Phenotyping chronic respiratory diseases with airways obstruction.

Given the high prevalence of asthma-chronic obstructive pulmonary disease overlap (ACO) in Vietnam, there is an urgent need to establish a simplified strategy for categorising patients as either having asthma or chronic obstructive pulmonary disease (COPD). This classification would streamline the application of treatment recommendations outlined by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).Patients with obstructive lung function were classified as having COPD, asthma, or ACO based on GINA/GOLD guidelines. We hypothesised that ACO-like asthma (ACO-A) would present with positive skin prick tests (SPTs) or early onset of symptoms without a history of tuberculosis (TB), while those with ACO-like COPD (ACO-B) would exhibit negative SPTs and late onset of symptoms and/or a history of TB.Among 235 patients, the prevalence of asthma, ACO-A, ACO-B, and COPD was respectively 21%, 22%, 17%, and 40%. Allergic history, rhinitis, and childhood asthma were associated with ACO-A, while high cumulative smoking was correlated with ACO-B. Socio-economic and demographic parameters, medical history, clinical features, smoking habits, lung function, and para-clinical investigations significantly differed between "all asthma" (i.e., individuals with asthma combined with ACO-A) and "all COPD" (i.e., individuals with COPD combined with ACO-B).Based on SPTs, history of TB, and onset age, ACO patients may be defined as people with asthma or COPD..

Sputum Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Asthma-COPD Overlap.

BACKGROUND: Asthma COPD overlap (ACO) is a consensus-based phenotype having characteristics of both COPD and asthma. Distinguishing ACO from other diseases is even more important as it is related to low health-related quality of life, augmented exacerbation rate and hospital admission, a rapid deterioration in lung function, and increased morbidity and mortality. But it cannot be diagnosed explicitly based on spirometry tests, patient demographics, radiology, or by-sputum cytology. There is an unmet need to develop biomarkers. OBJECTIVES: To assess the role of sputum neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of ACO. To find the correlation between sputum NGAL levels with forced expiratory volume 1 (FEV1) and exacerbation rate in ACO. To find the correlation between sputum NGAL level with sputum neutrophils and eosinophils in ACO. MATERIALS AND METHODS: In this comparative correlational study, 180 subjects were enrolled into four groups with 45 patients each with asthma, COPD, ACO, and healthy nonsmokers respectively, respectively. After taking detailed history and demographics, sputum was analyzed for the differential count and NGAL. RESULTS: Asthma COPD overlap (ACO) cases had high sputum NGAL levels; the second was the COPD group, and the last in the case asthma group. Nonsmokers had notably lower readings than the diseased. Out of three, receiver operating characteristic (ROC) figures, the validity of NGAL was best in selecting patients of ACO than COPD and asthma. The area under curve (AUC) was highest for ACO and less than the acceptable limit for the remaining two. NGAL cut-off value of 2473 pg/mL had 80% sensitivity and 50% specificity for ACO. CONCLUSION: The present study investigated the sputum NGAL levels as a biomarker in ACO identified by the syndromic approach. Sputum NGAL, a biomarker associated with airway inflammation in airway diseases, was supportive of clinically differentiating ACO from asthma to COPD. How to cite this article: Babu A, Narayanswamy H, Baburao A. Sputum Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Asthma-COPD Overlap. J Assoc Physicians India 2023;71(9):34-38.

Esclerodermia e Polimiosite em paciente evoluindo com calcinose severa: um relato de caso / Scleroderma and Polymyositis in a patient developing severe calcinosis: a case report

