Cigarette smoke exposure impairs respiratory epithelial ciliogenesis
ABSTRACT Cigarette smoke exposure is considered an important negative prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no clear mechanistic evidence implicating cigarette smoke exposure in the poor clinical evolution of the disease or in the maintenance of the inflammatory state characterizing CRS. This study aimed to evaluate the effects of cigarette smoke exposure on respiratory cilia differentiation.
Mouse nasal septal epithelium cultures grown at an air-liquid interface were used as a model of respiratory epithelium. After 5 days of cell growth, cultures were exposed to air on the apical surface. Additionally, cigarette smoke condensate (CSC; the particulate phase of tobacco smoke) or cigarette smoke extract (CSE; the volatile phase) were diluted in the basolateral compartment in different concentrations. After 15 days of continuous exposure, scanning electron microscopy and immunofluorescence for type IV tubulin were used to determine presence and maturation of cilia. Transepithelial resistance was also recorded to evaluate confluence and physiological barrier integrity.
CSC and CSE impair ciliogenesis in a dose-dependent manner with notable effects in concentrations higher than 30 microg/mL, yielding >70% nonciliation and shorter cilia compared with control. No statistical difference on transepithelial resistance was evident.
CSC and CSE exposure negatively impacts ciliogenesis of respiratory cells at concentrations not effecting transepithelial resistance. The impairment on ciliogenesis reduces the mucociliary clearance apparatus after injury and/or infection and may explain the poor response to therapy for CRS patients exposed to tobacco smoke.
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ABSTRACT: The coaxial circle system helps prevent heat loss during surgery, and it also acts as a humidifier. This study aimed to compare the coaxial breathing system and the conventional system in their ability to warm and moisturize inhaled gases, and we also analyzed lung function protection and saccharin clearance time in patients who underwent tympanomastoidectomy (TMT) with the aid of these two systems. Forty adult patients of ASA physical status I-II were scheduled for elective TMT. A standard volume-dependent ventilator setting was used to establish normocapnia. The coaxial circle system was used in the treated group (n=20), whereas the conventional circuit system was used in the control group (n=20). Saccharin clearance, VC (vital capacity), FRC (functional residual capacity), FEV1 (forced expiratory volume in 1 second), airway pressure, relative humidity and temperature of inspired gas, body temperature and adverse and hemodynamic effects were measured at different perioperative periods. The relative humidity (mg H2O Lt -1) of inspired gas in the treated group was higher than in the control group at 5, 15, 30, 45, 60 and 90 minutes after anesthesia induction. The temperature of inspired gas (Centigrade) in the treated group was higher than in the control group (p<0.05) after 5, 10, 15, 30, 45, and 90 minutes of anesthesia. Postoperative saccharin clearance time was lower than before the operation in the treated group (p<0.05). Postoperative FRC was lower than preoperative FRC in the study and control groups (p<0.05). The coaxial circle system decreased postoperative saccharin clearance time and increased postoperative FRC, relative humidity and the temperature of inspired fresh gas, without any adverse perioperative effects in patients who underwent TMT.08/2011; 43(2):92-8. DOI:10.5152/eajm.2011.21
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ABSTRACT: Background: Prevalence of passive smoke exposure is relatively unknown in chronic rhinosinusitis (CRS). Previous studies have attempted to establish this relationship using subjective, questionnaire-based methodologies to assess smoke exposure, thus introducing the potential for error bias. The purpose of this study was to accurately determine the prevalence of passive smoke exposure in CRS and control patients using hair nicotine levels as a quantitative measure of cigarette smoke exposure. Methods: Hair samples were obtained at time of surgery from 569 patients: 404 undergoing surgery for CRS and 165 controls undergoing surgery for repair of cerebrospinal fluid leak, removal of pituitary tumors, or adenoidectomy from 2007 to 2013. Patient charts were reviewed for reported smoking status. Hair nicotine was quantified using reversed-phase high-performance liquid chromatography. Nonsmoking patients were classified as passive smoke exposed or smoke naïve according to the hair nicotine results. Statistical analysis was performed to test for differences in demographic information and smoke exposure prevalence between CRS, CRS subtypes, and controls. Results: The prevalence of passive smoke exposure in CRS as documented by hair nicotine was lower than previously reported subjective estimates. Passive smoke exposure rates were equivalent between those with CRS versus controls and significantly higher in children. Severity of passive smoke exposure was also equivalent between CRS subsets and controls. Annual passive smoke exposure prevalence did not change over time. Conclusion: There is no clear evidence of avoidance of passive smoke exposure in the CRS population compared with controls. Passive smoke exposure also remained stable over time despite recent regional implementation of smoking bans. Given the constancy of exposure, it is critical that the impact of passive smoke on CRS exacerbation, outcomes, and pathophysiology be evaluated in large-scale clinical studies.American journal of rhinology & allergy 08/2014; 28(4). DOI:10.2500/ajra.2014.28.4058 · 2.18 Impact Factor
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ABSTRACT: Mucociliary clearance is the primary physical mechanism to protect the human airways against harmful effects of inhaled particles. Environmental factors play a significant role in the impairment of this defense mechanism, whereas cigarette smoke is discussed to be one of the clinically most important causes. Impaired mucociliary clearance in smokers has been connected to changes in ciliated cells such as decreased numbers, altered structure and beat frequency. Clinical studies have shown that cilia length is reduced in healthy smokers and that long-term exposure to cigarette smoke leads to reduced numbers of ciliated cells in mice. We present an in vitro model of primary normal human bronchiolar epithelial (NHBE) cells with in vivo like morphology to study the influence of cigarette mainstream smoke on ciliated cells. We exposed mucociliary differentiated cultures repeatedly to non-toxic concentrations of mainstream cigarette smoke (4 cigarettes, 5 days/week, 8 repetitions in total) at the air-liquid interface. Charcoal filter tipped cigarettes were compared to those being equipped with standard cellulose acetate filters. Histopathological analyses of the exposed cultures showed a reduction of cilia bearing cells, shortening of existing cilia and finally disappearance of all cilia in cigarette smoke exposed cells. In cultures exposed to charcoal filtered cigarette smoke, little changes in cilia length were seen after four exposure repetitions, but those effects were reversed after a two day recovery period. Those differences indicate that volatile organic compounds, being removed by the charcoal filter tip, affect primary bronchiolar epithelial cells concerning their cilia formation and function comparable with the in vivo situation. In conclusion, our in vitro model presents a valuable tool to study air-borne ciliatoxic compounds. Copyright © 2015. Published by Elsevier GmbH.Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 05/2015; DOI:10.1016/j.etp.2015.04.006 · 2.01 Impact Factor