tissue (BALT) and mucin subtype MUC5AC-producing cells significantly increased in all infected animals. Mh antigen was detected in association with the cilia of the bronchial and bronchiolar epithelium. Interleukin (IL)-5 and IL-13 were expressed consistently by epithelial and mononuclear cells of the airways of infected animals. The expression of these cytokines in the bronchial and bronchiolar tissues is related to the histological changes of PEN.

The role of alveolar type II cells in swine leptospirosis

Abstract: This study aimed to investigate a possible relationship between alveolar type II cells and the inflammatory response to infection with Leptospira spp., and thus comprise a further element that can be involved in the pathogenesis of lung injury in naturally infected pigs. The study group consisted of 73 adult pigs that were extensively reared and slaughtered in Teresina, Piauí state, and Timon, Maranhão state, Brazil. The diagnosis of leptospirosis was made using the microscopic agglutination test (MAT) aided by immunohistochemistry and polymerase chain reaction. The MAT registered the occurrence of anti-Leptospira antibodies in 10.96% (8/73) of the pigs. Immunohistochemistry allowed for the visualization of the Leptospira spp. antigen in the lungs of 87.67% (64/73) of the pigs. There was hyperplasia of bronchus-associated lymphoid tissue and circulatory changes, such as congestion of alveolar septa, parenchymal hemorrhage and edema within the alveoli. Lung inflammation was more intense (p = 0.0312) in infected animals, which also showed increased thickening of the alveolar septa (p = 0.0006). Evaluation of alveolar type II (ATII) cells using an anti-TTF-1 (Thyroid Transcription Factor-1) antibody showed that there were more immunostained cells in the non-infected pigs (53.8%) than in the infected animals (46.2%) and that there was an inverse correlation between TTF-1 positive cells and the inflammatory infiltrate. There was no amplification of Leptospira DNA in the lung samples, but leptospiral DNA amplification was observed in the kidneys. The results of this study showed that a relationship exists between a decrease in alveolar type II cells and a leptospire infection. Thus, this work points to the importance of studying the ATII cells as a potential marker of the level of lung innate immune response during leptospirosis in pigs.

Toxicity profile of the GATA-3-specific DNAzyme hgd40 after inhalation exposure

DNAzymes are single-stranded catalytic DNA molecules that bind and cleave specific sequences in a target mRNA molecule. Their potential as novel therapeutic agents has been demonstrated in a variety of disease models. However, no studies have yet addressed their toxicology and safety pharmacology profiles in detail. Here we describe a detailed toxicological analysis of inhaled hgd40, a GATA-3-specific DNAzyme designed for the treatment of allergic bronchial asthma. Subacute toxicity, immunotoxicity, and respiratory, cardiovascular, and CNS safety pharmacology were analyzed in rodents and non-rodents, and genotoxicity was assessed in human peripheral blood. Overall, hgd40 was very well tolerated when delivered by aerosol inhalation or slow intravenous infusion. Only marginal reversible histopathological changes were observed in the lungs of rats receiving the highest dose of inhaled hgd40. The changes consisted of slight mononuclear cell infiltration and alveolar histiocytosis, and moderate hyperplasia of bronchus-associated lymphoid tissue. No local or systemic adverse effects were observed in dogs. No compound-related respiratory, cardiovascular, or CNS adverse events were observed. The only relevant immunological findings were very slight dose-dependent changes in interleukin-10 and interferon-γ levels in bronchoalveolar lavage fluid. Taken together, these results support direct delivery of a DNAzyme via inhalation for the treatment of respiratory disease.