Introdução: As Doenças doTecido Conjuntivo são um grupo de doenças autoimunes ou idiopáticas, crônicas, de acometimento geralmente sistêmico e que podem, ou não, atacar o indivíduo de forma concomitante. O presente relato de caso apresenta a descrição de Esclerose Sistêmica e Polimiosite em uma mesma paciente. O fenômeno é conhecido como Sindrome de Overlap (presença simultânea de duas ou mais doenças do tecido conjuntivo, de natureza auto-imune em um paciente) e considerado raro. A Polimiosite e Dermatomiosite são doenças idiopáticas inflamatórias crônicas que afetam a musculatura estriada, a pele e outros órgãos. Esclerose sistêmica é outra doença não tão frequente, extremamente incapacitante pela sua repercussão multissistêmica, de evolução crônica e progressiva. As calcinoses, assim como fenômeno de Raynaud, mialgia, disfagia e queixas respiratórias, podem estar presentes em ambas as patologias, e no caso relatado não foi diferente.Métodos:Oestudo observacional descritivo relata o caso de uma paciente atendida pelo setor de reumatologia do Hospital do Servidor Público Municipal de São Paulo (HSPM), reunindo informações contidas em prontuários, do ano de 2014 até o presente momento. Discussão: A Dermatomiosite e a Síndrome de CREST, subtipos da esclerose sistêmica e das Miosites Inflamatórias, respectivamente, são doenças raras e de difícil diagnóstico devido a presença se sintomas em comum e passíveis de serem encontrados em outras comorbidades não auto-imunes. Seu tratamento é feito com imunossupressores e medicações voltadas para cada queixa clínica do paciente, a depender de uma boa investigação clínica e critérios diagnósticos fechados, evitando progressão acelerada e complicações clínicas. Conclusão: O tratamentoproposto para Esclerose sistêmica e Dermatomiosite já possui uma gama extensa de possibilidades farmacológicas e não-farmacológicas mas ainda sem protocolos específicos consensuais, sendo indicadas de acordo com a experiência pessoal do profissional, visando diminuição dos processos inflamatórios, recuperação de qualidade de vida e prevenção de complicações. Já o tratamento das calcinoses ainda não apresenta resultados satisfatórios, sendo propostos de acordo com a resposta clínica individual dos pacientes. Palavras-chave: Esclerose. Polimiosite. Dermatomiosite. Calcinose. Síndrome CREST.

Comparison of clinical features and outcomes for asthma-COPD overlap syndrome vs. COPD patients: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to review evidence to determine whether "pure" chronic obstructive pulmonary disease (COPD) patients without a history of asthma differ in the clinical characteristics, severity of airflow limitation, and clinical outcomes compared to patients with Asthma-COPD Overlap Syndrome (ACOS). MATERIALS AND METHODS: An electronic search was performed in the MEDLINE, EMBASE, SCOPUS and Web of Science databases to identify comparing the clinical characteristics and outcomes between ACOS and "pure" COPD. The included studies were subjected to meta-analysis and risk of bias assessment using ROBINS-E tool. Eleven observational studies were included. RESULTS: The results of the meta-analysis showed increased expression of lung function parameters like forced expiration volume (FEV) at 1 sec{mean difference (MD) 2.36; 95% CI [0.05,4.66] ; p=0.004; I2= 72%} and clinical symptoms in terms of fever {Relative Risk (RR) 0.34, p<0.0001}, wheezing {RR 0.39, p<0.0001} and dyspnea {RR 0.53, p<0.0001}. The comorbidities associated with ACOS patients were similar to that found in patients with "pure" COPD. Interestingly, higher body mass index (BMI) was found in patients with ACOS (MD -0.73 95% CI [-1.06, -0.41], p<0.0001. CONCLUSIONS: The result showed higher risk in onset of frequent acute exacerbations, severe exacerbations requiring hospitalization and higher number of exacerbations experienced per year in ACOS patients. Within the limitations of the review, ACOS can be regarded as separate entity of co-existence which is classically associated with higher BMI, worsened lung function parameters and exacerbations with a varying degree of clinical symptoms.

Asthma-chronic obstructive pulmonary disease overlap syndrome.

Overlap of asthma and chronic obstructive lung disease (ACO) in patients with obstructive lung disease is growing in recognition, though there is no consistent agreement on the diagnostic criteria for the disease process. Patients with ACO have distinct clinical characteristics and trajectories, which are representative of a heterogenous, multifactorial, and incompletely understood inflammatory pathophysiology. Current treatment strategies are focused on titration of inhaled therapies such as long-acting bronchodilators, with increasing interest in the use of targeted biologic therapies aimed at the underlying inflammatory mechanisms. Future directions for research will focus on elucidating the varied inflammatory signatures leading to ACO, the development of consistent diagnostic criteria and biomarkers of disease, and improving the clinical management with an eye toward targeted therapies.

