Chronic Obstructive Pulmonary Disease and Lung Cancer: A Review for Clinicians

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are common global causes of morbidity and mortality. Because both diseases share several predisposing risks, the two diseases may occur concurrently in susceptible individuals. The diagnosis of COPD has important implications for the diagnostic approach and treatment options if lesions concerning for LC are identified during screening. Importantly, the presence of COPD has significant implications on prognosis and management of patients with LC. In this monograph, we review the mechanistic linkage between LC and COPD, the impact of LC screening in patients at risk, and the implications of the presence of COPD on the approach to the diagnosis and treatment of LC. This manuscript succinctly reviews the epidemiology and common pathogenetic factors for the concurrence of COPD and LC. Importantly for the clinician, it summarizes the indications, benefits, and complications of LC screening in patients with COPD, and the assessment of risk factors for patients with COPD undergoing consideration of various treatment options for LC

Several clinical interests regarding lung volume reduction surgery for severe emphysema: meta-analysis and systematic review of randomized controlled trials

<p>Abstract</p> <p>Objectives</p> <p>We aim to address several clinical interests regarding lung volume reduction surgery (LVRS) for severe emphysema using meta-analysis and systematic review of randomized controlled trials (RCTs).</p> <p>Methods</p> <p>Eight RCTs published from 1999 to 2010 were identified and synthesized to compare the efficacy and safety of LVRS vs conservative medical therapy. One RCT was obtained regarding comparison of median sternotomy (MS) and video-assisted thoracoscopic surgery (VATS). And three RCTs were available evaluating clinical efficacy of using bovine pericardium for buttressing, autologous fibrin sealant and BioGlue, respectively.</p> <p>Results</p> <p>Odds ratio (95%CI), expressed as the mortality of group A (the group underwent LVRS) versus group B (conservative medical therapies), was 5.16(2.84, 9.35) in 3 months, 3(0.94, 9.57) in 6 months, 1.05(0.82, 1.33) in 12 months, respectively. On the 3^rd, 6^thand 12^thmonth, all lung function indices of group A were improved more significantly as compared with group B. PaO2 and PaCO2 on the 6^thand 12^thmonth showed the same trend. 6MWD of group A on the 6^thmonth and 12^thmonth were improved significantly than of group B, despite no difference on the 3^rdmonth. Quality of life (QOL) of group A was better than of group B in 6 and 12 months. VATS is preferred to MS, due to the earlier recovery and lower cost. And autologous fibrin sealant and BioGlue seems to be the efficacious methods to reduce air leak following LVRS.</p> <p>Conclusions</p> <p>LVRS offers the more benefits regarding survival, lung function, gas exchange, exercise capacity and QOL, despite the higher mortality in initial three postoperative months. LVRS, with the optimization of surgical approach and material for reinforcement of the staple lines, should be recommended to patients suffering from severe heterogeneous emphysema.</p

The Effect of ICS Withdrawal and Baseline Inhaled Treatment on Exacerbations in the IMPACT Study: A Randomized, Double-blind Multicenter Trial

RATIONALE: In the IMPACT trial fluticasone furoate/umeclidinium/ vilanterol (FF/UMEC/VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations. OBJECTIVES: Understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results given direct transition from prior maintenance medication to study medication at randomization. METHODS: Exacerbations and change from baseline in trough forced expiratory volume in 1 second (FEV1) and St George's Respiratory Questionnaire (SGRQ) were analyzed by prior ICS use. Exacerbations were also analyzed excluding data from the first 30 days. MEASUREMENTS AND MAIN RESULTS: FF/UMEC/VI significantly reduced annual moderate/severe exacerbation rate versus UMEC/VI in prior ICS users (29% reduction; p<0.001), but only a numerical reduction was seen among prior ICS non-users (12% reduction; p=0.115). To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF/UMEC/VI continued to significantly reduce annual on-treatment moderate/severe exacerbation rate (19%; p<0.001) versus UMEC/VI. Benefit of FF/UMEC/VI versus UMEC/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users: 35% reduction, p<0.001; non-ICS users: 35% reduction, p=0.018) and overall when excluding the first 30 days (29%, p<0.001). Improvements from baseline with FF/UMEC/VI versus UMEC/VI were also maintained throughout the study for both trough FEV1 and SGRQ regardless of prior ICS use. CONCLUSIONS: These data support important treatment effects from FF/UMEC/VI combination therapy on exacerbation reduction, lung function and quality of life that do not appear to be related to abrupt ICS withdrawal. FUNDING: GSK (CTT116855/NCT02164513). Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02164513. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis of the IMPACT Trial

