Modelling resistance and reactance with heterogeneous airway narrowing in mild to severe asthma

2015 ◽  
Vol 93 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Swati A. Bhatawadekar ◽  
Del Leary ◽  
Geoffrey N. Maksym
Keyword(s):  
Frequency Dependence ◽  
Severe Asthma ◽  
Respiratory System ◽  
Upper Airway ◽  
Airway Disease ◽  
Small Airway ◽  
Small Airways ◽  
Airway Narrowing ◽  
Ventilation Heterogeneity

Ventilation heterogeneity is an important marker of small airway dysfunction in asthma. The frequency dependence of respiratory system resistance (Rrs) from oscillometry is used as a measure of this heterogeneity. However, this has not been quantitatively assessed or compared with other outcomes from oscillometry, including respiratory system reactance (Xrs) and the associated elastance (Ers). Here, we used a multibranch model of the human lung, including an upper airway shunt, to match previously reported respiratory mechanics in mild to severe asthma. We imposed heterogeneity by narrowing a proportion of the peripheral airways to account for patient Ers at 5 Hz, and then narrowed central airways to account for the remaining Rrs at 18 Hz. The model required >75% of the small airways to be occluded to reproduce severe asthma. While the model produced frequency dependence in Rrs, it was upward-shifted below 5 Hz compared with in-vivo results, indicating that other factors, including more distributed airway narrowing or central airway wall compliance, are required. However, Ers quantitatively reflected the imposed heterogeneity better than the frequency dependence of Rrs, independent of the frequency range for the estimation, and thus was a more robust measure of small-airway function. Thus, Ers appears to have greater potential as a clinical measure of early small-airway disease in asthma.

scholarly journals Ventilation heterogeneity in children with severe asthma

2021 ◽  
Author(s):  
Amy G. Nuttall ◽  
Caroline S. Beardsmore ◽  
Erol A. Gaillard
Keyword(s):  
Severe Asthma ◽  
Airway Disease ◽  
Asthma Severity ◽  
Small Airway ◽  
Cross Sectional ◽  
Lung Clearance ◽  
Moderate Asthma ◽  
Lung Clearance Index ◽  
Children With Asthma ◽  
Ventilation Heterogeneity

AbstractSmall airway disease, characterised by ventilation heterogeneity (VH), is present in a subgroup of patients with asthma. Ventilation heterogeneity can be measured using multiple breath washout testing. Few studies have been reported in children. We studied the relationship between VH, asthma severity, and spirometry in a cross-sectional observational cohort study involving children with stable mild-moderate and severe asthma by GINA classification and a group of healthy controls. Thirty-seven participants aged 5–16 years completed multiple breath nitrogen washout (MBNW) testing (seven controls, seven mild-moderate asthma, 23 severe asthma). The lung clearance index (LCI) was normal in control and mild-moderate asthmatics. LCI was abnormal in 5/23 (21%) of severe asthmatics. The LCI negatively correlated with FEV1z-score.Conclusion: VH is present in asthmatic children and appears to be more common in severe asthma. The LCI was significantly higher in the cohort of children with severe asthma, despite no difference in FEV1 between the groups. This supports previous evidence that LCI is a more sensitive marker of airway disease than FEV1. MBNW shows potential as a useful tool to assess children with severe asthma and may help inform clinical decisions. What is Known:• Increased ventilation heterogeneity is present in some children with asthma• Spirometry is not sensitive enough to detect small airway involvement in asthma What is New• Lung clearance index is abnormal in a significant subgroup of children with severe asthma but rarely in children with mild-moderate asthma• Our data suggests that LCI monitoring should be considered in children with severe asthma

scholarly journals Lung clearance index: assessment and utility in children with asthma

2019 ◽  
Vol 28 (154) ◽  
pp. 190046 ◽  
Author(s):  
Amy G. L. Nuttall ◽  
Werner Velásquez ◽  
Caroline S. Beardsmore ◽  
Erol A. Gaillard
Keyword(s):  
Early Stage ◽  
Airway Disease ◽  
Small Airway ◽  
Small Airways ◽  
Lung Clearance ◽  
Additional Information ◽  
Small Airway Disease ◽  
Lung Clearance Index ◽  
Children With Asthma ◽  
Ventilation Heterogeneity

There is increasing evidence that ventilation heterogeneity and small airway disease are significant factors in asthma, with evidence suggesting that the small airways are involved from an early stage in childhood asthma. Spirometry is commonly used to monitor lung function in asthmatics; however, it is not sensitive to small airway disease. There has been renewed interest in multibreath washout (MBW) tests, with recognition of the lung clearance index (LCI) as a global index of abnormality in gas mixing of the lungs that therefore also reflects small airway disease. This review summarises the technical and practical aspects of the MBW/LCI in children, and the differences between commercially available equipment. Children with severe asthma are more likely to have an abnormal LCI, whereas most children with mild-to-moderate asthma have an LCI within the normal range, but slightly higher than age-matched healthy controls. Monitoring children with asthma with MBW alongside standard spirometry may provide useful additional information.

