Intraluminal Fibrosis Research Articles

Successful Surgical Repair of a Spontaneous Arterial Aneurysm in an Inland Bearded Dragon (Pogona vitticeps )

Abstract A 5-year-old, female, inland bearded dragon (Pogona vitticeps) was presented with a firm swelling on the ventromedial aspect of the left mandible. Fine-needle aspiration was consistent with blood aspiration; further investigations were declined. Surgical resection was performed successfully with minimal haemorrhage, and resected tissue was sent for histopathology. This was consistent with an aneurysm, fibrosis, and intraluminal fibrosis. The patient has since recovered well, and there has been no recurrence in seven months.

Histopathological significance of connective tissue disease-associated interstitial lung disease in transbronchial lung cryobiopsy specimens

Differentiating between idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia, particularly connective tissue disease-associated interstitial lung disease (CTD-ILD), can be challenging histopathologically, and there may be discrepancies among pathologists. While surgical lung biopsy has traditionally been considered the gold standard for diagnosing interstitial pneumonia, the usefulness of transbronchial lung cryobiopsy (TBLC) has been reported. If TBLC could effectively distinguish between primary and secondary diseases, it would provide a less invasive option for patients. The aim of this study was to identify specific pathologic findings in TBLC specimens that could assist in distinguishing CTD-ILD from IIP. A total of 93 underwent TBLC at Tenri Hospital between 2018 and 2022. We retrospectively reviewed cases of CTD-ILD exhibiting a nonspecific interstitial pneumonia (NSIP) pattern (CTD-NSIP) and cases of NSIP with an unknown etiology (NSIP-UE), as determined through multidisciplinary discussion. Nineteen patients with CTD-NSIP and 26 patients with NSIP-UE were included in the study for clinicopathological analysis. The CTD-NSIP group had a significantly higher proportion of female patients compared to the NSIP-UE group (79% vs. 31%; p = 0.002). The presence of both fresh and old intraluminal fibrosis within the same TBLC specimen was significantly more frequent in CTD-NSIP group than in the NSIP-UE group (p = 0.023). The presence of an NSIP pattern with co-existing fresh and old intraluminal fibrosis in TBLC specimens raised suspicion for CTD-ILD.

Advanced repair of recurrent and low-large hysterotomy defects using a myometrial glide flap

Background The resolution of factors linked to the recurrence of cesarean section defects can be accomplished through a comprehensive technique that effectively addresses the dehiscent area, eliminates associated intraluminal fibrosis, and establishes a vascularized anterior wall by creating a sliding myometrial flap. Objective Propose a comprehensive surgical repair for recurrent and large low hysterotomy defects in women seeking pregnancy or recurrent spotting. Study design A retrospective cohort analysis included 54 patients aged 25–41 with recurrent large cesarean scar defects treated at Otamendi, CEMIC, and Valle de Lili hospitals. Comprehensive surgical repair was performed by suprapubic laparotomy, involving a wide opening of the vesicouterine space, removal of the dehiscent cesarean scar and all intrauterine abnormal fibrous tissues, using a glide myometrial flap, and intramyometrial injection of autologous platelet-rich plasma. Qualitative variables were determined, and descriptive statistics were employed to analyze the data in absolute frequencies or percentages. The data obtained were processed using the InfostatTM statistic program. Results Following the repair, all women experienced normal menstrual cycles and demonstrated an adequate lower uterine segment thickness, with no evidence of healing defects. All patients experienced early ambulation and were discharged within 24 h. Uterine hemostasis was achieved at specific points, minimizing the use of electrocautery. The standard duration of the procedure was 60 min (skin-to-skin), and the average bleeding was 80–100 ml. No perioperative complications were recorded. A control T2-weighted MRI was performed six months after surgery. All patients displayed a clean, unobstructed endometrial cavity with a thick anterior wall (Median: 14.98 mm, IQR 13–17). Twelve patients became pregnant again, all delivered by cesarean between 36.1 and 38.0 weeks, with a mean of 37.17 weeks. The thickness of the uterine segment before cesarean ranged between 3 and 7 mm, with a mean of 3.91 mm. No cases of placenta previa, dehiscence, placenta accreta spectrum (PAS), or postpartum hemorrhage were reported. Conclusions The comprehensive repair of recurrent low-large defects offers a holistic solution for addressing recurrent hysterotomy defects. Innovative repair concepts effectively address the wound defect and associated fibrosis, ensuring an appropriate myometrial thickness through a gliding myometrial flap.

