Effect of budesonide formoterol combined with tiotropium bromide on pulmonary function and inflammatory factors in patients with asthma-COPD overlap syndrome.

OBJECTIVE: To investigate the clinical efficacy of combining budesonide formoterol with tiotropium bromide for treating asthma-chronic obstructive pulmonary disease overlap syndrome (AOCS). METHODS: The data of 104 patients with AOCS admitted to our hospital from December 2019 to December 2020 were assessed, randomly and divided into an experimental group (comprising 52 patients, receiving drug combination therapy) and a conventional group (comprising 52 patients, receiving drug therapy alone). Patients' clinical efficacy, pulmonary function, fractioned exhaled nitric oxide (FeNO), immune function, endothelial function, serum lipid peroxidation injury indexes, adverse reactions, and quality of life scores were compared. RESULTS: Prior to treatment, no significant differences were observed in various pulmonary function indicators, FeNO, immune function, endothelial function, and lipid peroxidation injury indexes between the two groups (P > 0.05). However, after treatment, all observation indexes in both groups improved to different levels, with the experimental group -demonstrating -significantly superior improvement, compared to the conventional group (P < 0.05). We also observed that adverse reactions in the experimental group were significantly lower than in the conventional group (P < 0.05). CONCLUSION: The combination of budesonide formoterol to tiotropium bromide in treating asthma-COPD overlap syndrome may significantly improve pulmonary function, endothelial function, and immune status of patients and encourage the recovery of serum lipid peroxidation injury; therefore, this may deserve widespread adoption and application.

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.

Does the asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) exist? A narrative review from epidemiology and practice.

Asthma and chronic obstructive pulmonary disease (COPD) have traditionally been approached as separate entities that must be researched and treated separately. There is growing recognition, however, that a substantial proportion of patients with obstructive lung disease have characteristics of both asthma and COPD (termed the asthma-COPD overlap syndrome (ACOS)). Lung disease experts have difficulty defining ACOS, and many still resist accepting the possibility that asthma and COPD may be linked. It is likely that practicing clinicians may be equally confused about how to identify and treat ACOS. This narrative review aims to clarify concepts of ACOS definition, argues that the best way to understand ACOS is to view the chronic lung disease process longitudinally rather than cross-sectionally, and presents evidence that ACOS can be the end result of the natural history of severe asthma. The review also points out the serious gaps in knowledge regarding therapy for ACOS and presents emerging data supporting the intracellular respiratory pathogen Chlamydia pneumoniae as a possible common etiologic agent in severe asthma and ACOS.

ß-Agonist exposure preferentially impacts lung macrophage cyclic AMP-related gene expression in asthma and asthma COPD overlap syndrome.

Bronchoalveolar lavage (BAL) samples from Severe Asthma Research Program (SARP) patients display suppression of a module of genes involved in cAMP-signaling pathways (BALcAMP) correlating with severity, therapy, and macrophage constituency. We sought to establish if gene expression changes were specific to macrophages and compared gene expression trends from multiple sources. Datasets included single-cell RNA sequencing (scRNA-seq) from lung specimens including a fatal exacerbation of severe Asthma COPD Overlap Syndrome (ACOS) after intense therapy and controls without lung disease, bulk RNA sequencing from cultured macrophage (THP-1) cells after acute or prolonged ß-agonist exposure, SARP datasets, and data from the Immune Modulators of Severe Asthma (IMSA) cohort. THP monocytes suppressed BALcAMP network gene expression after prolonged relative to acute ß-agonist exposure, corroborating SARP observations. scRNA-seq from healthy and diseased lung tissue revealed 13 cell populations enriched for macrophages. In severe ACOS, BALcAMP gene network expression scores were decreased in many cell populations, most significantly for macrophage populations (P < 3.9e-111). Natural killer (NK) cells and type II alveolar epithelial cells displayed less robust network suppression (P < 9.2e-8). Alveolar macrophages displayed the most numerous individual genes affected and the highest amplitude of modulation. Key BALcAMP genes demonstrate significantly decreased expression in severe asthmatics in the IMSA cohort. We conclude that suppression of the BALcAMP gene module identified from SARP BAL samples is validated in the IMSA patient cohort with physiological parallels observed in a monocytic cell line and in a severe ACOS patient sample with effects preferentially localizing to macrophages.

Occupation and subcategories of asthma: a population-based incident case-control study.

