Background Patients with chronic obstructive pulmonary disease (COPD) frequently present with psychological comorbidities, including anxiety and depression, which may contribute to poorer clinical outcomes. However, the prevalence and impact of these mental health conditions in COPD patients have long been underrecognized. Leveraging data from the Chinese Population Health and Multimorbidities Study (CPHMS), a large epidemiological survey on chronic respiratory diseases in China, this study aimed to estimate the prevalence of anxiety and depression comorbidities among community-dwelling COPD patients and to evaluate the diagnostic utility of the COPD Assessment Test (CAT) scale for detecting these conditions in spirometry-confirmed COPD patients. Methods Analytical data were derived from the CPHMS. Comprehensive information on sociodemographic characteristics, lifestyle factors, and health status was collected. COPD-related pulmonary and extra-pulmonary symptoms were assessed using the CAT scale, and anxiety and depression were evaluated via the Hospital Anxiety and Depression Scale. Multivariable logistic regression was employed to identify factors associated with anxiety or depression comorbidities, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of the CAT scale. Results Among 3641 spirometry-confirmed community COPD patients, the prevalence of anxiety and depression was 11.07% (95% confidence interval [CI]: 10.05–12.09%) and 14.23% (95% CI: 13.09–15.36%), respectively. Female gender, rural residence, unemployment, lower annual family income, and higher total CAT score, as well as higher scores on both pulmonary and extra-pulmonary symptom subscales of the CAT, were independently associated with an increased likelihood of anxiety and/or depression in COPD patients. The diagnostic yield of the CAT scale for identifying anxiety and depression in COPD patients was evaluated. In the overall COPD patients, the optimal total CAT cut-off value for detecting anxiety was 9 (area under the ROC curve [AUC]: 0.637; 95% CI: 0.607–0.666), and for depression was 7 (AUC: 0.633; 95% CI: 0.607–0.659). Notably, among rural-dwelling COPD patients, the optimal cut-off was 7 for both anxiety (AUC: 0.624; 95% CI: 0.582–0.665) and depression (AUC: 0.616; 95% CI: 0.579–0.653), whereas in urban patients, the corresponding cut-offs were 11 for anxiety (AUC: 0.652; 95% CI: 0.610–0.694) and 10 for depression (AUC: 0.654; 95% CI: 0.618–0.691). Conclusions This study delineated the prevalence of anxiety and depression among community COPD patients and validated the clinical utility of the CAT scale in detecting these psychological comorbidities. Our findings underscore the pressing need for tailored psychological support, particularly for COPD patients residing in rural area of China.

This study aimed to investigate the prevalence, awareness, treatment and control rates of chronic obstructive pulmonary disease (COPD) and their influencing factors among adults in regional China. In 2023, 6403 community-dwelling residents aged 40 years and older were randomly chosen from Nanjing municipality of China. COPD was determined as self-reported physician-diagnosed patients or post-bronchodilator FEV1/FVC < 0.70, and without other lung function impaired diseases. Multivariate logistic regression models were introduced to identify influencing factors for each rate. Totally, 5605 participants were analyzed. The spirometry-based COPD prevalence, awareness, treatment and control rates were 15.4%, 4.4%, 2.4% and 56.8%, separately, while the corresponding age- and sex-standardized rates were 15.5%, 4.6%, 2.4% and 56.5%, respectively. Age, marital status, education, physical activity and body weight status significantly correlated with COPD prevalence. Among COPD patients, these with higher educational level, chronic respiratory symptoms, or family history, and former smokers were more likely to be aware of COPD. Those smoking formerly, aged 60-79 years, with chronic respiratory symptoms, family history of COPD, higher educational level, or physical inactivity were more likely to receive treatment. Additionally, patients living in urban areas tended to have the disease under control. The prevalence of COPD among adults aged 40 years and older was high, but awareness, treatment and control rates remained limited in regional China. For the purpose to reduce COPD burden, it shall be a priority for policy-makers to initiate/provide effective and accessible education and lung function screening programs of COPD for adults in China.