HISTOPATHOLOGICAL FINDINGS OF ACUTE EOSINOPHILIC PNEUMONIA

TOPIC: Lung Pathology TYPE: Original Investigations PURPOSE: It has been reported that AEP histopathologically exhibits diffuse alveolar damage (DAD) with eosinophilia. However, acute respiratory distress syndrome (ARDS), acute interstitial pneumonia (AIP), and acute exacerbation of idiopathic pulmonary fibrosis, also exhibiting DAD histopathologically, are all life-threatening diseases. AFP is rapidly improved by steroids alone without remaining of fibrosis or sometimes even without treatment, whereas these diseases with the same histopathology show greatly different clinical courses, which remains a question to solve. METHODS: Here we investigated the histopathology of AEP in2surgical lung biopsy and 14 TBLB cases. Additionally, we determined the presence or absence of DAD by histopathology in these AEP cases. RESULTS: Characteristic histopathological findings of AEP consist of alveolar edema with infiltration of eosinophils and lymphocytes and edema of perivascular area and interlobular septa. The alveolar spaces showed fibrinous exudates. There were no hyaline membranes or massive intraluminal fibrosis. These histopathological findings of interstitial edema and fluid exudates are consist with radiological findings of lung edema and can explain the rapid and complete improvement. CONCLUSIONS: Because AEP dose not exhibit lung fibrosis histopathologically, it should not to be included in DAD which is associated with lung fibrosis. CLINICAL IMPLICATIONS: We reveal the true histopathology of AEP. DISCLOSURES: No relevant relationships by Hiroshi Mochimaru, source=Web Response

Aspiration: Should It Be Tested or Treated?

Research Article| September 01 2019 Aspiration: Should It Be Tested or Treated? AAP Grand Rounds (2019) 42 (3): 32. https://doi.org/10.1542/gr.42-3-32 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Aspiration: Should It Be Tested or Treated?. AAP Grand Rounds September 2019; 42 (3): 32. https://doi.org/10.1542/gr.42-3-32 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: aspirations (psychology), endotracheal aspiration, inspiration, pulmonary aspiration Source: Tanaka N, Nohara K, Ueda A, et al. Effect of aspiration on the lungs in children: a comparison using chest computed tomography findings. BMC Pediatr. 2019; 19(1): 162; doi: https://doi.org/10.1186/s12887-019-1531-6Google Scholar Investigators from multiple institutions in Osaka, Japan, conducted a retrospective study to assess the relationship between food aspiration and/or saliva aspiration and pneumonia in children and young adults with severe motor disturbances and/or developmental delay. Patients who were receiving care for dysphagia at the Osaka Developmental Rehabilitation Center, Osaka, Japan, were enrolled in the study. Chest CT was performed to detect signs of aspiration pneumonia in study participants. CT scans were evaluated by 2 of the authors who used a standardized method to classify specific radiographic signs of aspiration pneumonia, including parenchymal bands, bronchiolectasis, bronchial wall thickening, bronchiectasis, atelectasis, tree-in-bud pattern, intraluminal airway debris, fibrosis, and air trapping. If any of these findings were present, the patient was classified as having pneumonia. Within 1 week of CT, study participants underwent fiberoptic endoscopic evaluation of swallowing (FEES). The presence of food and/or saliva aspiration was categorized using the penetration-aspiration scale (PAS); PAS scores of 5–6 were classified as aspiration, and scores of 1–4 were classified as no aspiration. Food aspiration and saliva aspiration were categorized separately. The primary outcome was pneumonia at CT. The secondary outcome was a history of pneumonia in the past year based on medical record review. The associations between food or saliva aspiration and these outcomes were assessed with chi-square tests. Data were analyzed on 85 participants with a mean (standard deviation) age of 11.2 (7.2) years (range, 11 months to 26 years). All patients received nutrition orally, with 49.4% also receiving tube feedings. Among study participants, 48 (56.5%) had food aspiration, 26 (30.6%) had saliva aspiration, and 20 (23.5%) had both. Signs of pneumonia were found at CT in 34 (70.8%) patients with food aspiration compared to 20 (54.1%) patients with no food aspiration (P=.11). There was also no statistically significant association between food aspiration and a history of pneumonia in the previous year; 41.7% of those with food aspiration had a history of pneumonia compared to 35.1% of patients with no food aspiration (P=.55). However, among those with saliva aspiration, 88.5% had CT findings of pneumonia versus 52.5% of those without saliva aspiration (P=.002). There was no statistical association between saliva aspiration and a history of pneumonia. The authors conclude that saliva aspiration may be an indicator of aspiration pneumonia risk in contrast to the presence of food aspiration at FEES. Dr Bratton has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. The relationship of aspiration to both acute and chronic pulmonary injury remains poorly understood. The concept that aspiration of food contents causes lung injury is based on the observation of respiratory distress and fever developing within hours after an... You do not currently have access to this content.

