A severe tremor caused by a beta2 agonist in a patient with asthma-chronic obstructive pulmonary disease overlap.

A 46-year-old male developed respiratory distress due to asthma-chronic obstructive pulmonary disease overlap and experienced severe tremor caused by beta2 agonist inhalant. We present our successful experience with tizanidine administration.

Effects of plant protease inhibitors (Pep-3-EcTI, Pep-BbKI, and Pep-BrTI) versus corticosteroids on inflammation, remodeling, and oxidative stress in an asthma-COPD (ACO) model.

The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use.

Osteoporosis in Asthma and COPD.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are principally lifestyle related chronic inflammatory airway disease. They are globally associated with various systemic comorbidities and mortality. Osteoporosis is the common associated metabolic bone disease with respiratory disturbances, which affect the prognosis and increase mortality and morbidity in the patients. Apart from OSTEOPOROSIS, exhaustive attention has been paid towards other associated systemic comorbidities like cardiovascular diseases, cerebrovascular diseases, metabolic syndrome, malnutrition, skeletal muscle dysfunction (sarcopenia), anxiety, depression and so on (Iheanacho et al. in Int J Chronic Obstr Pulm Dis 15:439-460, 2020; Singh et al. in Eur Respir J 53:1900164, 2019). Osteoporosis is a significant extrapulmonary manifestation in asthma and COPD, which are grossly neglected and inadequately treated. The comorbidities have significant impact in terms of morbidity, mortality and economic burden in asthma and COPD patients, hence management of asthma and COPD should comprise thorough management, as this will also have an impact on the outcome of these patients. Various risk factors such as smoking, systemic inflammation, vitamin deficiency, and the use of oral or inhaled corticosteroid are responsible for osteoporosis in patients with asthma and COPD. The presence of osteoporosis in patients with asthma and COPD is invariably asymptomatic unless complicated by fragility fractures, therefore, it is necessary to explore the pathogenesis of osteoporosis in asthma and COPD and special attention is to be paid for early recognition of patients at high risk for osteoporosis in these patients. This chapter is focussed on osteoporosis as an extrapulmonary manifestation of asthma and COPD with an emphasis on the pathogenesis, risk factor, potential mechanism of osteoporosis, diagnosis, and prevention with passing reference to treatment as well in asthma and COPD patients.

Comparison of health-related quality of life measures in asthma-COPD overlap.

OBJECTIVE: The Asthma Quality of Life Questionnaire (AQLQ) and COPD assessment test (CAT) are used to assess the health status of asthma and chronic obstructive pulmonary disease (COPD), respectively. However, whether these questionnaires are appropriate in patients with asthma-COPD overlap (ACO) has not been reported. This study aimed to evaluate the performance of the AQLQ and CAT in subjects with ACO. METHODS: Subjects were enrolled from two previously described observational studies in Beijing, China. ACO was defined by a consensus definition from a roundtable discussion. All subjects completed the AQLQ, CAT, St George's Respiratory Questionnaire (SGRQ), pulmonary function tests, and the Asthma Control Questionnaire (ACQ)-5. Cross-sectional construct validity was evaluated by correlating the AQLQ and CAT with SGRQ score and other measures of asthma and COPD severity. RESULTS: 147 subjects with ACO were recruited. There were floor effects on non-respiratory components of the CAT, and ceiling effects on emotion domains of the AQLQ. Both questionnaires were significantly correlated with ACQ-5 score but were not correlated with FEV1% predicted or FVC% predicted. The AQLQ and CAT were strongly correlated with SGRQ score (r = -0.657 and r = 0.623, respectively). Multivariable linear regression analysis showed that the AQLQ (standardized ß-coefficient = -0.449, p < .001) had a stronger association with SGRQ score compared with CAT (standardized ß-coefficient = 0.211, p = .023). DISCUSSION: The AQLQ and CAT were both valid for assessing the health-related quality of life in subjects with ACO, but the AQLQ performed better than CAT.

Serum MMP3 and IL1-RA levels may be useful biomarkers for detecting asthma and chronic obstructive pulmonary disease overlap in patients with asthma.