BACKGROUND: We hypothesised that occupational exposures differently affect subtypes of adult-onset asthma. OBJECTIVE: We investigated potential relations between occupation and three subtypes of adult asthma, namely atopic asthma, non-atopic asthma and asthma-COPD overlap syndrome (ACOS). METHODS: This is a population-based case-control study of incident asthma among working-age adults living in Pirkanmaa Hospital District in Southern Finland. The determinant of interest was occupation at the time of diagnosis of asthma or the job that the subject had quit due to respiratory symptoms. Asthma was divided into three mutually exclusive subtypes on the basis of any positive IgE antibody (atopic and non-atopic asthma) and presence of persistent airways obstruction in spirometry (ACOS). We applied unconditional logistic regression analysis to estimate adjusted OR (aOR), taking into account gender, age and smoking. RESULTS: The following occupational groups showed significantly increased risk of atopic asthma: chemical industry workers (aOR 15.76, 95% CI 2.64 to 94.12), bakers and food processors (aOR 4.69, 95% CI 1.18 to 18.69), waiters (aOR 4.67, 95% CI 1.40 to 15.56) and those unemployed (aOR 3.06, 95% CI 1.52 to 6.17). The following occupations showed clearly increased risk of non-atopic asthma: metal workers (aOR 8.37, 95% CI 3.77 to 18.59) and farmers and other agricultural workers (aOR 2.36, 95% CI 1.10 to 5.06). Some occupational groups showed statistically significantly increased OR of ACOS: electrical and electronic production workers (aOR 30.6, 95% CI 6.10 to 153.35), fur and leather workers (aOR 16.41, 95% CI 1.25 to 215.85) and those retired (aOR 5.55, 95% CI 1.63 to 18.97). CONCLUSIONS: Our results show that different occupations are associated with different subtypes of adult-onset asthma.

Pref-1 induced lung fibroblast differentiation by hypoxia through integrin α5ß1/ERK/AP-1 cascade.

Chronic obstructive asthma is characterized by airway fibrosis. Hypoxia and connective tissue growth factor (CTGF) play important roles in airway fibrosis. Preadipocyte factor-1 (Pref-1) participates in adipocyte differentiation and liver fibrosis. Herein, we investigated the role of Pref-1 in airway fibrosis in chronic obstructive asthma. We found that Pref-1 was overexpressed in lung tissues from chronic obstructive asthma patients compared to normal subjects. Extracellular matrix proteins were inhibited by Pref-1 small interfering (si)RNA in airway fibroblasts from chronic obstructive asthma patients. Furthermore, ovalbumin induced prominent Pref-1 expression and fibronectin coexpression. Hypoxia induced Pref-1 upregulation and its release into medium of WI-38 cells. Hypoxia-induced CTGF expression was inhibited by Pref-1 siRNA. We also found that Pref-1-stimulated fibrotic protein expressions were reduced by ATN-161, curcumin, U0126, and c-Jun siRNA in WI-38. Furthermore, ATN161 inhibited Pref-1-induced ERK phosphorylation, and ITGA5 siRNA inhibited c-Jun phosphorylation. Moreover, expression of CTGF, Fibronectin, α-SMA, and ERK and c-Jun phosphorylation were all increased in fibroblasts from patients with chronic obstructive asthma. Taken together, these results suggest that Pref-1 participates in airway fibrosis and hypoxia-induced CTGF expression via the integrin receptor α5ß1/ERK/AP-1 pathway.

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).

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Our study revealed three promising biomarkers for the diagnosis of COPD, BA and ACOS.

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.

Lavado broncoalveolar y diagnóstico de enfermedades respiratorias bajas / Bronchoalveolar lavage and the diagnosis of lower respiratory infections

Las patologías respiratorias son una de las principales causas de enfermedad y muerte. En las estimaciones hechas por la Organización Mundial de la Salud (OMS) entre los años 2000 y 2019, la enfermedad pulmonar obstructiva crónica y las infecciones de las vías respiratorias inferiores fueron la tercera y cuarta causa de muerte, respectivamente, y la primera cuando el análisis se hacía únicamente con las enfermedades transmisibles, tanto antes de la pandemia por SARS-CoV-2 (COVID-19), como durante esta. Para modificar su impacto en la salud de la población, es importante, además de mantener y mejorar las actividades encaminadas a su prevención, establecer diagnósticos y tratamientos oportunos, certeros y eficaces

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.

A COVID-19 patient with intense burning pain.

