The use of roflumilast in COPD: a review

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Chronic inflammation and exacerbations play a central role in the progression of the disease. Currently, treatment options for COPD have been shown to improve the progressive decline in lung-function and/or decrease mortality rates. Roflumilast, a phosphodiesterase- 4 inhibitor, is an anti-inflammatory drug which has been licensed as an add-on therapy for COPD patients with forced expiratory volume in the first second <50% and frequent exacerbations. Clinical trials have demonstrated that roflumilast improves lung function and reduces exacerbation frequency. Roflumilast has a mechanism of action which allows it to obtain a significant additive effect to current therapeutic options for COPD patients. It is generally well tolerated, although the most common adverse effects include diarrhea, nausea, weight loss, and headache. This review article provides an overview of the positive effects of roflumilast on lung function, exacerbation frequency and glucose metabolism, and its interaction with concomitant inhaled treatments.

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Defining asthma–COPD overlap syndrome: a population-based study

European Respiratory Journal ◽

10.1183/13993003.02008-2016 ◽

2017 ◽

Vol 49 (5) ◽

pp. 1602008 ◽

Cited By ~ 28

Author(s):

Tobias N. Bonten ◽

Marise J. Kasteleyn ◽

Renee de Mutsert ◽

Pieter S. Hiemstra ◽

Frits R. Rosendaal ◽

...

Keyword(s):

Lung Function ◽

Patient Characteristics ◽

Population Based ◽

Forced Expiratory Volume ◽

Overlap Syndrome ◽

Self Report ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Adjusted Incidence Rate

Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) seems an important clinical phenotype, but multiple definitions have been proposed. This study's objectives were to assess the effect of different ACOS definitions on prevalence, patient characteristics and exacerbations.5675 individuals aged 45–65 years, with 846 asthma/COPD patients, were included in the Netherlands Epidemiology of Obesity study between 2008 and 2012, and followed-up for a median of 1.8 years. ACOS was defined by recent consensus criteria and five other definitions, based on registry, questionnaires and lung function.Prevalence of ACOS in the asthma/COPD population ranged between 4.4% and 38.3%, depending on the definition used. Agreement between registry-based and self-reported ACOS was 0.04 and 0.41 when lung function (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7) was added. With registry or self-report defined ACOS, only 51% and 33% had FEV1/FVC <0.7. Patient characteristics were similar, but asthma duration was longer with self-reported compared with registry-based ACOS (mean difference 22 years (95% CI 12–33)). Exacerbation risk was highest with registry-based ACOS compared with asthma (adjusted incidence rate ratio 1.6 (95% CI 1.2–2.1)).This study adds important knowledge about agreement between ACOS definitions and their relation with exacerbations. Given the low agreement, differences in prevalence, patient characteristics and risk of exacerbations, consensus about ACOS definition in different care settings is urgently needed.

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Roflumilast is effective in reducing COPD related exacerbations and improving CAT score

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2013.32 ◽

2015 ◽

Vol 79 (3-4) ◽

Author(s):

Biagio Polla

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Intensive Care Unit ◽

Intensive Care ◽

Lung Function ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Important Goal ◽

Obstructive Pulmonary Disease ◽

Copd Assessment Test ◽

Copd Patients

We present a case of a 85-year-old man who suffered from several chronic obstructive pulmonary disease (COPD) related exacerbations and hospitalizations. Traditional therapy, which also included intramuscular steroid therapy, did not help and caused several drug related adverse events. After yet another exacerbation followed by hospitalization at the intensive care unit, it was decided to start roflumilast treatment. In the year after beginning treatment, the patient did not experience any more exacerbations and his lung function also improved, as recorded by the COPD assessment test (CAT) score and improved forced expiratory volume in the first second (FEV1) value. In this patient roflumilast seems to be effective in reducing exacerbations, an important goal to be achieved in COPD patients.

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Prognostic and functional impact of perioperative LAMA/LABA inhaled therapy in patients with lung cancer and chronic obstructive pulmonary disease

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01537-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yoko Azuma ◽

Atsushi Sano ◽

Takashi Sakai ◽

Satoshi Koezuka ◽

Hajime Otsuka ◽

...

