Methacholine versus histamine: paradoxical response of spirometry and ventilation distribution

2001 ◽  
Vol 91 (6) ◽  
pp. 2587-2594 ◽  
Author(s):  
Sylvia Verbanck ◽  
Daniël Schuermans ◽  
Marc Noppen ◽  
Walter Vincken ◽  
Manuel Paiva
Keyword(s):  
Dose Group ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
Double Dose ◽  
Ventilation Distribution ◽  
Paradoxical Response ◽  
Airway Narrowing ◽  
Equal Dose ◽  
Ventilation Heterogeneity ◽  
Group A

We investigated the differential effect of histamine and methacholine on spirometry and ventilation distribution (where indexes S cond and S acin represent conductive and acinar ventilation heterogeneity; Verbanck S, Schuermans D, Van Muylem A, Noppen M, Paiva M, and Vincken W. J Appl Physiol 83: 1807–1816, 1997). Thirty normal subjects were challenged with cumulative doses of 6.52 μmol histamine and, on a separate day, with either 6.67 μmol methacholine (equal-dose group; n = 15) or 13.3 μmol methacholine (double-dose group; n = 15). Largest average forced expiratory volume in 1 s (FEV1) decreases or S cond increases obtained in either group were −9% and +286%, respectively; S acin remained unaffected at all times. In the equal-dose group, a smaller FEV1 decline ( P= 0.002) after methacholine was paralleled by a smaller S cond increase ( P = 0.041) than with histamine. However, in the double-dose group, methacholine maintained a smaller FEV1 decline ( P = 0.009) while inducing a larger S cond increase ( P = 0.006) than did histamine. The differential action of histamine and methacholine is confined to the conductive airways, where histamine likely causes the greatest overall airway narrowing and methacholine induces the largest parallel heterogeneity in airway narrowing, probably at the level of the large and small conductive airways, respectively. The observed ventilation heterogeneities predict a risk for dissociation between ventilation-perfusion mismatch and spirometry, particularly after methacholine challenge.

Respiratory impedance and multibreath N2 washout in healthy, asthmatic, and cystic fibrosis subjects

1990 ◽  
Vol 68 (5) ◽  
pp. 2139-2149 ◽  
Author(s):  
K. R. Lutchen ◽  
R. H. Habib ◽  
H. L. Dorkin ◽  
M. A. Wall
Keyword(s):  
Cystic Fibrosis ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
The Other ◽  
Poor Correlation ◽  
Base Line ◽  
Respiratory Impedance ◽  
Ventilation Distribution ◽  
Peripheral Airway ◽  
Lung Periphery

We measured forced expiratory volume in 1 s (FEV1), respiratory impedance (Zrs) from 4 to 60 Hz, and a multibreath N2 washout (MBNW) in 6 normal, 10 asthmatic, and 5 cystic fibrosis (CF) subjects. The MBNW were characterized by the mean dilution number (MDN) derived by a moment analysis. The Zrs spectra were characterized by the minimum resistance (Rmin), the drop in resistance (Rdrop) from 4 Hz to Rmin, and the first resonance frequency (Fr1). Measurements were repeated after bronchodilation in three normal and all asthmatic subjects. Before bronchodilation, six of the asthmatic subjects showed close to normal FEV1. The Zrs in the normal subjects showed low Rmin (1.9 +/- 0.7 cmH2O.l-1.s), Rdrop (0.4 +/- 0.4), and Fr1 (10 +/- 2 Hz). Four of the mildly obstructed asthmatic subjects had normal Zrs but elevated MDNs (i.e., abnormal ventilation distribution). The other six asthmatic subjects had significantly elevated Rmin (4.1 +/- 0.8), Rdrop (6.3 +/- 5.8), and Fr1 (34 +/- 0.4 Hz) and elevated MDNs. The CF patients had elevated Zrs features and MDNs. After bronchodilation, no changes in FEV1, MDN, or Zrs occurred in the normal subjects. All asthmatic subjects showed increased FEV1 and decreased MDN, but the Zrs was unaltered in the four asthmatic subjects whose base-line Zrs was normal. For the other six asthmatic subjects, there were large decreases in the Rmin, Rdrop, and Fr1. Finally, there was a poor correlation between the MDN and the Zrs features but high correlation between the Zrs features alone. These results imply that significant nonuniform peripheral airway obstruction can exist such that ventilation distribution is abnormal but Zrs from 4 to 60 Hz is not. Abnormalities in Zrs from 4 to 60 Hz occur only after significant overall obstruction in the peripheral and more central airways. Combining Zrs and the MBNW may permit us to infer whether the disease is predominantly in the lung periphery or in the more central airways.