Background: Asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) is characterized by concurrent features of asthma and COPD. Since disease pathogenesis, severities, and treatments differ between asthma and ACO, it is important to differentiate them. Objective: To clarify and compare the characteristics of ACO and asthma and identify the serum biomarkers for differentiating them, especially in older patients. Methods: This study used the data of 639 participants from the nationwide cohort study, the NHOM-Asthma study, an asthma registry in Japan, with complete information on smoking history, respiratory function, and serum biomarkers. ACO was defined as the self-reported comorbidity of COPD or emphysema, or with obstructive pulmonary function and smoking history (pack-years≥10). The clinical characteristics of patients with ACO and asthma without COPD were compared. The serum biomarkers for differentiation were examined using receiver operating characteristic curves and multivariable analysis. The associations between the biomarkers and age were also analyzed. Results: Of the 639 asthma patients, 125 (19.6%) were diagnosed with ACO; these patients were older and male-dominant and had a higher prevalence of comorbidities such as hypertension, diabetes, and stroke. Among the serum biomarkers that were significantly different between ACO and asthma without COPD, the YKL-40/CHI3L1, MMP3, and IL-1RA levels showed a high area under the curve for discriminating ACO. Only the MMP3 and IL-1RA levels were significantly higher among ACO patients, regardless of age and sex; the YKL-40/CHI3L1 levels were not different due to the effect of age. Conclusion: MMP3 and IL-1RA may be useful serum biomarkers for distinguishing ACO from asthma.

Investigating the Effects of a New Peptide, Derived from the Enterolobium contortisiliquum Proteinase Inhibitor (EcTI), on Inflammation, Remodeling, and Oxidative Stress in an Experimental Mouse Model of Asthma-Chronic Obstructive Pulmonary Disease Overlap (ACO).

The synthesized peptide derived from Enterolobium contortisiliquum (pep3-EcTI) has been associated with potent anti-inflammatory and antioxidant effects, and it may be a potential new treatment for asthma-COPD overlap-ACO). Purpose: To investigate the primary sequence effects of pep3-EcTI in an experimental ACO. BALB/c mice were divided into eight groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep3-EcTI (treated with inhibitor), ACO-DX (treated with dexamethasone), ACO-DX-pep3-EcTI (treated with dexamethasone and inhibitor), and SAL-pep3-EcTI (saline group treated with inhibitor). We evaluated the hyperresponsiveness to methacholine, exhaled nitric oxide, bronchoalveolar lavage fluid (BALF), mean linear intercept (Lm), inflammatory markers, tumor necrosis factor (TNF-α), interferon (IFN)), matrix metalloproteinases (MMPs), growth factor (TGF-ß), collagen fibers, the oxidative stress marker inducible nitric oxide synthase (iNOS), transcription factors, and the signaling pathway NF-κB in the airways (AW) and alveolar septa (AS). Statistical analysis was conducted using one-way ANOVA and t-tests, significant when p < 0.05. ACO caused alterations in the airways and alveolar septa. Compared with SAL, ACO-pep3-EcTI reversed the changes in the percentage of resistance of the respiratory system (%Rrs), the elastance of the respiratory system (%Ers), tissue resistance (%Gtis), tissue elastance (%Htis), airway resistance (%Raw), Lm, exhaled nitric oxide (ENO), lymphocytes, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, transforming growth factor (TGF)-ß, collagen fibers, and iNOS. ACO-DX reversed the changes in %Rrs, %Ers, %Gtis, %Htis, %Raw, total cells, eosinophils, neutrophils, lymphocytes, macrophages, IL-1ß, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, TGF-ß, collagen fibers, and iNOS. ACO-DX-pep3-EcTI reversed the changes, as was also observed for the pep3-EcTI and the ACO-DX-pep3-EcTI. Significance: The pep3-EcTI was revealed to be a promising strategy for the treatment of ACO, asthma, and COPD.

Higher Prevalence and Severity of Eosinophilic Otitis Media in Patients with Asthma-COPD Overlap Compared with Asthma Alone.

