Computational model of airway narrowing: mature vs. immature rabbit

2002 ◽  
Vol 93 (2) ◽  
pp. 611-619 ◽  
Author(s):  
R. K. Lambert ◽  
R. Ramchandani ◽  
X. Shen ◽  
S. J. Gunst ◽  
R. S. Tepper
Keyword(s):  
Computational Model ◽  
Airway Resistance ◽  
Fold Increase ◽  
Physiological Data ◽  
Airway Reactivity ◽  
Shear Moduli ◽  
Airway Narrowing ◽  
Immature Animal ◽  
Lower Shear ◽  
Airway Response

Immature rabbits have greater maximal airway narrowing and greater maximal fold increases in airway resistance during bronchoconstriction than mature animals. We have previously demonstrated that excised immature rabbit lungs have more distensible airways, a lower shear modulus, and structural differences in the relative composition and thickness of anatomically similar airways. In the present study, we incorporated anatomic and physiological data for mature and immature rabbits into a computational model of airway narrowing. We then investigated the relative importance of maturational differences in these factors as determinants of the greater airway narrowing that occurs in the immature animal. The immature model demonstrated greater sensitivity to agonist, as well as a greater maximal fold increase in airway resistance. Exchanging values for airway compliance between the mature and immature models resulted in the mature model exhibiting a greater maximal airway response than the immature model. In contrast, exchanging the shear moduli or the composition of the airway wall relative to the airway size produced relatively small changes in airway reactivity. Our results strongly suggest that the mechanical properties of the airway, i.e., greater compliance of the immature airway, can be an important factor contributing to the greater airway narrowing of the immature animal.

Development of chronic airway hyperresponsiveness in ragweed-sensitized dogs

1989 ◽  
Vol 66 (6) ◽  
pp. 2691-2697 ◽  
Author(s):  
A. B. Becker ◽  
J. Hershkovich ◽  
F. E. Simons ◽  
K. J. Simons ◽  
M. K. Lilley ◽  
...  
Keyword(s):  
Animal Model ◽  
Regression Analysis ◽  
Mast Cells ◽  
Bronchoalveolar Lavage ◽  
Airway Hyperresponsiveness ◽  
Airway Resistance ◽  
Fold Increase ◽  
Airway Responsiveness ◽  
Base Line ◽  
Airway Response

We studied dogs neonatally sensitized to ragweed and their littermate controls at 4, 6, 8, 10, 12, and 15 mo of age. Acute allergic airway response to inhalation of ragweed in the sensitized dogs was marked (greater than 12-fold increase from base line) and reproducible at all times. Nonallergic airway responsiveness, measured as the concentration of acetylcholine required to increase airway resistance by 5 cmH2O.l-1.s (PC5), increased in sensitized and decreased in nonsensitized dogs from 4 to 15 mo of age (P less than 0.01). Before antigen, at 12 and 15 mo, sensitized dogs were significantly (P less than 0.05) more responsive to acetylcholine than controls. Six hours after antigen, sensitized dogs were 11-fold more responsive (P less than 0.005) than controls at those times. More eosinophils and mast cells and fewer macrophages (P less than 0.05) were present in bronchoalveolar lavage (BAL) from 12- and 15-mo-old sensitized dogs than their controls. BAL fluid histamine was higher (P less than 0.05) in sensitized than control dogs. Regression analysis revealed r = -0.75 (P = 0.003) between BAL mast cells and PC5 in sensitized dogs and R2 = 0.89 for PC5 and BAL mast cells, macrophages, and eosinophils. Neonatally sensitized dogs represent an excellent animal model in which to study the pathophysiology of asthma.

