Interleukin-1β is one of the major cytokines involved in the initiation and persistence of airway inflammation in chronic obstructive pulmonary disease (COPD). However, the association between plasma interleukin-1β and lung function decline remains unclear. We aimed to explore the association between plasma interleukin-1β and lung function decline. This longitudinal evaluation of data from the Early COPD study analysed the association between the plasma interleukin-1β concentration, lung function decline, and COPD exacerbation. Overall, 1,328 participants were included in the baseline analysis, and 1,135 (85%) completed the 1-year follow-up. Increased plasma interleukin-1β was associated with accelerated lung function decline in non-smokers (forced expiratory volume in 1 s: per unit natural log-transformed increase, adjusted unstandardised β [95% confidence interval] 101.46 [16.73-186.18] mL/year, p=0.019; forced vital capacity: per unit natural log-transformed increase, adjusted unstandardised β [95% confidence interval] 146.20 [93.65-198.75] mL/year, p<0.001), but not in smokers. In non-smokers, participants with an interleukin-1β concentration in the top 30% (>5.02 pg/mL) had more respiratory symptoms, more severe emphysema and air trapping, and higher levels of inflammation-related biomarkers. In this study, a subgroup with increased plasma interleukin-1β was identified among non-smokers, and increased plasma interleukin-1β was associated with lung function accelerated decline.

Previous studies have shown that patients with chronic obstructive pulmonary disease (COPD) of severe or very severe airflow limitation have a reduced pectoralis muscle area (PMA), which is associated with mortality. However, whether patients with COPD of mild or moderate airflow limitation also have a reduced PMA remains unclear. Additionally, limited evidence is available regarding the associations between PMA and respiratory symptoms, lung function, computed tomography (CT) imaging, lung function decline, and exacerbations. Therefore, we conducted this study to evaluate the presence of PMA reduction in COPD and to clarify its associations with the referred variables.

This study was based on the subjects enrolled from July 2019 to December 2020 in the Early Chronic Obstructive Pulmonary Disease (ECOPD) study. Data including questionnaire, lung function, and CT imaging were collected. The PMA was quantified on full-inspiratory CT at the aortic arch level using predefined -50 and 90 Hounsfield unit attenuation ranges. Multivariate linear regression analyses were performed to assess the association between the PMA and airflow limitation severity, respiratory symptoms, lung function, emphysema, air trapping, and the annual decline in lung function. Cox proportional hazards analysis and Poisson regression analysis were used to evaluate the PMA and exacerbations after adjustment.

We included 1352 subjects at baseline (667 with normal spirometry, 685 with spirometry-defined COPD). The PMA was monotonically lower with progressive airflow limitation severity of COPD after adjusting for confounders (vs. normal spirometry; Global Initiative for Chronic Obstructive Lung Disease [GOLD] 1: β=-1.27, P=0.028; GOLD 2: β=-2.29, P<0.001; GOLD 3: β=-4.88, P<0.001; GOLD 4: β=-6.47, P=0.014). The PMA was negatively associated with the modified British Medical Research Council dyspnea scale (β=-0.005, P=0.026), COPD Assessment Test score (β=-0.06, P=0.001), emphysema (β=-0.07, P<0.001), and air trapping (β=-0.24, P<0.001) after adjustment. The PMA was positively associated with lung function (all P<0.05). Similar associations were discovered for the pectoralis major muscle area and pectoralis minor muscle area. After the 1-year follow-up, the PMA was associated with the annual decline in the post-bronchodilator forced expiratory volume in 1 s percent of predicted value (β=0.022, P=0.002) but not with the annual rate of exacerbations or the time to first exacerbation.

Patients with mild or moderate airflow limitation exhibit a reduced PMA. The PMA is associated with airflow limitation severity, respiratory symptoms, lung function, emphysema, and air trapping, suggesting that PMA measurement can assist with COPD assessment.