INTRODUCTION: Eosinophilic otitis media (EOM) is well-known to frequently co-exist with adult-onset asthma. Both diseases are similar type 2 inflammation and are considered to have a "one airway, one disease" relationship. Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO), characterized by airway obstruction caused by airway wall thickening (AWT), is a severe condition with a higher incidence of mortality compared to asthma alone or COPD alone. Based on the "one airway, one disease" concept, we hypothesized that the inflammatory pathophysiology of EOM differs depending on its comorbidity with ACO or with asthma alone. METHODS: A total of 77 chronic rhinosinusitis (CRS) patients with asthma were enrolled in this study. The subjects were divided into 2 groups: a group with comorbid asthma alone (asthma group; 46 patients), and a group with comorbid ACO (ACO group; 31 patients). The 2 groups were compared and assessed with regard to various factors, including the patients' clinical characteristics, prevalence rate of EOM, EOM severity, EOMs relationships with smoking and AWT, and the eosinophil and neutrophil cell counts in the middle ear effusion (MEE). RESULTS: The ACO group included significantly more males (p < 0.05), was significantly older (p < 0.05), and showed significantly lower lung function values (FEV1 [L], FEV1 [%pred]) (p < 0.01) compared with the asthma group. The ACO group also had a significant history of smoking as shown by the Brinkman index (p < 0.01) and greater AWT as assessed by high-resolution computed tomography (p < 0.05). The EOM prevalence rate was significantly higher in the ACO group (p < 0.05), especially with increased ACO severity (p < 0.05). The EOM severity was also significantly higher in the ACO group (p < 0.05) and also correlated with the ACO severity (p < 0.05). The pretreatment ear clinical characteristics score and the average air conduction hearing level were significantly higher in the ACO group (p < 0.05). The eosinophil percentage in the MEE/otorrhea was significantly lower in the ACO group (25.3%) than in the asthma group (54.7%) (p < 0.05). Conversely, the neutrophil percentage was significantly higher in the ACO group (75.7% vs. 41.9%) (p < 0.05). CONCLUSIONS: Our findings suggest that, in CRS patients with asthma, comorbidity with ACO may be a clinical factor leading to increased EOM prevalence and severity, as well as a higher neutrophil infiltration percentage in the middle ear. Cessation of smoking and early therapeutic intervention for ACO may mitigate progression of bronchial remodeling (i.e., reduce AWT) and help reduce the prevalence and severity of EOM.

Prospective Real-World Analysis of Asthma Patients With Preserved and Reduced Physical Activity.

BACKGROUND: Asthma is a highly heterogeneous airway disease, and the clinical characteristics of patients with asthma with preserved and reduced physical activity are poorly understood. OBJECTIVE: We aimed to investigate the risk factors and clinical phenotypes associated with reduced physical activity in a wide range of patients with asthma. METHODS: We conducted a prospective observational study of 138 patients with asthma, including patients with asthma without chronic obstructive pulmonary disease (COPD) (n = 104) and asthma-COPD overlap (n = 34), and 42 healthy controls. Physical activity levels were measured for 2 weeks using a triaxial accelerometer at baseline and 1 year later. RESULTS: Higher eosinophils and body mass index (BMI) were associated with reduced physical activity in patients with asthma without COPD. Cluster analysis of asthma without COPD revealed 4 asthma phenotypes. We identified a cluster with preserved physical activity (n = 43) that was characterized by good symptom control and lung function and included a high proportion of biologics users (34.9%). Multivariate regression analysis revealed that patients with late-onset eosinophilic (n = 21), high-BMI noneosinophilic (n = 14), and symptom-predominant asthma phenotypes (n = 26) had lower levels of physical activity than controls. Patients with asthma-COPD overlap also had significantly lower physical activity levels than controls. Similar trends in physical activity levels were observed in each asthma group at 1-year follow-up. CONCLUSION: This study showed the clinical features of patients with asthma with preserved and reduced physical activity. Reduced physical activity was observed in various asthma phenotypes and in asthma-COPD overlap.

The diabetic lung.

The coronavirus disease 2019 (COVID-19) pandemic drew our attention to the interplay between pulmonary health and diabetes. The impact of poorly controlled diabetes in worsening COVID-19 outcome is well-recognized. This article explores the broad spectrum of associations between the lung and diabetes. The lung can be the target of organ damage in diabetes, be the origin of a disease process affecting glycaemic status, and also contribute to metabolic complications. Diabetes can be a part of several pulmonary syndromes. Medications used for diabetes can adversely affect the lungs and vice versa. On the other hand, certain glucose-lowering drugs have the potential to improve respiratory function. The close link between diabetes and lung disease calls for a combined approach to managing these conditions.

