asthma-COPD Overlap Research Articles

Prevalence and Associated Factors of Suboptimal Daily Peak Inspiratory Flow and Technique Misuse of Dry Powder Inhalers in Outpatients with Stable Chronic Airway Diseases.

PurposeThe present study aimed to investigate the prevalence and associated factors of suboptimal daily peak inspiratory flow (PIF) and technical misuse of three commonly used dry powder inhalers (DPIs) in outpatients with stable chronic airway diseases.Patients and MethodsIncluded in this study were 85 outpatients with stable asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD Overlap (ACO) and had previously used any of Turbuhaler® (TUR), Diskus® (DIS), HandiHaler® (HAN) between December 2018 and September 2019. The patient’s daily PIF against the resistance of a specific DPI and operation technique was investigated by two pharmacists by using In-Check DIAL G16 and a checklist.ResultsOf the 85 patients, the proportion of patients with a suboptimal daily PIF and technical misuse was 38.8% and 65.9%, respectively. In logistic regression, we observed that the factors that increase the risk for suboptimal daily PIF were age (OR=1.06) and combination with respiratory diseases (OR = 6.59). The factor that decreases the risk for misuse was the higher education level (OR =0.63).ConclusionEven if patients have received training at the time of initial prescription, the standardization of the use of DPIs by patients in our center was still unoptimistic. Age and combined with respiratory diseases were associated with suboptimal PIF. Higher education level decreased the incidence of technique misuse.

The Plasma Levels of hsa-miR-19b-3p, hsa-miR-125b-5p, and hsamiR- 320c in Patients with Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS).

Bronchial Asthma (BA) and Chronic Obstructive Pulmonary Disease (COPD) are chronic airway inflammation diseases. In recent years, patients with signs of both BA and COPD have been assigned to a separate group as Asthma-COPD Overlap Syndrome (ACOS). Free-circulating plasma microRNAs are considered as potential biomarkers of pulmonology diseases, including BA, COPD, and ACOS. This study aimed to investigate the expression level of free-circulating plasma microRNAs, hsa-miR-19b-3p, hsa-miR-125b-5p, and hsa-miR-320c in patients with BA, COPD and ACOS for the detection and validation of new microRNAs as biomarkers for chronic lung diseases. The relative expression levels of 720 microRNAs were evaluated by Real Time-Polymerase Chain Reaction (RT-PCR) in patients with COPD and BA. Three upregulated microRNAs (hsa-miR-19b-3p, hsa-miR-125b-5p and hsa-miR-320c) were selected for further study. The obtained data were analyzed using the microRNA PCR Array Data Analysis tool. The sensitivity and specificity were estimated using the area under the Receiver Operating Characteristics curve (ROC). The expression level of free-circulating hsa-miR-19b-3p was decreased in the blood plasma of patients with BA and ACOS, and increased in patients with COPD. hsa-miR-125b-5p was downregulated in the blood plasma of patients with COPD and upregulated in patients with BA and ACOS. hsa-miR-320c was downregulated in the blood plasma of patients with BA, and upregulated in patients with COPD and ACOS. The ROC curves of patients with BA for hsa-miR-19b-3p, patients with ACOS for hsa-miR-125b-5p, and patients with COPD for hsa-miR-320c revealed the probability of them as valuable biomarkers with AUCs of 0.824, 0.825, and 0.855, respectively. Our study revealed three promising biomarkers for the diagnosis of COPD, BA and ACOS.

Lung Cancer Risk among Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap.

