Long-term variability of impulse oscillometry defined small airway dysfunction in participants with and without chronic obstructive pulmonary disease.

Associations of small airway dysfunction assessed by impulse oscillometry with lung function decline and exacerbations in participants with chronic obstructive pulmonary disease: A prospective cohort study in China.

BackgroundPersistent chronic airway inflammation and progressive airflow limitation are typical features of chronic obstructive pulmonary disease (COPD). Emerging evidence indicates that small airway dysfunction (SAD) plays a critical role in driving the sustained pathological progression of COPD. Preserved ratio impaired spirometry (PRISm) represents a spirometric pattern characterized by a reduced forced expiratory volume in 1 second (FEV₁) despite a preserved ratio. Current evidence inadequately elucidates the pathophysiological role of SAD and its intricate interplay with PRISm and COPD progression. On the other hand, impulse oscillometry (IOS) can be used as a complementary tool to spirometry to detect SAD. Detection of SAD in patients with chronic respiratory symptoms could help in the diagnosis of PRISm and COPD when spirometry is not achievable.ObjectiveTo investigate the diagnostic value of IOS for identifying SAD in patients with chronic respiratory symptoms, PRISm and COPD.MethodsBetween September 2021 and July 2023, 552 symptomatic patients without known structural lung disease who underwent both spirometry and IOS on the same day in the outpatient clinic were evaluated. The correlations between spirometry and the IOS parameters, and the ROC curves of the IOS parameters for SAD patients and COPD patients were analyzed.ResultsAmong the 552 patients included in the study, 96 patients had COPD, 39 patients had PRISm, and 417 patients had chronic cough. Among 456 chronic cough patients with preserved ratio spirometry, the incidence of PRISm was 8.55%. Based on spirometry-defined SAD, the incidence of SAD in the PRISm population was 71.8%, which was significantly higher than the 9.35% of the non-PRISm population. With increasing COPD GOLD stage, the IOS parameters R5-R20, R5, Fres, and Ax increased, whereas the traditional lung function parameters and X5 decreased. R5-R20, X5, Fres, and AX of COPD GOLD stage 1 patients were not substantially different from those of PRISm patients. In PRISm patients, R5-R20, R5 and Fres were strongly correlated with FEF25%-75%. R5-R20, R5, X5, Fres and AX were significantly associated with FEV1, FEV1/FVC, FEV1% predicted, FEF50%, FEF75% and FEF25%-75% in COPD patients. Through ROC curve analysis, the cutoffs for identifying SAD in patients with chronic respiratory symptoms and PRISm patients were obtained, with R5-R20 values of 0.075 and 0.105 kPa/L/s, respectively. The values of R5 were 0.365 and 0.375 kPa/L/s, respectively. The Fres values are 16.31 Hz and 17.11 Hz, respectively. The cutoff for detecting COPD in all patients was 0.485 kPa/L/s for R5, 0.125 kPa/L/s for R5-R20, -0.155 kPa/L/s for X5, and 17.98 Hz for Fres. Fres had the highest AUC value for both SAD and COPD detection, and it detected COPD the most in all patients, with a prevalence of 24.1%. R5 detected SAD the most in patients with chronic respiratory symptoms, with a prevalence of 47.5%. With a prevalence of 71.8%, spirometry identified SAD in patients with PRISm the most frequently.ConclusionAlmost all IOS parameters Linked to the small airways were significantly different in the PRISm population compared with patients with chronic respiratory symptoms. SAD severity in PRISm patients is similar to that in GOLD stage 2 COPD patients. The IOS can assess the disease severity of COPD.