BACKGROUND: In the IMPACT trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations, with a similar safety profile. Research Question Does age have an effect on trial outcomes? STUDY DESIGN AND METHODS: IMPACT was a Phase III, double-blind, 52-week trial. Patients ≥40 years of age with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 mcg, FF/VI 100/25 mcg, or UMEC/VI 62.5/25 mcg. Endpoints assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough forced expiratory volume in 1 second (FEV1), proportion of St George's Respiratory Questionnaire (SGRQ) responders (≥4 units decrease from baseline in SGRQ total score) and safety. RESULTS: The intent-to-treat population comprised 10,355 patients; 4724 (46%), 4225 (41%), and 1406 (14%) were ≤64, 65-74, and ≥75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates versus FF/VI (% reduction [95% confidence interval (CI)], ≤64 years: 8% [-1, 16], p=0.070; 65-74 years: 22% [14, 29], p<0.001; ≥75 years 18% [3, 31], p=0.021) and versus UMEC/VI (≤64 years: 16% [7, 25], p=0.002; 65-74 years: 33% [25, 41], p<0.001; ≥75 years 24% [6, 38], p=0.012), with greatest rate reduction seen in the 65-74 and ≥75 years subgroups. Post hoc analyses of CFB in trough FEV1, and proportion of SGRQ responders at Week 52 were significantly greater with FF/UMEC/VI than FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. INTERPRETATION: FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status versus FF/VI and UMEC/VI irrespective of age for most endpoints, with a similar safety profile. CLINICAL TRIAL REGISTRATION: GSK (CTT116855/NCT02164513)

Effect of chronic mucus hypersecretion on treatment responses to inhaled therapies in patients with chronic obstructive pulmonary disease: Post hoc analysis of the IMPACT trial.

This is the final version. Available from Wiley via the DOI in this record. DATA AVAILABILITY STATEMENT: Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.BACKGROUND AND OBJECTIVE: Chronic mucus hypersecretion (CMH) is a clinical phenotype of COPD. This exploratory post hoc analysis assessed relationship between CMH status and treatment response in IMPACT. METHODS: Patients were randomized to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg, FF/VI 100/25 μg or UMEC/VI 62.5/25 μg and designated CMH+ if they scored 1/2 in St George's Respiratory Questionnaire (SGRQ) questions 1 and 2. Endpoints assessed by baseline CMH status included on-treatment exacerbation rates, change from baseline in trough forced expiratory volume in 1 second, SGRQ total score, COPD Assessment Test (CAT) score, proportion of SGRQ and CAT responders at Week 52 and safety. RESULTS: Of 10,355 patients in the intent-to-treat population, 10,250 reported baseline SGRQ data (CMH+: 62% [n = 6383]). FF/UMEC/VI significantly (p < 0.001) reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in CMH+ (rate ratio: 0.87 and 0.72) and CMH- patients (0.82 and 0.80). FF/UMEC/VI significantly (p < 0.05) reduced on-treatment severe exacerbation rates versus UMEC/VI in CMH+ (0.62) and CMH- (0.74) subgroups. Similar improvements in health status and lung function with FF/UMEC/VI were observed, regardless of CMH status. In CMH+ patients, FF/VI significantly (p < 0.001) reduced on-treatment moderate/severe and severe exacerbation rates versus UMEC/VI (0.83 and 0.70). CONCLUSION: FF/UMEC/VI had a favourable benefit: risk profile versus dual therapies irrespective of CMH status. The presence of CMH did not influence treatment response or exacerbations, lung function and/or health status. However, CMH did generate differences when dual therapies were compared and the impact of CMH should be considered in future trial design.GlaxoSmithKleinNational Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC

Evidence of mycobacterial disease in COPD patients with lung volume reduction surgery; the importance of histological assessment of specimens: a cohort study

Background Patients with COPD are at risk of non-tuberculous mycobacterial infection (NTM). This study examined the histology of lung tissue from COPD patients following lung volume reduction with particular focus on evidence of mycobacterial infection. Methods Retrospective histological study of 142 consecutive lung volume reduction surgical specimens (126 separate patients) at Royal Brompton Hospital between 2000 – 2013, with prospectively collected preoperative data on exacerbation rate, lung function and body mass index. Results 92% of patients had at least one other histological diagnosis in addition to emphysema. 10% of specimens had histological evidence of mycobacterial infection, one with co-existent aspergilloma. Mycobacteria were only identified in those patients with granulomas that were necrotising. These patients had higher exacerbation rates, lower TLCO and FEV1. Conclusion A proportion of severe COPD patients will have evidence of mycobacterial infection despite lack of clinical and radiological suspicion. This may have implications for long-term management of these patients

Prognostic value of clinically important deterioration in COPD: IMPACT trial analysis