A woman in her forties with asthma and COPD was admitted to a general medical floor with respiratory symptoms, body aches, and anosmia. Reverse transcription polymerase chain reaction detected severe acute respiratory syndrome coronavirus-2. Admission labs, including biomarkers of the systemic immunological dysfunction seen in many cases of coronavirus disease 2019 (COVID-19), were within normal ranges. On the second day of admission, she developed neck and back pain that was constant, burning in quality, and exacerbated by light touch and heat. Wearing clothing caused pain and interfered with her sleep. The area was tender to light finger stroke. The patient was given acetaminophen, NSAIDs, and opioids with no relief of pain. However, gabapentin was effective. At follow-up 1 month later, her symptoms were improved and still relieved by gabapentin. Neuropathic pain was seen in over 2% of COVID-19 patients in one observational study. The pain seen in our case was bilateral, involved an area innervated by multiple levels of spinal nerves, and was limited to the back. While it is rare, a significant number of COVID-19 patients are afflicted by neuropathic pain, and our case illustrates that gabapentin may be effective.

Pharmacotherapeutic management of asthma in the elderly patient.

INTRODUCTION: Asthma is a heterogeneous syndrome with variable phenotypes. Reversible airway obstruction and airway hyper-responsiveness often with an atopic or eosinophilic component is common in the elderly asthmatic. Asthma chronic obstructive pulmonary disease overlap syndrome (ACOS), a combination of atopy-mediated airway hyper-responsiveness and a history of smoking or other environmental noxious exposures, can lead to some fixed airway obstruction and is also common in elderly patients. Little specific data exist for the treating the elderly asthmatic, thus requiring the clinician to extrapolate from general adult data and asthma treatment guidelines. AREAS COVERED: A stepwise approach to pharmacotherapy of the elderly patient with asthma and ACOS is offered and the literature supporting the use of each class of drugs reviewed. EXPERT OPINION: Inhaled, long-acting bronchodilators in combination with inhaled corticosteroids represent the backbone of treatment for the elderly patient with asthma or ACOS . Beyond these medications used as direct bronchodilators and topical anti-inflammatory agents, a stepwise approach to escalation of therapy includes multiple options such as oral leukotriene receptor antagonist or 5-lipoxygense inhibitor therapy, oral phosphodiesterase inhibitors, systemic corticosteroids, oral macrolide antibiotics and if evidence of eosinophilic/atopic component disease exists then modifying monoclonal antibody therapies.

Visual and Quantitative Assessments of Regional Xenon-Ventilation Using Dual-Energy CT in Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: A Comparison with Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To assess the regional ventilation in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) using xenon-ventilation dual-energy CT (DECT), and to compare it to that in patients with COPD. MATERIALS AND METHODS: Twenty-one patients with ACOS and 46 patients with COPD underwent xenon-ventilation DECT. The ventilation abnormalities were visually determined to be 1) peripheral wedge/diffuse defect, 2) diffuse heterogeneous defect, 3) lobar/segmental/subsegmental defect, and 4) no defect on xenon-ventilation maps. Emphysema index (EI), airway wall thickness (Pi10), and mean ventilation values in the whole lung, peripheral lung, and central lung areas were quantified and compared between the two groups using the Student's t test. RESULTS: Most patients with ACOS showed the peripheral wedge/diffuse defect (n = 14, 66.7%), whereas patients with COPD commonly showed the diffuse heterogeneous defect and lobar/segmental/subsegmental defect (n = 21, 45.7% and n = 20, 43.5%, respectively). The prevalence of ventilation defect patterns showed significant intergroup differences (p < 0.001). The quantified ventilation values in the peripheral lung areas were significantly lower in patients with ACOS than in patients with COPD (p = 0.045). The quantified Pi10 was significantly higher in patients with ACOS than in patients with COPD (p = 0.041); however, EI was not significantly different between the two groups. CONCLUSION: The ventilation abnormalities on the visual and quantitative assessments of xenon-ventilation DECT differed between patients with ACOS and patients with COPD. Xenon-ventilation DECT may demonstrate the different physiologic changes of pulmonary ventilation in patients with ACOS and COPD.

Analysis of Blood Biomarkers in Patients with Chronic Obstructive Pulmonary Disease (COPD) and with Asthma-COPD Overlap (ACO).