Cyclic Adenosine Monophosphate Stimulation of Mucociliary Activity in the Upper Airways in Vivo

1995 ◽  
Vol 104 (5) ◽  
pp. 388-393 ◽  
Author(s):  
Anders Cervin ◽  
Sven Lindberg ◽  
Jan Dolata ◽  
Ulf Mercke
Keyword(s):  
Upper Airway ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Airway Disease ◽  
Maxillary Artery ◽  
Dibutyryl Camp ◽  
Upper Airways ◽  
Maximum Increase ◽  
Xanthine Derivatives

Xanthine derivatives are known to accelerate mucociliary transport in the lower airways, probably by preventing degradation of cyclic adenosine monophosphate (cAMP) and thereby increasing its intracellular concentration. The purpose of this study was to investigate the effects of cAMP on mucociliary activity in the upper airways. The effect on the mucociliary activity in the rabbit maxillary sinus of the xanthine derivatives theophylline and enprophylline was compared to that of the cAMP analog dibutyryl cAMP. The compounds were administered into the maxillary artery, and the response was recorded with a photoelectric technique. Infusions of theophylline (1.0 and 10 mg/kg) increased mucociliary activity (22.8% ± 5.9%, n = 6, and 21.6% ± 4.9%, n = 7, p < .05, respectively). Infusions of enprophylline (1.0 and 10.0 mg/kg) accelerated mucociliary activity (at the highest dosage tested, 24.3% ± 4.1%). Infusions of dibutyryl cAMP (0.1 and 1.0 mg/kg) stimulated mucociliary activity, with the maximum increase (20.1% ± 3.0%, n = 13, p < .05) being observed at a dosage of 0.1 mg/kg. The infused substances increased mucociliary activity within 1 minute after the start of the infusion, the duration of the response being approximately 20 minutes for theophylline, 22 minutes for enprophylline, and 12 minutes for dibutyryl cAMP. The present results support the view that cAMP is involved in regulating mucociliary activity in the upper airways. It remains to be elucidated whether xanthines such as theophylline and enprophylline are beneficial in upper airway disease in which mucociliary function is impaired (eg, chronic sinusitis).

scholarly journals Phenotypic Clusters On Computed Tomography Reflects Asthma Heterogeneity And Severity

2021 ◽  
Author(s):  
Sujeong Kim ◽  
Sanghun Choi ◽  
Taewoo Kim ◽  
Kwang Nam Jin ◽  
Sang-Heon Cho ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Severe Asthma ◽  
Visual Analysis ◽  
Quantitative Computed Tomography ◽  
Airway Disease ◽  
Small Airways ◽  
Functional Changes ◽  
Severe Allergic Asthma ◽  
Emphysematous Lung ◽  
Severity Of The Disease

Abstract Background: Asthma comprises heterogeneous inflammatory airway disorders whose classification has not been established. Quantitative computed tomography (QCT) methods can differentiate lung disease using accurate assessment of location, extent, and severity of the disease. This study aimed to identify heterogeneous asthmatic groups by QCT metrics of airway and parenchymal structure, which is associated with radiologists’ visual analysis and bronchodilator responses in a prospective design.Methods: Using the input from QCT-based metrics, including hydraulic diameter (Dh), luminal wall thickness (WT), functional small airway disease (fSAD), and emphysematous lung (Emph), a cluster analysis was performed and compared with grouping based on site of airway involvement and remodeling evaluated by radiologists.Results: 61 asthmatics were grouped into four clusters with different clinical severities. From C1 to C4, more severe lung function deterioration, higher fixed obstruction rate, and more frequent asthma exacerbation in 5-year follow-up were observed. C1 presented non-severe asthma with increased WT, Dh of proximal airways, and fSAD. C2 was mixed with non-severe and severe asthma, which had reserved bronchodilator responses of proximal airways. C3 and C4 presented severe asthmatics that exhibited reduced Dh of proximal airway and its bronchodilator responsiveness; C3 was severe allergic asthma without fSAD, while C4 was ex-smokers with significantly high fSAD% and Emph%. These clusters were correlated with the grouping by radiologists and their clinical outcomes.Conclusions: Four QCT imaging-based clusters with distinct structural and functional changes in proximal and small airways can stratify heterogeneous asthmatics and may serve as complementary tools for predicting future asthma outcomes.