Rationale: Previous studies have identified exercise intolerance in patients with mild-to-moderate chronic obstructive pulmonary disease (COPD). The association of exercise tolerance with lung function decline and acute exacerbation risk in mild-to-moderate COPD is unclear, especially in the community population. Objectives: We evaluated exercise tolerance in patients with mild-to-moderate COPD and analyzed its associations with respiratory health outcomes. Methods: We analyzed data from the community-based ECOPD (Early Chronic Obstructive Pulmonary Disease) study of patients with mild-to-moderate COPD (postbronchodilator forced expiratory volume in 1 second (FEV1):forced vital capacity < 0.70 and FEV1 ≥ 50% predicted). Patients who completed questionnaires, spirometry, and cardiopulmonary exercise testing at baseline were included. Annual exacerbation assessment and spirometry were conducted for 2 years consecutively. Exercise tolerance was defined as the percentage of predicted peak oxygen uptake ([Formula: see text]o2peak% predicted). We analyzed the association between exercise tolerance, annual lung function decline, and acute exacerbation risk. Results: Overall, 338 patients were included in the baseline analysis, and 319 completed the 2-year follow up. The mean ± standard deviation of [Formula: see text]o2peak% predicted was 79.8 ± 13.7%. Low [Formula: see text]o2peak% predicted was associated with more chronic respiratory symptoms, worse lung function, severer emphysema, and air trapping at baseline. During the 2-year follow up, a decrease of 13.7% (1 standard deviation) in [Formula: see text]o2peak% predicted was associated with a decline in prebronchodilator FEV1:forced vital capacity (difference, 0.4% [95% confidence interval, 0.1-0.7%]; P = 0.003) and higher total exacerbation risk (relative risk, 1.25 [95% confidence interval, 1.08-1.46]; P = 0.004) after adjustment. Conclusions: Patients with mild-to-moderate COPD and exercise intolerance have worse respiratory health outcomes, for which low exercise tolerance is a prognostic marker. Clinical trial registered with www.chictr.org.cn (ChiCTR1900024643).

Small airway dysfunction (SAD) assessed by impulse oscillometry (IOS) was common in patients with chronic obstructive pulmonary disease (COPD). However, little is known about the associations between IOS-defined small airway dysfunction (SAD) and the long-term prognosis of COPD. This study aimed to explore the associations between IOS-defined SAD, lung function decline and exacerbations in patients with COPD.

We analyzed baseline and 2-year follow-up data from the prospective cohort study in China. We defined SAD using IOS parameters Z-score greater than the 1.645 or less than -1.645. Subsequently, these patients were divided into three groups based on the different criteria defined SAD using IOS (normal group [none IOS parameters abnormalities], inconsistent SAD [any IOS parameters abnormalities, but not all], consistent SAD [all of IOS parameters abnormalities]). Negative binomial regression was conducted to analyze the associations between SAD and exacerbations, while a multivariable linear regression model was utilized to identify associations between SAD and lung function decline.

833 patients with COPD were enrolled in our study. SAD (defined by X5, AX, and Fres z-score) was associated with a faster decline in lung function and higher risk of exacerbation. Meanwhile, for inconsistent diagnosis of SAD, we observed that patients with consistent SAD and inconsistent SAD experienced a faster decline in FEV1 and higher risk of exacerbations than those with normal group.

IOS-defined SAD was associated with worse outcomes in patients with COPD, and further clinical trials are needed to clarify whether early intervention to reduce the severity of small airway lesions can delay the progress of COPD.

Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July 2019.

Identifying high-risk patients is fundamental to slowing disease progression in mild-to-moderate COPD. Over one-fifth of these patients have impaired ventilatory efficiency, strongly associated with advanced disease severity, while its unclear prognostic value for high-risk case identification persists.

This was a prospective cohort study conducted from July 2019 to September 2024 (encompassing the COVID-19 pandemic period) in China. Non-COPD subjects and mild-to-moderate COPD patients who completed questionnaires, lung function tests and cardiopulmonary exercise tests at baseline were annually followed up over 3 years. Subjects with predefined high-risk criteria, including CAT score≥10, mMRC score≥2, postbronchodilator FEV1<60% predicted, and frequent exacerbations, were further excluded. Impaired ventilatory efficiency was defined as a nadir minute ventilation/CO2 output≥the upper limit of normal. Outcomes included annual lung function decline, exacerbation risks, and symptom scores.

