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IntroductionChronic lung disease is common among people living with HIV (PLWH). We hypothesised that PLWH receiving antiretroviral therapy (ART) have faster lung function decline than matched controls.MethodsWe performed a prospective matched cohort study by including ART-treated PLWH from the Copenhagen Co-morbidity in HIV Infection Study (n=705) and the INSIGHT Strategic Timing of Antiretroviral Treatment Pulmonary Substudy (n=425) and frequency matched population controls from the Copenhagen General Population Study (n=2895) in a 1:3 ratio. Eligible participants were ≥25 years old and had two spirometry tests separated by at least 2 years of follow-up. Forced expiratory volume in 1 s (FEV1) decline (mL/year) was compared between PLWH and controls using a linear mixed model adjusted for age, sex, ethnicity and smoking status. Effect modification by smoking was investigated in subgroup analyses.ResultsThe majority of PLWH were virally suppressed (96.1%). The adjusted mean annual decline in FEV1was faster in PLWH than in controls with 36.4 (95% CI 33.7 to 39.1) vs 27.9 (95% CI 26.9 to 28.8) mL/year, yielding a difference of 8.5 (95% CI 5.6 to 11.4) mL/year. The association between HIV and FEV1decline was modified by smoking, with the largest difference in current smokers (difference: 16.8 (95% CI 10.5 to 23.0) mL/year) and the smallest difference in never-smokers (difference: 5.0 (95% CI 0.7 to 9.3) mL/year). FEV1decline >40 mL/year was more prevalent in PLWH (adjusted OR: 1.98 (95% CI 1.67 to 2.34)).ConclusionWell-treated PLWH have faster lung function decline than controls and smoking seems to modify this association, suggesting that smoking may lead to more rapid lung function decline in PLWH than in controls.

Background: During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements. Methods: In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20–94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year. Findings: Across the ten included studies, we included 243 465 European participants (mean age 51·4 years, 95% CI 51·4–51·5) in our analysis, of whom 136 275 (56·0%) were female and 107 190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6–7·0; p1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09–0·14; p

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene–environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: “young” individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider “young” patients with COPD those patients in the age range of 20–50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age.

The increasing prevalence of reported annoyances in the indoor environment threatens public health. This study aimed to investigate the association between perceived annoyances from the home environment and respiratory infections among individuals with and without asthma or chronic obstructive pulmonary disease (COPD). A total of 16,688 individuals from the Danish Health and Morbidity Survey initiated in 2000 were grouped according to their patterns of perceived annoyances. Information on respiratory infections (all causes, bacterial, viral, and those leading to hospital admissions) was obtained from Danish registers up to 19 years after the survey. Poisson regression of incidence rates (IRs) was applied to estimate incidence rate ratios (IRRs). Annoyances significantly increased the IR for respiratory infections of all causes and bacterial respiratory infections in individuals without asthma or COPD, adjusted IRR 1.16 (95% CI: 1.01, 1.34) and 1.15 (95% CI: 1.02, 1.31), respectively. However, no difference was observed for viral respiratory infections nor hospital admissions. Individuals with asthma or COPD and a high level of annoyances had a non-significantly increased IR in all four analyses of respiratory infections. These findings provide support for perceived annoyances as an important risk factor for respiratory infections.

Rationale: Natural history of preserved ratio impaired spirometry (PRISm), often defined as FEV1/FVC ≥lower limit of normal and FEV1

Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity? Study Design and Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry. Results: Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV 1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels. Interpretation: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.

Daytime sleepiness is a cardinal symptom of obstructive sleep apnoea (OSA) and a well-recognised side effect of beta-blockers, therefore patients with OSA under this treatment may have worse sleepiness. However, the interaction between daytime sleepiness and beta-blockers use has not been thoroughly investigated in patients with OSA before. We analysed the data of 2183 individuals (1852 patients with OSA and 331 snorer controls) from 3 countries (Greece, Hungary and Moldova). Medical history, including medication usage and the Epworth Sleepiness Scale (ESS) were recorded. Patients and controls were divided into somnolent (ESS ≥ 11) and non-somnolent (ESS p = 0.24) or control (p = 0.64) groups. These results were similar in sensitivity analyses (all p > 0.05). ESS was related to BMI (ρ = 0.25), total sleep time (ρ = 0.07), AHI (ρ = 0.32), oxygen desaturation index (ρ = 0.33) and minimum oxygen saturation (ρ = – 0.32, all p p