Associação entre erosão dental e asma: uma revisão sistemática e meta-análise / Association between dental erosion and asthma: a systematic review and meta-analysis / Asociación entre erosión dental y asma: una revisión sistemática y meta-análisis

O objetivo desse plano de trabalho foi avaliar criticamente a evidência atual sobre a associação entre erosão dental e asma em crianças. Foi realizada uma revisão sistemática com estudos observacionais transversais do tipo caso-controle em crianças de 3 a 12 anos de idade. A pesquisa foi conduzida por dois revisores independentes (Kappa>0,8), em cinco bancos de dados eletrônicos primários, além de uma pesquisa de literatura cinzenta. O risco de viés dos artigos incluídos foi realizado usando o Joanna Briggs Institute Critical. Lista de verificação de avaliação para estudos transversais analíticos. RevMan 5.4 foi usado para gerar figura do risco de viés e realizar a meta- análise. A qualidade da evidência foi avaliada de acordo com o Classificação de Recomendações Avaliação, Desenvolvimento e Avaliação (GRADE). Cinco estudos foram incluídos para análise qualitativa, dos quais quatro foram incluídos para análise quantitativa, com total de 2047 crianças. Três dos trabalhos apresentaram moderado risco de viés, um com alto risco, e um com baixo risco de viés. A confiança na evidência foi classificada como "muito baixa". Concluiu-se que não há associação entre asma e erosão dental.

The aim of this study was to critically evaluate the current evidence on the association between dental erosion and asthma in children. A systematic review was carried out with case-control cross-sectional observational studies in children aged 3 to 12 years. The search was conducted by two independent reviewers (Kappa>0.8), across five primary electronic databases, in addition to a gray literature search. The risk of bias of included articles was performed using the Joanna Briggs Institute Critical. Evaluation checklist for analytical cross-sectional studies. RevMan 5.4 was used to generate the risk of bias figure and perform a meta-analysis. The quality of the evidence was assessed according to the Assessment, Development and Evaluation (GRADE) Recommendations Rating. Five studies were included for qualitative analysis, of which four were included for quantitative analysis, with a total of 2047 children. Three of the studies adopted moderate risk of bias, one with high risk, and one with low risk of bias. Confidence in the evidence was rated "very low". It was concluded that there is no association between asthma and dental erosion.

El objetivo de este plan de trabajo fue evaluar críticamente la evidencia actual sobre la asociación entre erosión dental y asma en niños. Se realizó una revisión sistemática con estudios observacionales transversales de casos y controles en niños de 3 a 12 años. La búsqueda fue realizada por dos revisores independientes (Kappa>0,8), en cinco bases de datos electrónicas primarias, además de una búsqueda en la literatura gris. El riesgo de sesgo de los artículos incluidos se realizó mediante el Joanna Briggs Institute Critical. Lista de verificación de evaluación para estudios transversales analíticos. Se utilizó RevMan 5.4 para generar la cifra de riesgo de sesgo y realizar el metanálisis. La calidad de la evidencia se evaluó de acuerdo con la Clasificación de recomendaciones de evaluación, desarrollo y evaluación (GRADE). Se incluyeron cinco estudios para el análisis cualitativo, de los cuales cuatro se incluyeron para el análisis cuantitativo, con un total de 2047 niños. Tres de los artículos tenían riesgo moderado de sesgo, uno con alto riesgo y uno con bajo riesgo de sesgo. La confianza en la evidencia se calificó como "muy baja". Se concluyó que no existe asociación entre el asma y la erosión dental.

Influence of GLCCI1 gene rs37973 polymorphism on the efficacy of ICSs in the treatment of asthma-chronic obstructive pulmonary disease overlap / 中国药房

