Paradoxical conducting airway responses and heterogeneous regional ventilation after histamine inhalation in rabbit studied by synchrotron radiation CT

2009 ◽  
Vol 106 (6) ◽  
pp. 1949-1958 ◽  
Author(s):  
Sam Bayat ◽  
Liisa Porra ◽  
Heikki Suhonen ◽  
Pekka Suortti ◽  
Anssi R. A. Sovijärvi

We studied both central conducting airway response and changes in the distribution of regional ventilation induced by inhaled histamine in healthy anesthetized and mechanically ventilated rabbit using a novel xenon-enhanced synchrotron radiation computed tomography (CT) imaging technique, K-edge subtraction imaging (KES). Images of specific ventilation were obtained using serial KES during xenon washin, in three axial lung slices, at baseline and twice after inhalation of histamine aerosol (50 or 125 mg/ml) in two groups of animals ( n = 6 each). Histamine inhalation caused large clustered areas of poor ventilation, characterized by a drop in average specific ventilation (sV̇m), but an increase in sV̇m in the remaining lung zones indicating ventilation redistribution. Ventilation heterogeneity, estimated as coefficient of variation (CV) of sV̇m significantly increased following histamine inhalation. The area of ventilation defects and CV were significantly larger with the higher histamine dose. In conducting airways, histamine inhalation caused a heterogeneous airway response combining narrowing and dilatation in individual airways of different generations, with the probability for constriction increasing peripherally. This finding provides further in vivo evidence that airway reactivity in response to inhaled histamine is complex and that airway response may vary substantially with location within the bronchial tree.

2001 ◽  
Vol 91 (6) ◽  
pp. 2511-2516 ◽  
Author(s):  
S. J. Gunst ◽  
X. Shen ◽  
R. Ramchandani ◽  
R. S. Tepper

The effect of deep inspiration (DI) on airway responsiveness differs in asthmatic and normal human subjects. The mechanism for the effects of DI on airway responsiveness in vivo has not been identified. To elucidate potential mechanisms, we compared the effects of DI imposed before or during induced bronchoconstriction on the airway response to methacholine (MCh) in rabbits. The changes in airway resistance in response to intravenous MCh were continuously monitored. DI depressed the maximum response to MCh when imposed before or during the MCh challenge; however, the inhibitory effect of DI was greater when imposed during bronchoconstriction. Because immature rabbits have greater airway reactivity than mature rabbits, we compared the effects of DI on their airway responses. No differences were observed. Our results suggest that the mechanisms by which DI inhibits airway responsiveness do not depend on prior activation of airway smooth muscle (ASM). These results are consistent with the possibility that reorganization of the contractile apparatus caused by stretch of ASM during DI contributes to depression of the airway response.


2020 ◽  
Author(s):  
Adam Polak ◽  
Andrzej Obojski ◽  
Janusz Mroczka

<i>Objective:</i> Although spirometry is the most common pulmonary function test, there is no method to quantitatively infer about airway resistance or other properties from the flow-volume curves. Recently, an identifiable inverse model for forced expiration was proposed, as well as the idea to deduce changes in airway resistances and compliances from spirometric curve evolution. The aim of this work was to combine the above advances in a method for assessing the airway response to bronchial tests from a spirometric curve shift. <i>Methods:</i> The approach is based on the differential measurement of the degree, site of maximal effect and width of changes, further recalculated into relative changes in the distribution of airway resistances (<i>δR<sub>g</sub></i>) and compliances (<i>δC<sub>g</sub></i>) along the bronchial tree. To this end, appropriate models were identified using the pre- and post-test spirometry data. The accuracy was validated using sets of data simulated by the anatomy and physiology based models. Finally, the method was used to analyze the bronchodilation tests of three asthmatic subjects. <i>Results:</i> The expected errors in assessing the degree, site and width of changes in the zone of conducting airways were 6.3%, 2.4 generations and 22%, respectively, and for <i>δR<sub>g</sub></i> and <i>δC<sub>g</sub></i> were 5-10% and 13-16%, respectively. The analyses of clinical data indicated a significant reduction in resistances and an increase in compliances of airway generations 8-12, consistent with clinical knowledge. <i>Conclusion:</i> An unprecedented method to plausibly transforming the spirometry data into the site and degree of changes in airway properties has been proposed. <i>Significance:</i> The method can be used to deduce about the effects of bronchial tests, as well as to monitor changes in the airways between visits or to investigate how inhaled pharmaceuticals affect the bronchi.