Small airway dysfunction (SAD) is prevalent in asthma and chronic obstructive pulmonary disease (COPD). Aging is acknowledged to be associated with the loss of small airway structures. However, the impact of aging and pathophysiological changes on SAD in asthma and COPD remains unclear. We aimed to investigate the impact of aging and disease entity on pathophysiological change-related SAD in asthma and COPD assessed by spirometry and impulse oscillometry (IOS). We retrospectively reviewed adult patients diagnosed with asthma or COPD between May 2017 and August 2021 in Taipei Veterans General Hospital. Treatment-naïve COPD patients aged ≥60 years were enrolled, along with age- and gender-matched elderly asthmatics (EA), and younger asthmatics aged <60 years (YA) for comparison. All participants underwent spirometry and IOS with a bronchodilator test. Blood eosinophil counts (BECs) and immunoglobulin E(IgE) levels were documented if blood tests were conducted at the time of diagnosis. The mean age of YA, EA, and COPD were 44, 73, and 73 years, respectively. The FEV1, FEV1/FVC and FEF25-75% were higher in the YA followed by EA and COPD groups. The spirometric values were significantly correlated with IOS parameters in both asthmatic and COPD groups. No significant differences were observed in baseline IOS parameters among the three groups for participants with FEV1 ≥80% predicted. However, in patients with FEV1< 80% predicted, COPD patients exhibited significantly worse spirometric values and most IOS parameters (except R5-R20) compared to asthmatics. Additionally, asthmatics with AX reduction ≥35% exhibited significantly higher levels of blood eosinophil counts and IgE. Aging process contributes to more impact on small airway reactance in asthma, while disease entity in COPD exhibits worse spirometric and IOS parameters compared to the age- and gender-matched EA.

Background: Small airway dysfunction (SAD) is a functional hallmark of chronic obstructive pulmonary disease (COPD). However, SAD prevalence and its role in COPD pathophysiology are not yet sufficiently studied.Background: Small airway dysfunction (SAD) is a functional hallmark of chronic obstructive pulmonary disease (COPD). However, SAD prevalence and its role in COPD pathophysiology are not yet sufficiently studied.Aim: To assess the prevalence of SAD in COPD patients by various functional diagnostic methods, such as spirometry, body plethysmography, and impulse oscillometry (IOS).Materials and methods: This was an cross-sectional study. Spirometry, body plethysmography and IOS were used in 132 COPD patients in remission under standard anti-COPD treatments. The presence of SAD was confirmed by at least one of the following criteria or their combination: 1) by spirometry: the difference between vital capacity (VC) and forced vital capacity (FVC) &gt; 10%; 2) the presence of air trapping by body plethysmography; 3) identification of the frequency dependence of the resistive resistance at 5 to 20 Hz (R5 - R20 &gt; 0.07 kPa x s/l), as assessed by IOS.Results: Mean forced expiratory volume in 1 s (FEV1) was 42.9% of predicted. Depending on the severity of the obstruction, the patients were divided into 4 groups: 7 patients (group 1) had the obstruction corresponding to GOLD 1 stage, 37 (group 2) to GOLD 2, 49 (group 3) to GOLD 3, and 39 (group 4) to GOLD 4. SAD was found in 96% of COPD patients, whereas in those with severe obstruction (GOLD 3-4), it was present in 100% of the cases. By spirometry, SAD was identified only in 67% of COPD patients, by body plethysmography in 75% of COPD patients (in those with severe obstruction (GOLD 3 and 4) in 88 and 97%, respectively). With IOS, it was possible to identify SAD in 94% of patients and in 100% of those with severe obstruction (GOLD 3-4).Conclusion: With deterioration of obstructive pulmonary ventilation abnormalities in COPD patients, there is a progressive increase in small airway dysfunction. Impulse oscillometry seems to be the most effective method for diagnosis of small airway dysfunction, as it helped to identify SAD in 94% of COPD patients and in 100% of those with severe and very severe obstruction.