Rationale: Chronic obstructive pulmonary disease (COPD) is a well-established independent risk factor for lung cancer; however, the literature on the association between asthma and lung cancer is mixed. Whether asthma-COPD overlap (ACO) is associated with lung cancer has not been studied. Objectives: We aimed to compare lung cancer risk among patients with ACO versus COPD and other conditions associated with airway obstruction. Methods: We studied 13,939 smokers from the National Lung Cancer Screening Trial who had baseline spirometry and used spirometric indices and history of childhood asthma to categorize participants into five specific airway disease subgroups. We used Poisson regression to compare unadjusted and adjusted lung cancer risk. Results: The incidence rate of lung cancer per 1,000 person-years was as follows: ACO, 13.2 (95% confidence interval [CI], 8.1-21.5); COPD, 11.7 (95% CI, 10.5-13.1); asthmatic smokers, 1.8 (95% CI, 0.6-5.4); Global Initiative for Chronic Obstructive Lung Disease-Unclassified, 7.7 (95% CI, 6.4-9.2); and normal spirometry smokers, 4.1 (95% CI, 3.5-4.8). Patients with ACO had increased adjusted risk of lung cancer compared with patients with asthma (incidence rate ratio [IRR], 4.5; 95% CI, 1.3-15.8) and normal spirometry smokers (IRR, 2.3; 95% CI, 1.3-4.2) in models adjusting for other risk factors. Adjusted lung cancer incidence in patients with ACO and COPD were not found to be different (IRR, 1.2; 95% CI, 0.7-2.1). Conclusions: The risk of lung cancer among patients with ACO is similar to those with COPD and higher than other groups of smokers. These results provide further evidence that COPD, with or without a history of childhood asthma, is an independent risk factor for lung cancer.

ACO (Asthma-COPD Overlap) Is Independent from COPD, a Case in Favor: A Systematic Review.

Asthma and chronic obstructive pulmonary disease (COPD) are now recognized to be able to co-exist as asthma–COPD overlap (ACO). It is clinically relevant to evaluate whether patients with COPD concurrently have components of asthma in primary care. This is because: (i) ACO is a relatively common condition among asthma (over 40 years of age) or COPD irrespective of its diagnosis criteria; (ii) patients with ACO can have higher frequency of exacerbation and more rapid decline in lung function than those with asthma or COPD; and (iii) asthmatic features such as eosinophilic airway inflammation are promising indicators for prediction of inhaled corticosteroid-responsiveness in COPD. The aim of this review to evaluate diagnostic markers for ACO. We searched PubMed for articles related to ACO published until 2020. Articles associated with diagnostic biomarkers were included. We identified a total of 25 studies, some of which have revealed that a combination of biomarkers such as fractional exhaled nitric oxide and serum immunoglobulin E is useful to discern type 2 inflammation in the airways of COPD. Here, we review the current understanding of the clinical characteristics, biomarkers and molecular pathophysiology of ACO in the context of how ACO can be differentiated from COPD.

Characteristics of inflammatory phenotypes among patients with asthma: relationships of blood count parameters with sputum cellular phenotypes

BackgroundThere is a need to identify the asthma inflammatory phenotypes of patients to facilitate personalized asthma treatment. Sputum induction is time-consuming and requires expert clinical technique. This study aimed to assess the distribution and characteristics of asthma inflammatory phenotypes in Jilin Province, China; it also aimed to identify an easier method for characterization of an asthma phenotype, rather than sputum cellular analysis.MethodsIn this study, 232 asthma patients underwent sputum induction following clinical assessment and blood collection. Inflammatory cell counts in sputum were used to classify asthma inflammatory phenotypes. Receiver operating characteristic curve and Spearman correlation coefficient analyses were used to identify correlations between clinical parameters.ResultsAmong the included patients, there had 52.1% paucigranulocytic, 38.4% eosinophilic, 4.3% neutrophilic, and 5.2% mixed granulocytic asthma phenotypes, respectively. In total, 129 (55.6%) patients had asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO); these patients had higher proportion of smokers, higher sputum neutrophil count, worse lung function, and worse asthma control, compared with patients who had asthma alone (p < 0.05). Sputum eosinophil/neutrophil counts were positively correlated with blood eosinophil/neutrophil counts (p < 0.01). To identify the presence of sputum eosinophil proportion ≥ 3%, optimal cut-off values for blood eosinophil count and fractional exhaled nitric oxide (FeNO) were 0.2 × 109/L and 30.25 ppd (area under the curve (AUC) = 0.744; AUC = 0.653, p < 0.001). AUCs did not significantly differ between FeNO and blood eosinophil count (p = 0.162), but both exhibited poor specificity (57% and 49%, respectively). To identify the presence of sputum neutrophil proportion ≥ 61%, the optimal cut-off value for blood neutrophil proportion was 69.3% (AUC = 0.691, p = 0.0003); however, this exhibited poor sensitivity (50%).ConclusionsPaucigranulocytic asthma was the most common phenotype, followed by eosinophilic asthma. Higher proportion of smokers, poor patient compliance, insufficient treatment, and poor asthma control may have been the main causes of high ACO proportion among patients in this study. Blood eosinophil/neutrophil counts exhibited poor specificity and sensitivity for prediction of airway eosinophilic/neutrophilic inflammation.

