-
ERJ Open Research Apr 2020Advanced glycation end-products (AGEs) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the association between AGE...
BACKGROUND
Advanced glycation end-products (AGEs) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the association between AGE accumulation in the skin measured by skin autofluorescence (SAF) and lung function in healthy subjects has not been explored in detail. We use a population-based study of 50-64-year-olds to assess spirometry, diffusing capacity of the lung for carbon monoxide ( ) and impulse oscillometry (IOS) in relation to SAF.
METHODS
Participants with information on SAF, lung function and potential confounding variables were included from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) cohort (spirometry, n=4111; , n=3889; IOS, n=3970). Linear regression was used to assess changes in lung function (as measured by spirometry (forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and FEV/FVC), and IOS (resistance measured at 5 ( ) and 20 Hz ( ), - , area of reactance, reactance measured at 5 Hz ( ), and resonant frequency)) by a 1-sd increase in SAF.
RESULTS
FEV, FVC and were significantly and inversely associated with SAF after adjustment for potential confounding factors (per 1-sd increase in SAF: FEV -0.03 L (95% CI -0.04- -0.02 L), p<0.001; FVC -0.03 L (95% CI -0.05- -0.02 L), p<0.001; -0.07 mmol·min·kPa (95% CI -0.11- -0.03 mmol·min·kPa), p<0.001). This association was also found in nonsmokers and in non-COPD subjects. Pulmonary reactance ( ) but not pulmonary resistance ( , and - ) was significantly associated with SAF (per 1-sd increase in SAF: -0.001 kPa·L·s (95% CI -0.003-0.00 kPa·L·s), p=0.042), which was mirrored in non-COPD patients but not in current nonsmokers.
CONCLUSIONS
AGE accumulation, as measured by SAF, is significantly associated with lung function decrements indicative of changes in the lung parenchyma.
PubMed: 32523964
DOI: 10.1183/23120541.00356-2019 -
Respiratory Medicine Jun 2023Welders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality...
BACKGROUND
Welders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity worldwide. It is difficult to detect COPD early and therefore mitigating measures may be delayed. The aim of this study was to investigate lung health in welders and evaluate new sensitive methods with potential to assess early onset pulmonary changes in occupational settings.
METHODS
This study assessed the lung health and symptoms in active welders (n = 28) and controls (n = 17). Lung measurements were performed with standard spirometry and new methods: airspace dimension assessment (AiDA), oscillometry, blood serum biomarkers (club cell secretory protein 16, surfactant protein D, matrix metalloproteinases, fibroblast, hepatocyte growth factor, interleukins), and one urine biomarker (desmosine).
RESULTS
According to spirometry measurements, all participants had normal lung function. However, prevalence of cough was significantly higher among welders compared with controls and lung changes were found in welders with the novel methods. Welders had significantly higher respiratory system resistance assessed with oscillometry, serum levels of metalloproteinases 9 and hepatocyte growth factor, compared with controls. Airspace dimensions were on average higher among welders compared with controls, but the difference was not significant. The number of welding years correlated with decreased respiratory system reactance and increased serum levels of matrix metalloproteinases 9, interleukin 6, and hepatocyte growth factor. Airspace dimension assessment indices were correlated with increasing levels of inflammatory markers and matrix metalloproteinases.
CONCLUSIONS
This study indicated the potential to use new and more sensitive methods for identification of changes in lungs when standard spirometry failed to do so.
Topics: Humans; Hepatocyte Growth Factor; Metal Workers; Respiratory Function Tests; Lung; Pulmonary Disease, Chronic Obstructive; Occupational Diseases; Occupational Exposure
PubMed: 37062499
DOI: 10.1016/j.rmed.2023.107244 -
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 -
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 -
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 -
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 -
International Journal of Chronic... 2018Alpha-1-antitrypsin (AAT) deficiency is a hereditary disorder that predisposes to emphysema. A cohort of severe (PiZZ) and moderate (PiSZ) AAT-deficient newborn infants...
BACKGROUND
Alpha-1-antitrypsin (AAT) deficiency is a hereditary disorder that predisposes to emphysema. A cohort of severe (PiZZ) and moderate (PiSZ) AAT-deficient newborn infants was identified by the Swedish national neonatal AAT screening program in 1972-1974 and has been followed-up since birth. Our aim was to study whether the cohort has signs of emphysema in pulmonary function tests (PFTs) and computed tomography (CT) densitometry at 38 years of age in comparison with an age-matched control group, randomly selected from the population registry.
METHODS
Forty-one PiZZ, 18 PiSZ, and 61 control subjects (PiMM) underwent complete PFTs, measurement of resistance and reactance in the respiratory system by impulse oscillometry (IOS)/forced oscillation technique (FOT), and CT densitometry. The results were related to self-reported smoking habits.
RESULTS
The total lung capacity (TLC) % of the predicted value was significantly higher in the PiZZ ever-smokers than in the PiZZ never-smokers (<0.05), PiSZ never-smokers (=0.01) and the PiMM never-smokers (=0.01). The residual volume (RV) % of the predicted value was significantly higher in the PiZZ ever-smokers compared to the PiMM never-smokers (<0.01). The PiZZ ever-smokers had a significantly lower carbon monoxide transfer coefficient (co) than the PiSZ never-smokers (<0.01) and PiMM never-smokers (<0.01). Respiratory system resistance at 5 Hz (<0.01), at 20 Hz (<0.01), and the area of low reactance (Alx; <0.05) were significantly lower and respiratory system reactance at 5 Hz (<0.05) was significantly higher in PiZZ subjects compared to the PiMM subjects. No statistically significant differences in the CT densitometry parameters were found between the Pi subgroups.