Asthma-Chronic Obstructive Pulmonary Disease Overlap.

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) defines a subgroup of patients with asthma who have persistent airflow obstruction or patients with COPD who may exhibit variable airflow limitation and/or evidence of type 2 inflammation. Additional investigations are needed to determine whether ACO represents a distinct disorder with unique underlying pathophysiology, whether ACO patients should be managed differently from those with asthma or COPD, and whether the diagnosis affects long-term outcomes. This article presents the data about the clinical features of ACO, the current information regarding the underlying pathophysiology of the syndrome, and current understanding of therapeutic options.

Current situation of asthma-COPD overlap in Chinese patients older than 40 years with airflow limitation: a multicenter, cross-sectional, non-interventional study.

BACKGROUND AND AIMS: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is poorly recognized in China. Our study determined the distribution of ACO and its clinical characteristics among patients (aged ⩾40 years) with airflow limitation at Chinese tertiary hospitals. METHODS: This cross-sectional, non-interventional study (NCT02600221), conducted between December 2015 and October 2016 in 20 Tier-3 Chinese hospitals, included patients aged ⩾40 years with post-bronchodilator (BD) FEV1/FVC <0.7. The primary variable was distribution of ACO in adults with post-BD forced expiratory volume /forced vital capacity (FEV1/FVC) <0.7 based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2015 and 2017 reports. Other variables included determination of characteristics of ACO and its clinical recognition rate. RESULTS: In 2003 patients (mean age 62.30 ± 9.86 years), distribution of ACO, COPD and asthma were 37.40%, 48.50% and 14.10%, respectively. Proportions of patients with A, B, C and D grouping were 11.70%, 31.00%, 6.90% and 50.30% as per GOLD 2017, whereas they were 15.10%, 51.10%, 3.60% and 30.20% as per GOLD 2015. Similar clinical symptoms were reported in all three groups. A higher percentage of ACO patients presented with dyspnea, wheezing and chest tightness. Compared with the COPD group, a greater proportion of ACO patients reported wheezing (74.6% and 65.40%), while a lower proportion in the ACO group reported cough (79.40% versus 82.70%) and expectoration (76.50% versus 81.60%). Blood eosinophil count ⩾0.3 × 109/L was observed in 34.6% of ACO patients. The clinical recognition rate of ACO was 31.4%. CONCLUSION: Despite ACO affecting two-fifths of the study population, the initial diagnosis rate was low at 6% in China, thus warranting concerted efforts to improve ACO diagnosis. CLINICALTRIALS.GOV: [ClinicalTrials.gov identifier: NCT02600221] registered 22 October 2015, https://clinicaltrials.gov/ct2/show/NCT02600221The reviews of this paper are available via the supplemental material section.

Triple Therapy with Budesonide/Glycopyrrolate/Formoterol Fumarate Improves Inspiratory Capacity in Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap.

