Metformin use and respiratory outcomes in asthma-COPD overlap.
Ontology highlight
ABSTRACT: Background
Metformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored.Objective
To determine the association between metformin use and respiratory outcomes in COPD and ACO.Study design and methods
Participants with COPD (FEV1/FVC?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?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.
SUBMITTER: Wu TD
PROVIDER: S-EPMC7908718 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Metformin use and respiratory outcomes in asthma-COPD overlap.
Wu Tianshi David TD Fawzy Ashraf A Kinney Gregory L GL Bon Jessica J Neupane Maniraj M Tejwani Vickram V Hansel Nadia N NN Wise Robert A RA Putcha Nirupama N McCormack Meredith C MC
Respiratory research 20210226 1
<h4>Background</h4>Metformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored.<h4>Objective</h4>To determine the association between metformin use and respiratory outcomes in COPD and ACO.<h4>Study design and methods</h4>Participants 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 ...[more]
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Project description:BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype.MethodsPatients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/μL).ResultsThe prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) - 9.1%; group B (light smoker with low BEC) - 3.7%; group C (moderate to heavy smoker with high BEC) - 73.8%; and group D (moderate to heavy smoker with low BEC) - 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups.ConclusionThe prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.
| S-EPMC9344038 | biostudies-literature
Project description:BackgroundEmphysema is a distinct feature for classifying COPD, and smoking history (≥10 pack-years) is one of several newly proposed criteria for asthma-COPD overlap (ACO). We studied whether or not a smoking history (≥10 pack-years) and emphysema are useful markers for classifying ACO and differentiating it from asthma with chronic airflow obstruction (CAO).MethodsWe retrospectively studied the mortalities and frequencies of exacerbation in 256 consecutive patients with ACO (161 with emphysema and 95 without emphysema) who had ≥10 pack-years smoking history, 64 asthma patients with CAO but less of a smoking history (<10 pack-years) and 537 consecutive patients with COPD (452 with emphysema and 85 without emphysema) from 2000 to 2016. In the patients with emergent admission, the causes were classified into COPD exacerbation, asthma attack, and others.ResultsNo asthma patients with CAO had emphysema according to computed tomography findings. The prognoses were significantly better in patients with asthma and CAO than in those with ACO and COPD and better in those with ACO than in those with COPD. In both ACO and COPD patients, the prognoses were better in patients without emphysema than in those with it (P=0.027 and P=0.023, respectively). The frequencies of emergent admission were higher in COPD patients than in ACO patients, and higher in patients with emphysema than in patients without emphysema. ACO/emphysema (+) patients experienced more frequent admission due to COPD exacerbation (P<0.001), while ACO/emphysema (-) patients experienced more frequent admission due to asthma attack (P=0.014).ConclusionA smoking history (≥10 pack-years) was found to be a useful marker for differentiating ACO and asthma with CAO, and emphysema was a useful marker for classifying ACO. These markers are useful for predicting the overall survival and frequency of exacerbation.
| S-EPMC5724421 | biostudies-literature
Project description: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.
| S-EPMC6534606 | biostudies-literature
Project description:Patients who have features of both Asthma & COPD are now known as Asthma COPD overlap (ACO). Prevalence of ACO based on the Global Initiative for Asthma (GINA) and Global initiative for obstructive lung disease (GOLD) Syndromic Approach is scarce. In this cross-sectional observational study, we recruited physician-diagnosed-pAsthma, pCOPD & pACO by simple random sampling. Clinical features, spirometry, 6-min walk test, Serum Immunoglobulin E, % blood eosinophils and chest x-rays were reviewed. Syndromic approach was applied, and the diagnosis was reclassified accordingly. In all, 877 patients were included (Male = 445, Female = 432). Physician diagnosis for these were: pAsthma-713, pCOPD-157 and pACO-7. They were reclassified using the Syndromic approach as: sAsthma, sCOPD and sACO. The 713 pAsthmatics were reclassified as follows: sAsthma-684 (95.94%), sCOPD-12 (1.68%) and sACO-17 (2.38%). Of the 157 pCOPD patients, 91 (57.96%) were reclassified as sCOPD, 23 (14.6%) as sACO, and 17 (927.38%) as sAsthma. Of the 7 previously diagnosed pACO patients, only 1 (14.28%) was reclassified as sACO, 5 (71.42%) as sAsthma and 1 (14.28%) as sCOPD. sCOPD patients had more exacerbations (52.88% vs 46.34%, p = 0.479), critical care admissions (16.35% vs 7.32%, p = 0.157) and intubations (17.31% vs 9.76%, p = 0.255) compared to sACO patients, the latter had more events than sAsthma patients: exacerbations 46.34% vs 10.11% (p < 0.001), critical care admissions 7.32% vs 1.64% (p = 0.010) and intubations 9.76% vs 1.5% (p < 0.001). The syndromic approach helped us to identify ACO and also more appropriately classified COPD & Asthma. There was a significant difference between physician diagnosis and diagnosis using Syndromic Approach. It revealed considerable misclassification of several Asthmatic and ACO subjects, who could have been denied inhaled corticosteroids, as they were wrongly categorised as COPD by physician diagnosis.
