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Respirology (Carlton, Vic.) Aug 2020Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral...
BACKGROUND AND OBJECTIVE
Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple-breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high-dose ICS/LABA treatment.
METHODS
A total of 19 subjects (14 females, mean age: 29.9 ± 13.6 years) with uncontrolled asthma, as defined by an ACQ5 > 1.5, taking 500 μg/day fluticasone equivalent or less, underwent spirometry, plethysmography, fractional exhaled FeNO, forced oscillatory resistance (Rrs ) and reactance (Xrs ), and indices of MBNW ventilation heterogeneity (lung clearance index (LCI), diffusion-convection-dependent (Sacin) and convection-dependent (Scond)). Measurements were made before and after 8 weeks of treatment with fluticasone/formoterol combination inhaler 250/10 μg, 2 puffs twice daily.
RESULTS
Treatment improved ACQ5 (P = 0.0002), FEV (P = 0.02), FVC (P = 0.04), FeNO (P = 0.0008), Xrs (P = 0.01), LCI (P = 0.0002), Sacin (P = 0.006) and Scond (P = 0.01). At baseline, ACQ5 correlated with Xrs (r = 0.52, P = 0.03) and Rrs (r = 0.55, P = 0.02). The improvement in ACQ5 was predicted by more abnormal baseline LCI (P = 0.03), Scond (P = 0.02) and Rrs (P = 0.006). Baseline Scond was the best predictor of a clinically meaningful improvement in asthma control (ΔACQ > 0.5, ROC-AUC = 0.91, P = 0.007).
CONCLUSION
Step-up to high-dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs and MBNW. Baseline MBNW and FOT parameters correlated with the improvement in symptoms and may predict a positive response to up-titration in uncontrolled asthmatic patients.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Asthma; Drug Combinations; Female; Fluticasone; Formoterol Fumarate; Humans; Lung; Male; Nitrogen; Oscillometry; Pulmonary Ventilation; ROC Curve; Respiration; Respiratory Function Tests; Spirometry
PubMed: 32026586
DOI: 10.1111/resp.13772 -
American Journal of Physiology. Lung... Dec 2020Recent clinical trials have shown improvements in neonatal outcomes after intratracheal administration of a combination of budesonide/surfactant (ITBS) in infants at...
Recent clinical trials have shown improvements in neonatal outcomes after intratracheal administration of a combination of budesonide/surfactant (ITBS) in infants at risk of bronchopulmonary dysplasia. However, the effect of ITBS on lung function and alveolar structure is not known. We aimed to determine the effect of ITBS on lung function, parenchymal structure, and inflammatory cytokine expression in a relevant preterm animal model for bronchopulmonary dysplasia. Premature neonatal rabbits were administered a single dose of ITBS on the day of delivery and exposed to 95% oxygen. Following 7 days of hyperoxia, in vivo forced oscillation and pressure-volume maneuvers were performed to examine pulmonary function. Histological and molecular analysis was performed to assess alveolar and extracellular matrix (ECM) morphology, along with gene expression of connective tissue growth factor (CTGF), IL-8, and CCL-2. ITBS attenuated the functional effect of hyperoxia-induced lung injury and limited the change to respiratory system impedance, measured using the forced oscillation technique. Treatment effects were most obvious in the small airways, with significant effects on small airway resistance and small airway reactance. In addition, ITBS mitigated the decrease in inspiratory capacity and static compliance. ITBS restricted alveolar septal thickening without altering the mean linear intercept and mitigated hyperoxia-induced remodeling of the ECM. These structural changes were associated with improved inspiratory capacity and lung compliance. Gene expression of CTGF, IL-8, and CCL-2 was significantly downregulated in the lung. Treatment with ITBS shortly after delivery attenuated the functional and structural consequences of hyperoxia-induced lung injury to of life in the preterm rabbit.
Topics: Animals; Budesonide; Disease Models, Animal; Humans; Hyperoxia; Lung Injury; Pulmonary Surfactants; Rabbits; Surface-Active Agents
PubMed: 32903026
DOI: 10.1152/ajplung.00162.2020 -
COPD 2022Respiratory oscillometry allows measuring respiratory resistance and reactance during tidal breathing and may predict exacerbations in patients with chronic obstructive...
Physiological Impairments on Respiratory Oscillometry and Future Exacerbations in Chronic Obstructive Pulmonary Disease Patients without a History of Frequent Exacerbations.
