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Frontiers in Immunology 2021Asthma is the most frequent cause of hospitalisation among children; however, little is known regarding the effects of asthma on immune responses in children.
BACKGROUND
Asthma is the most frequent cause of hospitalisation among children; however, little is known regarding the effects of asthma on immune responses in children.
OBJECTIVE
The present study aimed to evaluate cytokine responses of peripheral blood mononuclear cells (PBMCs), PBMC composition and lung function in children with and without asthma.
METHODS
Using a case-control design, we compared 48 children with asthma aged 3-11 years with 14 age-matched healthy controls. PBMC composition and cytokine production including interferon (IFN)-γ, interleukin (IL)-1β, IL-5 and lL-6 following stimulation with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS) were measured. Lung function was assessed using impulse oscillometry and nitrogen multiple breath washout.
RESULTS
The frequency of group 2 innate lymphoid cells were significantly higher in asthmatics and PBMCs from asthmatics had deficient IFN-γ production in response to both RV1B and LPS compared with controls (P<0.01). RV1B-induced IL-1β response and HDM-stimulated IL-5 production was higher in asthmatics than controls (P<0.05). In contrast, IL-1β and IL-6 were significantly reduced in response to HDM and LPS in asthmatics compared to controls (P<0.05). Children with asthma also had reduced pulmonary function, indicated by lower respiratory reactance as well as higher area of-reactance and lung clearance index values compared with controls (P<0.05).
CONCLUSION
Our study indicates that children with asthma have a reduced lung function in concert with impaired immune responses and altered immune cell subsets. Improving our understanding of immune responses to viral and bacterial infection in childhood asthma can help to tailor management of the disease.
Topics: Age Factors; Asthma; Biomarkers; Case-Control Studies; Child; Child, Preschool; Cytokines; Female; Humans; Immunity, Innate; Immunoglobulin E; Lymphocyte Count; Lymphocyte Subsets; Male; Respiratory Function Tests
PubMed: 34220812
DOI: 10.3389/fimmu.2021.664668 -
Journal of Applied Physiology... Jul 2021Assessing airway function during exercise provides useful information regarding mechanical properties of the airways and the extent of ventilatory limitation in COPD....
Assessing airway function during exercise provides useful information regarding mechanical properties of the airways and the extent of ventilatory limitation in COPD. The primary aim of this study was to use impulse oscillometry (IOS) to assess dynamic changes in airway impedance across a range of exercise intensities in patients with GOLD 1-4, before and after albuterol administration. A secondary aim was to assess the reproducibility of IOS measures during exercise. Fifteen patients with COPD (8 males/7 females; age = 66 ± 8 yr; prebronchodilator FEV = 54.3 ± 23.6%Pred) performed incremental cycle ergometry before and 90 min after inhaled albuterol. Pulmonary ventilation and gas exchange were measured continuously, and IOS-derived indices of airway impedance were measured every 2 min immediately preceding inspiratory capacity maneuvers. Test-retest reproducibility of exercise IOS was assessed as mean difference between replicate tests in five healthy subjects (3 males/2 females). At rest and during incremental exercise, albuterol significantly increased airway reactance (X) and decreased airway resistance (R, R-R), impedance (Z), and end-expiratory lung volume (60% ± 12% vs. 58% ± 12% TLC, main effect = 0.003). At peak exercise, there were moderate-to-strong associations between IOS variables and IC, and between IOS variables and concavity in the expiratory limb of the spontaneous flow-volume curve. Exercise IOS exhibited moderate reproducibility in healthy subjects which was strongest with R (mean diff. = -0.01 ± 0.05 kPa/L/s; ICC = 0.68), R-R (mean diff. = -0.004 ± 0.028 kPa/L/s; ICC = 0.65), and Z (mean diff. = -0.006 ± 0.021 kPa/L/s; ICC = 0.69). In patients with COPD, exercise evoked increases in airway resistance and decreases in reactance that were ameliorated by inhaled bronchodilators. The technique of exercise IOS may aid in the clinical assessment of dynamic airway function during exercise. This study provides a novel, mechanistic insight into dynamic airway function during exercise in COPD, before and after inhaled bronchodilators. The use of impulse oscillometry (IOS) to evaluate airway function is unique among exercise studies. We show strong correlations among IOS variables, dynamic hyperinflation, and shape-changes in the spontaneous expiratory flow-volume curve. This approach may aid in the clinical assessment of airway function during exercise.