Asthma-COPD Overlap: A more Simplistic Approach

Obstructive pulmonary diseases are a group of respiratory conditions characterized by airflow limitation. They are prevalent in the population and lead to significant morbidity and mortality. The two most commonly encountered conditions are asthma and Chronic Obstructive Pulmonary Disease (COPD). Although, for many years, the two conditions were regarded as separate, it was realized that some patients may have an overlap between these illnesses. This observation led to the identification of asthma-COPD overlap (ACO) syndrome. ACO is an umbrella term that is used “to collectively describe patients who have persistent airflow limitation together with clinical features that are consistent with both asthma and COPD”. Its importance in the field of respiratory medicine is increasing every year as there are more data that underline the importance of its timely diagnosis and management. The current review is a timely update of the advances in our understanding of ACO.

Distant Compliance with Treatment in Patients with Chronic Respiratory Diseases: Asthma, Copd and Asthma-Copd Overlap Syndrome. Prospective Study

Abstract Medications prescribed for chronic diseases such as asthma, chronic obstructive pulmonary disease (COPD) or asthma-COPD overlap (ACO) syndrome should be administered in the long term and compliance becomes a health care concern. Noncompliance adversely affects the outcome of treatment and results in the consumption of human and material resources. The aim of our study was to identify the factors that cause non-compliance with treatment in children, adolescents, and adults with asthma/COPD/ACO in Romania, the methods by which these factors can be understood and corrected, and the evaluation of symptoms. To achieve the goal, regular visits were carried out with symptom control questionnaires (Asthma Control Test (ACT), COPD Assessment Test (CAT)) and FEV1 evaluation using spirometry. The results obtained indicate low long-term compliance (12.35%) due to patients’ abstinence from regular check-ups. In conclusion, we can say that the factors related to doctors have been successfully corrected, but it remains a challenge in correcting the factors related to patients and the health regime.

Syk-Targeted, a New 3-Arylbenzofuran Derivative EAPP-2 Blocks Airway Inflammation of Asthma-COPD Overlap in vivo and in vitro.

IntroductionAsthma–chronic obstructive pulmonary (COPD) overlap (ACO) coexists with asthma and COPD syndrome characteristics, with more frequent exacerbations, heavier disease burden, higher medical utilization, and even lower quality of life. However, the ACO standard medications supported by evidence-based medicine have not yet appeared.MethodsBy using an ACO mouse model established previously and LPS-stimulated RAW264.7 macrophages in vitro, a potential therapeutic candidate, EAPP-2, was screened from derivatives of 3-arylbenzofuran, and its effect and mechanism on ACO inflammation were evaluated.ResultsEAPP-2 significantly alleviated airway inflammation in ACO mice and also inhibited the inflammatory reactions in LPS-induced RAW264.7 macrophages in vitro. Furthermore, EAPP-2 significantly inhibited the expression and phosphorylation of spleen tyrosine kinase (Syk), a common target regulating both eosinophils and neutrophils inflammation. In addition to this, EAPP-2 significantly down-regulates the expression of NF-κB, p-NF-κB, and NLRP3 in vivo and in vitro. Moreover, by using specific inhibitors in vitro, it was validated that EAPP-2 targeted on Syk and then regulated its downstream NF-κB and NLRP3.ConclusionEAPP-2 is shown to be a potentially useful therapeutic candidate for ACO, and its mechanism is at least partially achieved by targeting on Syk and then inhibiting NF-κB or NLRP3. Moreover, this study suggests that Syk may be a potentially effective target for ACO therapy.