Development of an Animal Model of Fibrous Cholangitis in Pigs

ABSTRACTIntroduction: The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). Material and Methods: Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0–5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. Results: Statistically significant differences were observed for most of the histopathological markers between the group of pigs’ offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. Conclusions: Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs.

Aqueous fraction of Sauropus androgynus might be responsible for bronchiolitis obliterans

Bronchiolitis obliterans (BO) has been reported to develop following ingestion of Sauropus androgynus (SA), a leafy shrub distributed in Southeast Asia. Little is known about direct effects of SA on airway resident cells or haematopoietic cells in vitro. Identification of the SA component responsible for the development of BO would be an important key to elucidate its mechanism. We sought to elucidate the direct effects of SA on airway resident cells or haematopoietic cells and identify the SA element responsible for the pathogenesis of BO. SA dry powder was partitioned into fractions by solvent extraction. Human and murine monocytic cells, epithelial cells and endothelial cells were cultured with SA solution or fractions eluted from SA. We also investigated the effect of SA in vivo using a murine BO syndrome (BOS) model. The aqueous fraction of SA induced significant increases of inflammatory cytokine and chemokine production from monocytic lineage cells. This fraction also induced significant apoptosis of endothelial cells and enhanced intraluminal obstructive fibrosis in allogeneic trachea allograft in the murine BOS model. We found individual differences in tumour necrosis factor α (TNF-α) production from monocytes of healthy controls stimulated by this aqueous fraction of SA, whereas it induced high-level TNF-α production from monocytes of patients with SA-induced BO. These results suggest that an aqueous fraction of SA may be responsible for the pathogenesis of BO.

The Future of Deep Venous Thrombosis and Post-thrombotic Syndrome in 2020

This manuscript addresses six major issues involving deep venous thrombosis (DVT) and post-thrombotic syndrome. Prevention will likely see modest advances in pharmacological therapy, mainly by extending prophylaxis in high-risk patients. More notable advances will be observed in mechanical means of prophylaxis, focusing on sustained application of devices that can move larger volumes of blood. Silent, large-vein thrombi continue to place patients at risk for fatal pulmonary embolism. Improved imaging techniques will permit us to identify these patients over the next eight years. In many of those patients, vena caval interruption will be required. Elimination of high-risk filters and the production of improved filters placed through low-profile systems with antithrombotic agents bound to their surface will improve the short- and long-term results for inferior vena cava filters. The long-term management of DVT will focus on establishing appropriate duration for the individual patient and will see the evolution towards direct Xa and IIa inhibitors. Patients with extensive DVT will more commonly receive treatment strategies designed to eliminate thrombus and restore patency. This will substantially reduce post-thrombotic morbidity and reduce recurrence. Post-thrombotic syndrome will see greater attention towards treating the intraluminal fibrosis, thereby eliminating post-thrombotic venous obstruction. Unfortunately, neovalves will still be searching for the appropriate application.