Topics: Aged; Airway Resistance; Bronchodilator Agents; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Oscillometry; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Spirometry
PubMed: 34013748
DOI: 10.1152/japplphysiol.00148.2021 -
Journal of Asthma and Allergy 2019Impulse oscillometry (IOS) has been proposed as an alternative test to evaluate the obstruction of small airways and to detect changes in airways earlier than...
Impulse oscillometry (IOS) has been proposed as an alternative test to evaluate the obstruction of small airways and to detect changes in airways earlier than spirometry. In this study, we sought to determine the utility and association of IOS parameters with spirometry and asthma control in an adult population. Adults 14-82 years of age with asthma were classified into uncontrolled asthma (n=48), partially controlled asthma (n=45), and controlled asthma (n=49) groups, and characterized with fractional exhaled nitric oxide (FE), IOS, and spirometry in a transversal analysis planned as a one-visit study. The basic parameters evaluated in IOS are resistance at 5 Hz (R), an index affected by the large and small airway; resistance at 20 Hz (R), an index of the resistance of large airways; difference between R and R (R-R), indicative of the function of the small peripheral airways; reactance at 5 Hz (X), indicative of the capacitive reactance in the small peripheral airways; resonance frequency (Fres), the intermediate frequency at which the reactance is null, and reactance area (XA), which represents the total reactance (area under the curve) at all frequencies between 5 Hz to Fres. There were statistical differences between groups in standard spirometry and IOS parameters reflecting small peripheral airways (R, R, R-R, Fres, XA and X) (<0.001). Accuracy of IOS and/or spirometry to discriminate between controlled asthma vs partially controlled asthma and uncontrolled asthma was low (AUC=0.61). Using linear regression models, we found a good association between spirometry and IOS. In order to evaluate IOS as an alternative or supplementary method for spirometry, we designed a predictive model for spirometry from IOS applying a penalized regression model (Lasso). Then, we compared the original spirometry values with the values obtained from the predictive model using Bland-Altman plots, and the models showed an acceptable bias in the case of FEV/FVC, FEV%, and FVC%. IOS did not show a discriminative capacity to correctly classify patients according to the degree of asthma control. However, values of IOS showed good association with values of spirometry. IOS could be considered as an alternative and accurate complement to spirometry in adults. In a predictive model, spirometry values estimated from IOS tended to overestimate in low values of "real" spirometry and underestimate in high values.
PubMed: 31410030
DOI: 10.2147/JAA.S193744 -
Pediatric Pulmonology Dec 2022In children, obesity typically reduces functional residual capacity (FRC), which reduces airway caliber and increases airway resistance. Whether these obesity-related...
BACKGROUND
In children, obesity typically reduces functional residual capacity (FRC), which reduces airway caliber and increases airway resistance. Whether these obesity-related changes in respiratory function can alter bronchodilator responsiveness is unknown.
OBJECTIVE
To investigate bronchodilator responsiveness in nonasthmatic children with and without obesity.
METHODS
Seventy nonasthmatic children, 8-12 years old, without (n = 19) and with (n = 51) obesity, completed spirometry, impulse oscillometry, and airway resistance measurements through plethysmography pre/post 360 µg of inhaled albuterol. FRC was assessed pre albuterol. A two-way analysis of variance determined the effects of obesity (group) and inhaled albuterol (pre-post) on outcome measures.
RESULTS
FRC (%total lung capacity) was 16% lower in children with obesity compared with those without obesity. There was no significant group by pre-post albuterol interaction on any outcome variables. Albuterol inhalation reduced total, central and peripheral airway resistance and increased airway reactance (i.e., less negative) to a similar degree in children with and without obesity. In children with obesity, airway resistance was increased whether measured by impulse oscillometry or plethysmography. However, once airway resistance was adjusted for lung volumes (i.e., specific airway resistance or sR ), there were no differences between children with and without obesity. In addition, significant but moderate associations were detected between chest mass and FRC (r = -0.566; p < 0.001), FRC and total airway resistance (i.e., R ; r = -0.445; p < 0.001).
