Constrictive Bronchiolitis Obliterans Research Articles

Constrictive bronchiolitis obliterans with a presumptive etiology of preceding feline herpesvirus infection in a cat

BackgroundBronchiolar disorders are rarely recognized in cats. Constrictive bronchiolitis obliterans is characterized by concentric peribronchiolar fibrosis and inflammation of the bronchioles, but the underlying causes remain poorly understood in current small animal medicine.Case presentationA 9-year-old cat presented with paroxysmal tachypnea, infrequent cough and persistent labor breathing. Thoracic radiography showed lung hyperinflation and bronchointerstitial pattern, and pulmonary function assessment revealed flow limitation in the late-expiratory phase and poor response to short-acting bronchodilator. Dorsally distributed subpleural ground glass opacities with distinct margin and tree-in-bud opacities were observed on lung high-resolution computed tomography. The cat underwent bronchoalveolar lavage (BAL) and showed severe neutrophilic inflammation. Feline herpesvirus was the only pathogen detected in the BAL fluid. Multiple therapeutic attempts were unsuccessful and the cat died 8 weeks after the initial presentation. Necropsy revealed the infiltration of inflammatory cells, obstruction of the bronchiolar lumen, and submucosal concentric fibrosis suggesting constrictive bronchiolitis obliterans. Combining the pre- and post-mortem findings, as well as the time from symptom onset or BAL to necropsy, constrictive bronchiolitis obliterans was possibly triggered by a preceding feline herpesvirus infection in this case.ConclusionsThe history of nonvaccinated status, lower airway neutrophilic inflammation, and presence of feline herpesvirus in the BAL fluid without coexistence of other pathogens led to the presumption that constrictive bronchiolitis obliterans was induced by a preceding feline herpesvirus infection in this cat. The pathological changes of bronchiolitis obliterans induced by a preceding feline herpesvirus infection could be different from that of cats with acute herpesvirus pneumonia, such as intranuclear inclusions would disappear over time and were no longer found 7–10 days after inoculation. The presence of patchy distribution of subpleural ground glass opacities on lung high-resolution computed tomography should raise the suspicion of peribronchiolar fibrosis. Clinical awareness of bronchiolar disorders as a differential diagnosis is important in cats with lung hyperinflation and labored breathing who show poor reversibility to bronchodilator.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: DIPNECH.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare premalignant condition. Over the past decade, there has been increased recognition and reporting of DIPNECH in the literature. Currently, our understanding is that DIPNECH has a predilection to nonsmoking females around their sixth decade of life. The patients usually present with chronic cough, dyspnea, and computed tomography (CT) showing multifocal pulmonary nodules with associated mosaic attenuation. The clinic history is largely driven by constrictive obliterative bronchiolitis, which typically has an indolent course with progressive respiratory decline and difficult to treat symptoms. DIPNECH has been found to be associated with carcinoid tumors. Recent data has found that symptomatic DIPNECH patients respond to somatostatin analog (SSA). SSAs provide improvement in symptoms and pulmonary function tests. According to small studies and case series SSAs can be used in conjunction with steroids and bronchodilators for the treatment of respiratory symptoms. DINPNECH is a premalignant condition that can transform into carcinoid tumors. Although the recent data suggest the potential efficacy of SSA, further studies are needed to validate such results in prospective fashion in addition to investigating other therapeutic agents.

Burden of respiratory abnormalities in microwave popcorn and flavouring manufacturing workers

ObjectivesDiacetyl, a butter flavour compound used in food and flavouring production, is a respiratory toxin. We characterised the burden of respiratory abnormalities in workers at popcorn and flavouring manufacturing facilities...

Bronchiectasis and other chronic lung diseases in adolescents living with HIV.

