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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

      39,063 Monthly downloads/views I 2.893 Impact Factor I 5.2 CiteScore I 1.16 Source Normalized Impact per Paper (SNIP) I 0.804 Scimago Journal & Country Rank (SJR)

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      Role of the Bronchodilator Test Defined by the Forced Vital Capacity in Chronic Obstructive Pulmonary Disease Phenotyping

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          Abstract

          Purpose

          In clinical practice, some chronic obstructive pulmonary disease (COPD) patients experienced a remarkable increase in forced vital capacity (FVC) after bronchodilator administration, whereas forced expiratory volume in the first second (FEV1) remains substantially unchanged. We assume this may relate to airway inflammatory type. We aim to analyze the clinical characteristics and explore the usefulness of the bronchodilator test, especially FVC, in this new COPD phenotype.

          Patients and Methods

          A total of 346 COPD patients with exacerbation who underwent bronchodilator tests, fractional exhaled nitric oxide (FeNO) measurements and blood eosinophil counts were analyzed. The characteristics, FeNO levels, and blood eosinophil counts were compared between patients with and without significant bronchodilator responsiveness in terms of FVC.

          Results

          Patients with significant FVC responsiveness displayed poorer lung function and higher FeNO levels compared with those without considerable FVC responsiveness (Z= −5.042 to −0.375, p=0.000–0.022). There is a discernible linear relationship between FeNO levels and FVC responsiveness to bronchodilator use (r=0.251, P=0.001). The application of bronchodilator responsiveness of FVC for detecting high FeNO levels in COPD patients exhibited relatively high sensitivity (61.8%) and specificity (86.7%).

          Conclusion

          We demonstrated that COPD patients with significant FVC responsiveness had higher FeNO levels than non-responders and established a simple method for detecting high FeNO values. FVC responders may be identified as a separate group of COPD patients.

          Most cited references18

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          Clinical COPD phenotypes: a novel approach using principal component and cluster analyses.

          D Caillaud, N. Roche, I Court-Fortune … (2010)
          Classification of chronic obstructive pulmonary disease (COPD) is usually based on the severity of airflow limitation, which may not reflect phenotypic heterogeneity. Here, we sought to identify COPD phenotypes using multiple clinical variables. COPD subjects recruited in a French multicentre cohort were characterised using a standardised process. Principal component analysis (PCA) was performed using eight variables selected for their relevance to COPD: age, cumulative smoking, forced expiratory volume in 1 s (FEV(1)) (% predicted), body mass index, exacerbations, dyspnoea (modified Medical Research Council scale), health status (St George's Respiratory Questionnaire) and depressive symptoms (hospital anxiety and depression scale). Patient classification was performed using cluster analysis based on PCA-transformed data. 322 COPD subjects were analysed: 77% were male; median (interquartile range) age was 65.0 (58.0-73.0) yrs; FEV(1) was 48.9 (34.1-66.3)% pred; and 21, 135, 107 and 59 subjects were classified in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1, 2, 3 and 4, respectively. PCA showed that three independent components accounted for 61% of variance. PCA-based cluster analysis resulted in the classification of subjects into four clinical phenotypes that could not be identified using GOLD classification. Importantly, subjects with comparable airflow limitation (FEV(1)) belonged to different phenotypes and had marked differences in age, symptoms, comorbidities and predicted mortality. These analyses underscore the need for novel multidimensional COPD classification for improving patient care and quality of clinical trials.
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            Stable COPD: predicting benefit from high-dose inhaled corticosteroid treatment.