OBJECTIVE To investigate the association between the functional GLCCI1 gene rs37973 polymorphism and inhaled corticosteroids （ICSs） response in patients with asthma-chronic obstructive pulmonary disease overlap （ACO）. METHODS Totally 173 newly diagnosed ACO patients were recruited from Shanghai Pudong New Area People’s Hospital during April 1st， 2019 to December 31st， 2020. All patients were treated with Salmeterol fluticasone inhalation powder， twice a day， for 24 weeks. The genotype of rs37973 locus was determined， and lung function indicators [forced expiratory volume in one second （FEV1）， FEV1/forced vital capacity （FVC）， the percentage of FEV1 to expected value （FEV1%pred）]， and lung function improvement （ΔFEV1 and ΔFEV1%pred） were all detected. RESULTS Totally 111 patients completed the whole 24-week follow-up and lung function detection. Among them， there were 42 cases of AA genotype， 52 cases of AG genotype， and 17 cases of GG genotype. After 12， 24 weeks of treatment， lung function indexes of patients were significantly better than baseline lung function indexes before treatment （P＜0.05）. After 24 weeks of treatment， ACO patients with AA and AG genotypes showed significantly better lung function improvement than GG genotype， and ΔFEV1%pred of AA genotype was significantly better than AG genotype （P＜ 0.05）. After 12， 24 weeks of treatment， the improvement of lung function in patients with a smoking history ≤20 pack year was significantly better than those with a smoking history ＞20 pack year， and among patients with a smoking history ≤20 pack year， only AA genotype had significantly better FEV1%pred than AG genotype （P＜0.05）. After 12 weeks of treatment， among patients with a smoking history ＞20 pack year， the improvement of lung function in AA genotype and AG genotype was significantly better than GG genotype， and the FEV1%pred in AA genotype was significantly better than AG genotype （P＜0.05）. After 24 weeks of treatment， the improvement of lung function of AA genotype and AG genotype was significantly better than GG genotype （P＜0.05）. CONCLUSIONS GG genotype of GLCCI1 gene rs37973 locus is associated with the poor treatment response to ICSs in patients with ACO， especially in patients with smoking history ＞20 pack year.

Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of "asthma and chronic obstructive pulmonary disease overlap" in the elderly.

BACKGROUND: Little is known about the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO). This study examined the molecular phenotypes of ACO in the elderly. METHODS: A genome-wide investigation of gene expression in sputum cells from the elderly with asthma, ACO, or COPD was performed using gene set variation analysis (GSVA) with predefined asthma- or COPD-specific gene signatures. We then performed a subsequent cluster analysis using enrichment scores (ESs) to identify molecular clusters in the elderly with ACO. Finally, a second GSVA was conducted with curated gene signatures to gain insight into the pathogenesis of ACO associated with the identified molecular clusters. RESULTS: Seventy elderly individuals were enrolled (17 with asthma, 41 with ACO, and 12 with COPD). Two distinct molecular clusters of ACO were identified. Clinically, ACO cluster 1 (N = 23) was characterized by male and smoker dominance, more obstructive lung function, and higher proportions of both neutrophil and eosinophil in induced sputum compared to ACO cluster 2 (N = 18). ACO cluster 1 had molecular features similar to both asthma and COPD, with mitochondria and peroxisome dysfunction as important mechanisms in the pathogenesis of these diseases. The molecular features of ACO cluster 2 differed from those of asthma and COPD, with enhanced innate immune reactions to microorganisms identified as being important in the pathogenesis of this form of ACO. CONCLUSION: Recognition of the unique biological pathways associated with the two distinct molecular phenotypes of ACO will deepen our understanding of ACO in the elderly.

The Role of Smoking in Asthma and Chronic Obstructive Pulmonary Disease Overlap.

Exposure to cigarette smoke has a key role in the development, adverse health outcomes, and impaired response to some therapies among individuals with features of asthma and chronic obstructive pulmonary disease overlap (ACO). To aid the identification of clinical subtypes, the description of ever smokers with features of asthma and COPD should include data on smoking status, cumulative smoking history, and the phenotype of asthma and smoking-related chronic airway disease. Pathogenic mechanisms in smoking-related ACO involve poorly understood, complex interactions between smoking-induced and asthma-induced airway inflammation, corticosteroid insensitivity, and tissue remodeling. Evidence for the clinical effectiveness of interventions for adults with smoking-related ACO is limited. Management currently involves the identification and targeting of treatable traits such as current smoking, type 2 high eosinophilic inflammation, symptomatic airflow obstruction, and extrapulmonary comorbidities.

The effectiveness of self-care interventions in chronic illness: A meta-analysis of randomized controlled trials.