Chronic pneumonia in calves after experimental infection with Mycoplasma bovis strain 1067: Characterization of lung pathology, persistence of variable surface protein antigens and local immune response

BackgroundMycoplasma bovis is associated with pneumonia in calves characterized by the development of chronic caseonecrotic lesions with the agent persisting within the lesion. The purposes of this study were to characterize the morphology of lung lesions, examine the presence of M. bovis variable surface protein (Vsp) antigens and study the local immune responses in calves after infection with M. bovis strain 1067.MethodsLung tissue samples from eight calves euthanased three weeks after experimental infection with M. bovis were examined by bacteriology and pathology. Lung lesions were evaluated by immunohistochemical (IHC) staining for wide spectrum cytokeratin and for M. bovis Vsp antigens and pMB67 antigen. IHC identification and quantitative evaluation of CD4+ and CD8+ T lymphocytes and immunoglobulin (IgG1, IgG2, IgM, IgA)-containing plasma cells was performed. Additionally, expression of major histocompatibility complex class II (MHC class II) was studied by IHC.ResultsSuppurative pneumonic lesions were found in all calves. In two calves with caseonecrotic pneumonia, necrotic foci were surrounded by epithelial cells resembling bronchial or bronchiolar epithelium. In all calves, M. bovis Vsp antigens were constantly present in the cytoplasm of macrophages and were also present extracellularly at the periphery of necrotic foci. There was a considerable increase in numbers of IgG1- and IgG2-positive plasma cells among which IgG1-containing plasma cells clearly predominated. Statistical evaluation of the numbers of CD4+ and CD8+ T cells, however, did not reveal statistically significant differences between inoculated and control calves. In M. bovis infected calves, hyperplasia of bronchus-associated lymphoid tissue (BALT) was characterized by strong MHC class II expression of lymphoid cells, but only few of the macrophages demarcating the caseonecrotic foci were positive for MHC class II.ConclusionsThe results from this study show that infection of calves with M. bovis results in various lung lesions including caseonecrotic pneumonia originating from bronchioli and bronchi. There is long-term persistence of M. bovis as demonstrated by bacteriology and immunohistochemistry for M. bovis antigens, i.e. Vsp antigens and pMB67. The persistence of the pathogen and its ability to evade the specific immune response may in part result from local downregulation of antigen presenting mechanisms and an ineffective humoral immune response with prevalence of IgG1 antibodies that, compared to IgG2 antibodies, are poor opsonins.

DEVELOPMENT OF BRONCHUS-ASSOCIATED LYMPHOID TISSUE HYPERPLASIA FOLLOWING LIPOPOLYSACCHARIDE-INDUCED LUNG INFLAMMATION IN RATS

Gram-negative bacterial endotoxin lipopolysaccharide (LPS) administration has been used as an animal model of sepsis-related acute lung injury and adult respiratory distress syndrome (ALI/ARDS). This paper describes the lung histology following lung injury induced by the intraperitoneal (i.p.) administration of endotoxin to rats, in comparison with earlier findings. ALI was induced by the i.p. administration of Esherichia coli LPS 2 (n = 8) or 3 (n = 5) mg/kg, whereas physiological saline was administered to the control animals (n = 5). Eighteen hours after the LPS injections, the animals were euthanized. The lungs and heart were removed in one block for histological study (hematoxylin and eosin [H&E], periodic acid–Schiff [PAS], Mason's trichrome; light microscopy). The lung tissue injury (bronchial wall, vessels, alveoli, interstitium) was graded via a scoring system (0 to 3+). The control animals showed intact lung tissue. Ten of the 13 LPS group had bronchus-associated lymphoid tissue (BALT) hyperplasia. Pathological signs of ALI/ARDS, diffuse alveolar damage (DAD) and emphysema, were observed in 5 and 8 cases, respectively. LPS injection induces primarily BALT hyperplasia and also the less characteristic DAD. This rat model is suitable for the investigation not only of ALI/ARDS but also of BALT hyperplasia occurring as a consequence of chronic pulmonary inflammatory processes.