A total of 780 subjects were included, with 684 (88%) completing follow-up. Patients with impaired ventilatory efficiency displayed a greater annual decline in postbronchodilator FEV1 (54 [95% CI: 32-76]mL/year) than patients with normal ventilatory efficiency (31 [15-47] mL/year, adjusted P=0.008) and non-COPD subjects (31 [22-40]mL/year, adjusted P=0.001). However, no significant difference existed between patients with normal ventilatory efficiency and non-COPD subjects (adjusted P=0.756). Similar results were observed for exacerbation risks and symptom scores.

Impaired ventilatory efficiency can identify high-risk mild-to-moderate COPD patients with poor prognosis independently of established risk factors. Further studies are needed to explore effective interventions for patients with impaired ventilatory efficiency.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome, resulting in inconsistent findings across studies. Identifying a core set of genes consistently involved in COPD pathogenesis, independent of patient variability, is essential.

We integrated lung tissue sequencing data from patients with COPD across two centers. We used weighted gene co-expression network analysis and machine learning to identify 13 potential pathogenic genes common to both centers. Additionally, a gene-based model was constructed to distinguish COPD at the molecular level and validated in independent cohorts. Gene expression in specific cell types was analyzed, and Mendelian randomization was used to confirm associations between candidate genes and lung function/COPD. Preliminary in vitro functional validation was performed on prioritized core candidate genes.

Tissue inhibitor of metalloproteinase 4 (TIMP4) was identified as a key pathogenic gene and validated in COPD cohorts. Further analysis using single-cell sequencing from mice and patients with COPD revealed that TIMP4 is involved in ciliated cells. In primary human airway epithelial cells cultured at the air-liquid interface, TIMP4 overexpression reduced ciliated cell numbers.

We developed a 13-gene model for distinguishing COPD at the molecular level and identified TIMP4 as a potential hub pathogenic gene. This finding provides insights into shared disease mechanisms and positions TIMP4 as a promising therapeutic target for further investigation.

Studies 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.

We 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.

2055 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.

There was low consistency in the assessment of SAD between spirometry and CT, between IOS and CT, as well as among spirometry, IOS, and CT.

Not applicable.

Small airway dysfunction (SAD) and impaired diffusion capacity of the lungs for carbon monoxide (D LCO) are positively associated with a worse prognosis. Individuals with both dysfunctions have been identified in clinical practice and it is unknown whether they have worse health status or need management. We conducted this study to explore the association between SAD and impaired D LCO, and the difference between the groups with two dysfunctions, with either one dysfunction and with no dysfunction.

This study involved subjects partly from those who had returned for the third-year follow-up (up to December 2022) of the Early Chronic Obstructive Pulmonary Disease study and those who newly participated. We assessed diffusion capacity, questionnaire, exacerbations, spirometry, impulse oscillometry (IOS) and computed tomography (CT). Impaired D LCO was defined as D LCO <80% predicted. Spirometry-defined SAD was defined using the percent predicted values of maximal mid-expiratory flow, and forced expiratory flow at 50% and 75% of forced vital capacity, at least two of these three values being <65% predicted after the use of a bronchodilator. IOS-defined SAD was defined when the difference in resistance at 5 and 20 Hz was >0.07 kPa·L-1·s. CT-defined SAD was defined when the percentage of expiratory low-attenuation areas <-856 HU comprised ≥15% of the total lung volume. Covariate analyses and logistic regression were performed to assess the association between impaired D LCO and SAD.

This study involved 581 subjects. The occurrence of both spirometry- and CT-defined SAD was significantly higher in subjects with impaired D LCO than normal D LCO. Subjects with two dysfunctions were associated with worse preceding year's exacerbations than controls.

Impaired diffusion capacity is positively associated with SAD. Subjects with impaired diffusion capacity and SAD may have a worse health status and need additional management.

Recently, the severities of chronic obstructive pulmonary disease (COPD) can also be assessed by impulse oscillometry (IOS). This study aimed to explore a new classification of severity of COPD based on IOS and associations with acute exacerbations (AE) in patients with COPD.

The data of our study were based on the baseline and 2-year follow-up data of a prospective cohort in China. COPD was defined as post-bronchodilator FEV1/FVC <0.70. A new severity classification (staging of airflow obstruction by IOS, SAIO) was evaluated based on IOS parameters (R5, R5-R20, and X5 z-scores). We quantified using the weighted Bangdiwala B for agreement of severities of COPD between IOS parameters and FEV1%pred. The differences among SAIO stages were performed in symptom scores and imaging using analysis of covariance, and in the AE using Poisson regression.