Introduction The COPD classification proposed by the Global Initiative for Obstructive Lung Disease was recently revised, and the A to D grouping is now based on symptoms and exacerbations only. Potential associations with comorbidities have not been assessed so far. Thus the aim of the present study was to determine the relationship between the revised (2017) GOLD groups A-D and major comorbidities. Methods We used baseline data from the COPD cohort COSYCONET. Comorbidities were identified from patient self-reports and disease-specific medication: gastrointestinal disorders, asthma, sleep apnea, hyperuricemia, hyperlipidemia, diabetes, osteoporosis, mental disorders, heart failure, hypertension, coronary artery disease. The A-D groups were based on either the COPD Assessment Test or the modified Medical Research Council scale. Exacerbations were also categorized as per GOLD recommendations. Results Data from 2228 patients were analyzed. Using GOLD group A as a reference, group D was associated with nearly all comorbidities, followed by group B and C. When groups A-D were dichotomized as AC vs. BD (symptoms) and AB vs. CD (exacerbations), all comorbidities correlated with symptoms and/or exacerbations. This was true for both mMRC- and CAT-based categorizations. Conclusions These findings suggest that the recently modified GOLD categorization is clinically relevant beyond being purely an assessment of symptoms and exacerbations. As the A-D groups correlated with the risk of important comorbidities, with some differences in terms of the correlation with symptoms and exacerbations, the findings underline the importance of identifying comorbidities in COPD, particularly in non-responders to therapy who have high symptoms and/or exacerbation rates.

The aim of this study was to characterize the practice of telemediated training for patients with very severe Chronic Obstructive Pulmonary Disease (COPD) and to inform the development of clinical/professional practice.Inspired by ethnographic methodology, participating observation, informal and formal interviews were conducted with patients (11), their partners (4), and physiotherapists (6) at sites where the telemediated training was practiced. Postphenomenology was used as theoretical and analytical framework.Telemediated training in the homes of the patients takes place where most daily activities happen, and together with activities in the rehabilitation units they are included in the training in a reduced or amplified version that may compromise the privacy of the patients. The mediated image and sound challenge the training and communication activities and the possibility for the physiotherapists to estimate the condition of the patients. Consequently, the physiotherapists lower how much they push the patients in the exercises.Making training accessible to very severely ill patients with COPD through homebased telemediation comes with several trade-offs. This study can be used to educate clinical practice before and during the practicing of telemediated services, which need to be organized in a way that allows continuous adjustment.IMPLICATIONS FOR PRACTICEThe technology itself is not a neutral device in online health care provision. Health professionals should therefore:Play an active role in structuring the content, communication, and inclusion of the patients' context during online health care provision.Receive training in how to spot ways in which online health care provision transforms traditional practice and to how to work around its limitations.Organize online health care practices in ways that allow for continuous adjustment (for which they need back up from management).

Background: Whether pharmacological therapy alters decline in forced expiratory volume in 1 second (FEV1) in chronic obstructive pulmonary disease (COPD) remains controversial. Because pharmacother...

BackgroundAs mortality from COVID-19 is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations.MethodsWe performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to SARS-CoV-2, including death, hospitalisation, Intensive Care Unit (ICU) admission, and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11th June 2021 in Ovid Medline and Embase. Results are presented as Odds Ratios (ORs) with 95% confidence intervals (95%C.I.) and absolute risk differences (RD) in deaths per 1,000 COVID-19 patients.FindingsWe included 88 cohort studies with age/gender adjusted data from 6,653,207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease, and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes, and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke, and liver disease.InterpretationThe results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of non-pharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions.FundingEuropean Centre for Disease Prevention and Control (ECDC) under specific contract No. 10 ECD.11843 within Framework contract ECDC/2019/001 Lot 1B.

Long-acting bronchodilators represent the mainstay of maintenance treatment of chronic obstructive pulmonary disease (COPD). This state-of-the-art review summarizes currently available data on the safety, efficacy, and clinical effectiveness of long-acting bronchodilators and describes their role in the management of COPD, as defined by current national and international guidelines. Data from extensive clinical trials and real-life studies have demonstrated that long-acting beta-2 agonists and long-acting muscarinic antagonists can safely reduce the frequency of exacerbations, alleviate symptoms, and improve quality of life, exercise tolerance, and lung function of patients with COPD. They are recommended as first-line maintenance treatment of COPD.