Lymphoid Interstitial Pneumonia: A Narrative Review

Lymphoid interstitial pneumonia (LIP) is regarded as both a disease and a nonneoplastic, inflammatory pulmonary reaction to various external stimuli or systemic diseases. It is an uncommon condition with incidence and prevalence rates that are largely unknown. Liebow and Carrington originally classified LIP as an idiopathic interstitial pneumonia in 1969. Although LIP had since been removed from that category, the most recent consensus classification sponsored by the American Thoracic Society and the European Respiratory Society recognizes that some cases remain idiopathic in origin, and its clinical, radiographic, and pathologic features warrant the return of LIP to its original classification among the idiopathic interstitial pneumonias. LIP also belongs within a spectrum of pulmonary lymphoproliferative disorders that range in severity from benign, small, airway-centered cellular aggregates to malignant lymphomas. It is characterized by diffuse hyperplasia of bronchus-associated lymphoid tissue. The dominant microscopic feature of LIP is a diffuse, polyclonal lymphoid cell infiltrate surrounding airways and expanding the lung interstitium. Classically, LIP occurs in association with autoimmune diseases, most often Sjögren syndrome. This has led to consideration of an autoimmune etiology for LIP, but its pathogenesis remains poorly understood. Persons who are seropositive for HIV, and children in particular, are at increased risk of acquiring LIP. Some studies suggest causal roles for both HIV and Epstein-Barr virus. The incidence of LIP is approximately twofold greater in women than men. The average age at diagnosis is between 52 years and 56 years. Symptoms of progressive cough and dyspnea predominate. There is great variability in the clinical course of LIP, from resolution without treatment to progressive respiratory failure and death. Although LIP is often regarded as a steroid-responsive condition, and oral corticosteroids continue to be the mainstay of therapy, response is unpredictable. Approximately 33 to 50% of patients die within 5 years of diagnosis, and approximately 5% of cases of LIP transform to lymphoma. Lymphoid interstitial pneumonia (LIP) is regarded as both a disease and a nonneoplastic, inflammatory pulmonary reaction to various external stimuli or systemic diseases. It is an uncommon condition with incidence and prevalence rates that are largely unknown. Liebow and Carrington originally classified LIP as an idiopathic interstitial pneumonia in 1969. Although LIP had since been removed from that category, the most recent consensus classification sponsored by the American Thoracic Society and the European Respiratory Society recognizes that some cases remain idiopathic in origin, and its clinical, radiographic, and pathologic features warrant the return of LIP to its original classification among the idiopathic interstitial pneumonias. LIP also belongs within a spectrum of pulmonary lymphoproliferative disorders that range in severity from benign, small, airway-centered cellular aggregates to malignant lymphomas. It is characterized by diffuse hyperplasia of bronchus-associated lymphoid tissue. The dominant microscopic feature of LIP is a diffuse, polyclonal lymphoid cell infiltrate surrounding airways and expanding the lung interstitium. Classically, LIP occurs in association with autoimmune diseases, most often Sjögren syndrome. This has led to consideration of an autoimmune etiology for LIP, but its pathogenesis remains poorly understood. Persons who are seropositive for HIV, and children in particular, are at increased risk of acquiring LIP. Some studies suggest causal roles for both HIV and Epstein-Barr virus. The incidence of LIP is approximately twofold greater in women than men. The average age at diagnosis is between 52 years and 56 years. Symptoms of progressive cough and dyspnea predominate. There is great variability in the clinical course of LIP, from resolution without treatment to progressive respiratory failure and death. Although LIP is often regarded as a steroid-responsive condition, and oral corticosteroids continue to be the mainstay of therapy, response is unpredictable. Approximately 33 to 50% of patients die within 5 years of diagnosis, and approximately 5% of cases of LIP transform to lymphoma.