Heart failure (HF) is a common comorbidity for older patients of chronic obstructive pulmonary disease (COPD). This study aimed to investigate the global burden of COPD-HF comorbidity among older adults from 1990 to 2021 and make a prediction till 2050. Data on prevalence and years lived with disability (YLDs) for COPD-HF comorbidity among older adults aged 60 or above were obtained from the Global Burden of Diseases Study 2021. Absolute number and age-standardized rate (ASR) per 100,000 individuals were used to compare the disease burden by sex, age, severity and region. Temporal trends in ASR from 1990 to 2021 were analyzed using Joinpoint models, while Bayesian age-period-cohort models were introduced to project ASR till 2050. From 1990 to 2021, global prevalent cases and YLDs of COPD-HF comorbidity among older adults increased, and ASRs also exhibited a sustained increase. The disease burden will continue to rise till 2050. Moreover, the comorbidity burden was higher in males than females, and increased with age. Additionally, severe and treated cases were the predominant subtypes of this comorbidity. Low and middle socio-demographic index (SDI) regions tended to bear higher disease burden. The global burden of COPD-HF comorbidity was substantially heavy with a consistent rising trend from 1990 to 2021 in older adults. The disease burden will rise till 2050. Disparities of the disease burden existed in sex, SDI, and geographic region worldwide. This study has implications for re-allocating resources to early identification and effective treatment of COPD, HF, and COPD-HF comorbidity.

Cryptococcosis is an opportunistic and potentially fatal fungal infectious disease. Pemphigus diseases are characterized by blistering of the cutaneous and mucous membranes. We report a case of pulmonary cryptococcosis (PC) following methylprednisolone treatment for pemphigus vulgaris. Additionally, we analyzed a case series of PC infections recorded in PUBMED from 2013 to 2023. A total of 229 cases of PC were included. The median age was 54 years, with 66.4% of patients being male. Those with previous use of corticosteroids or immunosuppressives accounted for 38.4% of cases. Underlying conditions included solid organ transplantations (25.7%), respiratory diseases (6.6%), malignant tumors (6.1%), rheumatoid arthritis (5.7%), hematological malignancies (4.4%), among others. The main source of infection was exposure to birds, poultry, and their feces (12.7%). Cryptococcus neoformans was most frequently isolated (76.4%). Overall mortality was 14.8%. Previous use of corticosteroids or immunosuppressants was a risk factor for disseminated cryptococcus (p < 0.05). Age, underlying disease, dissemination, and no antifungal therapy were independently associated with increased mortality (p < 0.05). Co-occurrence of pemphigus and PC is rare. Prompt diagnosis and appropriate treatment of PC are essential to prevent fatal consequences. Corticosteroids or immunosuppressive therapy are associated with the development of disseminated cryptococcal infection. Age, underlying disease, and dissemination are related to increased mortality. Timely antifungal therapy can improve prognosis.

AimsThis study aimed to examine the associations of vegetable consumption and physical activity (PA) with chronic obstructive pulmonary disease (COPD) among community-dwelling adults in regional China.MethodsEligible participants were community-dwelling adults aged 40 years or above and were randomly selected from Nanjing municipality of China in 2023. Spirometry-based newly-identified COPD was treated as the outcome event, which was defined as post-bronchodilator FEV1/FVC < 0.70 and without other lung function impaired diseases, and not previously diagnosed as COPD. Independent variables were vegetable intake and PA. Logistic regression models were employed to compute odds ratio (OR) and 95% confidence interval (CI) for investigating associations of vegetable consumption and PA with COPD.ResultsAmong the 5,567 participants analyzed, the prevalence of spirometry-based newly-identified COPD was 14.8% (95% CI = 13.9%, 15.8%). After adjustment for socio-demographic characteristics and other potential confounding factors, participants who met vegetable consumption criteria were less likely to experience COPD compared to those who did not meet vegetable intake recommendation (OR = 0.84; 95%CI = 0.71, 0.98), while participants with sufficient PA were also less likely to experience COPD compared to physically inactive subjects (OR = 0.79; 95%CI = 0.67, 0.94). Additionally, participant who met vegetable consumption recommendation and engaged in sufficient PA were also at much lower odds to experience COPD compared to those who did not meet vegetable intake recommendation and were physically inactive (OR = 0.67; 95%CI = 0.53, 0.85).ConclusionsVegetable consumption and PA were individually and jointly associated with CODP among community-dwelling adults in regional China. This study highlighted that, from public health perspective, intervention of vegetable consumption and PA may be of help for reducing the odds of experiencing COPD.