OBJECTIVE: To characterize and explain variation in the comparative effectiveness of self-care interventions on relevant outcomes of chronic illness compared with controls. DESIGN: Meta-analysis and meta-regression. METHODS: Data extraction was framed within the context of a previously-published scoping review of randomized trials designed to enhance self-care in type 2 diabetes mellitus, heart failure, hypertension, asthma, coronary artery disease, and chronic obstructive pulmonary disease (published between 2008 and 2019). Data were pooled using random-effects meta-analyses. Meta-regression was used to test the effect of potential moderators on trial effectiveness. RESULTS: 145 trials involving 36,853 participants were included. Overall, the effect size of self-care interventions on improving outcomes was small (Hedges' g = 0.29 (95% CI = 0.25-0.33), p < 0.001) with statistically significant heterogeneity across trials (Q = 514.85, p < 0.001, I2 = 72.0%). A majority of trials (n = 83, 57.2%) were rated as having a high risk of bias. There was no statistically significant difference in trial effectiveness based on the use of theory, specific components of self-care addressed, the number of modes of delivery, the number of behavioral change techniques, specific modes of delivery, specific behavioral change techniques, intervention duration, total number of hours of intervention, or either participant age or gender. CONCLUSIONS: Self-care interventions are modestly effective in improving outcomes. Poor trial quality limits the strength of conclusions in this area of science. There is much to be done to enhance the design, conduct and reporting of self-care trials in order to gain more insight into the effectiveness of self-care interventions. TWEETABLE ABSTRACT: New review highlights poor trial design as major impediment to understanding the contribution of self -care to outcomes in chronic illness.

Unraveling the Pathogenesis of Asthma and Chronic Obstructive Pulmonary Disease Overlap: Focusing on Epigenetic Mechanisms.

Asthma and COPD overlap (ACO) is characterized by patients presenting with persistent airflow limitation and features of both asthma and COPD. It is associated with a higher frequency and severity of exacerbations, a faster lung function decline, and a higher healthcare cost. Systemic inflammation in COPD and asthma is driven by type 1 T helper (Th1) and Th2 immune responses, respectively, both of which may contribute to airway remodeling in ACO. ACO-related biomarkers can be classified into four categories: neutrophil-mediated inflammation, Th2 cell responses, arachidonic acid-eicosanoids pathway, and metabolites. Gene-environment interactions are key contributors to the complexity of ACO and are regulated by epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs. Thus, this review focuses on the link between epigenetics and ACO, and outlines the following: (I) inheriting epigenotypes without change with environmental stimuli, or epigenetic changes in response to long-term exposure to inhaled particles plus intermittent exposure to specific allergens; (II) epigenetic markers distinguishing ACO from COPD and asthma; (III) potential epigenetic drugs that can reverse oxidative stress, glucocorticoid insensitivity, and cell injury. Improved understanding of the epigenetic regulations holds great value to give deeper insight into the mechanisms, and clarify their implications for biomedical research in ACO.

Evaluation of sports ability to improve patients with pulmonary disease / Avaliação da habilidade no esporte para a melhoria de pacientes com doença pulmonar / Evaluación de la habilidad en el deporte para la mejoría de pacientes con enfermedad pulmonar

ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) is one of the most common diseases in the lungs. Objective: To evaluate the clinical effect of respiratory rehabilitation training combined with Traditional Chinese and western medicine on the clinical treatment of motor function in patients with COPD. Methods: 156 patients with chronic obstructive pulmonary disease admitted to a hospital from December 2013 to June 2015 were selected as study subjects and randomly divided into groups for treatment. Results: comparing blood gas exchange rates of patients in the four groups, the experimental group, trained using integrated Chinese and Western medicine, was significantly better than the control groups A, B and C, in aspects such as PaCO2, PaO2, SaO2, pH, etc., the difference was statistically significant (p < 0.05). The improvement of lung function in the experimental group was significantly better than in the other three groups, with statistical significance (p < 0.05). Conclusions: Applying Chinese and Western Medicine combined with comprehensive respiratory rehabilitation training has a significant clinical effect. It effectively improved patients' related clinical indicators and should be widely promoted. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A doença pulmonar obstrutiva crônica (DPOC) é uma das doenças pulmonares mais comuns. Objetivo: Avaliar os efeitos clínicos de treino para reabilitação respiratória somado ao uso de medicina ocidental e medicina tradicional chinesa combinadas, no tratamento da função motora de pacientes com DPOC. Métodos: 156 pacientes com DPOC, hospitalizados entre dezembro de 2013 e junho de 2015, foram selecionados como objetos de estudo e aleatoriamente divididos em grupos de tratamento. Resultados: Quanto aos níveis de troca gasosa dos pacientes nos quatro grupos, o grupo experimental, treinado por meio de práticas de medicina ocidental e de medicina tradicional chinesa combinadas teve uma performance significativamente melhor que a dos grupos A, B, e C, em aspectos tais como PaCO2, PaO2, SaO2, pH, etc., com significância estatística (p<0,05). A melhoria da função pulmonar no grupo experimental também foi significativamente maior que nos outros grupos, mais uma vez com significância estatística (p<0,05). Conclusões: A aplicação da medicina chinesa e da medicina ocidental combinadas, somadas a um treino de reabilitação respiratória abrangente, teve um efeito clínico significativo, efetivamente melhorando indicadores clínicos relevantes. Tal aplicação deveria ser largamente promovida. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) es una de las enfermedades pulmonares más comunes. Objetivo: Evaluar los efectos clínicos de entrenamiento para rehabilitación respiratoria sumado al uso de medicina occidental y medicina tradicional china combinadas en el tratamiento de la función motora de pacientes con EPOC. Métodos: 156 pacientes con EPOC, hospitalizados entre diciembre de 2013 y junio de 2015, fueron seleccionados como objetos de estudio y aleatoriamente divididos en grupos de tratamiento. Resultados: En cuanto a los niveles de intercambio gaseoso de los pacientes de los cuatro grupos, el grupo experimental, entrenado mediante prácticas combinadas de medicina occidental y medicina tradicional china, obtuvo un rendimiento significativamente mejor que los grupos A, B y C, en aspectos como PaCO2, PaO2, SaO2, pH, etc., con significancia estadística (p<0,05). La mejora de la función pulmonar en el grupo experimental también fue significativamente mayor que en los otros grupos, una vez más con significancia estadística (p<0,05). Conclusiones: La aplicación de la medicina china y de la medicina occidental combinadas, sumadas a un entrenamiento de rehabilitación respiratorio abarcativo, tuvo un efecto clínico significativo, efectivamente mejorando indicadores clínicos relevantes. Tal aplicación debería ser largamente promovida. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Cigarette Smoking and Asthma.

Globally, around half the adult asthma population are current or former cigarette smokers. Cigarette smoking and asthma interact to induce an "asthma-smoking phenotype(s)," which has important implications for diagnosis, pathogenic mechanisms, and management. The lack of progress in understanding the effects of smoking on adults with asthma is due in part to their exclusion from most investigative studies and large clinical trials. In this review, we summarize the adverse clinical outcomes associated with cigarette smoking in asthma, highlight challenges in diagnosing asthma among cigarette smokers with chronic respiratory symptoms, particularly in older individuals with a long-standing smoking history, and review pathogenic mechanisms involving smoking- and asthma-related airway inflammation, tissue remodeling, corticosteroid insensitivity, and low-grade systemic inflammation. We discuss the key components of management including the importance of smoking cessation strategies, evidence for the effectiveness of the Global Initiative for Asthma recommendations on treatment in cigarette smokers, and the role of treatable traits such as type 2 eosinophilic airway inflammation. Lastly, we provide an algorithm to aid clinicians to manage current and former smokers with asthma. In the future, controlled and pragmatic trials in real-world populations should include cigarette smokers with asthma to provide an evidence base for treatment recommendations.

Mucus Plugs and Small Airway Dysfunction in Asthma, COPD, and Asthma-COPD Overlap.