scholarly journals Regional airflow obstruction after bronchoconstriction and subsequent bronchodilation in subjects without pulmonary disease

2019 ◽  
Vol 127 (1) ◽  
pp. 31-39 ◽  
Author(s):  
E. T. Geier ◽  
R. J. Theilmann ◽  
G. K. Prisk ◽  
R. C. Sá
Keyword(s):  
Healthy Subjects ◽  
Standard Dose ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
Bronchodilator Therapy ◽  
Ventilation Imaging ◽  
Ventilation Heterogeneity ◽  
Healthy Lung

Some subjects with asthma have ventilation defects that are resistant to bronchodilator therapy, and it is thought that these resistant defects may be due to ongoing inflammation or chronic airway remodeling. However, it is unclear whether regional obstruction due to bronchospasm alone persists after bronchodilator therapy. To investigate this, six young, healthy subjects, in whom inflammation and remodeling were assumed to be absent, were bronchoconstricted with a PC20 [the concentration of methacholine that elicits a 20% drop in forced expiratory volume in 1 s (FEV1)] dose of methacholine and subsequently bronchodilated with a standard dose of albuterol on three separate occasions. Specific ventilation imaging, a proton MRI technique, was used to spatially map specific ventilation across 80% of each subject’s right lung in each condition. The ratio between regional specific ventilation at baseline and after intervention was used to classify areas that had constricted. After albuterol rescue from methacholine bronchoconstriction, 12% (SD 9) of the lung was classified as constricted. Of the 12% of lung units that were classified as constricted after albuterol, approximately half [7% (SD 7)] had constricted after methacholine and failed to recover, whereas half [6% (SD 4)] had remained open after methacholine but became constricted after albuterol. The incomplete regional recovery was not reflected in the subjects’ FEV1 measurements, which did not decrease from baseline ( P = 0.97), nor was it detectable as an increase in specific ventilation heterogeneity ( P = 0.78). NEW & NOTEWORTHY In normal subjects bronchoconstricted with methacholine and subsequently treated with albuterol, not all regions of the healthy lung returned to their prebronchoconstricted specific ventilation after albuterol, despite full recovery of integrative lung indexes (forced expiratory volume in 1 s and specific ventilation heterogeneity). The regions that remained bronchoconstricted following albuterol were those with the highest specific ventilation at baseline, which suggests that they may have received the highest methacholine dose.

Effect of deep inspiration avoidance on ventilation heterogeneity and airway responsiveness in healthy adults

2011 ◽  
Vol 110 (5) ◽  
pp. 1400-1405 ◽  
Author(s):  
David G. Chapman ◽  
Norbert Berend ◽  
Gregory G. King ◽  
Cheryl M. Salome
Keyword(s):  
Healthy Subjects ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Deep Inspiration ◽  
Airway Closure ◽  
Airway Narrowing ◽  
Before And After ◽  
Ventilation Heterogeneity ◽  
Peripheral Airway ◽  
Diffusion Convection

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.

Similar ventilation distribution in normal subjects prone and supine during tidal breathing

2002 ◽  
Vol 92 (2) ◽  
pp. 622-626 ◽  
Author(s):  
M. J. Rodríguez-Nieto ◽  
G. Peces-Barba ◽  
N. González Mangado ◽  
M. Paiva ◽  
S. Verbanck
Keyword(s):  
Normal Subjects ◽  
Phase Iii ◽  
Ventilation Distribution ◽  
Tidal Breathing ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Residual Capacity ◽  
Slope Difference ◽  
The Difference ◽  
Phase Iii Slope

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O2, 5% He, and 5% SF6as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N2concentrations was evaluated in terms of its curvilinearity. The MBW N2normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907–1916, 1997). Also, the difference between SF6and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures ( P > 0.1; n= 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N2normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF6-He normalized phase III slope difference in the first MBW expiration ( P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.

scholarly journals Deep inspirations protect against airway closure in nonasthmatic subjects

2009 ◽  
Vol 107 (2) ◽  
pp. 564-569 ◽  
Author(s):  
David G. Chapman ◽  
Norbert Berend ◽  
Gregory G. King ◽  
Brent E. McParland ◽  
Cheryl M. Salome
Keyword(s):  
Protective Effect ◽  
Respiratory System ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Forced Oscillation Technique ◽  
Residual Volume ◽  
Airway Closure ◽  
Airway Narrowing ◽  
Ventilation Heterogeneity ◽  
Peripheral Airway

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.