CONCLUSION
The physiological parameters in the PiZZ ever-smokers showed evidence of hyperinflation and emphysema before the age of 40 years.
Topics: Adult; Age Factors; Case-Control Studies; Densitometry; Disease Progression; Female; Humans; Lung; Male; Predictive Value of Tests; Prognosis; Pulmonary Emphysema; Registries; Residual Volume; Respiratory Function Tests; Severity of Illness Index; Smoking; Sweden; Tomography, X-Ray Computed; Total Lung Capacity; alpha 1-Antitrypsin Deficiency
PubMed: 30510411
DOI: 10.2147/COPD.S167497 -
Respirology (Carlton, Vic.) Jun 2021Asthma guidelines emphasize the importance of assessing lung function and symptoms. The forced oscillation technique (FOT) and its longitudinal relationship with...
BACKGROUND AND OBJECTIVE
Asthma guidelines emphasize the importance of assessing lung function and symptoms. The forced oscillation technique (FOT) and its longitudinal relationship with spirometry and symptoms are unresolved. We examined concordance between longitudinal spirometry, FOT and symptom control, and determined FOT limits of agreement in stable asthma.
METHODS
Over a 3-year period, adults with asthma attending a tertiary clinic completed the asthma control test (ACT), fraction of exhaled nitric oxide (FeNO), FOT and spirometry. Analysis included between-visit concordance for significant change using Cohen's kappa (κ) and stable asthma FOT limits of agreement.
RESULTS
Data (n = 186) from 855 visits (mean ± SD 4.6 ± 3.0 visits), 114 ± 95 days apart, were analysed. Between-visit concordance was moderate between reactance at 5 Hz (X5) and forced expiratory volume in 1 s (FEV ) (κ = 0.34, p = 0.001), and weak between ACT and FEV (κ = 0.18, p = 0.001). Change in FeNO did not correlate with lung function or ACT (κ < 0.05, p > 0.1). Stable asthma between visits (n = 75; 132 visits) had reduced lung function variability, but comparable concordance to the entire cohort. Limits of agreement for FEV (0.42 L), resistance at 5 Hz (2.06 cm H O s L ) and X5 (2.75 cm H O s L ) in stable asthma were at least twofold greater than published values in health.
CONCLUSION
In adults with asthma, there is moderate concordance between longitudinal change in FOT and spirometry. Both tests relate poorly to changes in asthma control, highlighting the need for multi-modal assessment in asthma rather than symptoms alone. The derivation of longitudinal FOT limits of agreement will assist in its clinical interpretation.
Topics: Adult; Asthma; Forced Expiratory Volume; Humans; Oscillometry; Respiratory Function Tests; Spirometry
PubMed: 33797141
DOI: 10.1111/resp.14053 -
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 -
PloS One 2019A better understanding of sickle cell anemia (SCA) and improvements in drug therapy and health policy have contributed to the emergence of a large population of adults...
Respiratory resistance and reactance in adults with sickle cell anemia: Part 2-Fractional-order modeling and a clinical decision support system for the diagnosis of respiratory disorders.
BACKGROUND
A better understanding of sickle cell anemia (SCA) and improvements in drug therapy and health policy have contributed to the emergence of a large population of adults living with this disease. The mechanisms by which SCA produces adverse effects on the respiratory system of these patients are largely unknown. Fractional-order (FrOr) models have a high potential to improve pulmonary clinical science and could be useful for diagnostic purposes, offering accurate models with an improved ability to mimic nature. Part 2 of this two-part study examines the changes in respiratory mechanics in patients with SCA using the new perspective of the FrOr models. These results are compared with those obtained in traditional forced oscillation (FOT) parameters, investigated in Part 1 of the present study, complementing this first analysis.
METHODOLOGY/PRINCIPAL FINDINGS
The data consisted of three categories of subjects: controls (n = 23), patients with a normal spirometric exam (n = 21) and those presenting restriction (n = 24). The diagnostic accuracy was evaluated by investigating the area under the receiver operating characteristic curve (AUC). Initially, it was observed that biomechanical changes in SCA included increased values of fractional inertance, as well as damping and hysteresivity (p<0.001). The correlation analysis showed that FrOr parameters are associated with functional exercise capacity (R = -0.57), pulmonary diffusion (R = -0.71), respiratory muscle performance (R = 0.50), pulmonary flows (R = -0.62) and airway obstruction (R = 0.60). Fractional-order modeling showed high diagnostic accuracy in the detection of early respiratory abnormalities (AUC = 0.93), outperforming spirometry (p<0.03) and standard FOT analysis (p<0.01) used in Part 1 of this study. A combination of machine learning methods with fractional-order modeling further improved diagnostic accuracy (AUC = 0.97).
CONCLUSIONS
FrOr modeling improved our knowledge about the biomechanical abnormalities in adults with SCA. Changes in FrOr parameters are associated with functional exercise capacity decline, abnormal pulmonary mechanics and diffusion. FrOr modeling outperformed spirometric and traditional forced oscillation analyses, showing a high diagnostic accuracy in the diagnosis of early respiratory abnormalities that was further improved by an automatic clinical decision support system. This finding suggested the potential utility of this combination to help identify early respiratory changes in patients with SCA.
Topics: Adult; Airway Resistance; Anemia, Sickle Cell; Decision Support Systems, Clinical; Early Diagnosis; Female; Humans; Male; Models, Theoretical; ROC Curve; Respiration Disorders; Respiratory Function Tests; Respiratory Mechanics
PubMed: 30845242
DOI: 10.1371/journal.pone.0213257