The prevalence of Asthma-Copd Overlap Syndrome In Women Patients With Biomass Fuel Utilizing

Objective: Asthma-chronic obstructive pulmonary disease overlap (ACO) indicates that its characteristics with pulmonary exaggerated reactivity and airflow limitation chronically. We aimed to investigate the differences among women non smoker participants who have asthma, chronic obstructive pulmonary disease (COPD) and ACO with biomass smoke exposure.&#x0D; Method: Patients were examined at the outpatient clinic from September 2017 to March 2020. Non-smoker women patients aged ≥40 years, diagnosed with obstructive pulmonary disease were included in the study. pulmonary function tests (PFT), early reversibility testing (bronchodilator test), and sputum eosinophil analysis were performed to all patients.&#x0D; Results: A total of 102 patients were included. The mean age was 46.95±9.50 years. In the differential diagnosis, 65 patients (63.7%) had asthma and 37 patients (36.3%) had COPD. Among COPD patients, 10 (27.0%) were diagnosed with ACO. The actual prevalence rates of COPD and ACO were 26.5% and 9.8%, respectively. Poisson regression analysis showed that COPD compared to asthma, while holding the others variable constant in the model, are expected to have 2.976 times greater rate for exacerbations.( IRR, 95%CI ,2.976 (0.687 to 1.494), 5.296 (1.203 to 2.130), P&lt;0.001, Coef. 1.091, 1.667 respectively). Logistic Regression analysis demonstrated that, the count of sputum, blood eosinophil and total IgE results were correlated with the exacerbation times.&#x0D; Conclusion: Biomass smoke exposure in the women population is revealed as a significant factor for the diagnosis of ACO.

Economic Burden of Asthma-Chronic Obstructive Pulmonary Disease Overlap among Older Adults in the United States

The objective of this study is to estimate the excess economic burden of Asthma-COPD Overlap (ACO) among older adults in the United States. We used a cross-sectional study design with data from a nationally representative survey of Medicare beneficiaries (Medicare Current Beneficiary Survey) linked to Medicare fee-for-service claims. Older adults with ACO had higher average total healthcare expenditures ($45,532 vs. $12,743) and higher out-of-pocket spending burden (19% vs. 8.5%) compared to those with no-asthma no-COPD (NANC). Individuals with ACO also had almost two, and 1.5 times higher expenditures compared to individuals with asthma only and COPD only, respectively. Multivariable regression models indicated that the adjusted associations of ACO to economic burden remained positive and statistically significant. In comparison with NANC, nearly three-quarters of the excess total healthcare expenditures and 83% of the out-of-pocket spending burden of older adults with ACO were explained by differences in predisposing, enabling, need, personal healthcare practices, and external factors among the two groups. The higher number of unique medications and the increased incidence of fragmented care were the leading contributors to the excess economic burden among older adults with ACO comparing to NANC individuals. Interventions that reduce the number of medications and fragmented care have the potential to reduce the excess economic burden among older adults with ACO.

Analysis of the clinical efficacy and safety of bronchial thermoplasty in the treatment of patients with severe asthma and asthma-chronic obstructive pulmonary disease overlap