Introduction: Clinically important deterioration (CID) is a multicomponent measure for assessing disease worsening in chronic obstructive pulmonary disease (COPD). This analysis investigated the prognostic value of a CID event on future clinical outcomes and the effect of single-inhaler triple versus dual therapy on reducing CID risk in patients in the IMPACT trial. Methods: IMPACT was a phase III, double-blind, 52-week, multicentre trial. Patients with symptomatic COPD and at least one moderate/severe exacerbation in the prior year were randomised 2:2:1 to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg, FF/VI 100/25 µg or UMEC/VI 62.5/25 µg. CID at the time-point of interest was defined as a moderate/severe exacerbation, ≥100 mL decrease in trough forced expiratory volume in 1 s or deterioration in health status (increase of ≥4.0 units in St George's Respiratory Questionnaire total score or increase of ≥2.0 units in COPD Assessment Test score) from baseline. A treatment-independent post hoc prognostic analysis compared clinical outcomes up to week 52 in patients with/without a CID by week 28. A prospective analysis evaluated time to first CID with each treatment. Results: Patients with a CID by week 28 had significantly increased exacerbation rates after week 28, smaller improvements in lung function and health status at week 52 (all p<0.001), and increased risk of all-cause mortality after week 28 versus patients who were CID-free. FF/UMEC/VI significantly reduced CID risk versus dual therapies (all p<0.001). Conclusions: Prevention of short-term disease worsening was associated with better long-term clinical outcomes. FF/UMEC/VI reduced CID risk versus dual therapies; this effect may improve long-term prognosis in this population

InforMing the PAthway of COPD Treatment (IMPACT) trial: fibrinogen levels predict risk of moderate or severe exacerbations

Background: Fibrinogen is the first qualified prognostic/predictive biomarker for exacerbations in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial investigated fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI and UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This analysis used IMPACT trial data to examine the relationship between fibrinogen levels and exacerbation outcomes in patients with COPD. Methods: 8094 patients with a fibrinogen assessment at Week 16 were included, baseline fibrinogen data were not measured. Post hoc analyses were performed by fibrinogen quartiles and by 3.5 g/L threshold. Endpoints included on-treatment exacerbations and adverse events of special interest (AESIs). Results: Rates of moderate, moderate/severe, and severe exacerbations were higher in the highest versus lowest fibrinogen quartile (0.75, 0.92 and 0.15 vs 0.67, 0.79 and 0.10, respectively). The rate ratios (95% confidence interval [CI]) for exacerbations in patients with fibrinogen levels ≥ 3.5 g/L versus those with fibrinogen levels < 3.5 g/L were 1.03 (0.95, 1.11) for moderate exacerbations, 1.08 (1.00, 1.15) for moderate/severe exacerbations, and 1.30 (1.10, 1.54) for severe exacerbations. There was an increased risk of moderate/severe exacerbation (hazard ratio [95% CI]: highest vs lowest quartile 1.16 [1.04, 1.228]; ≥ 3.5 g/L vs < 3.5 g/L: 1.09 [1.00, 1.16]) and severe exacerbation (1.35 [1.09, 1.69]; 1.27 [1.08, 1.47], respectively) with increasing fibrinogen level. Cardiovascular AESIs were highest in patients in the highest fibrinogen quartile. Conclusions: Rate and risk of exacerbations was higher in patients with higher fibrinogen levels. This supports the validity of fibrinogen as a predictive biomarker for COPD exacerbations, and highlights the potential use of fibrinogen as an enrichment strategy in trials examining exacerbation outcomes. Trial registration: NCT0216451

The six-minute walk test in community dwelling elderly: influence of health status.

BACKGROUND: The 6 minutes walk test (6MWT) is a useful assessment instrument for the exercise capacity of elderly persons. The impact of the health status on the 6MWT-distance in elderly, however, remains unclear, reducing its value in clinical settings. The objective of this study was to investigate to what extent the 6MWT-distance in community dwelling elderly is determined by health conditions. METHODS: One hundred and fifty-six community dwelling elderly people (53 male, 103 female) were assessed for health status and performed the 6MWT. After clinical evaluation, electrocardiography and laboratory examination participants were categorized into a stratified six-level classification system according to their health status, going from A (completely healthy) to D (signs of active disease at the moment of examination). RESULTS: The mean 6MWT-distance was 603 m (SD = 178). The 6MWT-distance decreased significantly with increasing age (ANOVA p = 0.0001) and with worsening health status (ANCOVA, corrected for age p < 0.001). A multiple linear regression model with health status, age and gender as independent variables explained 31% of the 6MWT-distance variability. Anthropometrical measures (stature, weight and BMI) did not significantly improve the prediction model. A significant relationship between 6MWT-distance and stature was only present in category A (completely healthy). CONCLUSIONS: Significant differences in 6MWT-distance are observed according to health status in community-dwelling elderly persons. The proposed health categorizing system for elderly people is able to distinguish persons with lower physical exercise capacity and can be useful when advising physical trainers for seniors