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

Author(s):  
Swati a. Bhatawadekar ◽  
Anne E. Dixon ◽  
Ubong Peters ◽  
Nirav Daphtary ◽  
Kevin Hodgdon ◽  
...  

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.

2011 ◽  
Vol 110 (5) ◽  
pp. 1400-1405 ◽  
Author(s):  
David G. Chapman ◽  
Norbert Berend ◽  
Gregory G. King ◽  
Cheryl M. Salome

The mechanisms by which deep inspiration (DI) avoidance increases airway responsiveness in healthy subjects are not known. DI avoidance does not alter respiratory mechanics directly; however, computational modeling has predicted that DI avoidance would increase baseline ventilation heterogeneity. The aim was to determine if DI avoidance increased baseline ventilation heterogeneity and whether this correlated with the increase in airway responsiveness. Twelve healthy subjects had ventilation heterogeneity measured by multiple-breath nitrogen washout (MBNW) before and after 20 min of DI avoidance. This was followed by another 20-min period of DI avoidance before the inhalation of a single methacholine dose. The protocol was repeated on a separate day with the addition of five DIs at the end of each of the two periods of DI avoidance. Baseline ventilation heterogeneity in convection-dependent and diffusion-convection-dependent airways was calculated from MBNW. The response to methacholine was measured by the percent fall in forced expiratory volume in 1 s/forced vital capacity (FVC) (airway narrowing) and percent fall in FVC (airway closure). DI avoidance increased baseline diffusion-convection-dependent airways ( P = 0.02) but did not affect convection-dependent airways ( P = 0.9). DI avoidance increased both airway closure ( P = 0.002) and airway narrowing ( P = 0.02) during bronchial challenge. The increase in diffusion-convection-dependent airways due to DI avoidance did not correlate with the increase in either airway narrowing ( rs = 0.14) or airway closure ( rs = 0.12). These findings suggest that DI avoidance increases diffusion-convection-dependent ventilation heterogeneity that is not associated with the increase in airway responsiveness. We speculate that DI avoidance reduces surfactant release, which increases peripheral ventilation heterogeneity and also predisposes to peripheral airway closure.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniele Oliveira dos Santos ◽  
Larissa Perossi ◽  
Jéssica Perossi ◽  
Letícia Helena de Souza Simoni ◽  
Mayara Holtz ◽  
...  

AbstractImpulse oscillometry (IOS) allows evaluation of the compartmentalized resistance and reactance of the respiratory system, distinguishing central and peripheral obstruction. The IOS measurements are getting attention in the diagnosis and differentiation of chronic respiratory diseases. However, no data are available in the literature to differentiate between COPD and BE using IOS parameters. We aimed to evaluate the feasibility of IOS in the diagnosis of bronchiectasis non-cystic fibrosis (BE) in comparison to COPD. Whole breath, inspiration, expiration, and inspiratory-expiratory difference (Δ) were evaluated based on the IOS parameters: total resistance (R5), central airway resistance (R20), peripheral airway resistance (R5-R20), reactance (X5), reactance area (AX), and resonance frequency (Fres). Fifty-nine subjects (21 Healthy, 19 BE, and 19 COPD) participated in this study. It was observed a significant difference in the comparison of healthy and pulmonary disease groups (BE and COPD) for total breathing (R5-R20, X5, AX, and Fres), inspiratory phase (R5 and R5-R5), and expiratory phase (R5-R20 and X5). The comparison between BE and COPD groups showed significant difference in the expiratory phase for resistance at 5 and 20 Hz and, ΔR5 and ΔR20. The IOS evidenced an increase of R5, R20 and R5-R20 in patients with BE and COPD when compared to healthy subjects. Expiratory measures of IOS revealed increased airway resistance in COPD compared to BE patients who had similar FEV1 measured by spirometry, however, further studies are needed to confirm these differences.