Objective: To investigate the clinical efficacy and safety analysis of bronchial thermoplasty (BT) in the treatment of severe asthma and asthma-chronic obstructive pulmonary disease overlap. Methods: The clinical data of 49 patients with asthma-COPD overlap who received BT in the University of Chinese Academy of Sciences Shenzhen Hospital from January 2016 to December 2018 and 50 patients with severe asthma who received BT in the same period were retrospectively analyzed. Patients were divided into overlap group and asthma group, and the baseline data of two groups were recorded. The pulmonary function before and after treatment (including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1 as a percentage of predicted value (FEV1% pred)), hormone consumption, asthma control test (ACT) score, asthma quality of life questionnaire (AQLQ) score, asthma control questionnaire (ACQ) score, the overlap group before and after treatment COPD assessment test (CAT) score, modified British Medical Research Council (mMRC) score and postoperative respiratory adverse events in the next 3 weeks were comparatively analyzed. Results: The general baseline characteristics of the two groups are compared. The patients in the overlap group were older than those in the asthma group, and the course of disease and smoking history were longer than those in the asthma group. The inhaled hormone dosage in asthma group was greater than those in the overlap group ((64±11) years vs (48±11) years; 10.00 (10.00, 25.00) years vs 9.00 (1.75, 20.00) years; 20.00(2.00, 40.00) years vs 0 (0, 10.00) years; 320 (320, 640) μg/d vs 960 (320, 960) μg/d) (all P<0.05). The predicted values of lung function indexes FVC, FEV1, FEV1% pred in the overlap group before treatment were all lower than those in the asthma group (1.98 (1.43, 2.43) L vs 2.54 (2.02, 3.15) L; 0.92 (0.61, 1.26) L vs 1.69(1.17, 2.16) L; (50±16) L vs (65±14) L) (all P<0.05). There were no significant differences in ACT, ACQ, and AQLQ scores between the two groups before treatment (all P>0.05). Within 3 months after treatment, except for no significant improvement in FEV1% predicted value and inhaled hormone dosage in the overlap group (all P>0.05), other indexes in both groups were improved compared with those before treatment (all P<0.05). After 1 year of treatment, all indexes of the two groups were significantly improved than those before treatment, and all indexes of the asthma group were better than those of the overlap group (all P<0.05). In terms of respiratory adverse events occurring within 3 weeks after the operation, the incidence of cough and bloody sputum in the overlap group was higher than that in the asthma group, while the incidence of sputum and short-term wheezing was lower than that in the asthma group (all P<0.05). There were no statistically significant differences in the incidence of chest tightness, chest pain, segmental atelectasis and pneumonia between the two groups (all P>0.05), and the postoperative adverse reactions could be effectively controlled in a short period of time. Conclusion: BT treatment could not only improve the lung function, clinical symptoms and quality of life of asthmatic patients, but was also effective for asthma-COPD overlap patients. However, BT treatment had more benefits for asthmatic patients without serious adverse events occurred.

Comparative RNA-Seq Transcriptome Analysis on Pulmonary Inflammation in a Mouse Model of Asthma-COPD Overlap Syndrome.

Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is a severe clinical syndrome characterized to describe patients with both asthma and COPD clinical characteristics, which has posed a serious threat to patients’ quality of life and life safety. However, there are many difficulties and uncertainties in its diagnosis and treatment in clinic; especially, its animal model has not been fully and thoroughly established, and the evaluation of therapeutic drugs is still in its infancy. Here, we used ovalbumin (OVA), lipopolysaccharide (LPS), and smoke costimulation to establish an ACO mouse model and then used RNA-seq technology to detect gene expression in mouse lung tissue. The results showed that ACO mice showed an overlap syndrome of asthma and COPD in lung histological changes and the levels of inflammatory cytokines in bronchoalveolar lavage fluid. The RNA-seq analysis results showed that 6,324 differentially expressed genes (DEGs) were screened between the ACO group and the control group, of which 2,717 (42.7%) were downregulated, and 3,607 (57.3%) were upregulated. Metascape analysis results showed that in the ACO model we established, due to the damage of the respiratory system, the accumulated diseased tissue involves lung, spleen, blood, bone marrow, thymus, etc. It has certain characteristics of pneumonia, pulmonary fibrosis, and chronic obstructive airway disease, lung tumors, rheumatoid arthritis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were enriched in inflammation, immune system activation and imbalance, cell proliferation, and adhesion migration, and the upstream signaling pathways of inflammation were mainly affected by HLA-DRA, SYK, CTLA4, VAV1, NRAS, and JAK3. In short, our research established a mouse model that can better simulate the clinicopathological characteristics of ACO and suggested the foundations in elucidating the molecular mechanisms for pulmonary inflammation and fibrosis in ACO. This work may help further research and contribute substantially to prevention and clinical treatment of ACO in the future.