RATIONALE Number of small airway dysfunction (SAD) assessed by impulse oscillometry (IOS) is accumulated in patients with chronic obstructive pulmonary disease (COPD), and single SAD is associated with the previous year of exacerbations. However, little is known that the associations between accumulated number of SAD and Long-term prognosis of COPD. The study aimed to explore associations between accumulated number of SAD and lung function decline and exacerbations in patients with COPD. METHODS We analyzed baseline and 2-year follow-up data from the prospective cohort study in China. We used IOS parameters greater than ULN or LLN to defined SAD, then these patients were further divided into three accumulated nubmer of SAD groups (No airway abnormalities, 1-3 airway abnormalities, and 4-5 airway abnormalities). Negative Binomial Regression was performed to analyze the associations between accumulated SAD and exacerbations, and we used multivariable linear regression model to associations between accumulated SAD and lung function decline. RESULTS 833 patients with COPD were enrolled in our study. Single SAD was associated with faster decline in lung function and severer exacerbations. As the number of SAD increased, we found that patients with 4-5 airway abnormalities had a faster decline in lung function and severer exacerbations than those with no airway abnormalities, but no differences in prognosis was found between patients with 1-3 airway abnormalities and with no airway abnormalities. CONCLUSION SAD was associated with poor outcomes, and as the number of SAD increases, the prognosis became worse.

Rationale: Small airway dysfunction (SAD) is a key feature of chronic obstructive pulmonary disease (COPD). Pre-COPD represents an early stage in progression, identified by SAD or emphysema on computed tomography (CT), even without airflow obstruction. Impulse Oscillometry (IOS) and Parametric Response Mapping (PRM) can detect SAD in pre-COPD, but their correlation and efficacy remain underexplored. This study examines SAD in pre-COPD compared with smoker controls and COPD patients at varying severity. Methods: In this prospective cohort study, we enrolled smokers (≥10 pack-years) with respiratory symptoms in Taiwan. Participants underwent spirometry, IOS, high-resolution computed tomography (HRCT) for PRM Emp (Emphysema) and PRMfSAD (function SAD), and bronchoalveolar lavage (BAL) for airway cytokine analysis. Patients with asthma or structural lung diseases (e.g., interstitial lung disease or bronchiectasis) were excluded. Results: We analyzed 164 patients, including 46 pre-COPD patients (FEV₁/FVC ≥ 0.7, FEV₁ &amp;lt; 80%, and/or emphysema ≥ 5%), 27 patients with mild COPD, 43 patients with moderate-to-severe COPD, and 48 smoker controls (FEV₁/FVC ≥ 0.7, FEV₁ ≥ 80%, emphysema &amp;lt; 5%). IOS analysis showed that the prevalence of SAD increased from 32.6% in pre-COPD to 86% in moderate-to-severe COPD, indicating its progressive impact. PRMfSAD also rose with disease severity, from 9.6% in smoker controls to 33.4% in moderate-to-severe COPD, while PRMEmp increased to 8.3%, reflecting significant lung damage. Notably, 33% of smoker controls showed SAD despite minimal emphysema. Both PRMEmp and PRMfSAD effectively differentiated smoker controls from pre-COPD, with Area Under the Curve (AUC) of 0.84 (cutoff value 1.18%) and 0.73 (cutoff value 6.98%), respectively (Figure A). PRMfSAD and Fres from IOS were most effective in distinguishing pre-COPD from COPD, with AUCs of 0.72 (cutoff value: 23.07%) and 0.69 (cutoff value 17.1Hz), respectively (Figure B). A weak but significant positive correlation between PRMfSAD and AX (Pearson 0.237, p = 0.03) suggests a modest association between PRM and IOS in detecting SAD. BAL cytokine analysis showed that interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) levels increased progressively from pre-COPD to COPD, with IL-8 showing the strongest correlation with PRM and all IOS parameters (R5-R20, Fres, X5, and AX) for SAD. Conclusion: PRM and IOS effectively detect SAD in pre-COPD, distinguishing it from smoker controls and COPD, and supporting early detection. Weak but significant PRM and IOS correlations, along with links to inflammatory markers, highlight the potential for proactive SAD identification, which could enable timely interventions in COPD management.