Greater airway narrowing in immature than in mature rabbits during methacholine challenge

1996 ◽  
Vol 81 (6) ◽  
pp. 2637-2643 ◽  
Author(s):  
X. Shen ◽  
V. Bhargava ◽  
G. R. Wodicka ◽  
C. M. Doerschuk ◽  
S. J. Gunst ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Fold Increase ◽  
Methacholine Challenge ◽  
Morphometric Measurements ◽  
Airway Narrowing ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
Highly Correlated

Shen, X., V. Bhargava, G. R. Wodicka, C. M. Doerschuk, S. J. Gunst, and R. S. Tepper. Greater airway narrowing in immature than in mature rabbits during methacholine challenge. J. Appl. Physiol. 81(6): 2637–2643, 1996.—It has been demonstrated that methacholine (MCh) challenge produces a greater increase in lung resistance in immature than in mature rabbits (R. S. Tepper, X. Shen, E. Bakan, and S. J. Gunst. J. Appl. Physiol. 79: 1190–1198, 1995). To determine whether this maturational difference in the response to MCh was primarily related to changes in airway resistance (Raw) or changes in tissue resistance, we assessed airway narrowing in 1-, 2-, and 6-mo-old rabbits during intravenous MCh challenge (0.01–5.0 mg/kg). Airway narrowing was determined from measurements of Raw in vivo and from morphometric measurements on lung sections obtained after rapidly freezing the lung after the MCh challenge. The fold increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. Similarly, the degree of airway narrowing assessed morphometrically was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. The fold increase in Raw was highly correlated with the degree of airway narrowing assessed morphometrically ( r 2 = 0.82, P < 0.001). We conclude that the maturational difference in the effect of MCh on lung resistance is primarily caused by greater airway narrowing in the immature rabbits.

Positive Expiratory Pressure: A Potential Therapy to Mitigate Acute Bronchoconstriction in the Asthma of Obesity

2021 ◽  
Author(s):  
Swati a. Bhatawadekar ◽  
Anne E. Dixon ◽  
Ubong Peters ◽  
Nirav Daphtary ◽  
Kevin Hodgdon ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Late Onset ◽  
Rescue Therapy ◽  
Pharmacologic Therapy ◽  
Airway Closure ◽  
Airway Narrowing ◽  
Asthma Patients ◽  
Peripheral Airway ◽  
Central Airway ◽  
Positive Expiratory Pressure

Late-onset non-allergic (LONA) asthma in obesity is characterized by increased peripheral airway closure secondary to abnormally collapsible airways. We hypothesized that positive expiratory pressure (PEP) would mitigate the tendency to airway closure during bronchoconstriction, potentially serving as rescue therapy for LONA asthma of obesity. The PC20 dose of methacholine was determined in 18 obese participants with LONA asthma. At each of 4 subsequent visits, we used oscillometry to measure input respiratory impedance (Zrs) over 8 minutes; participants received their PC20 concentration of methacholine aerosol during the first 4.5 minutes. PEP combinations of either 0 or 10 cmH2O either during and/or after the methacholine delivery were applied, randomized between visits. Parameters characterizing respiratory system mechanics were extracted from the Zrs spectra. In 18 LONA asthma patients (14 females, BMI: 39.6±3.4 kg/m2), 10 cmH2O PEP during methacholine reduced elevations in the central airway resistance, peripheral airway resistance and elastance, and breathing frequency was also reduced. During the 3.5 min following methacholine delivery, PEP of 10 cmH2O reduced Ax and peripheral elastance compared to no PEP. PEP mitigates the onset of airway narrowing brought on by methacholine challenge, and airway closure once it is established. PEP thus might serve as a non-pharmacologic therapy to manage acute airway narrowing for obese LONA asthma.

Airway responses to inhaled histamine in asymptomatic smokers and nonsmokers

1977 ◽  
Vol 42 (4) ◽  
pp. 508-513 ◽  
Author(s):  
N. E. Brown ◽  
E. R. McFadden ◽  
R. H. Ingram
Keyword(s):  
Vital Capacity ◽  
Total Lung Capacity ◽  
Aerosol Deposition ◽  
Flow Volume ◽  
Maximal Flow ◽  
Airway Reactivity ◽  
Lung Capacity ◽  
Large Airway ◽  
Airway Response ◽  
Airway Responses

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.