PRELIMINARY STUDY TO TEST THE FEASIBILITY OF USING A LOCAL LYMPH NODE TYPE OF APPROACH TO CHARACTERIZE RESPIRATORY ALLERGENS

There is a critical need to develop animal models that can characterize the potential of respiratory allergy. Dust-mite allergens are one of the major etiological agents in the induction of allergy and asthma in humans. In this study, the effects of intratracheal injection with dust-mite allergen were investigated by analyzing the in vivo proliferative response of lung-draining hilar lymph nodes and histopathological changes in the lung parenchyma. Balb/c mice were inoculated intratracheally with dust-mite allergens, a mixture of Dermatophagoides farinae and D. pteronyssinus dissolved in phosphate-buffered saline, or with an equal volume of saline alone. After 1 week, all the mice were injected intravenously with radioactive 3H-thymidine and sacrificed 5 h later so as to assess the radioactivity incorporated into the hilar lymph nodes. The results indicated a marked increase in the proliferative response in the hilar lymph nodes of the animals treated with the dust-mite allergen as compared to the response of the control group. Treatment with dust-mite allergen also caused perivascular and interstitial eosinophilic inflammation of the lungs, hyperplasia of bronchus-associated lymphoid tissue, and an increase in the eosinophil peroxidase activity in the lungs. These results indicate that intratracheal injection with dust-mite allergen can trigger a number of changes consistent with respiratory allergy, including an increased proliferation in the draining lymph nodes.

Migratory patterns of thoracic duct lymphocytes into bronchus-associated lymphoid tissue of immunized rats.

Lymphocytes continuously circulate between the bloodstream and lymphoid organs, and their migration into lymphatic tissues presumably occurs through selective mechanisms. Although bronchus-associated lymphoid tissue (BALT) is known as an inductive tissue of the common mucosal immune system, little is known about how effectively the lymphocytes in the blood vessels migrate into the BALT, thereby enabling the BALT to act as an effector tissue in the immunologic responses of the lungs. To analyze whether or not thoracic duct lymphocytes (TDL) from immunized and nonimmunized rats possess different migratory patterns to the BALT, 5-(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled TDL were injected into rats with BALT hyperplasia that was produced by intratracheal administration of TNP-KLH, and then the number of labeled cells in the BALT were examined by immunohistochemical methods. We studied the following three groups at 12 h after the injection: group A, intraintestinally immunized donors and intratracheally immunized recipients; group B, nonimmunized donors and intratracheally immunized recipients; group C (control group), nonimmunized donors and nonimmunized recipients. Time course studies 0.5, 4, 12, and 24 h after the injection were done in groups A and C. In a cytokinetic study, larger numbers of CFSE-labeled lymphocytes were found at 12 h and 24 h in group A than in group C. At 12 h after the injection, the absolute number of CFSE-labeled lymphocytes per BALT was significantly higher in group A than in group B (p < 0.05), and was lowest in group C. Histologically, there was a marked proliferation of high endothelial venules (HEV), with findings of adhesion and influx of lymphocytes inside the HEV in group A. These observations indicate that the immunized BALT actively recruits immunized TDL through a specific mechanism of lymphocyte-endothelium recognition in HEV, which partially explains the process of BALT development as an effector tissue for local immunity.

Antigen uptake and subsequent cell kinetics in bronchus-associated lymphoid tissue.

Bronchus-associated lymphoid tissue (BALT) plays an important role in the immunological defence of airways. However, the mechanisms of BALT development, antigen sampling, and subsequent cell kinetics remain unclear. To clarify these chronological processes, we used a Pseudomonas aeruginosa-exposed mouse model. In BALB/c and C57BL/6 mice, BALT development was induced by inhalation of heat-killed P. aeruginosa after sensitization with subcutaneous injection of P. aeruginosa in the presence of Freund's complete adjuvant. Subsequently, we chronologically killed these mice who had inhaled PKH26-labelled P. aeruginosa and examined bacterial transport using fluorescence microscopy. The distribution of interleukin-4-positive cells and interferon-gamma-positive cells was studied immunohistochemically. The degree of BALT hyperplasia was greater in sensitized mice than in non-sensitized mice and in BALB/c mice than in C57BL/6 mice. PKH26-labelled bacteria were found in BALT earlier in sensitized mice than in non-sensitized mice. Immunohistochemical studies revealed that interleukin-4-positive cells predominated over interferon-gamma-positive cells in the peripheral areas of lymphoid follicles. These results indicate that administered antigens are actively transported into BALT and that sensitized Th2 lymphocytes play an important role in forming and maintaining BALT.

