China
Africa
Explore chapters and articles related to this topic
Macrophages and Their Potential Role in Hyperreactive Airways Disease
Published in Devendra K. Agrawal, Robert G. Townley, Inflammatory Cells and Mediators in Bronchial Asthma, 2020
Whereas many of the studies discussed have used bronchoalveolar lavage (BAL) to investigate mechanisms of disease in the lungs of patients with asthma, a few words about this important research tool are appropriate. In this procedure, several aliquots of a physiological solution are instilled and aspirated through a fiber-optic bronchoscope that has been wedged in a peripheral airway.1 Cellular- and fluid-phase material that lines the airways and alveoli (also referred to as lung lining fluid or epithelial lining fluid) is sampled. In some ways this procedure can be considered a liquid lung biopsy. For some lung diseases, data support the fact that results with BAL closely resemble results obtained at open lung biopsy. Similar data are not available for BAL and asthma, however. Nevertheless, this tool clearly has advantages: it is reasonably easy to perform, it is of low risk to the subject, and it directly samples the sites of disease. The use of BAL has permitted investigators to glean numerous important insights into the immunopathology of a large variety of lung diseases. Our understanding of asthma may benefit similarly.
Airway Wall Remodelling in the Pathogenesis of Asthma: Cytokine Expression in the Airways
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
Peter Bradding, Anthony E. Redington, Stephen T. Holgate
The procedure of bronchoalveolar lavage (BAL) allows sampling of epithelial lining fluid, and several groups have measured cytokine concentrations in BAL fluid in asthma. There are a number of methodological difficulties with such studies, including variable dilution, variable recovery of BAL fluid, and the possibility of degradation of cytokines by BAL fluid proteases. Nevertheless, Walker et al.183 reported increased concentrations of IL-4 and IL-5 in BAL fluid from allergic asthmatic subjects and increased concentrations of IL-2 and IL-5 in nonallergic asthmatic subjects compared with nonasthmatic control subjects. In this study, BAL fluid was concentrated up to 18–21 times, but, even so, cytokine concentrations were in the lower ranges of the assays employed. Using a similar approach, Broide et al.184 compared symptomatic with asymptomatic atopic asthmatic subjects and reported elevated levels of IL-1β, IL-2, IL-6, TNFα, and GM-CSF in concentrated BAL fluid. IL-4, however, was not detectable in this study, probably because of the relatively high detection limit of the assay employed (200 pg/ml). In our own studies we have shown that levels of TNFα in concentrated BAL fluid are increased in mild atopic asthmatic subjects when compared with healthy control subjects.185 However, neither IL-4 nor IFNγ were measurable in the control subjects, and these cytokines were only detectable in a small proportion of the asthmatic subjects.
Cethromycin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Although data in this field are still rather scarce, in a study on healthy volunteers receiving cethromycin, relevant pharmacokinetic/pharmacodynamic properties vis-à-vis leading respiratory pathogens were analyzed (Conte et al., 2004). Table 65.4 summarizes the main findings observed in epithelial lining fluid from this study.
Pharmacokinetics and lung distribution of macrolide antibiotics in sepsis model rats
Published in Xenobiotica, 2020
Shinji Kobuchi, Akihiro Fujita, Akihito Kato, Hiromu Kobayashi, Yukako Ito, Toshiyuki Sakaeda
This study has several limitations. First, macrolide concentrations were measured in the buffy coat, but not specifically in phagocytes or white blood cells. The buffy coat is a mixture of these cells and measuring drug levels in these cells after separation from the buffy coat in vivo is difficult due to small sample volume. Second, macrolide levels in the extracellular tissue space such as interstitial fluid, epithelial lining fluid and bronchoalveolar lavage could not be investigated. The drug concentration in tissue homogenates represents a mixture of drug concentrations in the intracellular and extracellular tissue spaces; drug concentrations in the infection site could not be evaluated. The interstitial fluid must be obtained from a pore formed on the skin by a dissolving microneedle array and the midline laparotomy used to produce the sepsis model precluded this sampling method. Additional investigations using other sepsis model animals are therefore required. Third, limitation is the difficulty in applying the present results directly toward developing strategic dosing regimens for patients as the species difference was not examined. Finally, although there are other possible explanations for AZM-specific clinical efficacy against macrolide-resistance strains, such as an inhibitory effect on pneumolysin production, we did not investigate this hypothesis.
Lung macrophages: current understanding of their roles in Ozone-induced lung diseases
Published in Critical Reviews in Toxicology, 2020
Luminal surfaces of the airways and alveolar spaces are lined with an aqueous epithelial lining fluid (ELF) layer. The ELF layer acts as a physical barrier that prevents the direct onslaught of epithelial cells by inhaled entities including O3. Thus, before interacting with the resident cells in airspaces, the inhaled O3 interacts with the ELF layer of the conducting airways and alveolar spaces (Pryor 1992; Gerrity et al. 1995). The low solubility of O3 in the ELF layer limits its rate of diffusion toward the apical surfaces of the epithelial cells (Gerrity et al. 1995). During its diffusion toward the epithelial cell surfaces, a portion of the dissolved O3 is detoxified by antioxidants, including urate, ascorbate, vitamin E, and reduced glutathione, normally found in the ELF (DeLucia et al. 1975; Housley et al. 1995; Duan et al. 1996; Kelly et al. 1996; Mudway et al. 1996; Mudway and Kelly 1998; Mudway et al. 1999). Kelly et al. (1995) previously provided a detailed overview of the antioxidant defense system against O3.
Antibiotic exposure at the site of infection: principles and assessment of tissue penetration
Published in Expert Review of Clinical Pharmacology, 2019
Nynke G. L. Jager, Reinier M. van Hest, Jeffrey Lipman, Jason A. Roberts, Menino O. Cotta
Pulmonary infection begins within the inner part of the lungs, i.e. the airspace, and thus antibiotic concentrations within the airspace are of direct importance. The inner part of the lungs is covered by a thin aqueous layer, which is called epithelial lining fluid (ELF). ELF is a natural barrier against pathogens, but also a medium in which the pathogens multiply before entering the lungs. It has been considered the likely site of extracellular respiratory infection [17]. Before an antibiotic agent enters the ELF, it has to pass the blood-alveolar barrier. This barrier, between the systemic circulation and the airspace, is composed of two membranes; the capillary wall and the alveolar wall separated by a compartment filled with interstitial fluid. The capillary wall contains fenestrations and allows free diffusion of small molecules from the bloodstream to the interstitial fluid. The alveolar wall, which separates the interstitial fluid from the inner part of the lungs, has no fenestrations to facilitate diffusion. Therefore, the antibiotic must pass through the alveolar epithelial cells themselves in order to reach the ELF [18]. Consequently, lipophilic agents, such as fluoroquinolones and macrolides, experience higher distribution into ELF, where hydrophilic agents such as aminoglycosides and glycopeptides, experience low distribution into ELF.