2009 ◽  
Vol 107 (2) ◽  
pp. 564-569 ◽  
Author(s):  
David G. Chapman ◽  
Norbert Berend ◽  
Gregory G. King ◽  
Brent E. McParland ◽  
Cheryl M. Salome

The mechanism by which deep inspirations protect against increased airway responsiveness in nonasthmatic subjects is not known. The aim was to investigate the role of airway closure and airway narrowing in deep inspiration bronchoprotection. Twelve nonasthmatic and nine asthmatic subjects avoided deep inspirations (DI) for 20 min, then took five DI expired to functional residual capaciy (DI-FRC) or, on a separate day, no DI (no DI) before inhaling a single dose of methacholine. On another day, eight nonasthmatic subjects took five DI expired to residual volume (DI-RV). Peripheral airway function was measured by respiratory system reactance (Xrs), using the forced oscillation technique, and by forced vital capacity (FVC) as an index of airway closure. Respiratory system resistance (Rrs) and forced expiratory volume in 1 s (FEV1)/FVC were measured as indexes of airway narrowing. In nonasthmatic subjects, DI-FRC reduced the response measured by FEV1 ( P = 0.019), Xrs ( P = 0.02), and FVC ( P = 0.0005) but not by Rrs ( P = 0.15) or FEV1/FVC ( P = 0.52) compared with no DI. DI-RV had a less protective effect than DI-FRC on response measured by FEV1 ( P = 0.04) and FVC ( P = 0.016). There was no difference between all protocols when the response was measured by Xrs ( P = 0.20), Rrs ( P = 0.88), or FEV1/FVC ( P = 0.88). DI had no effect on methacholine response in asthmatic subjects. DI protect against airway responsiveness through an effect on peripheral airways involving reduced airway closure. The protective effect of DI on FEV1 and FVC was abolished by expiration to residual volume. We speculate that the reduced airway closure is due to reduced baseline ventilation heterogeneity and/or reduced airway surface tension.


1993 ◽  
Vol 75 (4) ◽  
pp. 1486-1496 ◽  
Author(s):  
J. J. Perez Fontan ◽  
L. P. Kinloch

To characterize the perinatal maturation of the cholinergic control of the airways, we compared the effects of bilateral cervical vagotomy and supramaximal vagal stimulation on the airway resistances of 7 premature (130–133 days of gestation), 11 term newborn, and 9 9-wk-old lambs anesthetized with pentobarbital. Resistances were partitioned between central and peripheral airways with catheters placed retrogradely into peripheral bronchi and capsules attached to the pleural surface in communication with subpleural air spaces. The central and peripheral airway resistances of premature and term newborn lambs and the peripheral resistance of 9-wk-old lambs decreased after vagotomy but only when the lungs were ventilated with small tidal volumes at mean transpulmonary pressures < or = 7.5 cmH2O. Vagotomy caused smaller absolute changes in central airway resistance than vagal stimulation. In contrast, both vagotomy and vagal stimulation produced similar absolute changes in peripheral airway resistance, indicating that resting cholinergic outflow is preferentially distributed to the peripheral airways even at the earlier ages. The effects of vagal stimulation on airway resistance were prevented by atropine. Our results prove that a resting bronchomotor tone can be present in both central and peripheral airways before the term of gestation in sheep. This tone depends on the activity of cholinergic fibers in the vagus and can be regionally controlled.


2020 ◽  
Vol 6 (3) ◽  
pp. 32-35
Author(s):  
Melanie März ◽  
Sarah Howe ◽  
Bernhard Laufer ◽  
Knut Moeller ◽  
Sabine Krueger-Ziolek