Purpose: Asthma-chronic obstructive pulmonary disease overlap (ACO), characterized by airway limitation, is an important condition with high incidence and mortality. Although some guidelines recommend triple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting ß2 agonists, this treatment approach is based on the extrapolation of data from studies of asthma or chronic obstructive pulmonary disease (COPD) alone. Methods: A 12-week, randomized, open-label cross-over pilot study was conducted in 19 patients with ACO to investigate the effect of triple therapy with glycopyrrolate (GLY) 50 µg/day on budesonide/formoterol fumarate (BUD/FORM) 640/18 µg/day. The study period included a 4-week wash-out, 4-week run-in, and 4-week treatment period. Respiratory function tests, fractional exhaled nitric oxide (FeNO), a COPD assessment test (CAT) and an asthma control questionnaire (ACQ) were carried out 0, 4, and 8 weeks after randomization. Results: A total of 19 patients with stable ACO (19 males and no females) with a mean age of 70.7 ± 7.6 years (± standard deviation, SD; range 55-83 years) participated in this study. All patients were ex-smokers with a smoking history of 63.1 ± 41.1 pack-years (± SD). Mean values for inspiratory capacity (IC), an index of hyperinflation of the lung that causes exertional dyspnea and reduced exercise, were 1.93 L (± 0.47 L) after the run-in, 1.85 L (± 0.51 L) after the BUD/FORM dual therapy period and 2.11 L (± 0.58 L) after the BUD/GLY/FORM triple therapy period. IC values after the BUD/GLY/FORM triple therapy were significantly higher than those after the run-in (p < 0.02). FeNO values, ACQ, and CAT scores were not significantly different among the run-in, wash-out, and triple-therapy periods. Conclusion: The present pilot study showed that triple therapy with BUD/GLY/FORM results in an improvement in lung function parameters including IC, indicating the potential value of triple therapy as standard treatment for ACO.

Serum IL-8 and VEGFA are Two Promising Diagnostic Biomarkers of Asthma-COPD Overlap Syndrome.

Background: Asthma-COPD overlap (ACO; previously referred to as asthma-COPD overlap syndrome) is characterized by persistent airflow limitation consistent with COPD, together with several distinguishing features of asthma. Asthma-COPD overlap syndrome is a condition of mixing symptoms of asthma and COPD, because of its complexity, it is difficult to find effective diagnostic markers in clinic. Purpose: Our aims were to detect the expression of serum cytokines in patients with asthma, explore the diagnostic potential of differential serum cytokines in ACOS. Patients and Methods: Ninety asthmatic patients were divided into ACOS group and non-ACOS group according to the major and minor criteria of ACOS, 15 kinds of cytokines including IL-3, IL-4, IL-8, IL-9, IL-13, IL-17A, VEGFA, VEGFC, VEGFD, bFGF, Fit-1 PIGF, Tie-2 were detected by MSD, and IL-27 and TGF-beta were determined by ELISA assay. Results: The serum levels of IL-9, VEGFA and PIGF in patients with ACOS were significantly higher than those in non-ACOS group (P<0.05, respectively), while the level of IL-8 and IL-17A in subjects with ACOS was lower than that in the non-ACOS group (P<0.05, respectively). We analyzed the correlation between several difference factors and FEV1/FVC% in the ACOS group, found VEGFA was negatively correlated with FEV1/FVC%, while IL-8 and IL-17A were positively correlated with FEV1/FVC%. Finally, three correlation factors were analyzed by ROC curve for the occurrence of ACOS. Conclusion: The results suggested that IL-8 was highly sensitive and VEGFA was highly specificity, both of which could be used as biomarkers for the diagnosis of ACOS.

The relationship between inflammatory markers and spirometric parameters in ACOS, Asthma, and COPD.

Objective: The inflammatory mechanisms underpinning asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) have not been fully elucidated. Here, we examined the levels of cysteinyl leukotrienes (cys-LTs), prostaglandin D2 (PG-D2), prostaglandin E2 (PG-E2), interleukin 5 (IL-5), and a disintegrin and metalloprotease domain (ADAM 33) in ACOS patients to determine the relationship between levels of these inflammatory markers and pulmonary functions.Methods: Blood samples were obtained from asthma, COPD, and ACOS patients who received combined therapy and were stable for the last month to measure cys-LTs, PG-D2, PG-E2, IL-5, and ADAM33 levels. Differences between groups and their correlations with pulmonary function tests were evaluated.Results: In total, 24 ACOS, 27 asthma, and 35 COPD patients were included. . PG-D2 levels were higher in ACOS (120.9 ± 117.2 ng/L) and asthma (119.6 ± 111.7 ng/L) patients than in COPD (82.6 ± 46.7 ng/L) patients (p = 0.036 and p = 0.038, respectively). In ACOS patients, PG-D2, cys-LTs, and ADAM33 levels were negatively correlated with FEV1/FVC% values (p = 0.021, p = 0.008, and p = 0.028, respectively). In COPD patients, a negative correlation was detected between PG-E2 and FEV1/FVC% (p = 0.007), whereas positive correlations were detected between IL-5 and pulmonary function tests, including FVC, FVC%, FEV1, FEV1%, FEF25-75, and FEF25-75% (p = 0.047, p = 0.005, p = 0.002, p = 0.002, p = 0.010, and p = 0.005, respectively). In asthma patients, cys-LTs levels were negatively correlated with FEV1 and FEF25-75 values (p = 0.045 and p = 0.037, respectively).Conclusions: PG-D2 levels may be a valuable biomarker to differentiate COPD in asthma and ACOS patients.