Overall, 833 patients with COPD were included in this study. The weighted Bangdiwala B of R5, R5-R20, X5 z-scores, and FEV1%pred for evaluating agreement of the severities of COPD was 0.68, 0.70 and 0.83, respectively. The SAIO classifications system identified a greater number of patients with stage III-IV. SAIO provided significant discrimination between the stage I and stage III, IV for symptom scores, emphysema, and air trapping. SAIO provided significant discrimination between the stage I and other stages for AE.

The SAIO classifications provide discrimination between the stage I and stage III, IV for symptom scores, emphysema, air trapping, and AE, similar to the GOLD classifications.

Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

The previous findings on the correlation between spirometry and high-density lipoprotein (HDL) cholesterol are intriguing yet conflicting. The aim of this research is to evaluate the relationship between HDL levels and spirometry as well as imaging parameters in patients with chronic obstructive pulmonary disease (COPD) in China.

This study encompasses a total of 907 COPD patients. Participants with complete data from questionnaire interviews, lipid profile examinations, spirometry testing, and computed tomography (CT) scans were included in the analysis. A generalized additive model was employed to identify the non-linear relationship between HDL levels and both spirometry and imaging parameters. In the presence of non-linear correlations, segmented linear regression model was applied to ascertain threshold effects.

After adjusting for various factors, we found a non-linear correlation between HDL levels and spirometry/imaging parameters, with an inflection point at 4.2 (66 mg/dL). When Ln (HDL) was below 4.2, each unit increase correlated significantly with reduced post-bronchodilator FEV1 (0.32L, 95% CI: 0.09-0.55), decreased predicted FEV1% (11.0%, 95% CI: 2.7-19.3), and lowered FEV1/FVC (8.0%, 95% CI: 4.0-12.0), along with notable increases in Ln (LAA-950) by 1.20 (95% CI: 0.60-1.79) and Ln (LAA-856) by 0.77 (95% CI: 0.37-1.17). However, no significant associations were observed when Ln (HDL) was greater than or equal to 4.2.

A non-linear correlation existed between HDL levels with lung function and CT imaging in COPD patients. Prior to reaching 66 mg/dL, an elevation in HDL was significantly associated with impaired lung function, more severe gas trapping and emphysema.

Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China.

We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency.

The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below -950 Hounsfield units, logLAA-950: 0.19±0.65 vs -0.28±0.63, p<0.001) and air trapping (logLAA-856: 1.03±0.65 vs 0.68±0.70, p<0.001) than those with normal ventilatory efficiency. Older age (60-69 years, OR 3.10 (95% CI 1.33 to 7.21), p=0.009 and 70-80 years, OR 6.48 (95% CI 2.56 to 16.43), p<0.001 vs 40-49 years) and smoking (former, OR 3.19 (95% CI 1.29 to 7.86), p=0.012; current, OR 4.27 (95% CI 1.78 to 10.24), p=0.001 vs never) were identified as high risk factors of impaired ventilatory efficiency.

Impaired ventilatory efficiency was associated with poorer respiratory characteristics. Longitudinal studies are warranted to explore the progression of individuals with impaired ventilatory efficiency.

High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community.

We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/μL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma.

Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results.

COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.

There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes.

Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

RESULTS

The final analysis included 1140 participants with preserved spirometry (169 in the variable obstruction group) at baseline. Participants with variable obstruction were older, had lower lung function and had greater severe emphysema and computed tomography-defined air trapping than participants without variable obstruction. Participants with variable obstruction had a significantly increased risk of incident spirometry-defined COPD (relative risk: 3.22, 95% confidence interval 2.23 to 4.64, p <0.001) than those without variable obstruction after adjustment for covariates. These findings remained consistent among both former and current smokers, never smokers, and different variable obstruction types. Additionally, participants with variable obstruction had a faster decline in postbronchodilator FEV1/FVC (2.3±0.5%/year vs 0.9±0.4%/year, mean difference: 1.4 (95% confidence interval 0.5 to 2.3), p=0.002) than participants without variable obstruction after adjustment for covariates.