The incidence of pulmonary infections has declined dramatically with improved access to antiretroviral therapy (ART) and cotrimoxazole prophylaxis, but chronic lung disease (CLD) is an increasingly recognized but poorly understood complication in adolescents with perinatally acquired HIV. There is a high prevalence of chronic respiratory symptoms, abnormal spirometry and chest radiographic abnormalities among HIV-infected adolescents in sub-Saharan Africa, wherein 90% of the world's HIV-infected children live. The incidence of lymphocytic interstitial pneumonitis, the most common cause of CLD in the pre-ART era, has declined with increased ART access. Small airways disease, particularly constrictive obliterative bronchiolitis and bronchiectasis, are emerging as leading causes of CLD among HIV-infected adolescents in low-income and middle-income countries. Asthma may be more common in high-income settings. Likely risk factors for CLD include recurrent pulmonary infections, air pollution, HIV-related immune dysfunction, and untreated HIV infection, particularly during critical stages of lung development. Globally, the importance of HIV-associated CLD as a cause of morbidity and mortality is increasing, especially as survival has improved dramatically with ART and growing numbers of children living with HIV enter adolescence. Further research is urgently needed to elucidate the natural history and pathogenesis of CLD, and to determine optimal screening, diagnostic and treatment strategies.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome.

The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may be used to describe a clinico-pathological syndrome, as well as an incidental finding on histological examination, although there are obvious differences between these two scenarios. According to the World Health Organization, the definition of DIPNECH is purely histological. However, DIPNECH encompasses symptomatic patients with airway disease, as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumourlets/carcinoid tumours. DIPNECH is also considered a pre-neoplastic lesion in the spectrum of pulmonary neuroendocrine tumours, because it is commonly found in patients with peripheral carcinoid tumours.In this review, we summarise clinical, physiological, radiological and histological features of DIPNECH and critically discuss recently proposed diagnostic criteria. In addition, we propose that the term "DIPNECH syndrome" be used to indicate a sufficiently distinct patient subgroup characterised by respiratory symptoms, airflow obstruction, mosaic attenuation with air trapping on chest imaging and constrictive obliterative bronchiolitis, often with nodular proliferation of neuroendocrine cells with/without tumourlets/carcinoid tumours on histology. Surgical lung biopsy is the diagnostic gold standard. However, in the appropriate clinical and radiological setting, transbronchial lung biopsy may also allow a confident diagnosis of DIPNECH syndrome.

Pleuroparenchymal fibroelastosis and non-specific interstitial pneumonia: frequent pulmonary sequelae of haematopoietic stem cell transplantation.

Pulmonary sequelae, reported as chronic graft-versus-host disease (cGVHD), of haematopoietic stem cell transplantation (HSCT) include constrictive bronchiolitis obliterans (CBO), lymphocytic bronchiolitis (LB), and veno-occlusive disease (VOD); recently, pleuroparenchymal fibroelastosis (PPFE) has also been described in bone marrow transplant recipients. The histological features of pulmonary HSCT sequelae have not been described systematically. The aim of the study was to review and identify the histological features of PPFE after bone marrow transplant. A retrospective review of 20 patients who underwent lung transplantation for pulmonary disease following HSCT between 2004 and 2013 was conducted. The patient age at transplantation ranged from 8 years to 57 years (median, 27.5 years). Fifteen patients had cGVHD in other organs (skin, nine; liver, six; salivary gland, six). Lung transplantation was performed at a median of 4.6 years (range, 1.2-14.8 years) post-HSCT. Histologically, all cases had CBO, with concurrent LB in 10, and VOD in three. PPFE was identified in 15 cases (75%), with subpleural (15), paraseptal (11) and centrilobular (13) distributions; and non-specific interstitial pneumonia (NSIP) was identified in 15 cases (75%), with fibrotic (nine) and cellular (six) patterns. PPFE was distributed in all lobes, with a predominance in the upper lobe. NSIP was mostly focal, with two cases having diffuse involvement. PPFE and NSIP were frequently seen in HSCT patients. Possible causes may include reactions to drugs or radiation, or cGVHD.

Bronchiolitis obliterans associated with Stevens-Johnson Syndrome: histopathological bronchial reconstruction of the whole lung and immunohistochemical study

This study presents an extremely rare case of constrictive bronchiolitis obliterans (BO) associated with Stevens-Johnson Syndrome (SJS) provides the morphological and immunohistochemical features using histopathological bronchial reconstruction technique. A 27-year-old female developed progressive dyspnea after SJS induced by taking amoxicillin at the age of 10. Finally, she died of exacerbation of type II respiratory failure after 17 years from clinically diagnosed as having BO. Macroscopic bronchial reconstruction of the whole lungs at autopsy showed the beginning of bronchial obliterations was in the 4th to 5th branches, numbering from each segmental bronchus. Once they were obliterated, the distal and proximal bronchi were dilated. Microscopic bronchial reconstruction demonstrated the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal narrowing or obliteration. Moreover, CD3-, CD20-, and CD68-positive cells were found in the BO lesions. CD34- and D2-40-positive cells were mainly distributed in the peribronchiolar lesions and bronchiolar lumens, respectively. SMA- and TGF-β-positive cells were seen in the fibrous tissue of BO lesions.The virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1071703140102601.