AbstractElectrical impedance tomography (EIT), a noninvasive and radiation-free imaging technique can be used in pulmonary function monitoring for determining regional ventilation distribution within the lung. Gold standard in pulmonary function monitoring is spirometry/body plethysmography, a method using forced breathing maneuvers to obtain global lung function parameters. However, this method is heavily dependent on the cooperation of the patients. Within this observational study, a method under normal breathing was tested with 5 healthy volunteers, which provides regional information about ventilation distribution. The occlusion method Rocc, a method for determining airway resistance, was used to create a short-term airway closure. Regional ventilation during the airway closure was examined with EIT. Simultaneously four different artificial airway resistances were used to simulate airway obstructions. Results show that EIT in combination with the ROcc method is suitable for the detection of regional differences in ventilation during airway closure for all four artificial airway resistances. Although the sum of relative impedances at the end of the shutter maneuver are smaller (nearly -0.100 AU) for the airway resistances Ø 12.5 mm, Ø 10.5 mm and Ø 9.5 mm than for the smallest one with Ø 30.0 mm (~ -0.070 AU), the changes in impedance from the start to the end of the shutter maneuver differs only slightly between the four artificial airway resistances. All impedance changes are in the range of 0.100 to 0.130 AU. The combination of EIT and the ROcc method provides not only global parameters such as airway resistance under normal breathing conditions, but also results of regional ventilation, which could enable the identification of areas affected by airway obstructions. However, the obtained results indicate that EIT might be a useful tool in the diagnosis and follow-up of obstructive lung diseases.


2008 ◽  
Vol 104 (2) ◽  
pp. 521-533 ◽  
Author(s):  
Stephen J. Lai-Fook ◽  
Pamela K. Houtz ◽  
Yih-Loong Lai

The evaluation of airway resistance (Raw) in conscious mice requires both end-expiratory (Ve) and tidal volumes (Vt) (Lai-Fook SJ and Lai YL. J Appl Physiol 98: 2204–2218, 2005). In anesthetized BALB/c mice we measured lung area (AL) from ventral-to-dorsal x-ray images taken at FRC (Ve) and after air inflation with 0.25 and 0.50 ml (ΔVL). Total lung volume (VL) described by equation: VL = ΔVL + VFRC = KAL1.5 assumed uniform (isotropic) inflation. Total VFRC averaged 0.55 ml, consisting of 0.10 ml tissue, 0.21 ml blood and 0.24 ml air. K averaged 1.84. In conscious mice in a sealed box, we measured the peak-to-peak box pressure excursions (ΔPb) and x-rays during several cycles. K was used to convert measured AL1.5 to VL values. We calculated Ve and Vt from the plot of VL vs. cos(α − φ). Phase angle α was the minimum point of the Pb cycle to the x-ray exposure. Phase difference between the Pb and VL cycles (φ) was measured from ΔPb values using both room- and body-temperature humidified box air. A similar analysis was used after aerosol exposures to bronchoconstrictor methacholine (Mch), except that φ depended also on increased Raw. In conscious mice, Ve (0.24 ml) doubled after Mch (50–125 mg/ml) aerosol exposure with constant Vt, frequency (f), ΔPb, and Raw. In anesthetized mice, in addition to an increased Ve, repeated 100 mg/ml Mch exposures increased both ΔPb and Raw and decreased f to apnea in 10 min. Thus conscious mice adapted to Mch by limiting Raw, while anesthesia resulted in airway closure followed by diaphragm fatigue and failure.


2005 ◽  
pp. 53-57
Author(s):  
S. A. Sobchenko ◽  
O. S. Schetchikova ◽  
N. V. Yakovleva

The aim of the study was to investigate features of respiratory infection inducing acute non-atopic late-onset asthma (NLA). Virologic and microbiologic examinations of brash biopsy samples of rhinopharyngeal and bronchial mucosa and bronchial lavage fluid were performed in 116 NLA patients admitted to a hospital in autumn and winter. The leading cause of acute NLA was found to be respiratory viral infections. We noted that different clinical NLA types had different sensibility to various viruses: adenoviruses mainly caused exacerbations of aspirin-induced asthma, respiratory syncytial and influenza A viruses were prevalently determined in non-atopic asthma. Patients with posttuberculotic lesions of the lungs mostly had viral and bacterial associations. Such mixed infection resulted in more severe and prolonged exacerbations of NLA.