Background Severe asthma is a heterogeneous airway inflammatory disease presenting with varying clinicophysiological characteristics and response to treatments. The objectives of the present study were to determine the clinical phenotypes of the Chinese C-BIOPRED cohort and their link to the sputum proteome. Methods Partition-around-medoids clustering was applied to a training set of 362 nonsmoking, smoking or ex-smoking severe asthma patients, and nonsmoking mild–moderate asthma patients using eight clinicophysiological variables, with validation performed in the remaining 181. Results Three stable clusters were defined, with Cluster T1 composed of predominantly female patients with severe nonsmoking asthma experiencing frequent exacerbations with moderate airflow obstruction, and Cluster T3 of elderly male patients with smoking/ex-smoking late-onset severe asthma and severe airflow obstruction and a moderate number of exacerbations. Cluster T2 was composed of nonsmokers with a mild–moderate airflow obstruction and no previous exacerbations. Validation clusters (V1, V2 and V3) were similar to the training set clusters. Differentially expressed proteins in sputum supernatants measured by liquid chromatography with tandem mass spectrometry pointed to differences in the complement and coagulation cascade pathway between Cluster 1 (T1 and V1) and Cluster 3 (T3 and V3), as well as between Cluster 2 (T2 and V2) and Cluster 3. Galectin 10 was upregulated in Cluster 1 compared with Cluster 2, and correlated with exacerbations, fractional exhaled nitric oxide, blood and sputum eosinophil count and oral corticosteroid dose in Cluster 1. Conclusion The clinical clusters were differentiated by smoking status, degree of airflow obstruction and exacerbation history, and by sputum complement and coagulation pathways, and galectin 10 levels.

Background: Pulmonary rehabilitation (PR) has demonstrated efficacy in managing long COVID-19, underscoring the need to refine and tailor PR strategies for optimal patient outcomes. Objectives: To evaluate the impact of PR on patients with long COVID-19 and to compare the efficacy of different types and durations of PR interventions. Design: Systematic review and meta-analysis. Data sources and methods: We systematically searched randomized controlled trials (RCTs) of the effectiveness of PR in long COVID-19 patients published before April 2024. The primary outcomes were physical capacity assessed by the 6-minute walking test (6MWT), lung function measured by forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), health-related quality of life (HRQoL), and fatigue. Secondary outcomes were thirty-second sit-to-stand test (30STST), handgrip strength tests, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), dyspnea, depression, anxiety, perceived effort, and adverse events. Results: A total of 37 studies with 3363 patients were included. Compared to controls, PR improved physical capacity (6MWT, 30STST, handgrip), lung function (FEV1, FVC, MIP, MEP), HRQoL, fatigue, dyspnea, and anxiety but did not reach statistical significance for depression. Subgroup analyses of PR duration indicated that programs of ⩽4 weeks improved 6MWT; those between 4 and 8 weeks significantly improved 6MWT, lung function (FEV1, FVC), HRQoL, and reduced fatigue; and programs over 8 weeks improved HRQoL and reduced fatigue. Exercise type analysis revealed that breathing exercises improved 6MWT, lung function (FEV1, FVC), and HRQoL; multicomponent exercises enhanced 6MWT performance and reduced fatigue; the combination of both types improved 6MWT, FEV1 (L), FVC (%pred), HRQoL, and reduced fatigue. Conclusion: PR improves physical capacity, lung function, and quality of life and alleviates dyspnea, fatigue, and anxiety in long COVID-19 patients. A 4- to 8-week PR program and a combination of both breath exercises and multicomponent training is most effective for managing long-term COVID-19 syndromes. Trial registration: PROSPERO ID: CRD42024455008.

Recent studies have shown that in critically ill patients such as those with sepsis and shock, the lung and gut microbiomes undergo profound changes. Legionella pneumophila (Lp) can cause fatal infection, however, such changes have not been investigated in legionellosis. Here, we evaluated the microbiome of the lungs, blood, liver, and small intestine content in Lp-infected guinea pigs. We used a culture-independent method by analysing the conserved 16S rDNA sequences of bacteria from the organs of guinea pigs infected with legionellosis. Bacterial DNA was also identified through bacterial probe-fluorescence in situ hybridisation (BP-FISH). Bacterial entry from the intestinal lumen into the submucosa was examined via ultrastructural visualisation. Anoxybacillus kestanbolensis, Geobacillus vulcani, and other bacteria were identified in the small intestine content of healthy guinea pigs but not in other tissues. However, in Lp-infected guinea pigs, DNA from these bacteria was detected in the small intestine, lungs, blood, and liver tissues at 24 h and 48 h post-infection, indicating the possible translocation of gut bacteria to the remote tissues. This was validated through BP-FISH and ultrastructural visualisation. At 72 h post-infection, Pseudomonadota were the dominant gut bacteria, highlighting an imbalance in the gut microbiome. Infection with the Legionella pneumophila serotype 1 disrupted the intestinal microbiota in a subset of guinea pigs during a 72-hour period post-infection, with possible translocation of gut-associated anaerobic bacteria to the lungs and liver based on the presence of genomic DNA detected in tissue from infected guinea pigs.