Prospective development of practical screening strategies for diagnosis of asthma-COPD overlap.

BACKGROUND AND OBJECTIVE: ACO is a syndrome with high prevalence. However, a pragmatic diagnostic criterion to differentiate ACO is non-existent. We aimed to establish an effective model for screening ACO. METHODS: A multicentre survey was developed to assess the clinical criteria considered important and applicable by pulmonologists for screening ACO. These experts were asked to take the surveys twice. The expert grading method, analytic hierarchy process and ROC curve were used to establish the model, which was then validated by a cross-sectional study of 1066 patients. The GINA/GOLD document was the gold standard in assessing this model. RESULTS: Increased variability of symptoms, paroxysmal wheezing, dyspnoea, historical diagnosis of COPD or asthma, allergic constitution, exposure to risk factors, the FEV1 /FVC < 70% and a positive BDT were important for screening ACO. According to the weight of each criterion, we confirmed that patients meeting six or more of these eight criteria should be considered to have ACO. We called this Chinese screening model for ACO 'CSMA'. It differentiated patients with ACO with a sensitivity of 83.33%, while the sensitivity of clinician-driven diagnosis had a sensitivity of only 42.73%. CONCLUSION: CSMA is a workable model for screening ACO and provides a simple tool for clinicians to efficiently diagnose ACO.

Lung air trapping lowers respiratory arousal threshold and contributes to sleep apnea pathogenesis in COPD patients with overlap syndrome.

STUDY OBJECTIVES: Overlap syndrome occurs when obstructive sleep apnea (OSA) and chronic obstructive pulmonary disorder (COPD) coexist in the same patient. Although several studies highlighted the importance of clinical phenotyping in OSA, the trait contribution to OSA pathogenesis in overlap syndrome has not been investigated. With this pilot study, we aimed to measure OSA determinants and their relationship with functional respiratory parameters in a sample of patients with overlap syndrome. In particular, we hypothesize that patients with COPD have in the low arousal threshold a major contributor for the development of OSA. METHODS: Ten consecutive non-hypercapnic COPD patients (body mass index<35 kg/m2) suffering from overlap syndrome with no other relevant comorbidities underwent a phenotyping polysomnography. Traits were measured with CPAP dial-downs. RESULTS: Arousal threshold was found to be inversely associated to functional measures of lung air trapping and static hyperinflation. Particularly, correlations with residual volume (r2 = 0.49, p =  0.024) and residual volume to total lung capacity ratio (r2 = 0.48, p =  0.026) were evident. Only 20% of patients showed a high upper airway passive collapsibility as single pathological trait. In contrast, among those patients with multiple altered traits (6 out of 10), all had an elevated loop gain and 4 (∼65%) a low arousal threshold. CONCLUSIONS: High loop gain and particularly low arousal threshold seem important contributors to OSA pathogenesis and severity in patients with COPD. Recognizing in COPD patients these features as key traits may open avenues for personalized medicine in the field of overlap syndrome.

Asthma-COPD overlap: review of diagnosis and management.

