Sarcoidosis, firefighters sarcoidosis, and World Trade Center "sarcoid-like" granulomatous pulmonary disease.

Chest (Impact Factor: 7.13). 01/2008; 132(6):2053. DOI: 10.1378/chest.07-1259
Source: PubMed
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    ABSTRACT: Lung granulomas are associated with numerous conditions, including inflammatory disorders, exposure to environmental pollutants, and infection. Osteopontin is a chemotactic cytokine produced by macrophages, and is implicated in extracellular matrix remodeling. Furthermore, osteopontin is up-regulated in granulomatous disease, and osteopontin null mice exhibit reduced granuloma formation. Animal models currently used to investigate chronic lung granulomatous inflammation bear a pathological resemblance, but lack the chronic nature of human granulomatous disease. Carbon nanoparticles are generated as byproducts of combustion. Interestingly, experimental exposures to carbon nanoparticles induce pulmonary granuloma-like lesions. However, the recruited cellular populations and extracellular matrix gene expression profiles within these lesions have not been explored. Because of the rapid resolution of granulomas in current animal models, the mechanisms responsible for persistence have been elusive. To overcome the limitations of previous models, we investigated whether a model using multiwall carbon nanoparticles would resemble chronic human lung granulomatous inflammation. We hypothesized that pulmonary exposure to multiwall carbon nanoparticles would induce granulomas, elicit a macrophage and T-cell response, and mimic other granulomatous disorders with an up-regulation of osteopontin. This model demonstrates: (1) granulomatous inflammation, with macrophage and T-cell infiltration; (2) resemblance to the chronicity of human granulomas, with persistence up to 90 days; and (3) a marked elevation of osteopontin, metalloproteinases, and cell adhesion molecules in granulomatous foci isolated by laser-capture microdissection and in alveolar macrophages from bronchoalveolar lavage. The establishment of such a model provides an important platform for mechanistic studies on the persistence of granuloma.
    American Journal of Respiratory Cell and Molecular Biology 03/2011; 45(4):858-66. · 4.15 Impact Factor
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    ABSTRACT: On September 11, 2001, events at the World Trade Center (WTC) exposed residents of New York City to WTC dust and products of combustion and pyrolysis. The majority of WTC-exposed fire department rescue workers experienced a substantial decline in airflow over the first 12 months post-9/11, in addition to the normal age-related decline that affected all responders, followed by a persistent plateau in pulmonary function in the 6 years thereafter. The spectrum of the resulting pulmonary diseases consists of chronic inflammation, characterized by airflow obstruction, and expressing itself in different ways in large and small airways. These conditions include irritant induced asthma, non-specific chronic bronchitis, aggravated pre-existing obstructive lung disease (asthma or COPD), and bronchiolitis. Conditions concomitant with airways obstruction, particularly chronic rhinosinusitis and upper airway disease, and gastroesophageal reflux, have been prominent in this population. Less common have been reports of sarcoidosis or interstitial pulmonary fibrosis. Pulmonary fibrosis and bronchiolitis are generally characterized by long latency, relatively slow progression, and a silent period with respect to pulmonary function during its evolution. For these reasons, the incidence of these outcomes may be underestimated and may increase over time. The spectrum of chronic obstructive airways disease is broad in this population and may importantly include involvement at the bronchiolar level, manifested as small airways disease. Protocols that go beyond conventional screening pulmonary function testing and imaging may be necessary to identify these diseases in order to understand the underlying pathologic processes so that treatment can be most effective. Am. J. Ind. Med. 54:649–660, 2011. © 2011 Wiley-Liss, Inc.
    American Journal of Industrial Medicine 08/2011; 54(9):649 - 660. · 1.59 Impact Factor
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    ABSTRACT: Use of nanomaterials in manufactured consumer products is a rapidly expanding industry and potential toxicities are just beginning to be explored. Combustion-generated multiwall carbon nanotubes (MWCNT) or nanoparticles are ubiquitous in non-manufacturing environments and detectable in vapors from diesel fuel, methane, propane, and natural gas. In experimental animal models, carbon nanotubes have been shown to induce granulomas or other inflammatory changes. Evidence suggesting potential involvement of carbon nanomaterials in human granulomatous disease, has been gathered from analyses of dusts generated in the World Trade Center disaster combined with epidemiological data showing a subsequent increase in granulomatous disease of first responders. In this review we will discuss evidence for similarities in the pathophysiology of carbon nanotube-induced pulmonary disease in experimental animals with that of the human granulomatous disease, sarcoidosis.
    Nanomaterials (Basel, Switzerland). 06/2014; 4(2):508-521.


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