CONCLUSIONS
In nonasthmatic early pubescent children, obesity increases total, central, and peripheral respiratory system resistance. However, the added respiratory system resistance and low lung volume breathing with obesity are not sufficient to reduce bronchodilator responsiveness.
Topics: Child; Humans; Airway Resistance; Bronchodilator Agents; Albuterol; Lung; Obesity
PubMed: 35949183
DOI: 10.1002/ppul.26111 -
Diagnostics (Basel, Switzerland) May 2024The fact that some SARS-CoV-2 pneumonia patients benefit from changing body position, and some from continuous positive airways pressure (CPAP), indicates the functional...
The fact that some SARS-CoV-2 pneumonia patients benefit from changing body position, and some from continuous positive airways pressure (CPAP), indicates the functional character of hypoxia. We hypothesize that such effects could be explained by the closure of small airways. To prove the hypothesis, we evaluated the patency of small airways in 30 oxygen-dependent, spontaneously breathing patients with SARS-CoV-2 pneumonia during their hospital stay using the FOT method and then compared the results with data obtained three months later. During the acute period, total resistance (R5) and peripheral resistance (R5-20) rose above the upper limit of normal (ULN) in 28% and 50% of all patients, respectively. Reactance indices X5, AX and Fres exceeded ULN in 55%, 68% and 66% of cases. Significant correlations were observed between PaO/FiO, the time spent in the hospital and R5, X5, AX and Fres. After 3 months, 18 patients were re-examined. During the hospital stay, 11 of them had risen above the upper limit of normal (ULN), for both resistance (R5-20) and reactance (X5, AX) values. Three months later, ULN for R5-20 was exceeded in only four individuals, but ULN for X5 and AX was exceeded in five individuals. Lung function examination revealed a combined restrictive/obstructive ventilatory failure and reduced CO transfer factor. We interpret these changes as lung tissue remodeling due to the process of fibrosis. We conclude that during acute period of SARS-CoV-2 pneumonia, dilated pulmonary blood vessels and parenchymal oedema induce functional closure of small airways, which in turn induce atelectasis with pulmonary right-to-left shunting, followed by the resulting hypoxemia.
PubMed: 38893686
DOI: 10.3390/diagnostics14111160 -
BMJ Open Respiratory Research Dec 2020Asthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use...
BACKGROUND
Asthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use spirometric measures for asthma assessment. This systematic review aimed to assess whether the most commonly reported tests of small airways function could contribute to the diagnosis of asthma.
METHODS
Standard systematic review methodology was used, and a range of electronic databases was searched (Embase, MEDLINE, CINAHL, CENTRAL, Web of Science, DARE). Studies that included physiological tests of small airways function to diagnose asthma in adults were included, with no restrictions on language or date. The risk of bias and quality assessment tools used were Agency for Healthcare Research and Quality tool for cross-sectional studies and Quality Assessment of Diagnostic Accuracy Studies 2 for diagnostic test accuracy (DTA) studies.
RESULTS
7072 studies were identified and 10 studies met review criteria. 7 included oscillation techniques and 5 included maximal mid-expiratory flow (MMEF). Studies were small and of variable quality. In oscillometry, total resistance (R5) and reactance at 5 Hz (X5) was altered in asthma compared with healthy controls. The percentage predicted of MMEF was lower in patients with asthma compared with controls in all studies and lower than the % predicted forced expiratory volume in 1 s. In DTA of oscillometry, R5 showed a sensitivity between 69% and 72% and specificity between 61% and 86%.
CONCLUSION
There were differences in the results of physiological tests of small airway function in patients with asthma compared with controls. However, studies are small and heterogeneous. Further studies are needed to assess the effectiveness of these tests on a larger scale, including studies to determine which test methodology is the most useful in asthma.