2017 ◽  
Vol 122 (3) ◽  
pp. 503-510 ◽  
Author(s):  
S. Dubsky ◽  
G. R. Zosky ◽  
K. Perks ◽  
C. R. Samarage ◽  
Y. Henon ◽  
...  

Detailed information on the distribution of airway diameters during bronchoconstriction in situ is required to understand the regional response of the lungs. Imaging studies using computed tomography (CT) have previously measured airway diameters and changes in response to bronchoconstricting agents, but the manual measurements used have severely limited the number of airways measured per subject. Hence, the detailed distribution and heterogeneity of airway responses are unknown. We have developed and applied dynamic imaging and advanced image-processing methods to quantify and compare hundreds of airways in vivo. The method, based on CT, was applied to house dust-mite-sensitized and control mice during intravenous methacholine (MCh) infusion. Airway diameters were measured pre- and post-MCh challenge, and the results compared demonstrate the distribution of airway response throughout the lungs during mechanical ventilation. Forced oscillation testing was used to measure the global response in lung mechanics. We found marked heterogeneity in the response, with paradoxical dilation of airways present at all airway sizes. The probability of paradoxical dilation decreased with decreasing baseline airway diameter and was not affected by pre-existing inflammation. The results confirm the importance of considering the lung as an entire interconnected system rather than a collection of independent units. It is hoped that the response distribution measurements can help to elucidate the mechanisms that lead to heterogeneous airway response in vivo. NEW & NOTEWORTHY Information on the distribution of airway diameters during bronchoconstriction in situ is critical for understanding the regional response of the lungs. We have developed an imaging method to quantify and compare the size of hundreds of airways in vivo during bronchoconstriction in mice. The results demonstrate large heterogeneity with both constriction and paradoxical dilation of airways, confirming the importance of considering the lung as an interconnected system rather than a collection of independent units.


2020 ◽  
Author(s):  
Adam Polak ◽  
Andrzej Obojski ◽  
Janusz Mroczka

<i>Objective:</i> Although spirometry is the most common pulmonary function test, there is no method to quantitatively infer about airway resistance or other properties from the flow-volume curves. Recently, an identifiable inverse model for forced expiration was proposed, as well as the idea to deduce changes in airway resistances and compliances from spirometric curve evolution. The aim of this work was to combine the above advances in a method for assessing the airway response to bronchial tests from a spirometric curve shift. <i>Methods:</i> The approach is based on the differential measurement of the degree, site of maximal effect and width of changes, further recalculated into relative changes in the distribution of airway resistances (<i>δR<sub>g</sub></i>) and compliances (<i>δC<sub>g</sub></i>) along the bronchial tree. To this end, appropriate models were identified using the pre- and post-test spirometry data. The accuracy was validated using sets of data simulated by the anatomy and physiology based models. Finally, the method was used to analyze the bronchodilation tests of three asthmatic subjects. <i>Results:</i> The expected errors in assessing the degree, site and width of changes in the zone of conducting airways were 6.3%, 2.4 generations and 22%, respectively, and for <i>δR<sub>g</sub></i> and <i>δC<sub>g</sub></i> were 5-10% and 13-16%, respectively. The analyses of clinical data indicated a significant reduction in resistances and an increase in compliances of airway generations 8-12, consistent with clinical knowledge. <i>Conclusion:</i> An unprecedented method to plausibly transforming the spirometry data into the site and degree of changes in airway properties has been proposed. <i>Significance:</i> The method can be used to deduce about the effects of bronchial tests, as well as to monitor changes in the airways between visits or to investigate how inhaled pharmaceuticals affect the bronchi.


Author(s):  
J.L. Carson ◽  
A.M. Collier

The ciliated cells lining the conducting airways of mammals are integral to the defense mechanisms of the respiratory tract, functioning in coordination with secretory cells in the removal of inhaled and cellular debris. The effects of various infectious and toxic agents on the structure and function of airway epithelial cell cilia have been studied in our laboratory, both of which have been shown to affect ciliary ultrastructure.These observations have led to questions about ciliary regeneration as well as the possible induction of ciliogenesis in response to cellular injury. Classical models of ciliogenesis in the conducting airway epithelium of the mammalian respiratory tract have been based primarily on observations of the developing fetal lung. These observations provide a plausible explanation for the embryological generation of ciliary beds lining the conducting airways but do little to account for subsequent differentiation of ciliated cells and ciliogenesis during normal growth and development.