Bronchoprotective and bronchodilatory effects of deep inspiration in rabbits subjected to bronchial challenge

2001 ◽  
Vol 91 (6) ◽  
pp. 2511-2516 ◽  
Author(s):  
S. J. Gunst ◽  
X. Shen ◽  
R. Ramchandani ◽  
R. S. Tepper
Keyword(s):  
Human Subjects ◽  
Inhibitory Effect ◽  
Airway Responsiveness ◽  
Deep Inspiration ◽  
Contractile Apparatus ◽  
Airway Reactivity ◽  
Airway Response ◽  
Normal Human ◽  
Airway Responses

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.

Influence of sleep on tensor palatini EMG and upper airway resistance in normal men

1991 ◽  
Vol 70 (6) ◽  
pp. 2574-2581 ◽  
Author(s):  
D. J. Tangel ◽  
W. S. Mezzanotte ◽  
D. P. White
Keyword(s):  
Eye Movement ◽  
Airway Resistance ◽  
Sleep Stage ◽  
Upper Airway ◽  
Sleep Stages ◽  
Normal Male ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Airway Narrowing ◽  
Upper Airway Resistance

We propose that a sleep-induced decrement in the activity of the tensor palatini (TP) muscle could induce airway narrowing in the area posterior to the soft palate and therefore lead to an increase in upper airway resistance in normal subjects. We investigated the TP to determine the influence of sleep on TP muscle activity and the relationship between changing TP activity and upper airway resistance over the entire night and during short sleep-awake transitions. Seven normal male subjects were studied on a single night with wire electrodes placed in both TP muscles. Sleep stage, inspiratory airflow, transpalatal pressure, and TP moving time average electromyogram (EMG) were continuously recorded. In addition, in two of the seven subjects the activity (EMG) of both the TP and the genioglossus muscle simultaneously was recorded throughout the night. Upper airway resistance increased progressively from wakefulness through the various non-rapid-eye-movement sleep stages, as has been previously described. The TP EMG did not commonly demonstrate phasic activity during wakefulness or sleep. However, the tonic EMG decreased progressively and significantly (P less than 0.05) from wakefulness through the non-rapid-eye-movement sleep stages [awake, 4.6 +/- 0.3 (SE) arbitrary units; stage 1, 2.6 +/- 0.3; stage 2, 1.7 +/- 0.5; stage 3/4, 1.5 +/- 0.8]. The mean correlation coefficient between TP EMG and upper airway resistance across all sleep states was (-0.46). This mean correlation improved over discrete sleep-awake transitions (-0.76). No sleep-induced decrement in the genioglossus activity was observed in the two subjects studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhaled Albuterol, but Not Intravenous Lidocaine, Protects Against Intubation-induced Bronchoconstriction in Asthma

2000 ◽  
Vol 93 (5) ◽  
pp. 1198-1204 ◽  
Author(s):  
Andrew D. Maslow ◽  
Meredith M. Regan ◽  
Elliot Israel ◽  
Amir Darvish ◽  
Mary Mehrez ◽  
...  
Keyword(s):  
Tracheal Intubation ◽  
Controlled Trial ◽  
Transpulmonary Pressure ◽  
Intravenous Lidocaine ◽  
Pulmonary Resistance ◽  
Airway Reactivity ◽  
Double Blind ◽  
Asthmatic Patients ◽  
Airway Response ◽  
To Receive

Background The ability of intravenous lidocaine to prevent intubation-induced bronchospasm is unclear. The authors performed a prospective, randomized, double-blind, placebo-controlled trial to test the ability of intravenous lidocaine and inhaled albuterol to attenuate airway reactivity after tracheal intubation in asthmatic patients undergoing general anesthesia. Methods Sixty patients were randomized to receive either 1.5 mg/kg intravenous lidocaine or saline, 3 min before tracheal intubation. An additional 50 patients were randomized to receive 4 puffs of inhaled albuterol or placebo 15-20 min before tracheal intubation. Anesthesia was induced with propofol. Immediately after intubation and at 5-min intervals, transpulmonary pressure and airflow were recorded, and lower pulmonary resistance (RL) was calculated. Isoflurane was administered after the initial two measurements to assess reversibility of bronchoconstriction. A bronchoconstrictor response to intubation was defined as RL greater than or equal to 5 cm H2O. l-1. s-1 in the first two measurements after intubation and RL subsequently decreasing by 50% or more after isoflurane. Results The lidocaine and placebo groups were not different in the peak RL before administration of isoflurane (8.2 cm H2O. l-1. s-1 vs. 7.6 cm H2O. l-1. s-1) or frequency of airway response to intubation (lidocaine 6 of 30 vs. placebo 5 of 27). In contrast, the albuterol group had lower peak RL (5.3 cm H2O. l-1. s-1 vs. 8.9 cm H2O. l-1. s-1; P &lt; 0.05) and a lower frequency of airway response (1 of 25 vs. 8 of 23; P &lt; 0.05) than the placebo group. Conclusions Inhaled albuterol blunted airway response to tracheal intubation in asthmatic patients, whereas intravenous lidocaine did not.