Severe chronic obstructive pulmonary disease (COPD) has been associated with futile outcome after transcatheter aortic valve replacement (TAVR). Data on outcomes according to COPD severity are warranted to aid identification of patients who may not benefit from TAVR. We aimed to examine the association between risk of COPD exacerbation and 1-year mortality after TAVR. Using Danish nationwide registries we identified patients undergoing first-time TAVR during 2008-2021 by COPD status. COPD severity levels were defined as low or high risk of acute exacerbation of COPD (AE-COPD) and treatment intensity levels (none or short-term, mono/dual, triple therapy, or home oxygen). Kaplan-Meier functions and adjusted Cox regression models were used to assess 1-year mortality comparing COPD severity groups with patients without COPD. We identified 7,047 patients with TAVR of whom 644 had a history of COPD (low risk of AE-COPD: 439, high risk of AE-COPD: 205). The median age of the TAVR cohort was 81.4 years (IQR: 76.8-85.1) and 55.8% were males. One-year mortality for TAVR patients without COPD was 8.5% (95% CI: 7.8-9.2) and 15.4% (95% CI: 12.5-18.2) for those with COPD (adjusted HR: 1.63 [95% CI: 1.28-2.07]). Patients with low or high risk of AE-COPD had 1-year mortality of 13.1% (95% CI: 9.8-16.3) and 20.2% (95% CI: 14.6-25.8) corresponding to adjusted HRs of 1.31 (95% CI: 0.97-1.78) and 2.44 (95% CI: 1.70-3.50) compared with patients without COPD. Patients with high risk of AE-COPD and no/short term therapy or use of home oxygen represented the subgroups of patients with the highest 1-year mortality (31.6% [95% CI: 14.5-48.7] and 30.9% [95% CI: 10.3-51.6]). Among patients undergoing TAVR, increasing risk of exacerbation with COPD was associated with increasing 1-year mortality compared with non-COPD patients. Patients with a high risk of exacerbation with COPD not using any guideline recommended COPD medication and those using home oxygen had the highest 1-year mortality.

Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study

Small airways play a major role in the pathogenesis and prognosis of chronic obstructive pulmonary disease (COPD) and asthma. More data on small airway dysfunction (SAD) using spirometry and impulse oscillometry (IOS) in these populations are required. The objective of this study was to compare the two methods, spirometry and IOS, for SAD detection and its prevalence defined by spirometry and IOS in subjects with COPD and asthma with and without fixed airflow obstruction (FAO). This is a cross-sectional study. Spirometric and IOS parameters were compared across four groups (COPD, asthma with FAO, asthma without FAO, and healthy subjects). SAD defined by spirometry and IOS criteria were compared. A total of 262 subjects (67 COPD, 55 asthma with FAO, 101 asthma without FAO, and 39 healthy controls) were included. The prevalence of SAD defined by using IOS and spirometry criteria was significantly higher in patients with COPD (62.7 and 95.5%), asthma with FAO (63.6 and 98.2%), and asthma without FAO (38.6 and 19.8%) in comparison with healthy control (7.7 and 2.6%). IOS is more sensitive than spirometry in the detection of SAD in asthma without FAO (38.6% vs. 19.8%, p = 0.003) However, in subjects with FAO (COPD and asthma with FAO), spirometry is more sensitive than IOS to detect SAD (95.5% vs. 62.7%, p < 0.001 and 98.2% vs. 63.6%, p < 0.001, respectively). Small airway dysfunction was significantly detected in COPD and asthma with and without FAO. Although IOS shows more sensitivity than spirometry in the detection of SAD in asthma without FAO, spirometry is more sensitive than IOS in patients with FAO including COPD and asthma with FAO.

