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      The Value of FENO Measurement for Predicting Treatment Response in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

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          Fractional exhaled nitric oxide (FENO) has been shown to be a marker of airway inflammation in various pulmonary diseases, including chronic obstructive pulmonary disease (COPD). In this study, we assessed the FENO level in patients with acute exacerbations of COPD (AECOPD) and analyzed the predictive value of the FENO level for treatment response.


          Demographic data were collected at admission. FENO, lung function, blood gases, COPD Assessment Test (CAT), and modified Medical Research Council (mMRC) scores were measured at admission and on day 7. At the second visit, the patients were asked to report their health status; scores ranged from 1 to 5, representing “much better”, “slightly better”, “no change”, “slightly worse”, and “much worse”, respectively. The treatment response was evaluated based on the patient’s reported health status (responders were those who reported much better and slightly better) and lung function (responders were those who presented an increase in FEV 1 over 200 mL).


          A total of 182 patients were recruited into the analysis. The FENO level positively correlated with an increase in FEV 1 and FEV 1% (r = 0.291, p < 0.001 and r = 0.205, p = 0.005, respectively), but negatively correlated with a decrease in the COPD Assessment Test (CAT) score (r = −0.197, p = 0.008) and patient-reported health status (rho = −0.408, p<0.001). An inverse correlation was observed between FENO concentrations at admission and the length of hospital stay. The cut-off point for differentiating responders, identified by health status, was 18 ppb, with the sensitivity being 89.7% and specificity 88.9%.


          FENO levels, determined at hospital admission, are potential to predict the overall treatment response in AECOPD patients, including remission in subjective patient-reported health statuses and, also, improvements in lung function.

          Registry Number

          ChiCTR-ROC-16,009,087 ( ).

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          Most cited references 25

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          Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE).

          Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and not well understood. The forced expiratory volume in one second is used for the diagnosis and staging of COPD, but there is wide acceptance that it is a crude measure and insensitive to change over shorter periods of time. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) is a 3-yr longitudinal study with four specific aims: 1) definition of clinically relevant COPD subtypes; 2) identification of parameters that predict disease progression in these subtypes; 3) examination of biomarkers that correlate with COPD subtypes and may predict disease progression; and 4) identification of novel genetic factors and/or biomarkers that both correlate with clinically relevant COPD subtypes and predict disease progression. ECLIPSE plans to recruit 2,180 COPD subjects in Global Initiative for Chronic Obstructive Lung Disease categories II-IV and 343 smoking and 223 nonsmoking control subjects. Study procedures are to be performed at baseline, 3 months, 6 months and every 6 months thereafter. Assessments include pulmonary function measurements (spirometry, impulse oscillometry and plethysmography), chest computed tomography, biomarker measurement (in blood, sputum, urine and exhaled breath condensate), health outcomes, body impedance, resting oxygen saturation and 6-min walking distance. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points is the largest study attempting to better describe the subtypes of chronic obstructive pulmonary disease, as well as defining predictive markers of its progression.
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            Mortality and mortality-related factors after hospitalization for acute exacerbation of COPD.

            Acute exacerbations form a major component of the socioeconomic burden of COPD. As yet, little information is available about the long-term outcome of patients who have been hospitalized with acute exacerbations, although high mortality rates have been reported. The aim of this study was to investigate prospectively the outcome for all patients admitted to the hospital with acute exacerbations of COPD during hospital admission and after 1-year of follow-up. Furthermore, patient characteristics related to increased mortality rate were analyzed. We investigated prospectively the 1-year mortality rate and potential determinants of mortality for all patients admitted to the hospital with an acute exacerbation between January 1 and December 31, 1999. A total of 171 patients were included in the study. The mortality rate during hospital stay was 8%, increasing to 23% after 1 year of follow-up. Despite a comparable in-hospital mortality rate (6%), the 1-year mortality rate was significantly higher for patients admitted to the ICU for respiratory failure (35%). The multivariate Cox proportional hazards model was used to determine independent predictors of survival. Variables included in the regression model were age, sex, FEV(1), PaO(2), PaCO(2), body mass index, long-term use of oral corticosteroids, comorbidity index, and hospital readmissions. The maintenance use of oral glucocorticosteroids (relative risk [RR], 5.07; 95% confidence interval [CI], 2.03 to 12.64), PaCO(2) (RR, 1.17; 95% CI, 1.01 to 1.38), and age (RR, 1.07; 95% CI, 1.01 to 1.12) were independently related to mortality. We conclude that the prognosis for patients who have been admitted to the hospital for acute exacerbation of COPD is poor. Long-term use of oral corticosteroids, higher PaCO(2), and older age could be identified as risk factors associated with higher mortality.
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              Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study.

              Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function. No drug has been shown conclusively to reduce this decline. In a post hoc analysis of the Toward a Revolution in COPD Health (TORCH) study, we investigated the effects of combined salmeterol 50 microg plus fluticasone propionate 500 microg, either component alone or placebo, on the rate of post-bronchodilator FEV(1) decline in patients with moderate or severe COPD. A randomized, double-blind, placebo-controlled study was conducted from September 2000 to November 2005 in 42 countries. Of 6,112 patients from the efficacy population, 5,343 were included in this analysis. Spirometry was measured every 24 weeks for 3 years. There were 26,539 on-treatment observations. The adjusted rate of decline in FEV(1) was 55 ml/year for placebo, 42 ml/year for salmeterol, 42 ml/year for fluticasone propionate, and 39 ml/year for salmeterol plus fluticasone propionate. Salmeterol plus fluticasone propionate reduced the rate of FEV(1) decline by 16 ml/year compared with placebo (95% confidence interval [CI], 7-25; P < 0.001). The difference was smaller for fluticasone propionate and salmeterol compared with placebo (13 ml/year; 95% CI, 5-22; P = 0.003). Rates of decline were similar among the active treatment arms. FEV(1) declined faster in current smokers and patients with a lower body mass index, and varied between world regions. Patients who exacerbated more frequently had a faster FEV(1) decline. Pharmacotherapy with salmeterol plus fluticasone propionate, or the components, reduces the rate of decline of FEV(1) in patients with moderate-to-severe COPD, thus slowing disease progression. Clinical trial (GSK Study Code SCO30003) registered with (NCT00268216).

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of Chronic Obstructive Pulmonary Disease
                24 September 2020
                : 15
                : 2257-2266
                [1 ]Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University , Changsha, Hunan 410011, People’s Republic of China
                [2 ]Research Unit of Respiratory Disease, Central South University , Changsha, Hunan 410011, People’s Republic of China
                [3 ]Department of Respiratory Medicine, The First Affiliated People’s Hospital, Shaoyang College , Shaoyang, Hunan 422000, People’s Republic of China
                Author notes
                Correspondence: Ping Chen Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University , Changsha, Hunan410011, People’s Republic of China Email
                © 2020 Zhou et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( 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 (

                Page count
                Figures: 5, Tables: 6, References: 31, Pages: 10
                Original Research

                Respiratory medicine

                copd, exacerbation, feno, lung function, treatment response


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