Keyword(s):

Lung Cancer ◽

Chronic Obstructive Pulmonary Disease ◽

Postoperative Complications ◽

Lung Function ◽

Retrospective Review ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Inhaled Therapy ◽

Long Acting

Abstract Background Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting β2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients. Methods Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical record to evaluate that LAMA/LABA might be an optimal regimen for patients with COPD undergoing surgery for lung cancer. All patients were received perioperative rehabilitation and divided into 3 groups according to the type of perioperative inhaled therapy and management: LAMA/LABA (n = 64), LAMA (n = 23) and rehabilitation only (no bronchodilator) (n = 43). We conducted a retrospective review of their medical records. Results Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p < 0.001 for both forced expiratory volume in 1 s (FEV1) and percentage of predicted forced expiratory volume in 1 s (FEV1%pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, LAMA/LABA 223.1 mL vs. LAMA 130.0 mL, ΔFEV1%pred, LAMA/LABA 10.8% vs. LAMA 6.8%; both p < 0.05). Postoperative complications were lower frequent in the LAMA/LABA group than in the LAMA group (p = 0.007). In patients with moderate to severe air flow limitation (n = 61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with the LAMA (p = 0.049, p = 0.026) and rehabilitation-only groups (p = 0.001, p < 0.001). Perioperative LAMA/LABA therapy was also associated with lower recurrence rates (vs. LAMA p = 0.006, vs. rehabilitation-only p = 0.008). Conclusions We believe this treatment combination is optimal for patients with lung cancer and COPD.

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FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01409-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying Liu ◽

Jiawei Xu ◽

Tian Liu ◽

Jinxiang Wu ◽

Jiping Zhao ◽

...

Keyword(s):

Lung Function ◽

Airway Inflammation ◽

Cigarette Smoke ◽

Airway Remodeling ◽

Critical Factor ◽

Lavage Fluid ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

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Serum Albumin Concentrations in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10020269 ◽

2021 ◽

Vol 10 (2) ◽

pp. 269

Author(s):

Elisabetta Zinellu ◽

Alessandro G. Fois ◽

Elisabetta Sotgiu ◽

Sabrina Mellino ◽

Arduino A. Mangoni ◽

...

Keyword(s):

Systematic Review ◽

Chronic Obstructive Pulmonary Disease ◽

Serum Albumin ◽

Pulmonary Disease ◽

Meta Analysis ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Standard Mean Difference ◽

Copd Patients

Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and lung parenchyma damage. Systemic inflammation and oxidative stress also play a role in the pathogenesis of COPD. Serum albumin is a negative acute-phase protein with antioxidant effects and an important marker of malnutrition. The aim of this meta-analysis was to investigate differences in serum albumin concentrations between patients with stable COPD and non-COPD subjects. Methods: A systematic search was conducted, using the terms “albumin” and “chronic obstructive pulmonary disease” or “COPD”, in the electronic databases PubMed and Web of Science, from inception to May 2020. Results: Twenty-six studies were identified on a total of 2554 COPD patients and 2055 non-COPD controls. Pooled results showed that serum albumin concentrations were significantly lower in COPD patients (standard mean difference, SMD = −0.50, 95% CI −0.67 to −0.32; p < 0.001). No significant differences were observed in SMD of serum albumin concentrations between COPD patients with forced expiratory volume in the 1st second (FEV1) < 50% and those with FEV1 > 50%. Conclusions: Our systematic review and meta-analysis showed that serum albumin concentrations are significantly lower in patients with stable COPD compared to non-COPD controls. This supports the presence of a deficit in systemic anti-inflammatory and antioxidant defense mechanisms in COPD.

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Newborn DNA-methylation, childhood lung function, and the risks of asthma and COPD across the life course

European Respiratory Journal ◽

10.1183/13993003.01795-2018 ◽

2019 ◽

Vol 53 (4) ◽

pp. 1801795 ◽

Cited By ~ 17

Author(s):

Herman T. den Dekker ◽

Kimberley Burrows ◽

Janine F. Felix ◽

Lucas A. Salas ◽

Ivana Nedeljkovic ◽

...

Keyword(s):

Gene Expression ◽

Lung Function ◽

Life Course ◽

Cord Blood ◽

Childhood Asthma ◽

Respiratory Health ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

The Life Course

RationaleWe aimed to identify differentially methylated regions (DMRs) in cord blood DNA associated with childhood lung function, asthma and chronic obstructive pulmonary disease (COPD) across the life course.MethodsWe meta-analysed epigenome-wide data of 1688 children from five cohorts to identify cord blood DMRs and their annotated genes, in relation to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio and forced expiratory flow at 75% of FVC at ages 7–13 years. Identified DMRs were explored for associations with childhood asthma, adult lung function and COPD, gene expression and involvement in biological processes.ResultsWe identified 59 DMRs associated with childhood lung function, of which 18 were associated with childhood asthma and nine with COPD in adulthood. Genes annotated to the top 10 identified DMRs were HOXA5, PAOX, LINC00602, ABCA7, PER3, CLCA1, VENTX, NUDT12, PTPRN2 and TCL1A. Differential gene expression in blood was observed for 32 DMRs in childhood and 18 in adulthood. Genes related with 16 identified DMRs were associated with respiratory developmental or pathogenic pathways.InterpretationOur findings suggest that the epigenetic status of the newborn affects respiratory health and disease across the life course.