Lymphoma of bronchus‐associated lymphoid tissue resembling middle lobe syndrome

We describe three cases of lymphoma of bronchus‐associated lymphoid tissue (BALT). All three patients had long histories of right middle lobe and/or lingula infiltrates on chest radiographs that were compatible with chronic respiratory tract infection. On histological and immunological examination of lung biopsy specimens in the three cases, a lymphoepithelial lesion was identifiable. Phenotyping of the infiltrating lymphocytes showed predominantly B cells, but the lymphocytes were negative for CD10. In two of the cases, rearrangement of the immunoglobulin heavy chain genes was positive, while rearrangements of the bcl‐2 and T cell receptor genes were negative. Each patient had a long history of a productive cough, ranging from 5 to 7 years. Thus, the differential diagnosis of BALToma must be considered when serial chest radiographs show progression over years in the right middle lobe and/or lingula. Furthermore, because BALToma arises from BALT itself and hyperplasia of BALT is dependent on prolonged antigenic stimulation, the onset of these BALTomas may have been related to chronic respiratory tract infections.

Epstein-Barr-virus-associated lymphoproliferative disease of the lung: CT and histologic findings.

To assess the computed tomographic (CT) and histologic findings of intrathoracic lymphoproliferative disease (LPD) associated with the Epstein-Barr virus (EBV). The authors retrospectively reviewed the CT scans of the chest and the pathologic specimens obtained in 24 patients with histologically proved intrathoracic LPD and with positive serologic findings or immunohistochemical staining for EBV. Five patients had acquired immunodeficiency syndrome (AIDS); one had common variable immune deficiency; and 18 were receiving immunosuppressive therapy for heart, lung, or heart-lung (n =15) or bone marrow (n = 2) transplantation and vasculitis (n = 1). Final diagnoses included malignant lymphoma (n = 15), polyclonal LPD (n = 8), and hyperplasia of bronchus-associated lymphoid tissue (n = 1). CT findings included multiple nodules (n = 21), lymphadenopathy (n = 9), areas of groundglass opacification (n = 8), septal thickening (n = 7), consolidation (n = 5), pleural effusion (n = 4), and solitary endobronchial lesion (n = 2). The nodules were 2-4 cm in diameter, involved mainly the middle and lower lung zones, and frequently had a predominantly peribronchovascular (n = 15) or subpleural (n = 14) distribution. EBV-associated LPD may range from benign lymphoid hyperplasia to high-grade lymphoma. The most common CT manifestation consists of multiple nodules, frequently in a predominantly peribronchovascular or subpleural distribution.

Allergic sensitization increases airway reactivity in guinea pigs with respiratory syncytial virus bronchiolitis

Background: Respiratory syncytial virus (RSV) causes acute bronchiolitis in children and has been implicated in the pathogenesis of recurrent wheezing and asthma. However, few children exposed to RSV experience acute bronchiolitis or its sequelae, suggesting a subgroup of susceptible children. An allergic diathesis may predispose children to subsequent airway disease. Objective: This study was carried out to determine whether a preexisting allergic state, induced by repeated inhalational exposures to ovalbumin, potentiates nonspecific airway responsiveness to acetylcholine and increases airway inflammation during acute RSV bronchiolitis in guinea pigs. Methods: Forty guinea pigs were randomized into four groups: nonsensitized, noninfected (ovalbumin–, RSV–); sensitized, noninfected (ovalbumin+, RSV–); nonsensitized, infected (ovalbumin–, RSV+); sensitized, infected (ovalbumin+, RSV+). Depending on grouping, animals were exposed to either repeated aerosols of ovalbumin or saline solution and were subsequently inoculated with either human RSV or uninfected culture medium. Six days after inoculation, animals underwent acetylcholine challenge, and lung specimens were prepared for histologic scoring of airway inflammation. Results: Maximal increases in pulmonary resistance (centimeters of water per milliliter per second) to acetylcholine were greater for RSV alone (12.4 ± 3.9) and ovalbumin alone (13.7 ± 3.9) compared with controls (4.3 ± 1.1), but significantly greater increases occurred in ovalbumin+, RSV+ animals (34.0 ± 11.0). These ovalbumin+, RSV+ animals demonstrated the combined histologic changes noted with RSV alone and ovalbumin alone including airway epithelial necrosis, mononuclear and granulocyte infiltrates, airway wall edema, hyperplasia of bronchus-associated lymphoid tissue, and goblet cell metaplasia. Conclusion: Prior allergic sensitization potentiates the physiologic and structural changes induced by acute RSV bronchiolitis. These results suggest that an allergic diathesis may increase the severity of RSV infections in children. (J Allergy Clin Immunol;100:492-8.)