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS). Cells were isolated from surgical lung biopsies of eight HSCT patients with BOS. Proliferation was assessed by [(3)H]-thymidine incorporation. Biopsies revealed constrictive bronchiolitis obliterans in three patients and lymphocytic bronchiolitis in five patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Costimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1 of patients with bronchiolitis obliterans was unchanged. Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMF in vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT.

Lung Histology Predicts Outcome of Bronchiolitis Obliterans Syndrome after Hematopoietic Stem Cell Transplantation

Bronchiolitis obliterans (BO) is a severe complication after allogeneic hematopoietic stem cell transplantation with an unfavorable prognosis. Lung biopsy remains the gold standard for diagnosis. In this retrospective single-center study, we describe 33 patients who underwent biopsy for suspected BO. Ten patients had constrictive BO (CBO); 9 had lymphocytic bronchiolitis (LB), characterized by lymphocytic infiltration of the bronchioles. Six additional patients (4, CBO; 2, LB) had concomitant infection; 8 had other pathological diagnoses. Seven patients with CBO and 3 with LB met the National Institutes of Health consensus BO syndrome definition criteria. An additional 7 patients with histologically confirmed CBO did not meet the consensus definition, 4 of them because of concomitant airway infection. At diagnosis, there were no significant differences between the CBO and LB groups in clinical presentation; pulmonary function tests (median forced expiratory volume in one second [FEV1] at baseline, 90.4% and 99% predicted, at time of video-assisted thoracoscopic surgery, 55.1% and 60.8% for CBO and LB groups, respectively); and chest scans. Treatment was similar in both groups but outcome was different depending on histological findings. FEV1 significantly improved in LB patients compared with CBO patients. Survivals at 1 and 3 years were 77% ± 12% and 60% ± 14% for patients with CBO and 91% ± 9% for patients with LB (P = .028). Lung biopsy in patients with suspected BO enables better characterization of the pattern of BO syndrome. In contrast to CBO, LB is associated with a good long-term prognosis.

Toxicant-Induced Constrictive Bronchiolitis Obliterans and TIMP Interactions in an Animal Model

Toxicant-Induced Constrictive Bronchiolitis Obliterans and TIMP Interactions in an Animal Model

Histopathological bronchial reconstruction of human bronchiolitis obliterans

To clarify the morphological mechanisms of airway obliteration in bronchiolitis obliterans (BO) associated with various causes, we conducted a retrospective study of 9 patients with a histological diagnosis of BO. The morphological characteristics were analyzed by histopathological bronchial reconstruction. BO was classified into two major morphologic subtypes: constrictive BO (CoB) and cellular/destructive BO (CDB). CoB is characterized by concentric narrowing of the airway lumen due to submucosal fibrosis. In contrast, in CDB the narrowing of the airway lumen is due to intraluminal, mural, and peribronchiolar infiltration of inflammatory cells as well as proliferation of granulation tissue. The histopathological diagnosis was CoB in 6 patients and CDB in 3 patients. Macroscopic bronchial reconstruction in CoB demonstrated that the beginnings of bronchial obliterations were in the 4th to 7th branches, numbering from each segmental bronchus and the lesions were distributed intermittently. Histopathologically, the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal obliteration in CoB, whereas the primary lesions in CDB revealed more continuous obliteration of the bronchiolar lumen than observed in CoB. In conclusion, this bronchial reconstruction study demonstrated marked morphological differences in the mechanisms of airway obliteration between two major morphologic subtypes of BO.