Topics: Adult; Asthma; Cross-Sectional Studies; Diagnostic Tests, Routine; Forced Expiratory Volume; Humans; Spirometry; United States
PubMed: 33371011
DOI: 10.1136/bmjresp-2020-000770 -
Respiratory Research Jul 2022To establish the predicted value of pulmonary function determined by impulse oscillometry (IOS) in children (4-17 years old) in China. (Clinical Trial)
Clinical Trial
OBJECTIVE
To establish the predicted value of pulmonary function determined by impulse oscillometry (IOS) in children (4-17 years old) in China.
METHODS
A total of 6270 healthy children aged 4-17 years in China were included. The Master Screen IOS pulmonary function device (Jaeger Co, Germany) was used to detect the respiratory impedance (Zrs), resonant frequency (Fres), respiratory system resistance (Rrs) and respiratory system reactance (Xrs) at various oscillation frequencies, and the indices above were analysed. Stepwise multivariate regression was used to establish the regression equation of related parameters of IOS in different sexes, ages, height, and weight.
RESULTS
The differences in the main IOS parameters between different age stages were statistically significant regardless of sex (P < 0.05). The stepwise multivariate regression analysis showed that IOS parameters were related to height, age, and weight, and most IOS parameters were most closely related to height (the absolute value of the regression coefficient was the largest). With increasing age and height, the values of Z, R, R, R-R, and Fres decreased, while the value of X increased. Through height, age, and weight, we obtained the normal predicted values equation of children's IOS parameters. Compared with the other reference equations, our reference equation is more suitable for Chinese children.
CONCLUSIONS
The study revealed the reference values of IOS parameters in healthy Chinese children. In the evaluation of results for lung function measurements, this predicted value equation is more consistent with the characteristics of Chinese children than other reference equations.
CLINICAL TRIAL
ChiCTR: 1800019029.
Topics: Adolescent; Child; Child, Preschool; China; Humans; Lung; Oscillometry; Reference Values; Respiratory Function Tests; Spirometry
PubMed: 35831898
DOI: 10.1186/s12931-022-02080-z -
Journal of Family Medicine and Primary... Mar 2020Forced oscillometry technique (FOT) is a noninvasive technique that measures reactance and resistance capacity of the lung and is a practical and less time-consuming...
BACKGROUND
Forced oscillometry technique (FOT) is a noninvasive technique that measures reactance and resistance capacity of the lung and is a practical and less time-consuming technique for respiratory effort assessment. Recently, FOT has provided beneficial data regarding the screening of the patients with obstructive sleep apnea (OSA) and assessing the disease progression. The current study aimed to evaluate the correlation of FOT parameters with severity of the apnea-hypnea index (AHI).
METHODS
In the current case series, all patients who had a body mass index ranging between 30 and 35, suffering severe OSA with AHI of more than 30 times per hour, were enrolled. Patients underwent FOT before treatment to measure the following FOT parameters: Respiratory resistance at 5 and 20 Hz (R5 and R20, respectively), resistance difference between R5 and R20, reactance at 5 Hz (X5), and resonant frequency (Fres).
RESULTS
In the current study, 22 patients were enrolled; whereas 12 (54.5%) were male and 10 (45.5%) were female with a mean age of 5.27 ± 4.34. A statistically significant, strong negative correlation was observed between Fres and AHI, during Pearson correlation analysis ( (20) =0.59, < 0.0001). However, the relationship between the AHI and R5, R20, R5-R20 and X5 was not statistically significant. Similarly, the multiple regression model showed that, only Fres variable added statistically significantly to the prediction, = 0.01.
CONCLUSION
FOT is a useful tool in evaluation of AHI severity in patients suffering OSA and can be used as a diagnostic material in monitoring and management of these patients.
PubMed: 32509639
DOI: 10.4103/jfmpc.jfmpc_954_19 -
International Journal of Chronic... 2019The forced oscillation technique (FOT) is a non-invasive method to measure respiratory impedance, the respiratory resistance (Rrs) and reactance (Xrs). The disease...
PURPOSE
The forced oscillation technique (FOT) is a non-invasive method to measure respiratory impedance, the respiratory resistance (Rrs) and reactance (Xrs). The disease probability measure (DPM) is a useful computed tomography (CT) imaging variable for the assessment of gas trapping and emphysema in patients with chronic obstructive pulmonary disease (COPD) using pairs of inspiratory and expiratory CT images. We aimed to develop FOT-based phenotypes and determine whether the phenotypes and their imaging characteristics could facilitate the understanding of COPD pathophysiology.