Chronic obstructive pulmonary disease (COPD) is a heterogeneous entity with different clinical phenotypes, such as asthma-COPD overlap (ACO). The aim of this retrospective study was to compare routine blood biomarkers in patients with ACO and the remaning COPD phenotypes. Data were collected from stable COPD patients visited in during 2018, including C-reactive protein (CRP), fibrinogen, neutrophyl/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR).A total of 77 patients with COPD were included, 24 (31%) fulfilled the diagnosis of ACO. Clinically, patients with ACO presented more dyspnoea and wheezing. Regarding laboratory parameters, both groups had low levels of lymphocytes, especially the non-ACO group (24.2% vs. 29.3%; p = 0.031), patients with ACO had significantly higher eosinophil counts (4.7% vs. 1.9%; p < 0.001) but a lower percentage of neutrophils (56.8% vs. 64.7%; p = 0.003), NLR and PLR (2.5 vs. 3.8; p = 0.013 and 115 vs. 160; p = 0.063, respectively). In conclusion, besides the expected eosinophilic inflammation in patients with ACO, both groups had low levels of lymphocytes, especially the non-ACO group. The low levels of lymphocytes, in particular in non-ACO patients, should be confirmed in larger studies.

Clinical Phenotypes of Atopy and Asthma in COPD: A Meta-analysis of SPIROMICS and COPDGene.

BACKGROUND: Little is known about the concordance of atopy with asthma COPD overlap. Among individuals with COPD, a better understanding of the phenotypes characterized by asthma overlap and atopy is needed to better target therapies. RESEARCH QUESTION: What is the overlap between atopy and asthma status among individuals with COPD, and how are categories defined by the presence of atopy and asthma status associated with clinical and radiologic phenotypes and outcomes in the Genetic Epidemiology of COPD Study (COPDGene) and Subpopulation and Intermediate Outcome Measures in COPD Study (SPIROMICS)? STUDY DESIGN AND METHODS: Four hundred three individuals with COPD from SPIROMICS and 696 individuals from COPDGene with data about specific IgEs to 10 common allergens and mixes (simultaneous assessment of combination of allergens in similar category) were included. Comparison groups were defined by atopic and asthma status (neither, atopy alone, atopic asthma, nonatopic asthma, with atopy defined as any positive specific IgE (≥0.35 KU/L) to any of the 10 allergens or mixes and asthma defined as self-report of doctor-diagnosed current asthma). Multivariable regression analyses (linear, logistic, and zero inflated negative binomial where appropriate) adjusted for age, sex, race, lung function, smoking status, pack-years smoked, and use of inhaled corticosteroids were used to determine characteristics of groups and relationship with outcomes (exacerbations, clinical outcomes, CT metrics) separately in COPDGene and SPIROMICS, and then adjusted results were combined using meta-analysis. RESULTS: The prevalence of atopy was 35% and 36% in COPD subjects from SPIROMICS and COPDGene, respectively, and less than 50% overlap was seen between atopic status with asthma in both cohorts. In meta-analysis, individuals with nonatopic asthma had the most impaired symptom scores (effect size for St. George's Respiratory Questionnaire total score, 4.2; 95% CI, 0.4-7.9; effect size for COPD Assessment Test score, 2.8; 95% CI, 0.089-5.4), highest risk for exacerbations (incidence rate ratio, 1.41; 95% CI, 1.05-1.88) compared with the group without atopy or asthma. Those with atopy and atopic asthma were not at increased risk for adverse outcomes. INTERPRETATION: Asthma and atopy had incomplete overlap among former and current smokers with COPD in COPDGene and SPIROMICS. Nonatopic asthma was associated with adverse outcomes and exacerbation risk in COPD, whereas groups having atopy alone and atopic asthma had less risk.

Dynamic-Ventilatory Digital Radiography in Air Flow Limitation: A Change in Lung Area Reflects Air Trapping.

OBJECTIVE: The aim of this study was to determine the utility of dynamic-ventilatory digital radiography (DR) for pulmonary function assessment in patients with airflow limitation. METHODS: One hundred and eighteen patients with airflow limitation (72 patients with lung cancer before surgery, 35 patients with chronic obstructive pulmonary disease [COPD], 6 patients with asthma, and 5 patients with asthma-COPD overlap syndrome) were assessed with dynamic-ventilatory DR. The patients were instructed to inhale and exhale slowly and maximally. Sequential chest X-ray images were captured in 15 frames per second using a dynamic flat-panel imaging system. The relationship between the lung area and the rate of change in the lung area due to respiratory motion with respect to pulmonary function was analyzed. RESULTS: The rate of change in the lung area from maximum inspiration to maximum expiration (Rs ratio) was associated with the RV/TLC ratio (r = 0.48, p < 0.01) and the percentage of the predicted FEV1 (r = -0.33, p < 0.01) in patients with airflow limitations. The Rs ratio also decreased in an FEV1-dependent manner. CONCLUSION: The rate of change in the lung area due to respiratory motion evaluated with dynamic DR reflects air trapping. Dynamic DR is a potential tool for the comprehensive assessment of pulmonary function in patients with COPD.

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.