scholarly journals Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults

2015 ◽  
Vol 47 (1) ◽  
pp. 166-176 ◽  
Author(s):  
Sylvia Verbanck ◽  
Alain Van Muylem ◽  
Daniel Schuermans ◽  
Ivan Bautmans ◽  
Bruce Thompson ◽  
...  
Keyword(s):  
Lung Function ◽  
Reference Values ◽  
Transfer Factor ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Healthy Population ◽  
Ventilation Distribution ◽  
European Respiratory Society ◽  
Obstructive Pulmonary Disease ◽  
Ventilation Heterogeneity

Monitoring of chronic lung disease requires reference values of lung function indices, including putative markers of small airway function, spanning a wide age range.We measured spirometry, transfer factor of the lung for carbon monoxide (TLCO), static lung volume, resistance and ventilation distribution in a healthy population, studying at least 20 subjects per sex and per decade between the ages of 20 and 80 years.With respect to the Global Lung Function Initiative reference data, our subjects had average z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC of −0.12, 0.04 and −0.32, respectively. Reference equations were obtained which could account for a potential dependence of index variability on age and height. This was done for (but not limited to) indices that are pertinent to asthma and chronic obstructive pulmonary disease studies: forced expired volume in 6 s, forced expiratory flow, TLCO, specific airway conductance, residual volume (RV)/total lung capacity (TLC), and ventilation heterogeneity in acinar and conductive lung zones.Deterioration in acinar ventilation heterogeneity and lung clearance index with age were more marked beyond 60 years, and conductive ventilation heterogeneity showed the greatest increase in variability with age. The most clinically relevant deviation from published reference values concerned RV/TLC values, which were considerably smaller than American Thoracic Society/European Respiratory Society-endorsed reference values.

Effect of airways constriction on exhaled nitric oxide

2008 ◽  
Vol 104 (4) ◽  
pp. 925-930 ◽  
Author(s):  
Sylvia Verbanck ◽  
Yannick Kerckx ◽  
Daniel Schuermans ◽  
Walter Vincken ◽  
Manuel Paiva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vital Capacity ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
Exhaled Nitric Oxide ◽  
Lung Model ◽  
Airway Constriction ◽  
Exhaled No ◽  
Ventilation Heterogeneity ◽  
Mechanical Factors

While airway constriction has been shown to affect exhaled nitric oxide (NO), the mechanisms and location of constricted airways most likely to affect exhaled NO remain obscure. We studied the effects of histamine-induced airway constriction and ventilation heterogeneity on exhaled NO at 50 ml/s (FeNO,50) and combined this with model simulations of FeNO,50 changes due to constriction of airways at various depths of the lung model. In 20 normal subjects, histamine induced a 26 ± 15(SD)% FeNO,50 decrease, a 9 ± 6% forced expiratory volume in 1 s (FEV1) decrease, a 19 ± 9% mean forced midexpiratory flow between 25% and 75% forced vital capacity (FEF25–75) decrease, and a 94 ± 119% increase in conductive ventilation heterogeneity. There was a significant correlation of FeNO,50 decrease with FEF25–75 decrease ( P = 0.006) but not with FEV1 decrease or with increased ventilation heterogeneity. Simulations confirmed the negligible effect of ventilation heterogeneity on FeNO,50 and showed that the histamine-induced FeNO,50 decrease was due to constriction, with associated reduction in NO flux, of airways located proximal to generation 15. The model also indicated that the most marked effect of airways constriction on FeNO,50 is situated in generations 10–15 and that airway constriction beyond generation 15 markedly increases FeNO,50 due to interference with the NO backdiffusion effect. These mechanical factors should be considered when interpreting exhaled NO in lung disease.

Total lung capacity does not change during methacholine-stimulated airway narrowing

1986 ◽  
Vol 61 (6) ◽  
pp. 2144-2147 ◽  
Author(s):  
J. G. Kirby ◽  
E. F. Juniper ◽  
F. E. Hargreave ◽  
N. Zamel
Keyword(s):  
Lung Volume ◽  
Total Lung Capacity ◽  
Normal Subjects ◽  
Forced Expiratory Volume ◽  
Whole Body ◽  
Flow Volume ◽  
Airway Narrowing ◽  
Lung Capacity ◽  
Change In Mean ◽  
Whole Body Plethysmography

The accurate measurement of changes in flow rates from partial flow-volume curves depends on their measurement at the same lung volume. This lung volume can be standardized from total lung capacity (TLC) if this does not change at the same time. We examined the effect of methacholine-stimulated maximal airway narrowing [change in mean forced expiratory volume in 1 s (delta FEV1) = 26.4%] on TLC, measured by whole-body plethysmography, in 10 normal subjects and of moderate airway narrowing (mean delta FEV1 = 34.9%) in 10 asthmatics. The TLC changed from 5.88 to 6.03 liters in normal subjects (P greater than 0.05) and from 6.92 to 6.95 liters (P greater than 0.5) in asthmatics. The results of this study suggest that TLC does not change significantly after methacholine-stimulated maximal airway narrowing in normal subjects and after moderate narrowing in asthmatics.