Treatment Pathways Before and After Triple Therapy in COPD: A Population-based Study in Primary Care in Spain

BackgroundRecent data from real world clinical practices on the use of Triple Therapy (TT) in patients with COPD are scarce. MethodsObservational population-based study with longitudinal follow-up in patients with COPD identified in a primary care electronic medical records database in Catalonia, covering 80% of the general population. The aims were to characterize COPD patients who initiated TT and to describe treatment pathways before and after TT initiation. Time to and probability of step down or complete discontinuation of TT was described using restricted mean survival time and Kaplan•Meier analysis. ResultsA total of 34,018 COPD patients initiated TT during the study period. Of them, 23,867 (70.1%) were GOLD A/B. 18,453 (54.2%) were non-exacerbators, 9931 (29.2%) infrequent exacerbators, 5634 (16.5%) frequent exacerbators and 1923 (5.6%) had asthma-COPD overlap. Drugs most frequently used prior to initiation of TT were long-acting antimuscarinics (22.5%) and combination of long-acting beta2 agonists/inhaled corticosteroids (15.2%). A total of 11,666 (34.3%) stepped down and 1091 (3.2%) discontinued TT during follow-up. Step down following TT was more likely in patients with severe COPD, especially during the first year; however, discontinuation was more common among patients with mild COPD. ConclusionMost patients initiating treatment with TT were non exacerbators and continued on the same treatment over time regardless severity of disease. Stepping down was more frequent in severe patients, while discontinuation was more common among mild patients. Overall, it appears that TT is extensively used in primary care for treatment of patients with COPD.

Metformin use and respiratory outcomes in asthma-COPD overlap

BackgroundMetformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored.ObjectiveTo determine the association between metformin use and respiratory outcomes in COPD and ACO.Study design and methodsParticipants with COPD (FEV1/FVC < 0.70) in the Genetic Epidemiology of COPD study (COPDGene®) were categorized as ACO (n = 510), defined as concurrent physician-diagnosed asthma before age 40 years, or COPD alone (n = 3459). We estimated the association of baseline metformin use with (1) rate of total and severe respiratory exacerbations during follow-up, (2) cross-sectional St. George’s Respiratory Questionnaire (SGRQ) score, six-minute walk distance (6MWD), and post-bronchodilator FEV1 percent predicted (FEV1pp), and (3) 5-year change in SGRQ, 6MWD, and FEV1pp. We also examined change in SGRQ, 6MWD and FEV1pp among participants who initiated metformin during follow-up (n = 108) compared to persistent metformin non-users (n = 2080). Analyses were adjusted for sociodemographic factors, medications, and comorbidities.ResultsAmong participants with ACO, metformin use was associated with lower rate of total (adjusted incidence rate ratio [aIRR] 0.3; 95% confidence interval [95%CI] 0.11, 0.77) and severe exacerbations (aIRR 0.29; 95%CI 0.10, 0.89). Among participants with COPD alone, there was no association between metformin use with total (aIRR 0.98; 95%CI 0.62, 1.5) or severe exacerbations (aIRR 1.3; 95% CI 0.68, 2.4) (p-interaction < 0.05). Metformin use was associated with lower baseline SGRQ score (adjusted mean difference [aMD] − 2.7; 95%CI − 5.3, − 0.2) overall. Metformin initiation was associated with improved SGRQ score (aMD –10.0; 95% CI − 18.7, − 1.2) among participants with ACO but not COPD alone (p-interaction < 0.05). There was no association between metformin use and 6MWD or FEV1pp in any comparison.ConclusionsMetformin use was associated with fewer respiratory exacerbations and improved quality of life among individuals with ACO but not COPD alone. Results suggest a potential role for metformin in ACO which requires further prospective study.Trial Registry: NCT00608764

The autoreactivity phenomenon in the pathogenesis of asthma-COPD overlap (ACO)