Pathologic diagnosis and clinical analysis of chronic extrinsic allergic alveolitis

To study the clinicopathologic features and diagnostic approach of chronic extrinsic allergic alveolitis (EAA). Seven cases of chronic EAA diagnosed by open lung biopsy or lung transplant were enrolled into the study. The clinical and pathologic features were analyzed and the literature was reviewed. There were altogether 4 men and 3 women. The age of the patients ranged from 30 to 65 years (mean = 48 years). All cases represented chronic form and five cases diagnosed by open lung biopsy also showed features of recent aggravation, leading to hospitalization. Four cases had known history of exposure to inciting gases, pollens and pets, and only 2 cases were positive for allergens. High-resolution CT scan showed ground-glass attenuation and reticular pattern that often had a patchy distribution and central predominance. Bronchoalveolar lavage analysis showed marked lymphocytosis, with CD4(+)/CD8(+) ratio less than 1. Lung function test demonstrated a restrictive ventilatory defect, with decreased compliance, reduced diffusion capacity and high airway obstruction. Five cases had open lung biopsy performed and two cases had undergone lung transplantation. Pathologic examination showed bronchiolocentric cellular interstitial pneumonia, interstitial fibrosis, non-caseating epithelioid granulomas, epithelioid histiocytic infiltrate in the respiratory bronchioles and intraluminal budding fibrosis. The five cases with open lung biopsy performed also showed neutrophilic infiltrate in the alveoli. The two lung transplant cases were complicated by severe fibrotic changes. Chronic EAA demonstrates characteristic pathologic features. Definitive diagnosis requires correlation with clinical and radiologic findings due to possible morphologic mimicry of other diffuse parenchymal lung diseases.

Bronchiolitis Obliterans Syndrome: The Final Frontier for Lung Transplantation

Bronchiolitis obliterans syndrome (BOS) is a form of chronic lung allograft dysfunction that affects a majority of lung transplant recipients and is the principal factor limiting long-term transplant survival. BOS is characterized by progressive airflow obstruction unexplained by acute rejection, infection, or other coexistent condition. Although BOS is a proven useful clinical syndrome that identifies patients at increased risk for death, its clinical course and underlying causative factors are now recognized to be increasingly heterogeneous. Regardless of the clinical history, the primary pathologic correlate of BOS is bronchiolitis obliterans, a condition of intraluminal airway fibrosis. This article highlights the body of developing research illustrating the mechanisms by which BOS is mediated, including alloimmune reactivity, the emerging roles of humoral and autoimmunity, activation of innate immune cells, and response to nonimmune-related allograft insults, such as infection and aspiration. In addition, we underscore emerging clinical implications and promising future translational research directions that have the potential to advance our knowledge and improve patient outcomes.

Severe Airway Epithelial Injury, Aberrant Repair and Bronchiolitis Obliterans Develops after Diacetyl Instillation in Rats

BackgroundBronchiolitis obliterans (BO) is a fibrotic lung disease that occurs in a variety of clinical settings, including toxin exposures, autoimmunity and lung or bone marrow transplant. Despite its increasing clinical importance, little is known regarding the underlying disease mechanisms due to a lack of adequate small animal BO models. Recent epidemiological studies have implicated exposure to diacetyl (DA), a volatile component of artificial butter flavoring, as a cause of BO in otherwise healthy factory workers. Our overall hypothesis is that DA induces severe epithelial injury and aberrant repair that leads to the development of BO. Therefore, the objectives of this study were 1) to determine if DA, delivered by intratracheal instillation (ITI), would lead to the development of BO in rats and 2) to characterize epithelial regeneration and matrix repair after ITI of DA.Methods and Main ResultsMale Sprague-Dawley rats were treated with a single dose of DA (125 mg/kg) or sterile water (vehicle control) by ITI. Instilled DA resulted in airway specific injury, followed by rapid epithelial regeneration, and extensive intraluminal airway fibrosis characteristic of BO. Increased airway resistance and lung fluid neutrophilia occurred with the development of BO, similar to human disease. Despite rapid epithelial regeneration after DA treatment, expression of the normal phenotypic markers, Clara cell secretory protein and acetylated tubulin, were diminished. In contrast, expression of the matrix component Tenascin C was significantly increased, particularly evident within the BO lesions.ConclusionsWe have established that ITI of DA results in BO, creating a novel chemical-induced animal model that replicates histological, biological and physiological features of the human disease. Furthermore, we demonstrate that dysregulated epithelial repair and excessive matrix Tenacin C deposition occur in BO, providing new insights into potential disease mechanisms and therapeutic targets.