scholarly journals Regional lung function in nonsmokers and asymptomatic current and former smokers

2019 ◽  
Vol 5 (3) ◽  
pp. 00240-2018 ◽  
Author(s):  
Barbara Vogt ◽  
Kathinka Deuß ◽  
Victoria Hennig ◽  
Zhanqi Zhao ◽  
Ingmar Lautenschläger ◽  
...  
Keyword(s):  
Tobacco Consumption ◽  
Distribution Coefficients ◽  
Forced Expiratory Volume ◽  
Healthy Adults ◽  
Forced Expiration ◽  
Ventilation Distribution ◽  
Regional Ventilation ◽  
Impedance Tomography ◽  
Ventilation Heterogeneity ◽  
Image Pixels

Electrical impedance tomography (EIT) is able to detect rapid lung volume changes during breathing. The aim of our observational study was to characterise the heterogeneity of regional ventilation distribution in lung-healthy adults by EIT and to detect the possible impact of tobacco consumption.A total of 219 nonsmokers, asymptomatic ex-smokers and current smokers were examined during forced full expiration using EIT. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were determined in 836 EIT image pixels for the analysis of spatial and temporal ventilation distribution. Coefficients of variation (CVs) of these pixel values were calculated. Histograms and medians of FEV1/FVCEIT and times required to exhale 50%, 75%, 90% of FVCEIT (t50, t75 and t90) were generated.CV of FEV1/FVCEIT distinguished among all groups (mean±sd: nonsmokers 0.43±0.05, ex-smokers 0.52±0.09, smokers 0.62±0.16). Histograms of FEV1/FVCEIT differentiated between nonsmokers and the other groups (p<0.0001). Medians of t50, t75 and t90 showed the lowest values in nonsmokers. Median t90 separated all groups (median (interquartile range): nonsmokers 0.82 (0.67–1.15), ex-smokers 1.41 (1.03–2.21), smokers 1.91 (1.33–3.53)).EIT detects regional ventilation heterogeneity during forced expiration in healthy nonsmokers and its increase in asymptomatic former and current smokers. Therefore, EIT-derived reference values should only be collected from nonsmoking lung-healthy adults.

scholarly journals Preoperative predictors of dysphagia after transoral surgery

2021 ◽  
Author(s):  
Kazunori Fujiwara ◽  
Kenkichiro Taira ◽  
Ryohei Donishi ◽  
Satoshi Koyama ◽  
Tsuyoshi Morisaki ◽  
...  
Keyword(s):  
Head And Neck ◽  
Forced Expiratory Volume ◽  
Transoral Surgery ◽  
Postoperative Dysphagia ◽  
Swallowing Function ◽  
History Of ◽  
Group A ◽  
Low Bmi ◽  
Head And Neck Radiotherapy

Abstract Background Transoral surgery (TOS) has been used to remove pharyngeal and laryngeal cancers with the objective of improving functional without worsening survival. However, there is a risk of postoperative dysphagia, which can severely impair quality of life. The aim of this study was to evaluate the preoperative predictive factors for postoperative dysphagia in patients undergoing TOS. Methods One hundred and twenty patients who underwent TOS were evaluated in this study. The degree of dysphagia was evaluated using the Functional Outcome Swallowing Scale (FOSS) both preoperatively and 3 months postoperatively. Those whose FOSS stage was maintained postoperatively were classified into the FOSS-M group, while those with increased FOSS stage postopratively were classified into the FOSS-I group. The following parameters were assessed before surgery: age, weight, height, body mass index (BMI), forced expiratory volume in 1 s, and history of head and neck radiotherapy. Videofluoroscopy (VF) was performed preoperatively to evaluate swallowing function using the Penetration-Aspiration Scale (PAS). Results The BMI of the FOSS-M group was significantly higher than that of the FOSS-I group. A history of radiotherapy was significantly more common in the FOSS-I group than in the FOSS-M group. Finally, preoperative PAS in the FOSS-M group was lower than that in the FOSS-I group. Conclusion This study suggested that patients with preoperative aspiration detected using VF might develop postoperative dysphagia severely. In addition, preoperative low BMI and a history of previous radiotherapy for head and neck cancer were associated with postoperative dysphagia. Objective examinations such as VF should be performed preoperatively.

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