The modern concept of development of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) implies the leading role of immune reactions with the true inflammatory autoimmune pathogenetic components. Aim of the study was to evaluate the autoreactivity in patients with chronic immune-mediated respiratory diseases: BA, COPD, and their combination — ACO. Methods. The study enrolled 155 patients with the average age of 49 ± 17 years old. We modified quantitative ELISA for detection of IgE and IgG4-autoantibodies using commercial tissue antigens of epithelial keratin, type III and VI collagen, myosin and elastin (Sigma, USA), conjugates of monoclonal anti-IgE or anti-IgG4 antibodies and IgE and IgG4 reference reagents (Dr. Fooke, Germany). Results. Concomitant COPD and BA symptoms were accompanied by significantly higher levels of IgE autoAbs to epithelial keratin, type III and VI collagen and myosin and were associated with a higher detection rate of these Abs, especially in severe forms of the disease (50 — 80%). The IgE-autoAbs to myosin increased in individuals with ACO as compared to BA and reached the maximum values in patients with COPD. There was an opposite trend: the frequency of detection and concentration of IgG4-autoAbs decreased with the disease severity. The levels of IgG4-autoAbs to type III and IV collagens and to elastin decreased as the obstruction worsened and were undetectable in patients with COPD and ACO. IgE and IgG4 autoAbs were inversely correlated to type VI collagen, type III collagen, elastin and myosin (r = -0.38; -0.61). The spirometry showed the inverse correlations between the increased IgE-autoAbs to type III collagen and high-speed ventilation parameters (R = -0.79; p = 0.01). So, IgE-autoAbs may be considered a factor of the progressive course of BA in combination with COPD associated with a significant bronchial obstruction. Conclusion. Thus, the detection of IgE and IgG4-AT to tissue antigens of collagen, elastin and myosin can be further used for clinical and immunological monitoring of BA and COPD, especially with their combined phenotype (ACO). The increased levels of IgE-autoAbs can be considered one of the immunological prognostic markers of intense remodeling processes in the bronchial wall. These processes are also confirmed by an increased IgE-mediated immune response to miosine and elastine EG in patients with the severe disease. The developed assay of the level of autoAbs to tissue antigens can be used in the early diagnostics of adverse course of asthma, especially ACO, and can be used as a laboratory criterion of the control over the disease when making decisions on personalized pharmacotherapy and patient management.

Asthma-COPD overlap: current understanding and the utility of experimental models.

Pathological features of both asthma and COPD coexist in some patients and this is termed asthma-COPD overlap (ACO). ACO is heterogeneous and patients exhibit various combinations of asthma and COPD features, making it difficult to characterise the underlying pathogenic mechanisms. There are no controlled studies that define effective therapies for ACO, which arises from the lack of international consensus on the definition and diagnostic criteria for ACO, as well as scant in vitro and in vivo data. There remain unmet needs for experimental models of ACO that accurately recapitulate the hallmark features of ACO in patients. The development and interrogation of such models will identify underlying disease-causing mechanisms, as well as enabling the identification of novel therapeutic targets and providing a platform for assessing new ACO therapies. Here, we review the current understanding of the clinical features of ACO and highlight the approaches that are best suited for developing representative experimental models of ACO.

Work absence in patients with asthma and/or COPD: a population-based study

Chronic obstructive pulmonary disease (COPD) and asthma impact on work productivity, but their population-based burden and clinical predictors are understudied. In this observational, real-life study, work absence of 14,383 asthma and/or COPD patients present in the MAJORICA cohort (Spain) was compared with the general population. Using multivariable regression, we studied the association of work absence with demographic and clinical characteristics. Patients with asthma and/or COPD had more work absence than the general population (15.2% vs 8.9%, p < 0.0001). Patients with asthma had more often periods of work absence compared to patients with COPD (16.0% vs 12.8%, p < 0.0001). The number of days absent were, however, less in asthma than in COPD (median: 15 days [IQR: 5–51] vs 39 days [IQR: 13–134], p < 0.001). Patients with asthma–COPD overlap were in between (14.5% with absence; median: 27 days [IQR: 10–82]). Comorbid anxiety, allergic rhinitis, and sleep apnoea were independently associated with more work absence.