1982 ◽  
Vol 52 (3) ◽  
pp. 725-733 ◽  
Author(s):  
J. M. Fullton ◽  
D. A. Hayes ◽  
R. L. Pimmel

Retrograde catheter and forced random noise techniques were combined to study the distribution of resistance and compliance in dogs following the inhalation of aerosols containing 2.5 and 5.0 mg/ml of histamine. Mean base-line peripheral resistance was 0.367 cmH2O . l'1 . s, agreeing with previous estimates. After correction for the endotracheal tube, the mean central airway resistance was 0.040 cmH2O . l'1 . s, considerably lower than previous estimates. This discrepancy was attributed to an overcorrection for the endotracheal tube resistance. The lower histamine dose caused a substantial increase in peripheral resistance, a relatively small increase in central resistance, and substantial decreases in total and peripheral compliance. After the higher histamine dose, changes in peripheral resistance and both compliances were similar to those obtained with the lower dose; however, the increase in central resistance was much larger than at the lower dose. The difference between total and peripheral compliance yielded estimates of airway compliance of 0.00306 l/cmH2O before and 0.00104 l/cmH2O after 2.5 mg/ml of histamine.


1991 ◽  
Vol 70 (6) ◽  
pp. 2514-2521 ◽  
Author(s):  
A. Kaise ◽  
A. N. Freed ◽  
W. Mitzner

In the present study, we investigated the interaction between CO2 concentration and rate of delivered flow on peripheral airway resistance (Rp) in the intact canine lung. Dogs were anesthetized, intubated, paralyzed, and mechanically ventilated with room air to maintain end-tidal CO2 between 4.8 and 5.2%. Using a wedged bronchoscope technique, we measured Rp at functional residual capacity. The relationship between CO2 concentration and Rp was measured at flow rates of 100 and 400 ml/min with 5, 3, 2, 1, and 0% CO2 in air. Measurements were made at the end of a 3-min exposure to each gas. At low flow rates (100 ml/min) responses to hypocapnia were small, whereas at high flow rates (400 ml/min) responses were large. The PC50 (defined as the CO2 concentration required to produce a 50% increase in Rp above baseline Rp established on 5% CO2) at 400 ml/min (1.73%) was significantly larger than that at 100 ml/min (0.38%). We also directly measured the relationship between Rp and flow rate with 5% CO2 (normocapnia) or 1% CO2 (hypocapnia) delivered into the wedged segment. Increases in normocapnic flow caused small but significant decreases in Rp. In contrast, increases in hypocapnic flow from 100 to 400 ml/min caused a 108% increase in Rp. Thus the response to hypocapnia is augmented by increasing flow rate. This interaction can be explained by a simple model that considers the effect of local ventilation-perfusion ratio and gas mixing on the local CO2 concentration at the site of peripheral airway contraction.


1990 ◽  
Vol 68 (1) ◽  
pp. 187-192 ◽  
Author(s):  
K. K. Kirchner ◽  
J. T. McBride

We have previously shown that airway cross-sectional area increases 15-20% after pneumonectomy in weanling ferrets by measuring bronchial casts. We have now reanalyzed these same casts to quantitate changes in airway length after pneumonectomy. In each cast the distance from each of 120 airways to the terminal bronchiole along its axial pathway was measured. The relationship between the logarithm of this distance and that of the fraction of the lobe subtended by an airway could be described by a quadratic equation with a correlation coefficient greater than 0.85. Subsegmental and more distal airways of postpneumonectomy animals were 33-47% longer than those of controls. Overall the main axial pathway of airways in the left lower lobes was 12% longer in operated animals, but this increase was primarily accounted for by an increase in the length of the more peripheral airways. Central airways were little if any longer in operated animals. After pneumonectomy in weanling ferrets, subsegmental and peripheral airway lengths increase to a greater degree than lung volume and airway cross-sectional area, whereas central airway lengths increase to a lesser extent if at all. The mechanisms responsible for this difference between central and intralobar compensatory airway growth are unknown.


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