Prostaglandin E2 protects lower airways against bronchoconstriction

2006 ◽  
Vol 290 (1) ◽  
pp. L105-L113 ◽  
Author(s):  
John M. Hartney ◽  
Kenneth G. Coggins ◽  
Stephen L. Tilley ◽  
Leigh A. Jania ◽  
Alysia Kern Lovgren ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Cholinergic Receptor ◽  
Airway Responsiveness ◽  
Prostaglandin E ◽  
Airway Reactivity ◽  
Receptor Agonists ◽  
Diminished Capacity ◽  
Lung Resistance ◽  
Transgenic Lines ◽  
The Impact

Prostaglandin E2 (PGE2), similar to β-adrenergic receptor agonists, can protect airways from bronchoconstriction and resulting increase in airway resistance induced by a number of agents, including cholinergic receptor agonists and antigen. We examined the impact of sustained alterations in PGE2 pathways on changes in airway resistance. Genetic methods were utilized to alter PGE2 metabolism and signal transduction in the murine lung. PGE2 levels were elevated by generating mice lacking 15-hydroxyprostaglandin ( Hpgd−/−), the major catabolic enzyme of PGE2, and by generating a transgenic line in which mouse PGE2 synthase ( Ptges) expression is driven by a human lung-specific promoter, hSP-C. Conversely, to determine the impact of loss of PGE2 on airway reactivity, we examined mice lacking this synthase ( Ptges−/−) and receptors that mediate the actions of PGE2, particularly the PGE2 EP2 receptor ( Ptger2). Diminished capacity to produce and respond to PGE2 did not alter the response of mice to cholinergic stimuli. In contrast, the responsiveness to cholinergic stimulation was dramatically altered in animals with elevated PGE2 levels. The Hpgd−/− and hSP- C- Ptges transgenic lines both showed attenuated airway responsiveness to methacholine as measured by lung resistance. Thus, whereas compromise of the Ptges/PGE2/ Ptger2 pathway does not alter airway responsiveness, genetic modulation that elevates PGE2 levels in the lung attenuates airway responsiveness.

scholarly journals A composite computational model of liver glucose homeostasis. I. Building the composite model

2011 ◽  
Vol 9 (69) ◽  
pp. 689-700 ◽  
Author(s):  
J. Hetherington ◽  
T. Sumner ◽  
R. M. Seymour ◽  
L. Li ◽  
M. Varela Rey ◽  
...  
Keyword(s):  
Computational Model ◽  
Composite Model ◽  
Physiological Data ◽  
Small Scale ◽  
Model Parameters ◽  
High Scale ◽  
Composite Models ◽  
The Individual ◽  
Component Models

A computational model of the glucagon/insulin-driven liver glucohomeostasis function, focusing on the buffering of glucose into glycogen, has been developed. The model exemplifies an ‘engineering’ approach to modelling in systems biology, and was produced by linking together seven component models of separate aspects of the physiology. The component models use a variety of modelling paradigms and degrees of simplification. Model parameters were determined by an iterative hybrid of fitting to high-scale physiological data, and determination from small-scale in vitro experiments or molecular biological techniques. The component models were not originally designed for inclusion within such a composite model, but were integrated, with modification, using our published modelling software and computational frameworks. This approach facilitates the development of large and complex composite models, although, inevitably, some compromises must be made when composing the individual models. Composite models of this form have not previously been demonstrated.

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