Respiratory oscillometry allows measuring respiratory resistance and reactance during tidal breathing and may predict exacerbations in patients with chronic obstructive pulmonary disease (COPD). While the Global Initiative for Chronic Obstructive Lung Disease (GOLD) advocates the ABCD classification tool to determine therapeutic approach based on symptom and exacerbation history, we hypothesized that in addition to spirometry, respiratory oscillometry complemented the ABCD tool to identify patients with a high risk of exacerbations. This study enrolled male outpatients with stable COPD who were prospectively followed-up over 5 years after completing mMRC scale and COPD assessment test (CAT) questionnaires, post-bronchodilator spirometry and respiratory oscillometry to measure resistance, reactance, and resonant frequency (Fres), and emphysema quantitation on computed tomography. Total 134 patients were classified into the GOLD A, B, C, and D groups ( = 48, 71, 5, and 9) based on symptoms on mMRC and CAT and a history of exacerbations in the previous year. In univariable analysis, higher Fres was associated with an increased risk of exacerbation more strongly than other respiratory oscillometry indices. Fres was closely associated with forced expiratory volume in 1 sec (FEV). In multivariable Cox-proportional hazard models of the GOLD A and B groups, either lower FEV group or higher Fres group was associated with a shorter time to the first exacerbation independent of the GOLD group (A vs B) and emphysema severity. Adding respiratory oscillometry to the ABCD tool may be useful for risk estimation of future exacerbations in COPD patients without frequent exacerbation history.
Topics: Disease Progression; Emphysema; Forced Expiratory Volume; Humans; Male; Oscillometry; Pulmonary Disease, Chronic Obstructive; Spirometry
PubMed: 35392737
DOI: 10.1080/15412555.2022.2051005 -
Frontiers in Physiology 2019Lung mechanics using the forced oscillation technique (FOT) is suggested to be equivalent and more sensitive in determining exercise-induced bronchoconstriction (EIB)...
Lung mechanics using the forced oscillation technique (FOT) is suggested to be equivalent and more sensitive in determining exercise-induced bronchoconstriction (EIB) than spirometry. Dynamic alterations in minute ventilation (V) may affect this measurement. We investigated changes in FOT parameters post exercise challenge (EC) in people with asthma as compared to spirometry. The rate of recovery and any effect of raised V following exercise on FOT parameters were also assessed. Airway resistance (R) and reactance (X) at 5 Hz and V were measured prior to forced expiratory volume in 1 s (FEV) before and up to 20 min after a standard EC in people with asthma and healthy controls. Airway hyperresponsiveness to the hyperosmolar mannitol test was measured in the asthmatic subjects within 1 week of the EC. Baseline and sequential measures were assessed using repeated measures ANOVA and Pearson's correlation. Group demographics and recovery data were compared using an unpaired test. Subjects with current asthma ( = 19, mean ± SD age 28 ± 6 years) and controls ( = 10, 31 ± 5 years) were studied. Baseline FEV, R, X, and V were similar between groups ( > 0.09). Airway hyperresponsiveness was present in 12/19 asthmatic subjects. The EC max % change of R and X correlated with FEV ( > 0.90) and were only different to controls in those with asthma that responded by FEV criteria ( < 0.01). EC recovery of R was similar to FEV; however, X was greater ( = 0.03). Elevated V post EC did not affect the % change in FOT parameters across all subjects ( > 0.3). R and X were highly sensitive in determining a positive EC response (80-86%), but X was more specific (93 vs. 80%). FOT parameters tracked with forced maneuvers and were not influenced by increased ventilation following an exercise challenge designed to elicit EIB. FOT identified EIB similarly to spirometry in patients with asthma.
PubMed: 31803065
DOI: 10.3389/fphys.2019.01411 -
Lung Jun 2022Forced vital capacity (FVC) is often preserved in severe asthma unless there is evidence of either airway remodelling or air trapping. Area under the reactance curve...
INTRODUCTION
Forced vital capacity (FVC) is often preserved in severe asthma unless there is evidence of either airway remodelling or air trapping. Area under the reactance curve (AX) can be used to assess small airways dysfunction related lung stiffness and is related to disease control in severe asthma.
METHODS
We explore if there may be a potential synergistic interaction between FVC and AX in terms of impaired asthma control as ACQ and exacerbations requiring oral corticosteroids (OCS). We pragmatically defined < 100% and ≥ 1.0 kPa/L/s as impaired FVC or AX, respectively.
RESULTS
Patients with combined impairment of FVC and AX had significantly worse asthma control as higher ACQ, more severe exacerbations requiring OCS and worse spirometry (FEV and FEF) than those with impaired FVC but preserved AX.
CONCLUSION
This in turn supports using both spirometry and oscillometry to characterise airway physiology more comprehensively in patients with more severe asthma.
