Obliterative Bronchiolitis

Transplantation of solid organs and hematopoietic stem cells represents an important therapeutic option for a variety of end-stage pulmonary diseases, aggressive hematopoietic neoplasms, or severe immunodeficiencies. Although the overall survival following transplantation has generally improved over recent decades, long-time survival of lung and stem-cell transplant recipients is still alarmingly low with an average 5‑year survival rate of only 50-60%. Chronic allo-immunoreactions in general and pulmonary allo-immunoreactions with subsequent fibrosis in particular are major reasons for this poor outcome...

Occupational bronchiolitis is characterized by inflammation of the small airways, and represents a heterogeneous set of lung conditions that can occur following a range of inhalation exposures related to work. The most common clinical presentation includes insidious onset of exertional dyspnea and cough. Multiple reports in recent years have drawn attention to previously unrecognized risk factors for occupational bronchiolitis following exposures in several settings. Both current and past occupational exposures, including prior military deployment-related exposures, should be considered in patients undergoing evaluation for unexplained dyspnea...

Roasted coffee and many coffee flavorings emit volatile organic compounds (VOCs) including diacetyl and 2,3-pentanedione. Exposures to VOCs during roasting, packaging, grinding, and flavoring coffee can negatively impact the respiratory health of workers. Inhalational exposures to diacetyl and 2,3-pentanedione can cause obliterative bronchiolitis. This study summarizes exposures to and emissions of VOCs in 17 coffee roasting and packaging facilities that included 10 cafés. We collected 415 personal and 760 area full-shift, and 606 personal task-based air samples for diacetyl, 2,3-pentanedione, 2,3-hexanedione, and acetoin using silica gel tubes...

Single lung transplantation (LTx) is an option for post-bone marrow transplantation (BMT) lung injury. Herein, we report a patient who underwent right single LTx for post-BMT obliterative bronchiolitis, and suffered post-transplantation hypoxemia because of a marked ventilation-perfusion mismatch in his native lung. Pulmonary artery (PA) banding at 78 days after LTx decreased pulmonary arterial flow to the native lung and successfully resolved hypoxemia. When we encounter post-single LTx hypoxemia, ventilation-perfusion mismatch in the native lung should be considered as a possible diagnosis and surgical PA banding is a feasible option...

Chronic lung disease (CLD) is common in individuals living with perinatally acquired HIV (PA-HIV) in southern/eastern Africa. Most of the UK PA-HIV population are African. We conducted a case-note review of CLD in 3 UK PA-HIV cohorts (n = 98). Bronchiectasis or obliterative bronchiolitis occurred in 8.1% of patients and ring/tramline opacities occurred in 19.2% of patients on chest X-ray. There may be unrecognized and underdiagnosed CLD among PA-HIV in the UK.

Human lung transplant recipients undergoing rejection induce circulatory exosomes with lung self-antigens (SAgs), K-alpha 1 Tubulin and Collagen V, and immunization of C57BL/6 mice with exosomes induced obliterative airway disease (HEI-OAD). We analyzed whether exosomes with SAgs induced immunity in microRNA-155 knockout mice (miR-155KO), as microRNA-155 is an immune regulator. C57BL/6 and miR-155KO were immunized with exosomes from stable or chronic rejection (bronchiolitis obliterans syndrome (BOS) and on day 30, induction of exosomes, antibodies (Abs) to SAgs and cellular immunity were determined...

Bronchiolitis is injury to the bronchioles (small airways with a diameter of 2 mm or less) resulting in inflammation and/or fibrosis. Bronchioles can be involved in pathologic processes that involve predominantly the lung parenchyma or large airways, but, in some diseases, bronchioles are the main site of injury ("primary bronchiolitis"). Acute bronchiolitis caused by viruses is responsible for most cases of bronchiolitis in infants and children. In adults, however, there is a wide spectrum of bronchiolar disorders and most are chronic...

Chronic allograft dysfunction (CAD) resulting from fibrosis is the major limiting factor for long-term survival of lung transplant patients. Myofibroblasts promote fibrosis in multiple organs, including the lungs. In this study, we identified PLK1 as a promoter of myofibroblast differentiation and investigated the mechanism by which its inhibition alleviates transplant-associated obliterative bronchiolitis (OB) during CAD. High-throughput bioinformatic analyses and experiments using the murine heterotopic tracheal transplantation model revealed that PLK1 is upregulated in grafts undergoing CAD as compared with controls, and that inhibiting PLK1 alleviates OB in vivo ...

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a pulmonary disease characterized by disruption of surfactant homeostasis resulting in its accumulation in the alveoli. PAP is classically classified into three categories (Table 1): 1/primary (or autoimmune) with antibodies targeting the GM-CSF pathway, 2/secondary to another disease, typically a hematologic malignancy, and 3/genetic. CASE-REPORT: A 30 year-old woman received an allogenic hematopoietic stem cell transplantation (HSCT) after treatment for acute myeloid leukemia (AML)...