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Household Food Insecurity, Lung Function, and COPD in US Adults

Nutrients ◽

10.3390/nu13062098 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2098

Author(s):

Francisca de Castro Mendes ◽

Kirstie Ducharme-Smith ◽

Gustavo Mora-Garcia ◽

Saleh A. Alqahtani ◽

Maria Stephany Ruiz-Diaz ◽

...

Keyword(s):

Lung Function ◽

Food Insecurity ◽

Representative Sample ◽

Airflow Obstruction ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

The Us ◽

Nationally Representative ◽

Lung Health

Increasing epidemiological evidence suggests that optimal diet quality helps to improve preservation of lung function and to reduce chronic obstructive pulmonary disease (COPD) risk, but no study has investigated the association of food insecurity (FI) and lung health in the general population. Using data from a representative sample of US adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2012 cycles, we investigated the association between FI with lung function and spirometrically defined COPD in 12,469 individuals aged ≥ 18 years of age. FI (high vs. low) was defined using the US Department of Agriculture’s Food Security Scale). Population-weighted adjusted regression models were used to investigate associations between FI, and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio, and spirometrically defined restriction (FVC below the lower limit of normal) and airflow obstruction (COPD). The prevalence of household FI was 13.2%. High household FI was associated with lower FVC (adjusted β-coefficient −70.9 mL, 95% CI −116.6, −25.3), and with higher odds (OR) of spirometric restriction (1.02, 95% CI 1.00, 1.03). Stratified analyses showed similar effect sizes within specific ethnic groups. High FI was associated with worse lung health in a nationally representative sample of adults in the US.

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Prognostic and Functional Impact of Perioperative LAＭA/LABA Inhaled Therapy In Patients With Lung Cancer and Chronic Obstructive Pulmonary Disease

10.21203/rs.3.rs-200524/v1 ◽

2021 ◽

Author(s):

Yoko Azuma ◽

Atsushi Sano ◽

Takashi Sakai ◽

Satoshi Koezuka ◽

Hajime Otsuka ◽

...

Keyword(s):

Lung Cancer ◽

Chronic Obstructive Pulmonary Disease ◽

Postoperative Complications ◽

Lung Function ◽

Pulmonary Disease ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Long Acting

Abstract Background: Chronic obstructive pulmonary disease (COPD) is an important risk factor for postoperative complications and mortality. The utility of several perioperative bronchodilators in patients with COPD requiring surgery for lung cancer has been reported, but the most suitable agent and its specific effect on postoperative long-term prognosis remain unclear. To determine the effects of perioperative combination therapy, using a long-acting muscarinic antagonist (LAMA) and a long-acting β2 agonist (LABA), on preoperative lung function, postoperative morbidity and mortality, and long-term outcome in COPD patients.Methods: Between January 2005 and October 2019, 130 consecutive patients with newly diagnosed COPD underwent surgery for lung cancer. We conducted a retrospective review of their medical records. Patients were divided into 3 groups according to perioperative management: LAMA/LABA (n=64), LAMA (n=23) and rehabilitation only (no bronchodilator) (n=43). Results: Patients who received preoperative LAMA/LABA therapy showed significant improvement in lung function before surgery (p<0.001 for both forced expiratory volume in 1 second (FEV1) and percentage of predicted forced expiratory volume in 1 second (FEV1 %pred). Compared with patients who received preoperative LAMA therapy, patients with LAMA/LABA therapy had significantly improved lung function (ΔFEV1, 223.1 mL vs 130.0 mL, ΔFEV1 %pred, 10.8% vs 6.8%; both p<0.05). There was a trend toward a lower incidence of postoperative complications in the LAMA/LABA group compared with the LAMA and rehabilitation-only groups. In patients with moderate to severe air flow limitation (n=61), those who received LAMA/LABA therapy had significantly longer overall survival and disease-free survival compared with patients in the other groups. Perioperative LAMA/LABA therapy was also associated with lower recurrence rates. Conclusions: Patients who receive perioperative LAMA/LABA for moderate to severe COPD have improved prognosis and better pulmonary function with surgery for lung cancer. We believe this treatment combination is optimal for patients with lung cancer and COPD.