CONCLUSIONS

The results of our study revealed that variable obstruction can identify individuals who are at risk for the development of COPD and accelerated postbronchodilator FEV1/FVC decline in preserved spirometry.

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The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR.

Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model.

This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up.

The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR.

Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

The relationship between airway inflammation in chronic obstructive pulmonary disease (COPD) and clinical characteristics remains unclear. This study aimed to investigate the airway inflammatory phenotypes in COPD and their association with clinical characteristics.

895 patients with COPD were recruited from Guangdong Province, China in this study. Each patient underwent questionnaire interviews, spirometry testing, CT scans and induced sputum examination. Classification of airway inflammation phenotypes was based on sputum inflammatory cell counts. Covariance analysis was applied to assess associations with airway inflammation phenotypes.

In this study, we found that neutrophilic phenotype (NP, 58.0%) was the most common airway inflammation phenotype in patients with COPD, followed by mixed granulocytic phenotype (MGP, 32.6%), eosinophilic phenotype (EP, 5.4%) and paucigranulocytic phenotype (PP, 4.0%). Compared with NP patients, those with MGP exhibited more frequent chronic respiratory symptoms, and a higher proportion of individuals classified under Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4. After adjusting for confounding factors, MGP patients had lower lung function, and more severe emphysema and air trapping. On the contrary, patients with PP had the best pulmonary function and less emphysema and air trapping.

NP was the most common airway inflammation phenotype in patients with COPD. Patients with MGP had more respiratory symptoms, greater loss of lung function, and more severe emphysema and gas trapping compared with those with NP. Meanwhile, PP may be a phenotype of mild damage to lung structure in patients with COPD.

The inter-relationships among neutrophilic airway inflammation, air trapping and future exacerbation in chronic obstructive pulmonary disease (COPD) remain unclear.

To evaluate the associations between sputum neutrophil proportions and future exacerbation in COPD and to determine whether these associations are modified by significant air trapping.

Participants with completed data were included and followed up to the first year in the Early Chronic Obstructive Pulmonary Disease study (n=582). Sputum neutrophil proportions and high-resolution CT-related markers were measured at baseline. Sputum neutrophil proportions were dichotomised based on their median (86.2%) to low and high levels. In addition, subjects were divided into the air trapping or non-air trapping group. Outcomes of interest included COPD exacerbation (separately any, severe and frequent exacerbation, occurring in the first year of follow-up). Multivariable logistic regressions were performed to examine the risk of severe exacerbation and frequent exacerbation with either neutrophilic airway inflammation groups or air trapping groups.

There was no significant difference between high and low levels of sputum neutrophil proportions in the exacerbation in the preceding year. After the first year of follow-up, subjects with high sputum neutrophil proportions had increased risks of severe exacerbation (OR=1.68, 95% CI: 1.09 to 2.62, p=0.020). Subjects with high sputum neutrophil proportions and significant air trapping had increased odds of having frequent exacerbation (OR=3.29, 95% CI: 1.30 to 9.37, p=0.017) and having severe exacerbation (OR=2.72, 95% CI: 1.42 to 5.43, p=0.003) when compared with those who had low sputum neutrophil proportions and non-air trapping.

We found that subjects with high sputum neutrophil proportions and significant air trapping are prone to future exacerbation of COPD. It may be a helpful predictor of future exacerbation.

Evidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals with NOCB in the Chinese population.

We obtained data on participants in the Early Chronic Obstructive Pulmonary Disease Study who had normal spirometry (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ≥0.70). NOCB was defined as chronic cough and sputum production for at least 3 months for two consecutive years or more at baseline in participants with normal spirometry. We assessed the differences in demographics, risk factors, lung function, impulse oscillometry, CT imaging and frequency of acute respiratory events between participants with and without NOCB.

NOCB was present in 13.1% (149/1140) of participants with normal spirometry at baseline. Compared with participants without NOCB, those with NOCB had a higher proportion of men and participants with smoke exposure, occupational exposure, family history of respiratory diseases and worse respiratory symptoms (all p<0.05), but there was no significant difference in lung function. Never-smokers with NOCB had higher rates of emphysema than those without NOCB, but airway resistance was similar. Ever-smokers with NOCB had greater airway resistance than those without NOCB, but emphysema rates were similar. During 1-year follow-up, participants with NOCB had a significantly increased risk of acute respiratory events compared with participants who did not have NOCB, after adjustment for confounders (risk ratio 2.10, 95% CI 1.32 to 3.33; p=0.002). These results were robust in never-smokers and ever-smokers.