Clinicopathological findings in 5 patients with acute eosinophilic pneumonia

We studied 5 patients with acute eosinophilic pneumonia. Radiologic findings were Kerley's lines and pleural effusion on chest X-ray films, and interlobular septa on chest CT scans. Examination of transbronchial lung biopsy specimens revealed infiltration of eosinophils and lymphocytes into alveolar walls and edema of alveolar walls, interlobular septa, and perivascular connective tissue. The findings of interstitial edema were consistent with the radiological findings. Epithelial damage and bud-type intraluminal fibrosis were also seen, but residual alveolar structure was maintained. Bronchoalveolar lavage fluid contained abnormally high percentages of eosinophils and lympocytes. It also contained basophils and mast cells, which were not seen in fluid from normal subjects. Fluid from patients with chronic eosinophilic pneumonia had significantly fewer basophils than did fluid from those with acute eosinophilic pneumonia (p < 0.01). These findings suggest that release of chemical mediators from basophils plays a key role in interstitial edema in acute eosinophilic pneumonia.

Transbronchial biopsy is clinically useful in classifying patients with interstitial pneumonia associated with polymyositis and dermatomyositis

The histological type of intraluminal fibrosis is an important prognostic factor for interstitial pneumonia. We therefore examined whether transbronchial lung biopsy (TBLB) specimens are useful for predicting the clinical course and prognosis of patients with interstitial pneumonia associated with polymyositis and dermatomyositis (PM/DM), with particular attention to the different types of intraluminal fibrosis. Twenty-five cases of interstitial pneumonia associated with PM/DM were classified according to the pattern of intraluminal fibrosis as assessed by TBLB, and the clinical course and response to treatment were compared. Interstitial fibrosis was evaluated by sequential thin-section CT scans. In 19 of 25 (76%) cases, there was sufficient intraluminal fibrosis to perform an evaluation. Intraluminal fibrosis was classified as bud (polyp) type or mural incorporation type (either alone or mixed with bud type). The bud type was seen in five cases and these improved following treatment with corticosteroids only. The mural incorporation type was seen in 14 cases. In 11 of these 14 cases, progressive long-term fibrosis developed and four cases were fatal, in spite of corticosteroid and immunosuppressive therapy. The response to drugs (P < 0.01) and survival (P < 0.05) were significantly greater in patients with bud-type than mural incorporation-type intraluminal fibrosis. Classification of the pattern of intraluminal fibrosis as assessed by TBLB is useful for predicting the response to treatment, clinical course and prognosis of interstitial pneumonia associated with PM/DM.

Radiological Imaging of Aortic Aneurysms

The development of radiological equipment such as MDCT or ultrasonography has increased the diagnostic accuracy of aortic aneurysms and has allowed for improvements in surgical and interventional treatment techniques. However, the mortality and morbidity rate of aortic aneurysms has not decreased significantly. For this reason, there is continuous interest in radiological evaluations of aortic aneurysms. This report reviews the radiological image findings and useful indications for both the diagnosis and surveillance of aortic aneurysms. The popular radiological features of an aortic aneurysm are aortic expansion, combined atherosclerosis, intraluminal mural thrombus, perianeurysmal inflammation and fibrosis, and perianeurysmal hemorrhage due to rupture. As rupture is the most important complication of an aortic aneurysm, various signs of an impending rupture have been suggested. These include the following: a maximum aneurysmal diameter larger than the threshold value, a high expansion rate, periaortic sentinel hemorrhage, and a hyperattenuating crescent in the mural thrombus or aneurysmal wall. To acknowledge the impending rupture of an aortic aneurysm, careful depiction of the clues is indispensable. (Korean Circulation J 2007;37:337-347)