Mechanical properties of the upper airway

1983 ◽  
Vol 55 (2) ◽  
pp. 335-342 ◽  
Author(s):  
M. Cauberghs ◽  
K. P. Van de Woestijne
Keyword(s):  
Mechanical Properties ◽  
Lung Disease ◽  
Frequency Dependence ◽  
Respiratory System ◽  
Obstructive Lung Disease ◽  
Forced Oscillation ◽  
Valsalva Maneuver ◽  
Upper Airway ◽  
Forced Oscillations ◽  
Forced Oscillation Technique

The series and shunt components of the impedance of the upper airway (Zuaw) were evaluated from measurements obtained during a Valsalva maneuver by means of a modified forced oscillation technique. When the cheeks are supported, the upper airway can be represented by a single distributed transmission line. The homogeneity of this line was confirmed by measuring separately Zuaw and the impedance of the mouth. Correction of the impedance of the respiratory system, determined by means of the forced oscillations technique, for the shunt properties of Zuaw results in some modifications of the frequency dependence of resistance (Rrs) in healthy adults and in marked changes of the absolute values of Rrs in children and in patients with obstructive lung disease.

scholarly journals Reactance and elastance as measures of small airways response to bronchodilator in asthma

2019 ◽  
Vol 127 (6) ◽  
pp. 1772-1781 ◽  
Author(s):  
S. A. Bhatawadekar ◽  
D. Leary ◽  
V. de Lange ◽  
U. Peters ◽  
S. Fulton ◽  
...  
Keyword(s):  
Respiratory System ◽  
Healthy Subjects ◽  
Low Frequency ◽  
Upper Airway ◽  
Study Groups ◽  
Small Airways ◽  
Tree Model ◽  
Effective Measure ◽  
Bronchodilator Response ◽  
Airway Function

Bronchodilation alters both respiratory system resistance (Rrs) and reactance (Xrs) in asthma, but how changes in Rrs and Xrs compare, and respond differently in health and asthma, in reflecting the contributions from the large and small airways has not been assessed. We assessed reversibility using spirometry and oscillometry in healthy and asthma subjects. Using a multibranch airway-tree model with the mechanics of upper airway shunt, we compared the effects of airway dilation and small airways recruitment to explain the changes in Rrs and Xrs. Bronchodilator decreased Rrs by 23.0 (19.0)% in 18 asthma subjects and by 13.5 (19.5)% in 18 healthy subjects. Estimated respiratory system elastance (Ers) decreased by 23.2 (21.4)% in asthma, with no significant decrease in healthy subjects. With the use of the model, airway recruitment of 15% across a generation of the small airways could explain the changes in Ers in asthma with no recruitment in healthy subjects. In asthma, recruitment accounted for 40% of the changes in Rrs, with the remaining explained by airway dilation of 6.8% attributable largely to the central airways. Interestingly, the same dilation magnitude explained the changes in Rrs in healthy subjects. Shunt only affected Rrs of the model. Ers was unaltered in health and unaffected by shunt in both groups. In asthma, Ers changed comparably to Rrs and could be attributed to small airways, while the change in Rrs was split between large and small airways. This implies that in asthma Ers sensed through Xrs may be a more effective measure of small airways obstruction and recruitment than Rrs. NEW & NOTEWORTHY This is the first study to quantify to relative contributions of small and large airways to bronchodilator response in healthy subjects and patients with asthma. The response of the central airways to bronchodilator was similar in magnitude in both study groups, whereas the response of the small airways was significant among patients with asthma. These results suggest that low-frequency reactance and derived elastance are both sensitive measures of small airway function in asthma.

scholarly journals Gene expression profiling of bronchial brushes is associated with the level of emphysema measured by computed tomography-based parametric response mapping

2020 ◽  
Vol 318 (6) ◽  
pp. L1222-L1228
Author(s):  
Senani N. H. Rathnayake ◽  
Firdaus A. A. Mohamed Hoesein ◽  
Craig J. Galban ◽  
Nick H. T. ten Hacken ◽  
Brian G. G. Oliver ◽  
...  
Keyword(s):  
Gene Expression ◽  
Computed Tomography ◽  
Airway Disease ◽  
Small Airway ◽  
Study Cohort ◽  
Small Airways ◽  
Air Trapping ◽  
Response Mapping ◽  
Small Airway Disease ◽  
Parametric Response