Never-smokers and ever-smokers with NOCB had more chronic obstructive pulmonary disease-related risk factors, evidence of airway disease and greater risk of acute respiratory events than those without NOCB. Our findings support expanding the criteria defining pre-COPD to include NOCB.

The role of airway impairment assessed by impulse oscillometry (IOS) in patients with chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aimed to analyze the proportion and clinical characteristics of airway impairment assessed by IOS across COPD severities, and explore whether airway impairment is a subtype of COPD.

This study was based on cross-sectional data from the ECOPD cohort in Guangdong, China. Subjects were consecutively recruited from July 2019 to August 2021. They filled out questionnaires and underwent lung function tests, IOS and computed tomography (CT). COPD was defined as post-bronchodilator forced expiratory volume in one second/forced vital capacity < lower limit of normal (LLN). Meanwhile, airway impairment was defined as IOS parameters > upper limit of normal or < LLN. On the one hand, Poisson regression was employed to analyze the associations between acute exacerbations of COPD (AECOPD) in the previous year and airway impairment. On the other hand, logistic regression was used to assess differences in CT imaging between patients with IOS parameters' abnormalities and patients with normal IOS parameters.

768 COPD subjects were finally enrolled in the study. The proportion of airway impairment assessed by R₅, R₂₀, R₅-R₂₀, X₅, AX, and F_res was 59.8%, 29.7%, 62.5%, 52.9%, 60.9% and 67.3%, respectively. Airway impairment assessed by IOS parameters (R₅, R₅-R₂₀, X₅, AX, and F_res) in patients with COPD was present across all severities of COPD, particularly in GOLD 3-4 patients. Compared with patients with normal IOS parameters, patients with IOS parameters' abnormalities had more respiratory symptoms, more severe airway obstruction and imaging structural abnormalities. Patients with IOS parameters' abnormalities assessed by R₅ [risk ratio (RR): 1.58, 95% confidential interval (CI): 1.13-2.19, P = 0.007], R₅-R₂₀ [RR: 1.73, 95%CI: 1.22-2.45, P = 0.002], X₅ [RR: 2.11, 95%CI: 1.51-2.95, P < 0.001], AX [RR: 2.20, 95%CI: 1.53-3.16, P < 0.001], and F_res [RR: 2.13, 95%CI: 1.44-3.15, P < 0.001] had a higher risk of AECOPD in the previous year than patients with normal IOS parameters.

Airway impairment assessed by IOS may be a subtype of COPD. Future studies are warranted to identify the underlying mechanisms and longitudinal progression of airway impairment.

Aging has been evidenced to bring about some structural and functional lung changes, especially in COPD. However, whether aging affects SAD, a possible precursor of COPD, has not been well characterized.

We aimed to comprehensively assess the relationship between aging and SAD from computed tomography, impulse oscillometry, and spirometry perspectives in Chinese.

We included 1859 participants from ECOPD, and used a linear-by-linear association test for evaluating the prevalence of SAD across various age subgroups, and multivariate regression models for determining the impact of age on the risk and severity of SAD. We then repeated the analyses in these subjects stratified by airflow limitation.

The prevalence of SAD increases over aging regardless of definitional methods. After adjustment for other confounding factors, per 10-yrs increase in age was significantly associated with the risk of CT-defined SAD (OR 2.57, 95% CI 2.13 to 3.10) and the increase in the severity of air trapping (β 2.09, 95% CI - 0.06 to 4.25 for LAA_-856), airway reactance (β - 0.02, 95% CI - 0.04 to - 0.01 for X5; β 0.30, 95% CI 0.13 to 0.47 for AX; β 1.75, 95% CI 0.85 to 2.66 for Fres), as well as the decrease in expiratory flow rates (β - 3.95, 95% CI - 6.19 to - 1.71 for MMEF%predicted; β - 5.42, 95% CI - 7.88 to - 2.95 for FEF₅₀%predicted) for SAD. All these associations were generally maintained in SAD defined by IOS or spirometry. After stratification of airflow limitation, we further found that the effect of age on LAA_-856 was the most significant among almost all subgroups.