Clinicopathological differences between acute and chronic eosinophilic pneumonia

Considerable confusion exists regarding the proper classification of idiopathic eosinophilic pneumonia (IEP). Furthermore, there are no reports describing the clinicopathological differences between the various forms of eosinophilic pneumonias. The histological findings in acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) were examined and the clinical and radiological features were contrasted with them. Radiologically, ground glass opacity and interlobular septal thickening were characteristic of the AEP cases, while air space consolidation was seen in all CEP cases. Histologically, interstitial oedema and fibrin deposition were prominent in the AEP cases. Type II cells were detached from the alveolar walls, although the basal lamina was predominantly intact. In CEP, in addition to cellular infiltration, there was prominent intraluminal fibrosis. Disruption of the basal lamina was observed and nests of intraluminal fibrosis were directly adjacent and connected to the alveolar walls. An essential histological difference between AEP and CEP is the severity of basal lamina damage and the amount of subsequent intraluminal fibrosis. In AEP particularly, these findings explain the radiographical findings, as well as the rapid and complete improvement noted in such cases.

Histopathologic Changes Related to Fibrotic Oviduct Occlusion After Genital Tract Infection of Mice With Chlamydia muridarum

We sought to determine if intraluminal occluding fibrosis of the oviduct occurs after urogenital Chlamydia muridarum infection in mice. Oviduct occlusion was assessed by infusing dye into the distal uterus and tracking the diffusion of the dye into the oviduct. We also conducted histologic assessment of the affected tissues using hematoxylin and eosin (H&E) and Masson trichrome stains. All previously infected susceptible mice had occluded oviducts compared with 17.5% of previously uninfected mice. Oviduct occlusion correlated with hydrosalpinx formation and infertility. Intraluminal oviduct fibrosis was observed in several sections of tissue displaying hydrosalpinx but not in tissues without hydrosalpinx. Fibrosis was localized to the oviduct isthmus and oviduct proper, proximal to the uterus. Intralumenal occluding fibrosis of the oviduct is a sequela of infection with C. muridarum in this model. These observations support the use of the murine model to study pathogenesis of chlamydial upper genital tract infection.

Hermansky-Pudlak Syndrome with Interstitial Pneumonia without Mutation of HSP1 Gene

A 57-year-old man with occulocutaneous albinism was admitted to our hospital because of exertional dyspnea and an abnormal shadow on chest roentgenogram. Chest CT revealed diffuse interstitial shadows with reticulonodular opacities in the bilateral whole lung fields and his pulmonary function test was consistent with a restrictive finding. Histologically, intraluminal diffuse fibrosis and interstitial fibrosis existed and ceroid-like materials within alveolar macrophages were demonstrated in a transbronchial lung biopsy specimen. In addition, because platelet dysfunction and ceroid-like materials within the reticuloendothelial cells of urine and bone marrow aspiration were recognized, we made a diagnosis of Hermansky-Pudlak syndrome (HPS). Gene analysis of the patient's peripheral blood cells did not reveal that he was a compound homogeneity for HPS1 gene mutations. Concerning treatment, although corticosteroid therapy was administered, his clinical symptoms and abnormal chest shadow have not changed.

Respiratory Reovirus 1/L Induction of Intraluminal Fibrosis, a Model of Bronchiolitis Obliterans Organizing Pneumonia, Is Dependent on T Lymphocytes

Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinical syndrome characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intraalveolar fibrosis. We have developed an animal model of BOOP where CBA/J mice infected with 1 x 10(6) plaque-forming units (PFU) reovirus 1/L develop follicular bronchiolitis and intraalveolar fibrosis similar to human BOOP. In this report, we demonstrate a role for T cells in the development of intraluminal fibrosis associated with BOOP. Corticosteroid treatment of reovirus 1/L-infected mice both inhibited the development of fibrotic lesions when administered early in the time-course and promoted the resolution of fibrotic lesions when corticosteroid administration was delayed. Further, the depletion of either CD4(+) or CD8(+) T cells before reovirus 1/L infection also inhibited fibrotic lesion development. Both corticosteroid treatment and depletion of CD4(+) or CD8(+) T cells also resulted in decreased expression of the proinflammatory and profibrotic cytokines, interferon (IFN)-gamma and monocyte chemoattractant protein-1 (MCP-1). Further, treatment of mice with a neutralizing monoclonal antibody to IFN-gamma also significantly inhibited the development of fibrosis. Taken together, these results suggest a significant role for T cells in the development of reovirus 1/L-induced BOOP fibrotic lesions in CBA/J mice and suggests that T(H)1-derived cytokines, especially IFN-gamma, may play a key role in fibrotic lesion development.