PURPOSE: Bronchiolitis obliterans (BOS) remains a major cause of death for lung transplant recipients, and mechanisms that drive BOS remain poorly understood. Genetically encoded deficiencies in mitophagy, a specialized autophagy that targets the removal of damaged mitochondria, have been shown to promote Parkinson's disease, but it is unclear if they play a role in other chronic diseases. Recent work has shown that the rs2241880 mutation in the autophagy regulator ATG16L1 leads to protein instability resulting in deficiency of ATG16L1 in monocyte-derived macrophages...

PURPOSE: Chronic lung allograft dysfunction (CLAD) remains the major obstacle to long-term survival after lung transplantation. Two different phenotypes have recently been described. About 80% of patients have primarily obstructive lung disease associated with obliterative bronchiolitis, airway fibrosis with intraluminal narrowing (OB-CLAD) while a smaller subset has lung restriction with hypoxemia and parenchymal fibrosis (R-CLAD). Preclinical modeling is essential to better analyze the pathophysiological processes leading to CLAD development...

BACKGROUND: Obliterative bronchiolitis (OB) is a known issue during minor histocompatibility antigen (mHA) disparity during lung transplantation. This study evaluated gene expression in a murine orthotropic lung transplantation model using microarray analysis. METHODS: Left lungs from C57BL/10(H-2b) donor mice were transplanted into mHA-mismatched C57BL/6(H-2b) recipient mice. Three groups (OB, non-OB, and sham controls) were confirmed pathologically and analyzed...

Bronchiolitis obliterans syndrome (BOS) had been considered to be the representative form of chronic rejection or chronic lung allograft dysfunction (CLAD) after lung transplantation. In BOS, small airways are affected by chronic inflammation and obliterative fibrosis, whereas peripheral lung tissue remains relatively intact. However, recognition of another form of CLAD involving multiple tissue compartments in the lung, termed restrictive allograft syndrome (RAS), raised a fundamental question: why there are two phenotypes of CLAD? Increasing clinical and experimental data suggest that RAS may be a prototype of chronic rejection after lung transplantation involving both cellular and antibody-mediated alloimmune responses...

BACKGROUND: Constrictive (obliterative) bronchiolitis (CB) is an uncommon form of obstructive lung disease that can occur in patients with identifiable causes including connective tissue diseases (CTDs) as a form of lung involvement. We explored whether CB can be the presenting manifestation of CTD. METHODS: We identified 44 patients with cryptogenic CB and examined the presenting clinical, laboratory, and radiologic features, as well as their clinical course. RESULTS: The mean age at presentation was 60...

Bronchioles are noncartilaginous small airways with internal diameter of 2 mm or less, located from approximately the eighth generation of purely air conducting airways (membranous bronchioles) down to the terminal bronchioles (the smallest airways without alveoli) and respiratory bronchioles (which communicate directly with alveolar ducts and are in the range of 0.5 mm or less in diameter). Bronchiolar injury, inflammation, and fibrosis may occur in myriad disorders including connective tissue diseases, inflammatory bowel diseases, lung transplant allograft rejection, graft versus host disease in allogeneic stem cell recipients, neuroendocrine cell hyperplasia, infections, drug toxicity (e...

BACKGROUND: Obliterative bronchiolitis (OB) remains the major complication limiting long-term survival of patients after lung transplantation. We aimed to explore the effects of the selective Nlrp3 inflammasome inhibitor MCC950 on the pathogenesis of OB. METHODS: Mouse orthotopic tracheal transplants were performed to mimic OB. MCC950 (50 mg/kg) or saline was intraperitoneally injected daily. The luminal occlusion rate and collagen deposition were evaluated by HE and Masson's trichrome staining, respectively...

Introduction: Respiratory hazards in the coffee roasting and packaging industry can include asthmagens such as green coffee bean and other dust and alpha-diketones such as diacetyl and 2,3-pentanedione that can occur naturally from roasting coffee or artificially from addition of flavoring to coffee. We sought to describe the burden of respiratory abnormalities among workers at 17 coffee roasting and packaging facilities. Methods: We completed medical surveys at 17 coffee roasting and packaging facilities that included interviewer-administered questionnaires and pulmonary function testing...

Ferrets are an attractive mammalian model for several diseases especially those affecting the lungs, liver and kidneys. Many chronic human diseases have been difficult to model in rodents due to differences in size and cellular anatomy. This is particularly the case for the lung where ferrets provide an attractive mammalian model of both acute and chronic lung diseases such as influenza, cystic fibrosis, A1A emphysema and obliterative bronchiolitis, closely recapitulating disease pathogenesis as it occurs in humans...

Background: Long-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade...

BACKGROUND: Obliterative bronchiolitis (OB) is the major complication limiting the long-term survival of allografts after lung transplantation. In this study, we investigated the effect of tacrolimus (FK506) combined with GM6001，a matrix metalloproteinase (MMP) inhibitor， on the formation of OB using a mouse heterotopic tracheal transplantation model. METHODS: Syngeneic tracheal grafts were transplanted heterotopically from BALB/c mice to BALB/c mice. Allografts from C57BL/6 mice were transplanted to BALB/c mice...