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Project description:BackgroundIL-17 is a modulator of the inflammatory response and is implicated in lung remodeling in both asthma and chronic obstructive pulmonary disease (COPD). Well as and probably in patients with asthma-COPD overlap (ACO).MethodsIn this study, we evaluated the response of the airways and alveolar septa to anti-IL-17 treatment in an ACO model. Fifty-six male BALB/c mice were sensitized with ovalbumin (OVA group), received porcine pancreatic elastase (PPE group), or both (ACO group). Mice were then treated with either anti-IL-17 monoclonal antibody or saline. We evaluated hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, and mean alveolar diameter. We quantified inflammatory, response, extracellular matrix remodeling, oxidative stress markers, and signaling pathway markers.ResultsAnti-IL-17 treatment in the ACO anti-IL-17 group reduced the maximum response of respiratory system Rrs, Ers, Raw, Gtis, this when compared to the ACO group (p<0.05). There was a reduction in the total number of inflammatory cells, neutrophils, and macrophages in the BALF in the ACO anti-IL-17 group compared to the ACO group (p<0.05). There was attenuated dendritic cells, CD4+, CD8+, FOXP3, IL-1β, IL-2, IL-6, IL-13, IL-17, IL-33 in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p<0.05). We observed a reduction of MMP-9, MMP-12, TIMP-1, TGF-β, collagen type I in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p < 0.05). We also observed a reduction of iNOS and 8-iso-PGF2α in the airways and in the alveolar septum was reduced in the ACO anti-IL-17group compared to the ACO group (p < 0.05). Regarding the signaling pathways, NF-kB, ROCK-1, and ROCK-2 in the airway and alveolar septum were attenuated in the ACO anti-IL-17 group when compared to the ACO group (p<0.05).ConclusionsOur results suggest that inhibiting IL-17 modulates cell-associated cytokine production in lung tissue, extracellular matrix remodeling, and oxidative stress in ACO through the modulation of NF-kB and FOXP3.
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Project description:Although chronic obstructive pulmonary disease (COPD) and asthma are well-characterized diseases, they can coexist in a given patient. The term asthma-COPD overlap (ACO) was introduced to describe patients that have clinical features of both diseases and may represent around 25% of COPD patients and around 20% of asthma patients. Despite the increasing interest in ACO, there are still substantial controversies regarding its definition and its position within clinical guidelines for patients with obstructive lung disease. In general, most definitions indicate that ACO patients must present with non-reversible airflow limitation, significant exposure to smoking or other noxious particles or gases, together with features of asthma. In patients with a primary diagnosis of COPD, the identification of ACO has therapeutic implication because the asthmatic component should be treated with inhaled corticosteroids and some studies suggest that the most severe patients may respond to biological agents indicated for severe asthma. This manuscript aims to summarize the current state-of-the-art of ACO. The definitions, prevalence, and clinical manifestations will be reviewed and some innovative aspects, such as genetics, epigenetics, and biomarkers will be addressed. Lastly, the management and prognosis will be outlined as well as the position of ACO in the COPD and asthma guidelines.
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| S-EPMC6917785 | biostudies-literature
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