Aging is significantly associated with the prevalence, increased risk, as well as worse severity of SAD. CT may be a more optimal measure to assess aging-related SAD. The molecular mechanisms for the role of aging in SAD need to be explored in the future. Trial registration Chinese Clinical Trial Registry ChiCTR1900024643. Registered on 19 July 2019.

Eosinophils are involved in the development of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroid responsiveness. We evaluated clinical predictors of high sputum eosinophil levels in a COPD cohort in China.

We conducted an observational, prospective, population-based, cross-sectional study. Participants were tested for COPD and underwent spirometry, computed tomography scans, and a blood test. Participants also produced induced sputum and responded to an information-gathering questionnaire. High sputum eosinophils were defined as ≥3.0%. Multivariate logistic regression was used to identify predictors of high sputum eosinophil levels.

We recruited 895 patients with complete and quality control data. The median percentage of sputum eosinophil abundance was 2.00% (interquartile range: 0.75-5.00) and the prevalence of COPD with high sputum eosinophils was 38.0%. Covariance analysis indicated that the high sputum eosinophil group had lower lung function, more severe emphysema, and air trapping. Multivariate logistic regression indicated that high blood eosinophil levels, severe respiratory symptoms, being a former smoker, and a family history of respiratory diseases were associated with high sputum eosinophil levels.

High blood eosinophil levels, severe respiratory symptoms, being a former smoker, and a family history of respiratory diseases may be predictors of high sputum eosinophil levels in Chinese COPD patients. High sputum eosinophils were associated with lower lung function, more emphysema, and gas trapping.

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 FEF_75%) < 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.

Preserved ratio impaired spirometry (PRISm) refers to decreased forced expiratory volume in 1 s (FEV₁) in the setting of preserved ratio. Little is known about the role of PRISm and its complex relation with small airway dysfunction (SAD) and lung volume. Therefore, we aimed to investigate the associations between PRISm and SAD and lung volume.

We conducted a cross-sectional community-dwelling study in China. Demographic data, standard respiratory epidemiology questionnaire, spirometry, impulse oscillometry (IOS) and computed tomography (CT) data were collected. PRISm was defined as post-bronchodilator FEV₁/FVC ≥ 0.70 and FEV₁ < 80% predicted. Spirometry-defined SAD was defined as at least two of three of the post-bronchodilator maximal mid-expiratory flow (MMEF), forced expiratory flow 50% (FEF50), and forced expiratory flow 75% (FEF75) less than 65% of predicted. IOS-defined SAD and CT-defined gas trapping were defined by the fact that the cutoff value of peripheral airway resistance R5-R20 > 0.07 kPa/L/s and LAA_- 856>20%, respectively. Analysis of covariance and logistic regression were used to determine associations between PRISm and SAD and lung volume. We then repeated the analysis with a lower limit of normal definition of spirometry criteria and FVC definition of PRISm. Moreover, we also performed subgroup analyses in ever smoker, never smoker, subjects without airway reversibility or self-reported diagnosed asthma, and subjects with CT-measured total lung capacity ≥70% of predicted.

The final analysis included 1439 subjects. PRISm had higher odds and more severity in spirometry-defined SAD (pre-bronchodilator: odds ratio [OR]: 5.99, 95% confidence interval [95%CI]: 3.87-9.27, P < 0.001; post-bronchodilator: OR: 14.05, 95%CI: 8.88-22.24, P < 0.001), IOS-defined SAD (OR: 2.89, 95%CI: 1.82-4.58, P < 0.001), and CT-air trapping (OR: 2.01, 95%CI: 1.08-3.72, P = 0.027) compared with healthy control after adjustment for confounding factors. CT-measured total lung capacity in PRISm was lower than that in healthy controls (4.15 ± 0.98 vs. 4.78 ± 1.05 L, P < 0.05), after adjustment. These results were robust in repeating analyses and subgroup analyses.

Our finding revealed that PRISm was associated with SAD and reduced total lung capacity. Future studies to identify the underlying mechanisms and longitudinal progression of PRISm are warranted.