Sauropus androgynus-associated bronchiolitis obliterans of mother and daughter – autopsy report

Sauropus androgynus (SA) is a vegetable that causes constrictive bronchiolitis obliterans (BO) with consequent findings classified into injury, inflammation and fibrosis, according to clinical factors including amount of SA exposure, period of SA exposure, and individual predisposition. We reported mother and daughter SABO autopsy cases with similar clinical course, including 11 month SA exposure and Aspergillosis infection after high dose prednisolone therapy. Their major differences were in the amount of SA exposure (mother: 1440 g, daughter: 2190 g) and the survival period post exposure (mother: 21 months, daughter: 32 months). The histopathological comparison between them showed a statistical difference in the density of foamy macrophage accumulation of moderately obstructed airways, but not in the extent of fibrosis, elastic lamina destruction, or smooth muscle hyperplasia. Foamy macrophages tend to accumulate relatively early in the course of SABO at the site with severe damage, accelerating BO formation for as long as the patient survives.

Effectiveness of magnetic resonance angiography in the evaluation of lung perfusion in constrictive bronchiolitis obliterans

Childhood constrictive bronchiolitis obliterans (CBO) is characterized clinically by the persistence of obstructive respiratory symptoms following a prolonged episode of lower respiratory viral infection. The diagnosis depends on the clinical, radiological and laboratory findings. Perfusion defects on scintigraphy may predict the severity. This report describes a 2-year-old girl who presented with a 15-day history of respiratory distress despite treatment. Auscultation of the lungs revealed prolonged expiration and bilateral crepitant rales. CXR revealed bilateral paracardiac infiltration. She improved with a treatment regimen of bronchodilators, systemic steroids and antibiotherapy; however, rales were detected again 10 days after discharge. HRCT of the lung revealed an oligaemic-mosaic pattern, more prominent in the left lung. The diagnosis of CBO was made on the basis of these clinical and radiological findings. Perfusion was normal in the right lung but diffusely decreased in the left lung on perfusion scintigraphy by Tc99m-MAA. Magnetic resonance (MR) angiography source images of the lungs revealed significant but not diffuse perfusion defects in the left lung, in contrast to radionuclide scintigraphy. There were areas of low perfusion in the right lung, which were not evident in radionuclide scintigraphy. The use of source images of MRI angiography of the lungs may be more sensitive and specific for the detection of perfusion defects in patients with CBO and may assist in determining the prognosis.

BLOCKING ELEVATED MATRIX METALLOPROTEINASE PATHWAYS OF CBO: FUTURE THERAPY?

PURPOSE: Gelatinases impact the pathogenesis of constrictive bronchiolitis obliterans (CBO), the pathologic correlate of chronic allograft rejection which limits lung transplant survival. We have shown elevation of MMP-9 in tissue and BAL of inbred rodent models with CBO pathology. We hypothesize that inhibition of phosphorylation pathways will reduce MMP-9 and attenuate CBO. We tested three inhibitor chemicals acting on phosphorylation pathways between TGFβ and MMP-9 for 1) cellular toxicity and 2) inhibition of MMP-9 in vitro.

Popcorn lung and bronchiolitis obliterans: a critical appraisal

To perform a critical review of a series of journal articles and Health Hazard Evaluation Reports (HHER) by the National Institute for Occupational Safety and Health (NIOSH), where they have described the incidence of fixed obstructive pulmonary disease in a population of workers exposed to butter flavorings. The clinical presentations, diagnostic modalities frequently employed and a review of the pertinent clinical literature are discussed for constrictive bronchiolitis and bronchiolitis obliterans with intraluminal polyps; two distinct forms of bronchiolitis obliterans (BO). An analysis of the NIOSH reports and scientific articles is provided, followed by suggestions for evaluating this public and occupational health concern moving forward. Cases of lung disease in the food flavorings industry discussed in the literature have not been sufficiently documented to allow the conclusion that BO has been caused by diacetyl or butter flavoring. Further research is required to establish the causative agent(s). The diagnosis of bronchiolitis obliterans should be reserved for those individuals who have diagnostic lung biopsy findings, obtained and interpreted by clinicians who are experienced with this complex disorder.