            F Maltais, John R. Leigh, F Hargreave … (2006)
            The role of inhaled corticosteroids in the management of chronic obstructive pulmonary disease (COPD) remains controversial. The purpose of this study was to evaluate whether sputum eosinophilia (defined as eosinophils > or = 3%) predicts clinical benefit from inhaled corticosteroid treatment in patients with smoking-related clinically stable moderate-to-severe COPD. Forty consecutive patients with effort dyspnoea (mean age 67 yrs; 52 pack-yr smoking history; post-bronchodilator forced expiratory volume in one second (FEV1) <60% predicted, consistent with moderate-to-severe smoking-related chronic airflow limitation) were enrolled. Subjects were treated with inhaled placebo followed by inhaled budesonide (Pulmicort Turbuhaler 1,600 microg.day(-1)), each given for 4 weeks. While the treatment was single-blind (subject level), sputum cell counts before and after treatment interventions were double-blind, thus removing bias. Outcome variables included spirometry, quality-of-life assessment and 6-min walk test. Sputum eosinophilia was present in 38% of subjects. In these, budesonide treatment normalised the eosinophil counts and, in comparison to placebo treatment, resulted in clinically significant improvement in the dyspnoea domain of the disease-specific chronic respiratory questionnaire (0.8 versus 0.3) and a small but statistically significant improvement in post-bronchodilator spirometry (FEV1 100 mL versus 0 mL; p<0.05). In conclusion, sputum eosinophilia predicts short-term clinical benefit from high-dose inhaled corticosteroid treatment in patients with stable moderate-to-severe chronic obstructive pulmonary disease.
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              Nitric oxide synthase isoenzyme expression and activity in peripheral lung tissue of patients with chronic obstructive pulmonary disease.

              W. Crawford Elliott, Caterina Brindicci, Misako Ito … (2010)
              Nitric oxide (NO) is increased in the lung periphery of patients with chronic obstructive pulmonary disease (COPD). However, expression of the NO synthase(s) responsible for elevated NO has not been identified in the peripheral lung tissue of patients with COPD of varying severity. Protein and mRNA expression of nitric oxide synthase type I (neuronal NOS [nNOS]), type II (inducible NOS [iNOS]), and type III (endothelial NOS [eNOS]) were quantified by Western blotting and reverse transcription-polymerase chain reaction, respectively, in specimens of surgically resected lung tissue from nonsmoker control subjects, patients with COPD of varying severity, and smokers without COPD, and in a lung epithelial cell line (A549). The effects of nitrative/oxidative stress on NOS expression and activity were also evaluated in vitro in A549 cells. nNOS nitration was quantified by immunoprecipitation and dimerization of nNOS was detected by low-temperature SDS-PAGE/Western blot in the presence of the peroxynitrite generator, 3-morpholinosydnonimine-N-ethylcarbamide (SIN1), in vitro and in vivo. Lung tissue from patients with severe and very severe COPD had graded increases in nNOS (mRNA and protein) compared with nonsmokers and normal smokers. Hydrogen peroxide (H(2)O(2)) and SIN1 as well as the cytokine mixture (IFN-gamma, IL-1beta, and tumor necrosis factor-alpha) increased mRNA expression and activity of nNOS in A549 cells in a concentration-dependent manner compared with nontreated cells. Tyrosine nitration resulted in an increase in nNOS activity in vitro, but did not affect its dimerization. Patients with COPD have a significant increase in nNOS expression and activity that reflects the severity of the disease and may be secondary to oxidative stress.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Chron Obstruct Pulmon Dis
                Journal ID (iso-abbrev): Int J Chron Obstruct Pulmon Dis
                Journal ID (publisher-id): COPD
                Journal ID (pmc): copd
                Title: International Journal of Chronic Obstructive Pulmonary Disease
                Publisher: Dove
                ISSN (Print): 1176-9106
                ISSN (Electronic): 1178-2005
                Publication date (Electronic): 28 May 2020
                Publication date Collection: 2020
                Volume: 15
                Pages: 1199-1206
                Affiliations
                [1 ]Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University , Jinan 250021, Shandong, People’s Republic of China
                [2 ]Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University , Jinan 250000, Shandong, People’s Republic of China
                [3 ]Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Shandong First Medical University , Jinan 250000, Shandong, People’s Republic of China
                [4 ]Shandong Key Laboratory of Infectious Respiratory Disease , Jinan 250000, Shandong, People’s Republic of China
                Author notes
                Correspondence: Shujuan Jiang Email zhangxl120923@163.com
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: 252902
                DOI: 10.2147/COPD.S252902
                PMC ID: 7266342
                PubMed ID: 32547006
                SO-VID: d7353344-b0b5-4666-b040-b7d1d5b2feb1
                Copyright © © 2020 Zhang et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Page count
                Figures: 3, Tables: 1, References: 34, Pages: 8
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Respiratory medicine
                Keywords: copd,pulmonary function test,bronchodilator responsiveness,forced vital capacity,fractional exhaled nitric oxide
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: copd, pulmonary function test, bronchodilator responsiveness, forced vital capacity, fractional exhaled nitric oxide

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