Objective : Assessment of gas and electrolytic composition of venous blood in patients with chronic obstructive pulmonary disease (COPD) in relation to basic parameters of functional state of kidneys. Methods : 60 patients with COPD were divided into low and high exacerbation risk groups and were examined. Standard examinations were carried out; electrolytic and gas composition of venous blood and kidney functions were assessed. Results : Patients with high risk of COPD exacerbation demonstrated symptoms of respiratory failure, hyperchloremia, higher levels of potassium and albuminuria; there was a relationship between albuminuria and oximetric parameters. A significant dependence between glomerular filtration rate and COPD exacerbation rate was not detected, but there was its relationship with the smoking index, the result of the CAT questionnaire, Gensler index, instantaneous expiratory flow rate, lung capacity and peak expiratory flow rate were recorded. Conclusions : COPD is often characterized by combination of gas and electrolytic composition imbalance of venous blood and renal dysfunction. With a high risk of exacerbations, signs of respiratory failure, hyperchloremia, higher levels of potassium and albuminuria are more often observed. The relationship between daily albuminuria and oximetric parameters, glomerular filtration rate and partial blood oxygen tension, found in people at high risk of COPD exacerbation may indicate the need for correction of blood gas composition to prevent renal dysfunction.

BackgroundStudies on consistency among spirometry, impulse oscillometry (IOS), and histology for detecting small airway dysfunction (SAD) remain scarce. Considering invasiveness of lung histopathology, we aimed to compare spirometry and IOS with chest computed tomography (CT) for SAD detection, and evaluate clinical characteristics of subjects with SAD assessed by these three techniques.MethodsWe collected baseline data from the Early COPD (ECOPD) study. CT-defined SAD was defined as parametric response mapping quantifying SAD (PRMfSAD) ≥ 15%. Spirometry-defined SAD was defined as at least two of maximal mid-expiratory flow (MMEF), forced expiratory flow 50% (FEF50), and forced expiratory flow 75% (FEF75) less than 65% of predicted. IOS-defined SAD was defined as peripheral airway resistance R5 − R20 > 0.07 kPa/L/s. The consistency of spirometry, IOS and CT for diagnosing SAD was assessed using Kappa coefficient. Correlations among the three techniques-measured small airway function parameters were assessed by Spearman correlation analysis.Results2055 subjects were included in the final analysis. There was low agreement in SAD assessment between spirometry and CT (Kappa = 0.126, 95% confidence interval [CI]: 0.106 to 0.146, p < 0.001), between IOS and CT (Kappa = 0.266, 95% CI: 0.219 to 0.313, p < 0.001), as well as among spirometry, IOS, and CT (Kappa = 0.056, 95% CI: 0.029 to 0.082, p < 0.001). The correlation was moderate (|r|: 0.5 to 0.7, p < 0.05) between spirometry and CT-measured small airway function parameters, and weak (|r|< 0.4, p < 0.05) between IOS and CT-measured small airway function parameters. Only spirometry-defined SAD group had more lower lung function (FEV1/FVC: adjusted difference=-10.7%, 95% CI: -13.5% to -7.8%, p < 0.001) and increased airway wall thickness (Pi 10: adjusted difference = 0.3 mm, 95% CI: 0 to 0.6 mm, p = 0.046) than only CT-defined SAD group. Only IOS-defined SAD group had better lung function (FEV1/FVC: adjusted difference = 3.9%, 95% CI: 1.9 to 5.8%, p < 0.001), less emphysema (inspiratory LAA− 950: adjusted difference=-2.1%, 95% CI:-3.1% to -1.1%, P < 0.001; PRMEmph: adjusted difference=-2.3%, 95% CI: -3.2% to -1.4%, p < 0.001), and thicker airway wall (Pi 10: adjusted difference = 0.2 mm, 95% CI: 0.1 mm to 0.4 mm, p = 0.005) than only CT-defined SAD group.ConclusionsThere was low consistency in the assessment of SAD between spirometry and CT, between IOS and CT, as well as among spirometry, IOS, and CT.Clinical trial numberNot applicable.

