Response of the Central and Peripheral Airways to Cigarette Smoking in Humans and Rats

Melville, Norris; Kumar, Mohan; Ismail, Suriani; Mills, James L.

doi:10.1159/000194459

Cited by 6 publications

(6 citation statements)

References 13 publications

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“…These data suggest the induction of a mild, agonist-independent AHR after chronic TS exposure, suggesting that the mechanism of TS-induced AHR is unlikely to be due to the up-regulation of a specific receptor. Melville and colleagues demonstrated significant changes in airway resistance in central and peripheral airways of Wistar rats after 6 weeks of TS exposure (9). After 15 weeks of TS exposure (three cigarettes per day; 5 d/wk), Xu and colleagues demonstrated AHR in Long Evans rats (10).…”

Section: Discussionmentioning

confidence: 99%

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Involvement of IL-13 in Tobacco Smoke–Induced Changes in the Structure and Function of Rat Intrapulmonary Airways

Cooper¹,

Poll²,

Barnes³

et al. 2010

Am J Respir Cell Mol Biol

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Chronic obstructive pulmonary disease (COPD) involves disease of small airways with an increase in airway smooth muscle sensitivity to spasmogens and with structural changes described as airway remodeling. We investigated the effect of tobacco smoke (TS) exposure on the structure and function of small airways in rats and the role of IL-13 in this response. Precision-cut lung slices (230-280 microm) were prepared from male Sprague-Dawley rats after acute (3 d) or chronic (8 or 16 wk) daily exposure to TS or air. Carbachol (CCh) and 5-hydroxytryptamine (5HT) concentration responses were performed on airways (50-400 microm diameter). The effect of IL-13 in vitro on small airway sensitivity to CCh and 5HT was also determined. Acute exposure to TS did not affect the sensitivity of the intrapulmonary airways to either spasmogen. After 8 weeks of TS exposure, airway hyperresponsiveness (AHR) to CCh was evident (log EC(50) CCh: air = 0.22 microM; TS = -0.12 microM; P = 0.019); AHR to 5HT was also observed after the 16-week exposure to TS (air = -0.85 microM; TS = -1.06 microM; P = 0.038). Chronic TS exposure increased airway wall SMA content, which correlated with increased expression of IL-13 and transforming growth factor (TGF)-beta(1) in the lung tissues. In vitro incubation with IL-13, but not TGF-beta(1), induced changes in small airway sensitivity to CCh and 5HT. Chronic TS exposure induces increased responsiveness in intrapulmonary airways of rats that may be mediated in part by an increase in IL-13.

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Section: Discussionmentioning

confidence: 99%

“…In one such study, a modest increase in procollagen gene expression in the small airway walls of rats exposed to TS was reported (8). In addition, these models have focused on studying the effects of TS exposure on large airway structure and function (7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

Involvement of IL-13 in Tobacco Smoke–Induced Changes in the Structure and Function of Rat Intrapulmonary Airways

Cooper¹,

Poll²,

Barnes³

et al. 2010

Am J Respir Cell Mol Biol

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“…The conventionally used rodent species in inhalation toxicity studies not only have higher ventilation rates relative to body mass than humans; they also have rodent-specific defense systems, making it particularly difficult to distinguish unequivocally clearly adaptive changes from early adverse effects. The increased responsiveness of the respiratory system of rodents may be attributed to, inter alia, an increased vagal activity, mucosal swelling and disturbances of the lungs' defense mechanisms, and imbalance in and easy accessibility to adrenoreceptors (Melville et al, 1982;Persson et al, 1996). Based on the comparison of the phosgene-induced changes of protein in BAL fluid from dogs, one may conclude that similar changes in rats must be at least three times higher to be of pathophysiological significance.…”

Section: Tablementioning

confidence: 99%

Acute Head-Only Exposure of Dogs to Phosgene. Part III. Comparison of Indicators of Lung Injury in Dogs and Rats

