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.

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

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 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.

Relationships between the lung clearance index and conductive and acinar ventilation heterogeneity

2012 ◽  
Vol 112 (5) ◽  
pp. 782-790 ◽  
Author(s):  
Sylvia Verbanck ◽  
Manuel Paiva ◽  
Daniel Schuermans ◽  
Shane Hanon ◽  
Walter Vincken ◽  
...  
Keyword(s):  
Compartment Model ◽  
Normal Subjects ◽  
Bronchial Tree ◽  
Small Airways ◽  
Lung Clearance ◽  
Lung Clearance Index ◽  
Asthma Patients ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout ◽  
Washout Curves

The lung clearance index (LCI) derived from a multiple breath washout test has regained considerable popularity in recent years, alternatively being promoted as an early detection tool or a marker of small airways function. In this study, we systematically investigated the link between LCI and indexes of acinar and conductive airways ventilation heterogeneity (Sacin, Scond) to assess potential contributions from both lung zones. Relationships were examined in 55 normal subjects after provocation, where only Scond is known to be markedly increased, and in 55 asthma patients after bronchodilation, in whom both Scond and Sacin ranged between normal and abnormal. LCI was correlated to Scond in both groups ( R = 0.37–0.43; P < 0.01 for both); in the asthma group, LCI was also tightly correlated to Sacin ( R = 0.70; P < 0.001). Potential mechanisms operational at various levels of the bronchial tree were identified by considering washout curvilinearity in addition to LCI to distinguish specific ventilation and dead space effects (also illustrated by simple 2-compartment model simulations). Although the asthma data clearly demonstrate that LCI can reflect very peripheral ventilation heterogeneities, the normal provocation data also convincingly show that LCI increases may be the exclusive result of far more proximal ventilation heterogeneities. Because LCI potentially includes heterogeneities at all length scales, it is suggested that ventilation imaging in combination with LCI measurement at the mouth could identify the scale of relevant ventilation heterogeneities. In the meantime, interpretations of LCI results in the clinic based on washout curves collected at the mouth should be handled with caution.

Inspiratory and Expiratory Chest High-Resolution CT: Small-Airway Disease Evaluation in Patients with COVID-19

2021 ◽  
Vol 17 ◽  
Author(s):  
Renjun Huang ◽  
Jingfen Zhu ◽  
Jianguo Zhou ◽  
Yalei Shang ◽  
Xiaoming Lin ◽  
...  
Keyword(s):  
High Resolution ◽  
Early Stage ◽  
Airway Disease ◽  
Ct Images ◽  
Small Airway ◽  
Time Interval ◽  
Air Trapping ◽  
Small Airway Disease ◽  
Significant Difference

Background: An outbreak of coronavirus disease 2019 (COVID-19) has occurred worldwide. However, the small-airway disease in patients with COVID-19 has not been explored. Aim: This study aimed to explore the small-airway disease in patients with COVID-19 using inspiratory and expiratory chest high-resolution computed tomography (CT). Methods: This multicenter study included 108 patients with COVID-19. The patients were classified into five stages (0–IV) based on the CT images. The clinical and imaging data were compared among CT images in different stages. Patients were divided into three groups according to the time interval from the initial CT scan, and the clinical and air trapping data were compared among these groups. The correlation between clinical parameters and CT scores was evaluated. Results: The clinical data, including age, frequency of breath shortness and dyspnea, neutrophil percentage, lymphocyte count, PaO2, PaCO2, SaO2, and time interval between the onset of illness and initial CT, showed significant differences among CT images in different stages. A significant difference in the CT score of air trapping was observed between stage I and stage III. A low negative correlation was found between the CT score of air trapping and time interval between the onset of symptoms and initial CT. No significant difference was noted in the frequency and CT score of air trapping among different groups. Conclusions: Some patients with COVID-19 developed small-airway disease. Air trapping was more distinguished in the early stage of the disease and persisted during the 2-month follow-up. Longer-term follow-up studies are needed to confirm the findings.

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.

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 Small airway disease: A different phenotype of early stage COPD associated with biomass smoke exposure

Respirology ◽  
2017 ◽  
Vol 23 (2) ◽  
pp. 198-205 ◽  
Author(s):  
Dongxing Zhao ◽  
Yumin Zhou ◽  
Changbin Jiang ◽  
Zhuxiang Zhao ◽  
Fang He ◽  
...  
Keyword(s):  
Early Stage ◽  
Airway Disease ◽  
Smoke Exposure ◽  
Small Airway ◽  
Biomass Smoke ◽  
Small Airway Disease ◽  
Biomass Smoke Exposure

scholarly journals Small Airway Disease in Pulmonary Hypertension—Additional Diagnostic Value of Multiple Breath Washout and Impulse Oscillometry

2018 ◽  
Vol 7 (12) ◽  
pp. 532 ◽  
Author(s):  
Frederik Trinkmann ◽  
Joshua Gawlitza ◽  
Monique Künstler ◽  
Julia Schäfer ◽  
Michele Schroeter ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Airway Disease ◽  
Small Airway ◽  
Healthy Controls ◽  
Impulse Oscillometry ◽  
Alveolar Volume ◽  
Therapeutic Implications ◽  
Small Airway Disease ◽  
Ventilation Heterogeneity ◽  
Multiple Breath Washout

Airways obstruction is frequent in patients with pulmonary hypertension (PH). Small airway disease (SAD) was identified as a major contributor to resistance and symptoms. However, it is easily missed using current diagnostic approaches. We aimed to evaluate more elaborate diagnostic tests such as impulse oscillometry (IOS) and SF6-multiple-breath-washout (MBW) for the assessment of SAD in PH. Twenty-five PH patients undergoing body-plethysmography, IOS and MBW testing were prospectively included and equally matched to pulmonary healthy and non-healthy controls. Lung clearance index (LCI) and acinar ventilation heterogeneity (Sacin) differed significantly between PH, healthy and non-healthy controls. Likewise, differences were found for all IOS parameters between PH and healthy, but not non-healthy controls. Transfer factor corrected for ventilated alveolar volume (TLCO/VA), frequency dependency of resistance (D5-20), resonance frequency (Fres) and Sacin allowed complete differentiation between PH and healthy controls (AUC (area under the curve) = 1.0). Likewise, PH patients were separated from non-healthy controls (AUC 0.762) by D5-20, LCI and conductive ventilation heterogeneity (Scond). Maximal expiratory flow (MEF) values were not associated with additional diagnostic values. MBW and IOS are feasible in PH patients both providing additional information. This can be used to discriminate PH from healthy and non-healthy controls. Therefore, further research targeting SAD in PH and evaluation of therapeutic implications is justified.

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