Topics: Adrenal Cortex Hormones; Asthma; Forced Expiratory Volume; Humans; Lung; Spirometry; Vital Capacity
PubMed: 35662363
DOI: 10.1007/s00408-022-00542-1 -
Frontiers in Medicine 2023To use minimally-invasive transcatheter electrical impedance spectroscopy measurements for tissue differentiation among healthy lung tissue and pathologic lung tissue...
PURPOSE
To use minimally-invasive transcatheter electrical impedance spectroscopy measurements for tissue differentiation among healthy lung tissue and pathologic lung tissue from patients with different respiratory diseases (neoplasm, fibrosis, pneumonia and emphysema) to complement the diagnosis at real time during bronchoscopic procedures.
METHODS
Multi-frequency bioimpedance measurements were performed in 102 patients. The two most discriminative frequencies for impedance modulus (|Z|), phase angle (PA), resistance (R) and reactance (Xc) were selected based on the maximum mean pair-wise Euclidean distances between paired groups. One-way ANOVA for parametric variables and Kruskal-Wallis for non-parametric data tests have been performed with tests. Discriminant analysis has also been performed to find a linear combination of features to separate among tissue groups.
RESULTS
We found statistically significant differences for all the parameters between: neoplasm and pneumonia ( < 0.05); neoplasm and healthy lung tissue ( < 0.001); neoplasm and emphysema (p < 0.001); fibrosis and healthy lung tissue ( ≤ 0.001) and pneumonia and healthy lung tissue ( < 0.01). For fibrosis and emphysema ( < 0.05) only in |Z|, R and Xc; and between pneumonia and emphysema ( < 0.05) only in |Z| and R. No statistically significant differences ( > 0.05) are found between neoplasm and fibrosis; fibrosis and pneumonia; and between healthy lung tissue and emphysema.
CONCLUSION
The application of minimally-invasive electrical impedance spectroscopy measurements in lung tissue have proven to be useful for tissue differentiation between those pathologies that leads increased tissue and inflammatory cells and those ones that contain more air and destruction of alveolar septa, which could help clinicians to improve diagnosis.
PubMed: 37113605
DOI: 10.3389/fmed.2023.1108237 -
BMJ Open Respiratory Research Apr 2022Markers of idiopathic pulmonary fibrosis (IPF) severity are based on measurements of forced vital capacity (FVC), diffusing capacity (DLCO) and CT. The pulmonary vessel...
BACKGROUND
Markers of idiopathic pulmonary fibrosis (IPF) severity are based on measurements of forced vital capacity (FVC), diffusing capacity (DLCO) and CT. The pulmonary vessel volume (PVV) is a novel quantitative and independent prognostic structural indicator derived from automated CT analysis. The current prospective cross-sectional study investigated whether respiratory oscillometry provides complementary data to pulmonary function tests (PFTs) and is correlated with PVV.
METHODS
From September 2019 to March 2020, we enrolled 89 patients with IPF diagnosed according to international guidelines. We performed standard spectral (5-37 Hz) and novel intrabreath tracking (10 Hz) oscillometry followed by PFTs. Patients were characterised with the gender-age-physiology (GAP) score. CT images within 6 months of oscillometry were analysed in a subgroup (26 patients) using automated lung texture analysis. Correlations between PFTs, oscillometry and imaging variables were investigated using different regression models.
FINDINGS
The cohort (29F/60M; age=71.7±7.8 years) had mild IPF (%FVC=70±17, %DLCO=62±17). Spectral oscillometry revealed normal respiratory resistance, low reactance, especially during inspiration at 5 Hz (X5in), elevated reactance area and resonance frequency. Intrabreath oscillometry identified markedly low reactance at end-inspiration (XeI). XeI and X5in strongly correlated with FVC (r=0.499 and 0.435) while XeI was highly (p=0.004) and uniquely correlated with the GAP score. XeI and PVV exhibited the strongest structural-functional relationship (r=0.690), which remained significant after adjusting for %FVC, %DLCO and GAP score.
INTERPRETATION
XeI is an independent marker of IPF severity that offers additional information to standard PFTs. The data provide a cogent rationale for adding oscillometry in IPF assessment.
Topics: Aged; Cross-Sectional Studies; Humans; Idiopathic Pulmonary Fibrosis; Middle Aged; Oscillometry; Respiratory Function Tests; Tomography, X-Ray Computed
PubMed: 35396320
DOI: 10.1136/bmjresp-2021-001163 -
ERJ Open Research Oct 2021We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide...
INTRODUCTION
We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function.