PURPOSE OF REVIEW: Asthma and chronic obstructive pulmonary disease are both commonly encountered respiratory conditions. The term asthma--COPD overlap (ACO) has been used to identify patients presenting with features of both conditions. Controversy exists regarding its definition, approach to diagnosis and management. In this publication, recent evidence has been reviewed that provides insight into diagnosis and management of this condition. RECENT FINDINGS: Previously, multiple criteria were used to define Asthma--COPD overlap. In this publication, the most recent guidelines to identify this condition have been reviewed. This publication provides a summary of the recent evidence with regard to the role of various diagnostic modalities including the use of biomarkers, such as exhaled nitric oxide, serum IgE and provides updated evidence on available treatment choices for this condition. SUMMARY: ACO is a commonly encountered clinical condition with patients experiencing frequent exacerbations and resulting in increased healthcare resource utilization. Recent interest in ACO has led to development of a framework towards diagnosis and management of this condition. Therapeutic choices for ACO range from bronchodilator therapy to immunomodulatory therapy, highlighting the heterogeneity of this condition. Additional research is required to improve understanding of pathogenesis and improve outcomes in ACO.

A comparison of diagnostic consistency for asthma-chronic obstructive pulmonary disease overlap and clinical characteristics study.

BACKGROUND: The diagnostic criteria for asthma-chronic obstructive pulmonary disease overlap have not been unified. Different studies have used different criteria, and this has led to diagnostic inconsistencies. METHODS: We collected data of patients who were older than 40 years and hospitalised because of chronic bronchial diseases. One hundred and seventy-one patients were included in this study. We compared seven different diagnostic criteria, examined their consistency, and analysed differences among groups classified with each set. RESULTS: The prevalence of ACO ranged between 7.02 and 27.49% depending on the criteria applied. The patients who met the Soler-Cataluna et al. criteria also met the GesEPOC criteria. Rhee has proposed the strictest diagnostic criteria; hence, the number of patients who met these criteria was the smallest, and those patients also met the diagnostic criteria proposed by the other studies. We found that applying the different sets of criteria did not lead to the selection of the same population, while there were no statistical differences in age, disease duration, allergens, and inflammatory markers. CONCLUSIONS: The diagnostic criteria of ACO have not been unified, which hinders the design and progress of clinical studies that would investigate the ACO phenotypes and underlying mechanisms.

Clinical Characteristics Of Patients With Asthma COPD Overlap (ACO) In Australian Primary Care.

Purpose: Many older adults with a history of smoking and asthma develop clinical features of both asthma and COPD, an entity sometimes called asthma-COPD overlap (ACO). Patients with ACO may be at higher risk of poor health outcomes than those with asthma or COPD alone. However, understanding of ACO is limited in the primary care setting and more information is needed to better inform patient management. We aimed to compare the characteristics of patients with ACO or COPD in Australian general practices. Patients and methods: Data were from the RADICALS (Review of Airway Dysfunction and Interdisciplinary Community-based care of Adult Long-term Smokers) trial, an intervention study of an interdisciplinary community-based model of care. Baseline demographic and clinical characteristics, pre- and post-bronchodilator spirometry, dyspnoea and St. George's Respiratory Questionnaire scores were compared between 60 ACO patients and 212 with COPD alone. Results: Pre-bronchodilator Forced Expiratory Volume in 1 second (mean±SD 58.4±14.3 vs 67.5±20.1% predicted) and Forced Vital Capacity (mean 82.1±16.9 v 91.9±17.2% predicted) were significantly lower in the ACO group (p<0.001), but no difference was found in post-bronchodilator spirometry. Demographic and clinical characteristics, dyspnoea, quality of life, comorbidities and treatment prescribed did not differ significantly between groups. Conclusion: This is the first study describing the clinical characteristics of ACO patients in Australian general practices. Our finding of lower pre-bronchodilator lung function in the ACO group compared to those with COPD reinforces the importance of spirometry in primary care to inform management. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12614001155684.