Pauluhn

2006

Inhalation Toxicology

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To better understand the relevance of phosgene-induced changes in bronchoalveolar lavage (BAL) fluid protein observed in acutely exposed rats, groups of beagle dogs were similarly exposed for 30 min to phosgene using a head-only mode of exposure. The actual exposure concentrations were 9, 16.5, and 35 mg/m3, with resultant C x t products of 270, 495, and 1050 mg/m3 x min. In rats, a C x t product of 270 mg/m3 x min caused a significant elevation of protein in the bronchoalveolar lavage (BAL) fluid, while the nonlethal threshold concentration (LCt01) was estimated to be 1075 mg/m3 x min. The endpoints examined in dogs focused on changes in BAL, lung weights, arterial blood gases, and lung histopathology approximately 24 h postexposure. Mortality did not occur at any C x t product. Increased lung weights and elevations in protein, soluble collagen, and polymorphonuclear leukocyte (PMN) counts in BAL were observed at 1050 mg/m3 x min with borderline changes at 495 mg/m3 x min. Following exposure to 1050 mg/m3 x min, the analysis of arterial blood gases provided evidence of a significantly decreased arterial pO2. Histopathology revealed a mild, although distinctive, inflammatory response at the bronchoalveolar level at 495 mg/m3 x min, whereas serofibrinous exudates and edema were observed at 1050 mg/m3 x min. The magnitude of effects correlated with the individual dogs' respiratory minute volume and breathing patterns (panting). Collectively, phosgene-induced indicators of acute lung injury appeared to be characterized best by protein in BAL fluid. With regard to both the inhaled dose and the associated increase of protein in BAL, the responses obtained in dogs appear to be more similar to humans. In contrast, elevations in BAL protein occurred in rats at three-fold lower concentrations when compared to dogs. The results of this study demonstrate that the magnitude of elevations of plasma exudate in BAL fluid following acute exposure to the pulmonary irritant phosgene is markedly more pronounced in rats when compared to the dog which is considered more human-like than rats. This is believed to be associated with the higher ventilation of small rodents and with rodent-specific sensory bronchopulmonary defense reflexes.

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“…SAFs for a male cigarette smoker (ratio of SAFs male smoker/ICRP reference worker) found to increase in smokers by around 6% [35][36][37]. Given that the FRC refers to the volume of air remaining in the lungs after a passive exhalation, the relative FRC used in the present study was calculated as the FRC normalised by the total lung capacity (reported for the same cohorts [35][36][37].…”

Section: Depositionmentioning

confidence: 99%

Changes induced in the human respiratory tract by chronic cigarette smoking can reduce the dose to the lungs from exposure to radon progeny

et al. 2023

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Chronic cigarette smoking leads to changes in the respiratory tract that might affect the dose received from exposure to radon progeny. In this study, changes induced by cigarette smoking in the respiratory tract were collected from the literature and used for calculation of the dose received by the lungs and organs outside the respiratory tract. Morphological and physiological parameters affected by chronic smoking were implemented in the Human Respiratory Tract Model (HRTM) used by the International Commission of Radiological Protection (ICRP). Smokers were found to receive lung doses 3% smaller than the ICRP reference worker (non-smoking reference adult male) in mines and 14% smaller in indoor workplaces and tourist caves. A similar dose reduction was found for the extrathoracic region of the HRTM. Conversely, kidneys, brain, and bone marrow of smokers were found to receive from 2.3- up to 3-fold of the dose received by the respective organ in the ICRP reference worker, although they remained at least 2 orders of magnitude smaller than the lung dose. These results indicate that the differences in the lung dose from radon progeny exposure in cigarette smokers and non-smokers are smaller than 15%.

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Response of the Central and Peripheral Airways to Cigarette Smoking in Humans and Rats

Cited by 6 publications

References 13 publications

Involvement of IL-13 in Tobacco Smoke–Induced Changes in the Structure and Function of Rat Intrapulmonary Airways

Involvement of IL-13 in Tobacco Smoke–Induced Changes in the Structure and Function of Rat Intrapulmonary Airways

Acute Head-Only Exposure of Dogs to Phosgene. Part III. Comparison of Indicators of Lung Injury in Dogs and Rats

Changes induced in the human respiratory tract by chronic cigarette smoking can reduce the dose to the lungs from exposure to radon progeny

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