Obliterative Airway Remodeling

Abstract

Obliteration of the small airways is a largely unresolved challenge in pulmonary medicine. It represents either the irreversible cause of functional impairment or a morphologic disorder of limited importance in a multitude of diseases. Bronchiolitis obliterans is a key complication of lung transplantation. No predictive markers for the onset of obliterative remodeling are currently available. To further elucidate the molecular mechanisms of airway remodeling, compartment-specific expression patterns were analyzed in patients. For this purpose, remodeled and nonremodeled bronchioli were isolated from transplanted and nontransplanted lung explants using laser-assisted microdissection (n ‫؍‬ 24). The histologic term "bronchiolitis obliterans" describes obliterative changes in the airways that commonly occur in a variety of pulmonary diseases. These changes demonstrate divergent histologic and radiologic findings, various potencies to progress to additional compartments of the lung, and different clinical outcomes.1,2 At histologic analysis, two major variants can be distinguished. The first is varying degrees of discontinuous submucosal collagenous deposits that narrow the lumen of the bronchioli up to the point of total obliteration, referred to as "constrictive bronchiolitis." This type is most commonly observed after hematopoietic stem cell transplantation or allogeneic lung transplantation, in which it significantly limits long-term survival and is considered the hallmark of chronic graft dysfunction.3 The second variant is bronchiolitis obliterans with intraluminal polyps, in which mesenchymal protrusions bulge into the lumen of the airways and the adjacent alveoli.

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

“…Alveolar macrophages have been demonstrated to increase expression of endothelin receptors in the donor lung in animal models [115]. This may then prime passenger macrophages for further activation by recipient ET-1, which is generated in the pro-inflammatory environment of chronic lung disease, surgery, and the posttransplant course [115, 190]. …”

Physiological Measurement of the Small Airways

“…those for which reasonable evidence exists that small airways could be implicated at all. Over the past decade, dedicated small airways studies with invasive or imaging techniques have gathered evidence to substantiate the presence of structural abnormalities in the small airways of asthma patients [1,2,3], smokers [4,5,6], patients with chronic obstructive pulmonary disease [7,8,9,10,11], lung transplant patients developing bronchiolitis obliterans syndrome [12], acute respiratory distress syndrome patients [13] and cystic fibrosis patients [14]. Based on these solid datasets collected over the past decade and all studies preceding these, it is fair to assume that the small airways are a potential target for disease, and hence for therapy whenever this is possible.…”

MicroRNA expression in Epstein-Barr virus-associated post-transplant smooth muscle tumours is related to leiomyomatous phenotype

“…In brief, cells were digested in proteinase K and RNA was extracted with phenol/chloroform [2,18,19]. Synthesis of cDNA from microRNA, subsequent pre-amplification of cDNA and real-time quantitative PCR with a 7900HT Fast Real-Time PCR system were performed according to the manufacturers’ instructions (Applied Biosystems).…”