Predictive factors for COPD exacerbations and mortality in patients with overlap syndrome.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA)-overlap syndrome-have a substantially greater risk of morbidity and mortality, compared to those with either COPD or OSA alone. OBJECTIVES: The aim of this retrospective study was to identify clinical modifiable factors associated with COPD exacerbations and all-cause mortality in patients with overlap syndrome. METHODS: The electronic records of patients with simultaneous COPD and OSA who had a documented acute exacerbation of COPD during a 42-month period were evaluated for reviewed. A control group of overlap syndrome patients without exacerbations was matched 1:1 for age and body mass index. Vital status and cause of death were assessed through the population death registry. RESULTS: Out of 225 eligible cases, 92 patients had at least one episode of COPD exacerbation. There was no significant association between severity of airflow limitation and apnoea hypopnea index (P = .31). After adjusting for confounding variables, patients who had at least one COPD exacerbation were more likely to be active smokers (P = .01), have poorer lung function (P = .001) and less likely to adhere to continuous positive airway pressure (CPAP) use (P = .03). All-cause mortality was also correlated with low forced expiratory volume in 1 second (P = .006), CPAP use (P = .007), and burden of comorbidities (P < .001). CONCLUSION: Lung function and CPAP use were independent predictors of COPD exacerbations and all-cause mortality in a cohort of patients with overlap syndrome. These factors should be taken into account when considering the management and prognosis of these patients.

Metabolomic signatures of asthma-COPD overlap (ACO) are different from asthma and COPD.

INTRODUCTION: Asthma-chronic obstructive pulmonary disease (COPD) overlap, termed as ACO, is a complex heterogeneous disease without any clear diagnostic or therapeutic guidelines. The pathophysiology of the disease, its characteristic features, and existence as a unique disease entity remains unclear. Individuals with ACO have a faster lung function decline, more frequent exacerbations, and worse quality of life than those with COPD or asthma alone. OBJECTIVES: The present study aims to determine whether ACO has a distinct metabolic profile in comparison to asthma and COPD. METHODS: Two different groups of patients were recruited as discovery (D) and validation (V) cohorts. Serum samples obtained from moderate and severe asthma patients diagnosed as per GINA guidelines [n = 34(D); n = 32(V)], moderate and severe COPD cases identified by GOLD guidelines [n = 30(D); 32(V)], ACO patients diagnosed by joint GOLD and GINA guidelines [n = 35(D); 40(V)] and healthy controls [n = 33(D)] were characterized using nuclear magnetic resonance (NMR) spectrometry. RESULTS: Multivariate and univariate analysis indicated that 12 metabolites [lipid, isoleucine, N-acetylglycoproteins (NAG), valine, glutamate, citric acid, glucose, L-leucine, lysine, asparagine, phenylalanine and histidine] were dysregulated in ACO patients when compared with both asthma and COPD. These metabolites were further validated in a fresh cohort of patients, which again exhibited a similar expression pattern. CONCLUSIONS: Our findings suggest that ACO has an enhanced energy and metabolic burden associated with it as compared to asthma and COPD. It is anticipated that our results will stimulate researchers to further explore ACO and unravel the pathophysiological complexities associated with the disease.

Physiological and morphological differences of airways between COPD and asthma-COPD overlap.

Overlap of asthma and COPD has attracted attention recently. We aimed to clarify physiological and morphological differences of the airways between COPD and asthma-COPD overlap (ACO). Respiratory resistance and reactance and three-dimensional computed tomography data were evaluated in 167 patients with COPD. Among them, 43 patients who fulfilled the diagnosis of asthma were defined as having ACO. Among 124 patients with COPD without ACO, 86 with a comparable smoking history and airflow limitation as those with ACO were selected using propensity score matching (matched COPD). The intraluminal area (Ai) and wall thickness (WT) of third- to sixth-generation bronchi were measured and adjusted by body surface area (BSA; Ai/BSA and WT/√BSA, respectively). Patients with ACO had higher respiratory resistance and reactance during tidal breathing, but a smaller gap between the inspiratory and expiratory phases, compared with matched patients with COPD. Patients with ACO had a greater WT/√BSA in third- to fourth-generation bronchi, smaller Ai/BSA in fifth- to sixth-generation bronchi, and less emphysematous changes than did matched patients with COPD. Even when patients with ACO and those with COPD have a comparable smoking history and fixed airflow limitation, they have different physiological and morphological features of the airways.