Effect of 6-fluoro-8-methoxy quinolone (AM-1155) against chronic airway infection with Pseudomonas aeruginosa in a rat model.

We studied the effect of AM-1155, a newly developed quinolone, against chronic airway infection with Pseudomonas aeruginosa using a previously described rat model. AM-1155 (25 mg/kg) or ciprofloxacin (25 mg/kg) or saline (controls) were injected s.c. for 14 days (from day 4 to day 17) after the inoculation of agar beads containing P. aeruginosa. The number of viable cells of intrapulmonary P. aeruginosa, histological findings of the lungs and immunoglobulin levels of serum and bronchoalveolar lavage fluid were examined in rats 11 and 18 days after the treatment. The findings indicated that the number of viable cells of P. aeruginosa in lungs was significantly decreased in the AM-1155- or ciprofloxacin-treated group compared with the non-treated control group. Histological examination in the non-treated control group showed hyperplasia of bronchus-associated lymphoid tissue as well as cellular infiltration in airways, but not prominently in the AM-1155- or ciprofloxacin-treated group. The IgG and IgA levels in serum and bronchoalveolar lavage fluid were significantly lower in the AM-1155- and ciprofloxacin-treated groups than in the control group. These in-vivo effects of AM-1155 were comparable to those of ciprofloxacin. These findings suggest that treatment with AM-1155 and ciprofloxacin suppressed excessive immune responses, preventing progression of airway damage in the chronic infectious state.

A study of bronchus-associated lymphoid tissue in a rat model of chronic pulmonary infection with Pseudomonas aeruginosa.

The immunologic pathogenesis of conditions characterized by chronic pulmonary infections, such as diffuse panbronchiolitis and those associated with cystic fibrosis, had not been fully clarified. Organized lymphoid tissue along the airway has been termed bronchus-associated lymphoid tissue (BALT), and hyperplasia of BALT is frequently observed in chronic pulmonary infections in humans. To investigate the role of BALT, we intratracheally inoculated rats with Pseudomonas aeruginosa (PA) enmeshed in agar beads according to the method of Cash et al., thereby establishing a chronic pulmonary infection model. Histopathological examination of tissue from this rat model revealed the accumulation of lymphocytes and foamy cells around bronchioles. This finding corresponds to chronic bronchiolitis in humans. Hyperplasia of BALT was also observed. Immunohistochemical examination demonstrated that Ia+ cells, helper T cells, surface IgM-positive (sIgM+) cells and sIgA+ cells had gradually increased in BALT and the walls of peripheral airways during the period from day 4 to 7. The anti-PA IgA antibody titer in bronchoalveolar lavage fluid (BALF) was also elevated during this period. After day 21, non-helper T cells became predominant in tissue sections, and the numbers of various immunoglobulin-positive cells as well as the anti-PA IgA antibody titer in BALF were reduced. Histological examination revealed that the inflammatory findings had also diminished. The time course of changes in the various immune cells in BALT and the walls of peripheral airways, paralleled the reductions in anti-PA IgA antibody titers in BALF. Our findings suggest that hyperplastic BALT may be one source of the Ig producing cells which play an important role in the local immune response characteristic of chronic pulmonary infections.