1989 ◽  
Vol 66 (2) ◽  
pp. 606-612 ◽  
Author(s):  
S. Bellofiore ◽  
D. H. Eidelman ◽  
P. T. Macklem ◽  
J. G. Martin

We examined the effects of elastase-induced emphysema on lung volumes, pulmonary mechanics, and airway responses to inhaled methacholine (MCh) of nine male Brown Norway rats. Measurements were made before and weekly for 4 wk after elastase in five rats. In four rats measurements were made before and at 3 wk after elastase; in these same animals the effects of changes in end-expiratory lung volume on the airway responses to MCh were evaluated before and after elastase. Airway responses were determined from peak pulmonary resistance (RL) calculated after 30-s aerosolizations of saline and doubling concentrations of MCh from 1 to 64 mg/ml. Porcine pancreatic elastase (1 IU/g) was administered intratracheally. Before elastase RL rose from 0.20 +/- 0.02 cmH2O.ml-1.s (mean +/- SE; n = 9) to 0.57 +/- 0.06 after MCh (64 mg/ml). A plateau was observed in the concentration-response curve. Static compliance and the maximum increase in RL (delta RL64) were significantly correlated (r = 0.799, P less than 0.01). Three weeks after elastase the maximal airway response to MCh was enhanced and no plateau was observed; delta RL64 was 0.78 +/- 0.07 cmH2O.ml-1.s, significantly higher than control delta RL64 (0.36 +/- 0.7, P less than 0.05). Before elastase, increase of end-expiratory lung volume to functional residual capacity + 1.56 ml (+/- 0.08 ml) significantly reduced RL at 64 mg MCh/ml from 0.62 +/- 0.05 cmH2O.ml-1.s to 0.50 +/- 0.03, P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)


2014 ◽  
Vol 24 (1) ◽  
pp. 1341-1349
Author(s):  
Lijun Xu ◽  
Andi Zhang ◽  
Guohao Du ◽  
Honglan Xie ◽  
Ying Chen

1977 ◽  
Vol 42 (4) ◽  
pp. 508-513 ◽  
Author(s):  
N. E. Brown ◽  
E. R. McFadden ◽  
R. H. Ingram

Bronchia reactivity to inhaled histamine was assessed in asymptomatic cigarette smokers and in nonsmoking atopic and nonatopic subjects. The only prechallenge between-group difference was the ratio of maximal flow on 80% helium-20% oxygen (Vmax HeO2) to maximal flow on air (Vmax air) from partial expiratory flow volume curves at 25% vital capacity (25% VC PEFV): Mean +/- SEM for smokers 1.18 /+- 0.06, atopics 1.45 +/- 0.08, nonatopics 1.51 +/- 0.03. This suggests that prior to inhalation to total lung capacity, the predominant site of resistance at flow limitation was in smaller airways of the smokers and in larger airways of both groups of nonsmokers. Following inhalation of histamine, smokers and nonatopics had similar changes in lung volumes and Vmax air which were less than in atopics. The Vmax HeO2/Vmax air ratios at 25% VC PEFV increased in smokers and decreased in nonsmokers: smokers 1.48 +/- 0.08, atopics 1.22 +/- 0.10, nontopics 1.16 +/- 0.06. This suggests a predominant large airway response in smokers and a prominent small airway response in nonsmokers. These responses may reflect differences in the predominant site of aerosol deposition rather than in airway reactivity.


1986 ◽  
Vol 60 (6) ◽  
pp. 2089-2093 ◽  
Author(s):  
K. P. Agrawal ◽  
R. E. Hyatt

Tracheal Na+-K+-ATPase activity is positively correlated with in vivo airway responsiveness to histamine. We wondered whether this were a chance association or whether it was directly related to the mechanism of hyperreactivity. Therefore, we obtained dose-response curves to aerosols of histamine and ouabain in guinea pigs to determine whether an in vivo relationship existed between the excitatory effects of histamine and the enzyme-inhibiting effect of ouabain. Airway responsiveness to ouabain was measured as the ouabain concentration producing a 30% decrease in specific airway conductance (ED30) or that producing a half-maximal response (ED50). Responsiveness to histamine was measured either as ED30 or as ED50. Significant positive correlations were noted between the log ED50 of ouabain and log histamine ED30 or ED50 (r = 0.81 and 0.83, respectively; P less than 0.001), and between log ouabain ED30 and log histamine ED30 and ED50 (r = 0.76 and 0.77, respectively; P less than 0.002). Pretreatment with ouabain increased airway responsiveness to histamine (P less than 0.05). We suggest that in hyperreactive airways Na+-K+-ATPase serves a homeostatic function of preventing Na+ and Ca2+ loading of the cell and that it is not directly responsible for the hyperreactivity.


Sign in / Sign up

Export Citation Format

Share Document