METHODS
Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance ( ) and reactance ( ) at 6 Hz, before and after inhalation of salbutamol 200 μg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in and 95th percentile increase in in a healthy subgroup.
RESULTS
Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for Δ was -1.38 cmHO·s·L (-30.0% or -1.42 Z-scores) and upper threshold for Δ was 0.57 cmHO·s·L (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, Δ was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score.
DISCUSSION
This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry.
PubMed: 34761000
DOI: 10.1183/23120541.00439-2021 -
Journal of Applied Physiology... May 2021In this case study, we evaluate the unique physiological profiles of two world-champion breath-hold divers. At close to current world-record depths, the extreme...
In this case study, we evaluate the unique physiological profiles of two world-champion breath-hold divers. At close to current world-record depths, the extreme physiological responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure are profound. As such, these professional athletes must be capable of managing such stress, to maintain performing at the forefront human capacity. In both divers, pulmonary function before and after deep dives to 102 m and 117 m in the open sea was assessed using noninvasive pulmonary gas exchange (indexed via the O deficit, which is analogous to the traditional alveolar to arterial oxygen difference), ultrasound B-line scores, airway resistance, and airway reactance. Hydrostatic-induced lung compression was also quantified via spirometry. Both divers successfully performed their dives. Pulmonary gas exchange efficiency was impaired in both divers at 10 min but had mostly restored within a few hours. Mild hemoptysis was transiently evident immediately following the 117-m dive, whereas both divers experienced nitrogen narcosis. Although B-lines were only elevated in one diver postdive, reductions in airway resistance and reactance occurred in both divers, suggesting that the compressive strain on the structural characteristics of the airways can persist for up to 3.5 h. Marked echocardiographic dyssynchrony was evident in one diver after 10 m of descent, which persisted until resolving at ∼77 m during ascent. In summary, despite the enormous hydrostatic and physiological stress to diving beyond 100 m on a single breath, these data provide valuable insight into the extraordinary capacity of those at the pinnacle of apneic performance. This study shows that world-champion breath-hold divers demonstrate incredible tolerability to extreme levels of hydrostatic-induced lung compression. Immediately following dives to >100 m, there were acute impairments in pulmonary gas exchange efficiency, mild accummulation of extravascular lung fluid, noticable intrathoracic discomfort, and evident nitrogen narcosis, however, within a few hours, these had all mostly resolved.
Topics: Breath Holding; Diving; Humans; Oxygen; Respiratory Physiological Phenomena; Spirometry
PubMed: 33600279
DOI: 10.1152/japplphysiol.00877.2020 -
International Journal of Chronic... 2022Pulmonary fibrosis and emphysema result in relatively maintained ventilation and reduced diffusing capacity. This pulmonary functional impairment complicates the...
PURPOSE
Pulmonary fibrosis and emphysema result in relatively maintained ventilation and reduced diffusing capacity. This pulmonary functional impairment complicates the evaluation of pulmonary function in patients with combined pulmonary fibrosis and emphysema (CPFE). Therefore, a single and easy-to-use pulmonary function index to evaluate patients with CPFE warrants further studies. Respiratory impedance can easily be provided by oscillometry and might be a candidate index to evaluate pulmonary function in patients with CPFE. As a preliminary study to assess the utility of respiratory impedance, we investigated the associations of physiological indices, including respiratory impedance, in patients with idiopathic pulmonary fibrosis (IPF) with and without emphysema.
PATIENTS AND METHODS
This retrospective study evaluated patients with IPF who did and did not satisfy the diagnostic criteria of CPFE. All patients underwent oscillometry, spirometry, and diffusing capacity for carbon monoxide (D). Correlations of the obtained physiological indices were analyzed.
RESULTS
In total, 47 patients were included (18 and 29 patients with CPFE and IPF, respectively). Respiratory reactance (Xrs) at 5 Hz (X5) in the inspiratory phase was associated with forced vital capacity (FVC) % predicted in patients with CPFE (r=0.576, =0.012) and IPF (r=0.539, =0.003). Inspiratory X5 positively correlated with D % predicted only in patients CPFE (r=0.637, =0.004).
CONCLUSION
Emphysema might associate Xrs with ventilation and diffusing capacity in patients with IPF and emphysema. Given the multiple correlations of Xrs with FVC and D, this study warrants further studies to verify the utility of oscillometry in a large-scale study for patients with CPFE.
Topics: Electric Impedance; Emphysema; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis; Pulmonary Diffusing Capacity; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Retrospective Studies
PubMed: 35801120
DOI: 10.2147/COPD.S368162