Comprehensive analysis of allergen-specific IgE in COPD: mite-specific IgE specifically related to the diagnosis of asthma-COPD overlap

BackgroundAlthough the relationship between allergic sensitization and increased respiratory symptoms of chronic obstructive pulmonary disease (COPD) has been suggested, which allergen has a significant effect on COPD pathology is unclear. This study aimed to identify the specific IgE related to clinical features of COPD and the diagnosis of asthma-COPD overlap (ACO).MethodsWe recruited 76 patients with COPD and analyzed 39 IgE using panel IgE test (View Allergy 39®). ACO was diagnosed according to the Japanese Respiratory Society Guidelines.ResultsAs for perennial aeroallergens, the positivity for moth (31.5%), Candida (23.7%), Dermatophagoides pteronyssinus (22.4%) and house dust (22.4%), and concerning pollen, Japanese cedar (35.5%) and Japanese cypress (22.2%) exceeded 20%. Only the positivity of IgE for Dermatophagoides pteronyssinus and house dust was significantly higher in ACO compared with that in non-ACO COPD. Moreover, it contributed to the diagnosis of ACO in an IgE class-dependent manner. Patients with cockroach IgE exhibited higher residual volume, whereas those with Japanese cedar IgE exhibited better diffusion capacity than negative patients. The contribution for ACO diagnosis by the receiver operating characteristic curve analysis was comparable among total IgE (cutoff value: 158 IU/mL), blood eosinophil count (234/μL), and fraction of exhaled nitric oxide (31.0 ppb).ConclusionsThe prominent role of mite-specific IgE in the diagnosis and pathology of ACO and the potentially detrimental effect of cockroach sensitization on air trapping in COPD were suggested. The finding highlights the future development of a treatment targeting IgE as a treatable trait in COPD.

Asthma-chronic obstructive pulmonary disease overlap and cost-related medication non-adherence among older adults in the United States

Background Cost-related medication non-adherence (CRN) can negatively impact health outcomes in older adults with asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) by reducing access and adherence to essential medications. The objective of this study is to examine the association of ACO to any CRN and specific forms of CRN among a nationally representative sample of older (age ≥ 65 years) adults. Methods We adopted a cross-sectional study design using data from pooled cross-sectional Medicare Current Beneficiary Surveys (MCBS) (2006–2013) and linked fee-for-service Medicare claims. Unadjusted and adjusted logistic regressions that accounted for the complex survey design examined the association of ACO to any CRN and specific forms of CRN. Results Among older adults with ACO, 16% reported any CRN. The most common form of CRN was “failing to get prescription”. As compared to older adults with no asthma and no COPD, those with ACO were more likely to report any CRN (adjusted odds ratios [AOR] = 1.50, 95%CI = [1.14, 1.96]) and all forms of CRN. However, when the number of unique medications was added to the model, there were no statistically significant differences in CRN between the two groups. Conclusions Older adults with ACO represent a vulnerable population with increased risk for CRN. Multiple factors can contribute to CRN including: a higher number of prescribed medications, multiple co-morbidities, and cost of therapies. Medication comprehensive review interventions have the potential of reducing the risk of CRN among the older Medicare beneficiaries with ACO.

Deconstruyendo los fenotipos en la EPOC: un análisis de la cohorte TRACE

ObjectivesIn a clinical phenotype-based management strategy for COPD, it would be preferable to at least assign all patients to a phenotype, but to a single phenotype only. The aim of this study was to evaluate whether all patients are assigned to one and only one phenotype using the Spanish COPD guidelines (GesEPOC) and to evaluate the criteria that define these categories. MethodThe Time-based Register and Analysis of COPD Endpoints study (TRACE; clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients attending annual visits since 2012, which collects GesEPOC phenotypes. Although the GesEPOC recommends that patients considered to be at low risk are not phenotyped, an analysis of the criteria for identifying high- and low-risk phenotypes was performed, comparing the distribution of phenotypes and the criteria applied between these 2 groups. ResultsThe cohort included 970 patients with a confirmed diagnosis of COPD, divided into 427 (44.02%) low-risk and 543 (55.9%) high-risk patients. The most frequent phenotype was the non-exacerbator (44.9% of high-risk patients). Overall, 20.6% of low-risk patients met criteria for asthma-COPD overlap syndrome, while 9.2% of the cohort did not meet the diagnostic criteria for any phenotype, and 19.1% met the criteria for 2 phenotypes, with no differences between risk groups. ConclusionsOur data highlight some of the weaknesses of the current clinical phenotype strategy, revealing overlapping categories in some cases, and patients to whom no phenotype was assigned.