PURPOSE: There are reports concerning mucus plugs detected on high-resolution computed tomography images and airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). However, little is known about the associations between mucus plugs and small airway dysfunction (SAD). We evaluated the relationship between mucus plugs and pulmonary function in patients with asthma, COPD, and asthma-COPD overlap (ACO), and investigated the relevance to SAD and type 2 inflammation in a retrospective study. METHODS: Subjects included 49 asthmatic, 40 ACO, and 41 COPD patients. ACO was diagnosed based on the Japanese Respiratory Society ACO guidelines. Clinical and laboratory parameters, including blood eosinophil count, serum total IgE levels, fractional exhaled nitric oxide (FeNO), spirometry, and forced oscillation technique (FOT), were compared between patients with and without mucus plugs. RESULTS: Mucus plugs were found in 29 (59%) asthmatic, 25 (65%) ACO, 17 (41%) COPD patients. Patients with mucus plugs had reduced spirometry and larger FOT parameters, especially in COPD patients. Mucus scores correlated positively with IgE in ACO and FeNO in asthmatic patients, but not in COPD patients. Multivariate logistic regression analysis revealed that SAD parameters, including forced vital capacity and resonant frequency, a respiratory reactance parameter, were significantly associated with the presence of mucus plugs in the whole studied population. CONCLUSIONS: SAD, rather than large airway dysfunction, was associated with mucus plugs in asthma, ACO, and COPD patients.

Prevalence and impact of airway diseases on clinical outcomes in idiopathic pulmonary fibrosis.

BACKGROUND/AIMS: The prevalence and effects of airway diseases, including asthma, eosinophilic bronchitis (EB), chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) have not been thoroughly studied in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to evaluate the prevalence of airway diseases in patients with IPF and to identify the differences in symptoms based on the presence of airway diseases. METHODS: This single-institution prospective cohort study was conducted from June 2017 to September 2018, at the Seoul National University Hospital. Spirometry with bronchodilator, methacholine bronchial provocation test, induced sputum with eosinophil stain, and exhaled nitric oxide were performed to confirm the presence of airway disease. The modified Medical Research Council (mMRC) dyspnea scale, COPD assessment test (CAT), St. George's Respiratory Questionnaire (SGRQ), EuroQol-5 dimension (EQ-5D) index, and cough-specific quality of life questionnaire (CQLQ) data were collected to assess symptom severity. RESULTS: Total 147 patients with IPF were screened, and 70 patients were analyzed. The prevalence of airway diseases in the participants was as follows: 5.0% had COPD, 1.7% had asthma, 3.3% had ACO, and 1.7% had EB. The mMRC, CAT, SGRQ, EQ-5D, and CQLQ scores did not differ regardless of combined airway disease. After 3 months, the SGRQ (p = 0.028) and CQLQ (p = 0.030) scores were significantly higher in patients with airway disease than in those without. CONCLUSION: The prevalence of airway diseases in patients with IPF is low, but when airway diseases are accompanied by IPF, symptom severity and quality of life may worsen rapidly.

Asthma and COPD Overlap Syndrome (ACOS): Risk Factors and Contributing Factors.

Background:The exact description of asthma and chronic obstructive pulmonary disease overlap syndrome (ACOS) is uncertain. This study aims to determine the frequency and symptoms of ACOS and to verify certain risk factors associated with ACOS. Methods:Severe asthmatic patients with and without ACOS above 40 years old participated in this cross-sectional study. The receiver operating curve analysis (ROC) was used to assess the best cutoff values of age, body mass index (BMI), and spirometric data to distinguish asthma patients with overlap syndrome from asthma patients without overlap syndrome. Univariable and multivariable binary logistic regression was used to determine demographic and clinical factors that were associated with ACOS and asthma. Results:Of the 88 patients, 46 (52.2%) had ACOS and 42 (47.7%) had just severe asthma. The mean age of ACOS patients (Sd) was 54.91(12.57) years and in asthma-only patients was 48.69 (13.51). The ROC analysis for age and BMI showed that age ⩾ 49 years and BMI ⩾ 27 kg/m2were the best predictors of ACOS in this study. Spirometry data showed that the forced vital capacity (FVC) (lit) > 2.16, forced expiratory volume in the first second (FEV1) > 69, FEV1 / FVC > 96.5, and FVC (%) > 63 cut points could be used to determine the diagnostic criteria between ACOS and asthma only, respectively. Multivariate modeling showed that among the demographic and clinical variables, only age over 49 years (odds ratio [OR], 3.53 [95% CI, 1.07-11.63]p= 0.025) and living in a big city (OR, 7.42 [95% CI, 1.75-31.49]p= 0.007) were significant. Conclusion:Age over 49 and BMI above 27 have a significant association with ACOS. Also, living in a big city is considered to be another risk factor for ACOS compared with asthma. Spirometry can help distinguish ACOS from severe asthma in this study.