Parametric response mapping (PRM) is a computed tomography (CT)-based method to phenotype patients with chronic obstructive pulmonary disease (COPD). It is capable of differentiating emphysema-related air trapping with nonemphysematous air trapping (small airway disease), which helps to identify the extent and localization of the disease. Most studies evaluating the gene expression in smokers and COPD patients related this to spirometric measurements, but none have investigated the relationship with CT-based measurements of lung structure. The current study aimed to examine gene expression profiles of brushed bronchial epithelial cells in association with the PRM-defined CT-based measurements of emphysema (PRMEmph) and small airway disease (PRMfSAD). Using the Top Institute Pharma (TIP) study cohort (COPD = 12 and asymptomatic smokers = 32), we identified a gene expression signature of bronchial brushings, which was associated with PRMEmph in the lungs. One hundred thirty-three genes were identified to be associated with PRMEmph. Among the most significantly associated genes, CXCL11 is a potent chemokine involved with CD8+ T cell activation during inflammation in COPD, indicating that it may play an essential role in the development of emphysema. The PRMEmph signature was then replicated in two independent data sets. Pathway analysis showed that the PRMEmph signature is associated with proinflammatory and notch signaling pathways. Together these findings indicate that airway epithelium may play a role in the development of emphysema and/or may act as a biomarker for the presence of emphysema. In contrast, its role in relation to functional small airways disease is less clear.

scholarly journals EVALUATION OF SMALL AIRWAY REVERSIBILITY AMONG ASTHMATIC PATIENTS WITH NON-OBSTRUCTIVE PATTERNS OF SPIROMETRY

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Tarig Merghani ◽  
Azza Alawad
Keyword(s):  
Airway Disease ◽  
Forced Expiratory Volume ◽  
Small Airway ◽  
Small Airways ◽  
Asthmatic Patients ◽  
Peripheral Airways ◽  
Flow Parameters ◽  
Small Airway Disease ◽  
Forced Expiratory Flow ◽  
Airway Reversibility

Background: Although the forced expiratory flow parameters are increasingly used in the diagnosis of small airway disease (SAD), the reversibility of these indicators is rarely described. The aim of this study is to evaluate the association of small airways reversibility with the presence of SAD and bronchodilator reversibility (BDR) of the proximal airways. Methods: The forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the indicators of SAD (FEF25%, FEF50%, FEF75%, FEF25-75%, and FEF75-85%) were measured before and 20 minutes after salbutamol administration (200 mcg by using inhaler/Spacer). Positive BDR was accepted when FEV1 or FVC was increased ? 12% and > 200 ml, indicating responsive proximal airways. Positive small airway reversibility was diagnosed when any of the small airway indicators is increased ? 30% above the baseline results. All measurements were performed with the All-flow spirometer (Clement Clarke International, Harlow, UK). Results: Evidence of SAD was found in 62.1% of all participants and in 75.2% of those who showed responsive proximal airways. The positive predictive value of the SAD in diagnosing responsive proximal airways was 67.8%. The reversibility of the small airway indicators showed insignificant association with the FEV1 or FVC BDR. The reversibility of FEF50%, FEF75% and FEF25-75% showed significant association with the diagnosis of SAD, with specificities ranging from 75.5%-81.1%. Conclusion: SAD has a significant association with positive reversibility of both the proximal and the peripheral airways. Further studies are needed to evaluate the clinical significance of positive small airway reversibility in the diagnosis and management of obstructive lung diseases. Keywords: Asthma; Small airway disease; Bronchodilator Reversibility, FEV1, FVC; FEF25-75%

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 Determining Response to Treatment for Drug-Induced Bronchocentric Granulomatosis by the Forced Oscillation Technique

Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1315
Author(s):  
Susumu Fukahori ◽  
Yasushi Obase ◽  
Chizu Fukushima ◽  
Daisuke Takao ◽  
Jun Iriki ◽  
...  
Keyword(s):  
Forced Oscillation ◽  
Airway Disease ◽  
Small Airway ◽  
Response To Treatment ◽  
Chronic Obstructive ◽  
Forced Oscillation Technique ◽  
Small Airways ◽  
Small Airway Disease ◽  
Bronchocentric Granulomatosis ◽  
Effect Of Treatment

Anti-tumor necrosis factor alpha (TNFα) therapy is widely used to treat various inflammatory conditions. Paradoxically, there are several case reports describing the development of bronchocentric granulomatosis treated with TNFα inhibitors, and it is difficult to determine the effect of treatment using conventional spirometry because the lesions are located in small airways. However, it has been reported that the forced oscillation technique (FOT) is useful in the evaluation of small airway disease in bronchial asthma or chronic obstructive pulmonary disease. We performed the FOT to determine the effect of treatment on bronchocentric granulomatosis and found it to be useful. We report the case of a 55-year-old female with ulcerative colitis who was treated with golimumab and who developed bronchocentric granulomatosis as a sarcoid-like reaction to golimumab. She was successfully treated with prednisone, and the treatment efficacy was confirmed by the FOT. The FOT may be useful in the evaluation of small airway disease in bronchocentric granulomatosis. This case may help inform clinicians of the usefulness of the FOT to assess small airway disease in various diseases.

Sign in / Sign up

Export Citation Format

Share Document