The term small airways disease encompasses a generally poorly understood group of lung diseases that may arise primarily within the small airways or secondarily from diseases primarily affecting the bronchi or lung parenchyma. Their histology may be confusing; however, because treatments and prognoses vary, correct pathologic diagnosis is important.
To present a nonexhaustive review of the pathology of primary and secondary small airways diseases, including small airways disease related to tobacco; to various other exposures, including mineral dusts; to diseases involving other areas of the lung with secondary bronchiolar involvement; and to recently described bronchiolitic disorders.
Current literature is reviewed.
Small airways diseases include a wide variety of diseases of which the pathologist must consider. Uncommon conditions such as diffuse idiopathic neuroendocrine cell hyperplasia and diffuse panbronchiolitis may show relatively specific diagnostic features histologically; however, most small airways diseases exhibit nonspecific histologic features. Conditions not considered primary pulmonary diseases, such as collagen vascular diseases, bone marrow transplantation, and inflammatory bowel disease, must also be considered in patients with small airways changes histologically. Clinical and radiologic correlation is important for obtaining the best possible diagnosis.
"Under conditions of decreased GSH, patients typically exhibit decreased pathogen clearance leading to chronic inflammation . This is especially important since many of these lung disease have high levels of airway inflammation and recurrent exacerbations . "
[Show abstract][Hide abstract] ABSTRACT: A number of inflammatory lung diseases have abnormally low glutathione (GSH) levels in the airway fluids. Lung macrophages are common mediators of inflammation, make up the majority of cells that are found in the airway epithelial lining fluid (ELF), and are commonly elevated in many lung diseases. Several animal models with altered ELF GSH levels are associated with similar alterations in the intracellular GSH levels of bronchoalveolar lavage (BAL) cells. The possible mechanisms and outcomes for this association between ELF GSH levels and intracellular BAL cell GSH are unknown. To investigate these issues, macrophages were grown in media supplemented with 500 µM GSH. GSH supplementation resulted in a 2-3 fold increase in macrophage intracellular GSH levels. The increase in macrophage intracellular GSH levels was associated with a significant reduction in NF-κB nuclear translocation and tumor necrosis factor α (TNFα) release upon LPS stimulation. Furthermore, co-treatment of macrophages with GSH and inhibitors of GSH breakdown or synthesis did not block GSH accumulation. In contrast, treatment with cytochalasin D, an inhibitor of actin dependent endocytosis, and amiloride, an inhibitor of macropinocytosis blocked, at least in part, GSH uptake. Furthermore, using two cigarette smoke exposure paradigms that result in two different GSH levels in the ELF and thus in the BAL cells resulted in modulation of cytokine release when stimulated with LPS ex vivo. These data suggest that macrophages are able to utilize extracellular GSH which can then modulate inflammatory signaling in response to proinflammatory stimuli. This data also suggests the lung can modulate inflammatory responses triggered by proinflammatory stimuli by altering ELF GSH levels and may help explain the dysregulated inflammation associated with lung diseases that have low ELF GSH levels.
PLoS ONE 11/2011; 6(10):e25704. DOI:10.1371/journal.pone.0025704 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Workers in microwave popcorn plants are at risk of developing bronchiolitis obliterans associated with exposure to butter flavoring volatiles, including diacetyl.
To investigate the risk of bronchiolitis obliterans for chemical workers producing diacetyl, with exposure to less complex mixtures of chemicals.
We interviewed and conducted spirometry on 175 of 196 workers from a chemical production plant that produced diacetyl between 1960 and 2003. We used all available historical exposure data to classify all workers into three exposure groups with varying exposure profiles to diacetyl, based on frequency and level of exposure.
Workers with fixed airway obstruction underwent further pulmonary function testing (including diffusing capacity and lung volumes) and paired inspiratory and expiratory high-resolution computed tomography studies. We identified three cases consistent with bronchiolitis obliterans syndrome with air trapping on high-resolution computed tomography of the lungs, in the highest exposure group of 102 process operators. Two of these cases were lifelong nonsmokers. Potential exposures included acetoin, diacetyl, acetaldehyde, and acetic acid, with diacetyl exposures in the range previously reported to be associated with fixed airway obstruction in the microwave popcorn industry.
Exposure to an agent during diacetyl production appears to be responsible for causing bronchiolitis obliterans syndrome in chemical process operators, consistent with the suspected role of diacetyl in downstream food production.
American Journal of Respiratory and Critical Care Medicine 10/2007; 176(5):498-504. DOI:10.1164/rccm.200611-1620OC · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The term "small airway disease" has been used in reference to abnormalities occurring secondary to cigarette smoking in the context of chronic obstructive pulmonary disease (COPD), and the small airways are the major site of obstruction in patients with COPD. The histologic features associated with smoking-related small airway disease are largely nonspecific and overlap with those of other bronchiolitides. The pathogenesis of smoking-related small airway disease is poorly understood; however, insights into the development of airway remodeling and matrix production continue to evolve. The aim of this article will be to review the histologic findings and pathogenesis of smoking-related small airway disease in the context of COPD, and review other small airway disorders affecting cigarette smokers, namely respiratory bronchiolitis and Langerhans cell histiocytosis, and a newly described entity of respiratory bronchiolitis with fibrosis and associated issues with this entity.
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