Constrictive bronchiolitis obliterans: the fibrotic airway disorder

Constrictive bronchiolitis obliterans is an important respiratory illness because of its underlying irreversible fibrotic process, and is defined as concentric fibrosis in the bronchiolar submucosal layer with continual external circular scarring. The fibrotic and destructive nature of this lesion is the defining characteristic. Although patchy, the airway may become slit-like or obliterated from this fibrotic process, resulting in bronchiolitis obliterans. Constrictive bronchiolitis is limited to the bronchioles and does not extend into the alveoli. The clinical features of constrictive bronchiolitis consist of a chest radiograph that is often normal, early inspiratory crackles and irreversible airflow obstruction by pulmonary function testing. Chest CT scans show a mosaic pattern, air trapping by the expiratory film, bronchiolectasis and thickened small airway walls. Although idiopathic constrictive bronchiolitis is rare, the lesion is common among lung-transplant recipients. The lesion also occurs from certain types of toxic fumes, some of the connective tissue diseases, specific types of medications and post respiratory infection. Unusual exposures have also been described as a cause of constrictive bronchiolitis, such as consumption of the leafy vegetable Sauropus androgynus in far eastern Asia and from inhaling diacetyl, the ketone butter flavoring used in microwave popcorn production. Empirical treatment consists of corticosteroid and immunosuppressive agents. Antifibrotic agents may be successful in the future. This is generally a nonsteroid-responsive lesion and for disabling disease, lung transplantation can be a successful option.

Small Chronic Pneumothoraces and Pulmonary Parenchymal Abnormalities After Bone Marrow Transplantation

The features of 4 allogeneic bone marrow transplant patients with an unusual late-onset complication of pulmonary abnormalities with small chronic pneumothoraces are described. Thin-section computed tomography demonstrated upper zone fibrotic changes and diffuse abnormalities suggestive of constrictive obliterative bronchiolitis. An important feature of the pneumothoraces was that they tended to be recurrent and small. We suggest that awareness of this unusual association may be useful in the radiologic evaluation of late-onset pulmonary complications after allogeneic bone marrow transplantation.

Obliterative bronchiolitis in a 13-year-old pre-transplant cystic fibrosis patient

Cystic fibrosis (CF)-related lung disease is characterized by a broad spectrum of pathologic changes. Most of these changes relate to progressive bronchiectasis and airway destruction due to recurrent infections. Other airway pathologies include but are not limited to nasal polyposis, bronchial hyperactivity, pneumothorax and allergic bronchopulmonary aspergillosis (ABPA). Constrictive obliterative bronchiolitis (COB) in CF is usually seen in post-transplant settings including lung and heart–lung transplants. We report a 13-year-old boy with CF and intractable deterioration in lung function that was ultimately diagnosed as COB.

63-jährige Türkin mit rezidivierenden Pneumonien

The differential diagnosis of a sinubronchial syndrome includes cystic fibrosis, allergic bronchopulmonic aspergillosis, Kartagener's syndrome, hypogammaglobulinemia and bronchioli-associated processes. The latter include cryptogenic organising pneumonia, constrictive bronchiolitis obliterans as well as the respiratory bronchiolitis. Our case presented a persistent interstitial shadow in the x-rax of the thorax and a relevant, mixed ventilation disturbance in lung function. A surgically performed lung biopsy finally allowed the diagnosis of diffuse panbronchiolitis, which is seldom found in central Europe. This disease is of unknown etiology and responds to long-term macrolide therapy.

Paraneoplastic autoimmune multiorgan syndrome: Review of the literature and support for a cytotoxic role in pathogenesis

Paraneoplastic autoimmune multiorgan syndrome (PAMS), first described as paraneoplastic pemphigus in 1990, is an autoimmune blistering disease associated with neoplasia. Patients with this rare disorder have severe blistering and painful erosions of the oral cavity and various other cutaneous findings ranging from classic pemphigus vulgaris-like erosions to targetoid lesions resembling erythema multiforme and papular to more confluent lichenoid eruptions. This syndrome involves multiple organ systems, and its high rate of mortality often stems from constrictive bronchiolitis obliterans. The histologic findings are as diverse as the clinical presentation, often making diagnosis difficult initially. Immunodermatologic and serologic laboratory findings typically establish the diagnosis. These results can be confirmed with immunoprecipitation profiling of specific molecular weight protein markers. The proposed pathogenesis of PAMS continues to evolve, and recent reports implicate the involvement of cell-mediated, cytotoxic immunity, in addition to humoral autoantibodies. This review characterizes and summarizes the clinical, pathologic, and immunohistologic features of PAMS and outlines the possible role of cytotoxic T lymphocytes in the pathogenesis of this syndrome.