Small Airway Dysfunction by Impulse Oscillometry in Symptomatic Patients with Preserved Pulmonary Function

Background and objective: Spirometry is commonly used to assess small airway dysfunction (SAD). Impulse oscillometry (IOS) can complement spirometry. However, discordant spirometry and IOS in the diagnosis of SAD were not uncommon. We examined the association between spirometry and IOS within a large cohort of subjects to identify variables that may explain discordant spirometry and IOS findings.Methods: 1,836 subjects from the ECOPD cohort underwent questionnaires, symptom scores, spirometry, and IOS, and 1,318 subjects were examined by CT. We assessed SAD with R5-R20 > the upper limit of normal (ULN) by IOS and two of the three spirometry indexes (maximal mid-expiratory flow (MMEF), forced expiratory flow (FEF)50%, and FEF75%) < 65% predicted. Multivariate regression analysis was used to analyze factors associated with SAD diagnosed by only spirometry but not IOS (spirometry-only SAD) and only IOS but not spirometry (IOS-only SAD), and line regression was used to assess CT imaging differences.Results: There was a slight agreement between spirometry and IOS in the diagnosis of SAD (kappa 0.322, p < 0.001). Smoking status, phlegm, drug treatment, and family history of respiratory disease were factors leading to spirometry-only SAD. Spirometry-only SAD had more severe emphysema and gas-trapping than IOS-only SAD in abnormal lung function. However, in normal lung function subjects, there was no statistical difference in emphysema and gas-trapping between discordant groups. The number of IOS-only SAD was nearly twice than that of spirometry.Conclusion: IOS may be more sensitive than spirometry in the diagnosis of SAD in normal lung function subjects. But in patients with abnormal lung function, spirometry may be more sensitive than IOS to detect SAD patients with clinical symptoms and CT lesions.

Small airway dysfunction (SAD) in asthma is characterized by the inflammation and narrowing of airways with less of 2 mm in diameter between generations 8 and 23 of the bronchial tree. It is now widely accepted that small airways are involved in the pathogenesis of asthma and are a major determinant of airflow obstruction in this disease. In recent years, specialized tests have been developed, such as Impulse Oscillometry (IOS) and Multiple Breath Nitrogen Washout (MBNW) tests, which have been deemed more accurate in detecting SAD than conventional spirometry. Clinical studies show that SAD is associated with more severe bronchial hyperresponsiveness, worse asthma control, and a higher risk of exacerbations. Recent data from a large cohort study showed that the prevalence of SAD in asthma patients increases with asthma severity. Overall, SAD seems to represent a treatable trait, which makes it appealing for asthma control optimization and exacerbation rate reduction, especially in moderate-to-severe asthma.Biologic agents are now available for the treatment of different severe asthma phenotypes and endotypes. However, the effect of these therapies on SAD remains poorly characterized. Literature showing that biologic agents can also favorably improve small airway function is accumulating. In particular, anti-IL5 agents (mepolizumab and benralizumab) seems to have a greater impact on SAD as compared to other biological agents, but direct comparisons in prospective randomized controlled trials are lacking.In this mini-review article, we address the latest evidence on the effect of biological therapies on SAD in patients with severe asthma.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by airflow limitation and persistent respiratory symptoms. A key factor in the progression of COPD is small airway dysfunction (SAD), which originates in airways smaller than 2 mm in diameter. Chronic exposure to smoke and toxins leads to inflammatory remodeling and luminal obstruction, detectable through micro-computed tomography (CT) studies before spirometric airflow limitations become evident. SAD exacerbates COPD by increasing airway resistance and promoting dynamic airway collapse during exhalation. Clinically, SAD presents as gas trapping, hyperinflation, and exercise intolerance, which are associated with a rapid decline in lung function. Recent evidence indicates that SAD may be a modifiable and clinically significant trait in COPD, with management strategies including extrafine-particle inhalers, smoking cessation, pulmonary rehabilitation, and emerging biologic therapies. Various assessment methods, such as pulmonary function tests and CT imaging, are used to assess SAD. This review focuses on the role of SAD in the pathophysiology of COPD and the clinical implications of easily applicable measurements, including forced expiratory flow between 25% and 75% of forced vital capacity, impulse oscillometry, Pi10, and parametric response mapping, as well as potential treatment modalities for SAD in COPD.