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Randomised controlled trial to investigate the use of high-frequency airway oscillations as training to improve dyspnoea (TIDe) in COPD

Thorax ◽

10.1136/thoraxjnl-2021-217072 ◽

2021 ◽

pp. thoraxjnl-2021-217072

Author(s):

Enya Daynes ◽

Neil Greening ◽

Sally J Singh

Keyword(s):

Muscle Weakness ◽

High Frequency ◽

Controlled Trial ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Registration Number ◽

Randomised Controlled ◽

Double Blinded

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by symptomatic dyspnoea and reduced exercise tolerance, in part as a result muscle weakness, for which inspiratory muscle training (IMT) may be useful. Excess mucus hypersecretion commonly coexists in COPD and may lead to reduce ventilation, further impacting on breathlessness. Devices for sputum clearance may be employed to aid mucus expectoration. This trial aimed to explore the effectiveness of a combined IMT and high-frequency airway oscillating (HFAO) device in the management of dyspnoea.MethodsThis was a double-blinded, randomised sham-controlled trial which recruited symptomatic patients with COPD. Patients were randomised to either a HFAO device (Aerosure) or sham device for 8 weeks, three times a day. The primary outcome was the Chronic Respiratory Questionnaire dyspnoea (CRQ-D) domain. Pre-specified subgroup analyses were performed including those with respiratory muscle weakness, excessive sputum and frequent exacerbators.Results104 participants (68% men, mean (SD) age 69.75 years (7.41), forced expiratory volume in 1 s per cent predicted 48.22% (18.75)) were recruited to this study with 96 participants completing. No difference in CRQ-D was seen between groups (0·28, 95% CI −0.19 to 0.75, p=0.24), though meaningful improvements were seen over time in both groups (mean (SD) HFAO 0.45 (0.78), p<0.01; sham 0.73 (1.09), p<0.01). Maximal inspiratory pressure significantly improved in the HFAO group over sham (5.26, 95% CI 0.34 to 10.19, p=0.05). Similar patterns were seen in the subgroup analysis.ConclusionThere were no statistical differences between the HFAO and the sham group in improving dyspnoea measured by the CRQ-D.Trial registration numberISRCTN45695543.

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Association of Plasma Heat Shock Protein 70 with Disease Severity, Smoking and Lung Function of Patients with Chronic Obstructive Pulmonary Disease

10.21203/rs.3.rs-41671/v1 ◽

2020 ◽

Author(s):

Iva Hlapčić ◽

Andrea Hulina-Tomašković ◽

Marija Grdić Rajković ◽

Sanja Popović-Grle ◽

Andrea Vukić Dugac ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Heat Shock ◽

Lung Function ◽

Heat Shock Protein ◽

Disease Severity ◽

Heat Shock Protein 70 ◽

Smoking Status ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients

Abstract Background: Extracellular heat shock protein 70 (eHsp70) acts like a damage-associated molecular pattern (DAMP) and it might modulate immune responses in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore plasma eHsp70 concentration in patients with stable COPD, its association with disease severity and smoking status as well as its diagnostic performance in COPD assessment.Methods: Blood samples were collected from 137 COPD patients and 95 healthy individuals. COPD patients were subdivided into GOLD 2-4 stages based on airflow obstruction severity and GOLD A-D groups regarding symptoms and exacerbations. Concentration of eHsp70 was assessed in EDTA plasma by the commercially available ELISA kit. Statistic analysis was performed by MedCalc statistical software.Results: eHsp70 concentration was increased in COPD patients when compared to controls and was increasing with the severity of airflow limitation as well as symptoms burden and exacerbation history. There were no differences in eHsp70 concentrations among COPD patients based on smoking status, yet eHsp70 was increased in healthy smokers compared to healthy non-smokers. Interestingly, healthy smokers had similar eHsp70 level as COPD patients in GOLD 2 stage and those in GOLD A group. In addition, eHsp70 showed significant negative correlation with lung function parameters FEV1 and FEV1/FVC and positive correlation with COPD multicomponent indices BODCAT, BODEx, CODEx and DOSE. Finally, eHsp70 showed great predictive value (OR=7.63) and correctly classified 76% of cases.Conclusions: Plasma eHsp70 is associated with COPD prediction and disease severity and might have a potential of becoming an additional biomarker in COPD assessment.

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