Idiopathic pulmonary fibrosis (IPF), characterized by fibroblast activation and collagen deposition, is a progressive lung disease that lacks effective interventions. Ubiquitin-specific peptidase 10 (USP10) acts as a multifunctional player in inflammatory response and progression of cancers, the effect on pulmonary fibrosis is unknown. Here, we demonstrated downregulated expression of USP10 in fibrotic lung tissues of IPF patients. In the current study, lung tissues were collected at the end of weeks 1, 2, or 3 post bleomycin (BLM)-intratracheal delivery. Consistently, USP10 expression levels were reduced after BLM challenge in a time-dependent manner. Mice treated with lentivirus overexpressing USP10 exhibited mitigative lung injury and reduced collagen deposition. USP10 overexpression enhanced autophagy in BLM-treated mouse lungs. Interestingly, the protective effect of USP10 was attenuated as the pulmonary autophagy flux was blocked by autophagy inhibitor 3-methyladenine (3-MA). Primary human and mouse lung fibroblasts were treated with pro-fibrotic TGF-β1 to verify the role of USP10 in vitro. Mechanically, the deubiquitinating enzyme USP10 interacted with Sirtuin 6 (Sirt6) and inhibited its degradation. Furthermore, USP10 overexpression inhibited the activation of Sirt6-mediated AKT/mTOR pathway in both lung tissues and fibroblasts. Our findings suggest that USP10 might attenuate pulmonary fibrosis through the promotion of Sirt6/AKT/mTOR-mediated autophagy. These data prioritize USP10 as a therapeutic target for treating IPF.

Background Type 2 inflammation is a key inflammatory endotype of chronic obstructive pulmonary disease (COPD). The precise identification and targeted intervention of treatable traits related to type 2 inflammation are crucial directions in the current management of COPD. Recently, a growing body of evidence-based medical data has accumulated regarding the clinical characteristics, biomarkers, therapeutic agents, and efficacy evaluation of type 2 inflammation in COPD, providing strong support for clinical diagnosis and treatment. This clinical practice recommendation systematically reviewed the evidence-based medical literature and integrated clinical experience to present expert opinions, aiming to standardize and improve the management of type 2 inflammation in COPD. Methods This clinical practice recommendation followed Appraisal of Guidelines for Research and Evaluation II (AGREE II) and the Reporting Items for Practice Guidelines in HealThcare (RIGHT) statement to ensure the thoroughness and transparency. Clinical questions were primarily derived from surveys among experts in the field and thorough discussion at meetings. The evidence grading levels and recommendation grades adopted in the clinical practice recommendation follow the evidence grading levels and recommendation grades established by the Oxford Centre for Evidence-Based Medicine. The expert opinions were formulated through open discussion and expert voting. Expert opinions with an agreement rate of 80 % or higher among the experts are incorporated in the clinical practice recommendation. Results Eight clinical questions concerning diagnosis and treatment were proposed after expert discussion. In addition, fifteen specific major points of expert opinions about type 2 inflammation in COPD, involving clinical features, biomarkers, correlation with clinical outcomes, inhaled corticosteroid (ICS) treatment, biologic treatment and treatment response, were determined. Conclusions A set of comprehensive clinical practice recommendations focusing on the treatable trait of type 2 inflammation in COPD was established, which may provide potential guidance for the precision management of COPD.

BackgroundThe prevalence, epidemiological and clinical heterogeneities, and impact profiles of individuals with preserved ratio impaired spirometry (PRISm), pre-COPD, young COPD, and mild COPD in general Chinese population were not known yet.MethodsData were obtained from the China Pulmonary Health study (2012–2015), a nationally representative cross-sectional survey that recruited 50,991 adults aged 20 years or older. Definitions of the four early disease status were consistent with the latest publications and the Global Initiative for Chronic Obstructive Lung Disease criteria.FindingsThe age-standardised prevalences of PRISm, pre-COPD, young COPD, and mild COPD were 5.5% (95% confidence interval, 4.3–6.9), 7.2% (5.9–8.8), 1.1% (0.7–1.8), and 3.1% (2.5–3.8), respectively. In summary, mild COPD was under more direct or established impact factor exposures, such as older age, male gender, lower education level, lower family income, biomass use, air pollution, and more accumulative cigarette exposures; young COPD and pre-COPD experienced more personal and parents’ events in earlier lives, such as history of bronchitis or pneumonia in childhood, frequent chronic cough in childhood, parental history of respiratory diseases, passive smoke exposure in childhood, and mother exposed to passive smoke while pregnant; pre-COPD coexisted with heavier symptoms and comorbidities burdens; young COPD exhibited worse airway obstruction; and most of the four early disease status harbored small airway dysfunction. Overall, older age, male gender, lower education level, living in the urban area, occupational exposure, frequent chronic cough in childhood, more accumulated cigarette exposure, comorbid with cardiovascular disease and gastroesophageal reflux disease were all associated with increased presence of the four early COPD status; different impact profiles were additionally observed with distinct entities. Over the four categories, less than 10% had ever taken pulmonary function test; less than 1% reported a previously diagnosed COPD; and no more than 13% had received pharmaceutical treatment.InterpretationSignificant heterogeneities in prevalence, epidemiological and clinical features, and impact profiles were noted under varied defining criteria of early COPD; a unified and validated definition for an early disease stage is warranted. Closer attention, better management, and further research need to be administrated to these population.FundingChinese Academy of Medical Sciences Institute of Respiratory Medicine Grant for Young Scholars (No. 2023-ZF-9); China International Medical Foundation (No. Z-2017-24-2301); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2021-I2M-1-049); National High Level Hospital Clinical Research Funding (No. 2022-NHLHCRF-LX-01); Major Program of National Natural Science Foundation of China (No. 82090011).

BackgroundMaternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. ObjectiveThis study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). MethodsThis case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the “bootstrap” method. ResultsThe study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (β=.097; P<.001). There was an association between MSDP and TD (β=.074; P<.001) as well as between TD and COPD (β=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: β=.094; P<.001 and indirect: β=.004; P=.03). The indirect effect remains present in the smoking population (direct: β=.120; P<.001 and indirect: β=.002; P=.03). ConclusionsThis study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

INTRODUCTION:Despite increasing studies confirming the efficacy of vedolizumab (VDZ) in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. In this article, we investigated the efficacy of combined treatment of VDZ and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD. METHODS:From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with VDZ from 2 inflammatory bowel disease centers were retrospectively selected. Forty-one patients received treatment of VDZ with concomitant 16-week EEN (VDZ + EEN cohort), and 40 patients received VDZ treatment alone (VDZ cohort). Clinical and biological outcomes were evaluated. Endoscopic response and mucosal healing were assessed by colonoscopy at weeks 16 and 52. RESULTS:There was no statistically significant difference between 2 groups at baseline for demographic and clinical characteristics. Compared with patients treated with VDZ alone, patients in the VDZ + EEN cohort achieved higher rates of clinical response (84.2% vs 40.0%), clinical remission (81.6% vs 30.0%), endoscopic response (91.4% vs 34.6%), including mucosal healing (85.7% vs 26.9%) at week 16. The superiority of VDZ + EEN treatment sustained in maintenance, with 76.7% (vs 33.3%) clinical response, 70.0% (vs 26.7%) clinical remission, 76.9% (vs 33.3%) endoscopic response, and 61.5% (vs 26.7%) mucosal healing at week 52. None of the patients experienced severe adverse events. DISCUSSION:VDZ with concomitant 16-week EEN might be an effective and optimized approach with solid efficacy in the induction and maintenance treatment of active CD.

Abstract Background It remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients. Methods We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events. Results In all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I2 = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I2 = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I2 = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO2. In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days. Conclusions COT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations.

BACKGROUND:Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE:To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS:MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting β2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS:Of 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS:MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Rationale: Spirometry reference equations that are derived from a large, nationally representative general population are warranted in China, and the impact of using prebronchodilator (pre-BD) and post-BD spirometry reference values has yet to be assessed in Chinese populations. Objectives: To present the pre-BD and post-BD spirometry reference values for Chinese adults using the China Pulmonary Health (CPH) Study. Methods: A reference population of 17,969 healthy, nonsmoking participants in the CPH Study was used to calculate the pre- and post-BD reference values for FEV1, FVC, and FEV1/FVC ratio. Pre- and post-BD reference values were applied to the entire CPH population (N = 50,991) to illustrate the divergence between the use of different references in determining disease prevalence and severity grading. Measurements and Main Results: The prevalences of airflow limitation were 5.36% using the pre-BD reference and 8.02% using the post-BD reference. Individuals who had a post-BD FEV1/FVC ratio lower than the post-BD reference value but higher than the pre-BD reference value were found to have significantly higher rates of self-reported respiratory symptoms and significantly lower values on spirometry indicators than those whose post-BD FEV1/FVC ratio was greater than the post-BD reference value. An additional 3.51% of participants were identified as having grade II-IV chronic obstructive pulmonary disease using the post-BD FEV1 predicted values. Conclusions: This study generated and applied pre- and post-BD spirometry reference values in a nationally representative Chinese adult population. Post-BD reference values may serve as an additional criterion in identifying individuals at risk for obstructive pulmonary diseases, and their diagnostic and prognostic values should be further investigated.