Creation of ureteropelvic junction obstruction and its correction by chemical glue-assisted laparoscopic dismembered pyeloplasty.

We established a porcine model of ureteropelvic junction (UPJ) obstruction using a laparoscopic technique and assessed the outcome of standard suture-assisted and chemical glue-assisted laparoscopic pyeloplasty. Female domestic pigs (N = 20) underwent laparoscopic suture-ligature to create UPJ obstruction. One month later, laparoscopic end-to-end anastomosis was performed to correct the obstruction: with standard suturing techniques in 10 animals and with chemical (cyanoacrylate) glue in the other 10. Postoperative ureteral stents were not used. Four weeks postoperatively, intravenous urography was performed to evaluate the patency of the anastomoses. The UPJ was procured by laparotomy to assess the anastomoses and periureteral fibrosis histologically. The UPJ obstruction was created in an average of 15 +/- 6 minutes. There was no early postoperative mortality. Eighteen pigs survived for at least 1 month, and UPJ obstruction developed in 17 (95%). Microscopically, the lumen of the UPJ was partially occluded, measuring an average of 40% +/- 5% of normal. After laparoscopic correction, a patent UPJ was found in seven of nine animals treated with traditional sutures. Among the eight animals with chemically glued anastomoses, none had a patent UPJ, and severe periureteral adhesions and intraluminal fibrosis were noted at the pyeloplasty site. Marked ureteral tortuosity was present in six of the eight pigs receiving glue-assisted pyeloplasty but in none of the animals having suture-assisted pyeloplasty. Ureteropelvic junction obstruction was established by laparoscopic suture-ligature in a porcine model with a 95% success rate. Chemical glue-assisted anastomosis was inferior to standard laparoscopic sutures for pyeloplasty to correct the obstruction.

Differential role for T cells in the development of fibrotic lesions associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia versus Acute Respiratory Distress Syndrome.

Bronchiolitis obliterans organizing pneumonia (BOOP) and Acute Respiratory Distress Syndrome (ARDS) are two pulmonary diseases with fibrotic components. BOOP is characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intra-alveolar fibrosis. ARDS is a biphasic disease that includes an acute phase, consisting of severe leukocyte infiltration, edema, hemorrhage, and the formation of hyaline membranes, and a chronic phase, which is characterized by persistent intra-alveolar and interstitial fibrosis. CBA/J mice infected with 1 x 10(6) plaque-forming units (pfu) reovirus 1/L develop follicular bronchiolitis and intra-alveolar fibrosis similar to BOOP. In contrast, CBA/J mice infected with 1 x 10(7) pfu reovirus 1/L develop histologic characteristics of ARDS including diffuse alveolar damage, hyaline membranes, and intra-alveolar fibrosis. In this report, we demonstrate a differential role for T lymphocytes in the development of fibrosis associated with BOOP versus ARDS. Neonatally thymectomized CBA/J mice infected with 1 x 10(7) pfu (ARDS) reovirus 1/L still develop the hallmark characteristics of ARDS, including a severe viral pneumonia with cellular infiltrates comprised mainly of macrophages and neutrophils, hyaline membrane formation, and hemorrhage during the acute phase of the disease and persistent intra-alveolar fibrosis during the chronic phase of the disease. In contrast, neonatally thymectomized CBA/J mice infected with 1 x 10(6) pfu (BOOP) reovirus 1/L do not develop intra-alveolar fibrosis associated with BOOP. Therefore, while T cells are necessary for the development of intraluminal fibrosis associated with BOOP, they are not necessary for the development of intraluminal fibrosis associated with ARDS. Furthermore, we suggest that interferon-gamma plays a key role in the fibrotic process and that elevated levels of interferon-gamma are associated with a continuum from least to more severe fibrosis.