PATIENTS AND METHODS
FOT and spirometry were examined in 164 COPD patients and 22 non-COPD smokers. COPD patients were divided into four FOT-based phenotypes (NL, normal group; RD, resistance-dominant group; XD, reactance-dominant group; and MIX, mixed group) based on the 3rd quartile values of R5 (Rrs at 5Hz) and X5 (Xrs at 5Hz) in the non-COPD group. The emphysematous lesions and the airway lesions were quantitatively assessed in CT images by low attenuation volume and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), respectively. DPM imaging analysis was also performed in 131 COPD patients. We investigated the differences in COPD parameters between the FOT-based phenotypes.
RESULTS
√Aaw at Pi10 were significantly higher in the RD, XD, and MIX groups than in the NL group. The XD group showed lower pulmonary function and higher dyspnea scores than the RD group. No significant changes in DPM values were observed between the RD and the NL groups. The gas-trapping area was significantly higher in the XD group than in the NL group. The MIX group showed the highest dyspnea score, most emphysematous lesions, and the lowest forced expiratory volume in 1 s % predicted value.
CONCLUSION
The FOT-based phenotyping may be useful to assess pathophysiological changes of COPD with CT assessments.
Topics: Airway Resistance; Biological Variation, Population; Electric Impedance; Female; Humans; Male; Middle Aged; Oscillometry; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Reproducibility of Results; Respiratory Function Tests; Tomography, X-Ray Computed
PubMed: 31908445
DOI: 10.2147/COPD.S224902 -
Journal of Applied Physiology... Aug 2021Asthma is characterized by heterogeneous ventilation as measured by three-dimensional ventilation imaging. Combination inhaled corticosteroid/long-acting β-agonist...
Asthma is characterized by heterogeneous ventilation as measured by three-dimensional ventilation imaging. Combination inhaled corticosteroid/long-acting β-agonist (ICS/LABA) treatment response is variable in asthma, and effects on regional ventilation are unknown. Our aims were to determine whether regional ventilation defects decrease after ICS/LABA treatment and whether small airways dysfunction predicts response in uncontrolled asthma. Twenty-two symptomatic participants with asthma underwent single-photon emission computed tomography (SPECT)/CT imaging with Technegas, before and after 8-wk fluticasone/formoterol (1,000/40 µg/day) treatment. Lung regions that were nonventilated, low ventilated, or well ventilated were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. Multiple-breath nitrogen washout (MBNW) was used to measure diffusion-dependent and convection-dependent small airways function (Sacin and Scond, respectively). Forced oscillation technique (FOT) was used to measure respiratory system resistance and reactance. At baseline and posttreatment, Scond -score was related to percentage of nonventilated lung, whereas Sacin -score was related to percentage of low-ventilated lung. Although symptoms, spirometry, FOT, and MBNW improved following treatment, there was no mean change in ventilation measured by SPECT. There was, however, a wide range of changes in SPECT ventilation such that greater percentage of nonventilated lung, older age, and higher Scond predicted a reduction in nonventilated lung after treatment. SPECT ventilation defects are overall unresponsive to ICS/LABA, but the response is variable, with improvement occurring when small airways dysfunction and ventilation defects are more severe. Persistent ventilation defects that correlate with Scond suggest that mechanisms such as non-ICS responsive inflammation or remodeling underlie these defects. This study provides insights into the mechanisms of high-dose ICS treatment in uncontrolled asthma. Ventilation defects as measured by SPECT/CT imaging respond heterogeneously to increased ICS/LABA treatment, with improvement occurring when ventilation defects and impairment of convection-dependent small airways function are more severe. Persistent correlations between ventilation defects and measures of small airways function suggest the potential presence of ICS nonresponsive inflammation and/or remodeling.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Asthma; Drug Therapy, Combination; Humans; Lung; Respiration; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
PubMed: 34166109
DOI: 10.1152/japplphysiol.01068.2020