Rationale: Chronic obstructive pulmonary disease (COPD) can develop not only through a lung function trajectory dominated by an accelerated decline of FEV(1) from normal maximally attained FEV(1) in early adulthood (normal maximally attained FEV(1) trajectory) but also through a trajectory with FEV(1) below normal in early adulthood (low maximally attained FEV(1) trajectory). Objectives: To test whether the long-term risk of exacerbations and mortality differs between these two subtypes of COPD. Methods: The cohort included 1,170 young adults enrolled in the Copenhagen City Heart Study during the 1970s and 1980s. In 2001–2003, which served as the baseline for the present analyses, 79 participants had developed COPD through normal maximally attained FEV(1) trajectory, 65 had developed COPD through low maximally attained FEV(1) trajectory, and 1,026 did not have COPD. Measurements and Main Results: From 2001 until 2018, we observed 139 severe exacerbations of COPD and 215 deaths, of which 55 were due to nonmalignant respiratory disease. In Cox models, there was no difference with regard to risk of severe exacerbations between the two trajectories, but individuals with normal maximally attained FEV(1) had an increased risk of nonmalignant respiratory disease mortality (using inverse probability of censoring weighting with adjusted hazard ratio [HR], 6.20; 95% confidence interval [CI], 2.09–18.37; P = 0.001) and all-cause mortality (adjusted HR, 1.93; 95% CI, 1.14–3.26; P = 0.01) compared with individuals with low maximally attained FEV(1). Conclusions: COPD developed through normal maximally attained FEV(1) trajectory is associated with an increased risk of respiratory and all-cause mortality compared with COPD developed through low maximally attained FEV(1) trajectory.

Rationale: Identification of younger adults at high risk of developing chronic obstructive pulmonary disease (COPD) could lead to implementation of preventive measures before disease onset and halt progression.Objectives: To investigate the prevalence, characteristics, and prognosis of individuals with early COPD in the general population.Methods: We investigated 105,630 randomly chosen adults from a Danish contemporary population-based cohort. Early COPD was defined as FEV1/FVC less than the lower limit of normal in individuals under 50 years of age with 10 pack-years or greater of tobacco consumption.Measurements and Main Results: Among 8,064 individuals under 50 years of age with 10 pack-years or greater of tobacco consumption, 1,175 (15%) had early COPD, of whom 58% were current smokers. Individuals with early COPD more often had chronic respiratory symptoms, severe lung function impairment, asthma, and a history with bronchitis/pneumonia. During the 14.4-year follow-up, we observed 117 acute hospitalizations with obstructive lung disease, 227 acute hospitalizations with pneumonia, and 185 deaths among the 8,064 younger adults. Compared with individuals without COPD, those with early COPD had multivariable adjusted hazard ratios of 6.42 (95% confidence interval, 3.39-12.2) for acute obstructive lung disease hospitalizations, 2.03 (1.43-2.88) for acute pneumonia hospitalizations, and 1.79 (1.28-2.52) for all-cause mortality.Conclusions: Among individuals under 50 years of age and 10 pack-years or greater of tobacco consumption from the general population, 15% fulfill criteria of early COPD. Individuals with early COPD more often have chronic respiratory symptoms and severe lung function impairment, and an increased risk of acute respiratory hospitalizations and early death.

Background Chest computed tomography (CT) findings in well-treated people with HIV infection (PWH) remain poorly characterized. Methods Cross-sectional analysis examining interstitial chest CT findings in PWH (n = 754) and uninfected controls (n = 470). Results HIV infection was independently associated with 1.82 (95% CI, 1.18–2.88) and 5.15 (95% CI, 1.72–22.2) higher adjusted odds of any interstitial lung abnormality and findings suspicious for interstitial lung disease, respectively. Conclusions HIV infection was independently associated with interstitial lung abnormalities and findings suspicious for interstitial lung disease. Whether these abnormalities develop into more recognizable disease states over time is unknown but warrants further investigation.

Traditional efficacy double-blind randomised controlled trials (DBRCTs) measure the benefit a treatment produces under near-ideal test conditions in highly selected patient populations; however, the behaviour of patients and investigators in such trials is highly controlled, highly compliant and adherent, and non-representative of routine clinical practice. Pragmatic effectiveness trials measure the benefit a treatment produces in patients in everyday “real-world” practice. Ideally, effectiveness trials should recruit patients as similar as possible to those who will ultimately be prescribed the medicine, and create freedom within the study design to allow normal behaviours of patients and healthcare professionals (HCPs) to be expressed. The Salford Lung Study (SLS) was a world-first, prospective, phase III, pragmatic randomised controlled trial (RCT) programme in patients with chronic obstructive pulmonary disease and asthma to evaluate the effectiveness of a pre-licensed medication (fluticasone furoate/vilanterol) in real-world practice using electronic health records and through collaboratively engaging general practitioners and community pharmacists in clinical research. The real-world aspect of SLS was unique, requiring careful planning and attention to the goals of maximising the external validity of the trials while maintaining scientific rigour and securing suitable electronic processes for proper interpretation of safety data. Key learnings from SLS that may inform the design of future pragmatic effectiveness RCTs include: (1) ensuring the trial setting and operational infrastructure are aligned with routine clinical care; (2) recruiting a broad patient population with characteristics as close as possible to patients in routine clinical practice, to maximise the generalisability and applicability of trial results; (3) ensuring that patients and HCPs are suitably engaged in the trial, to maximise the chances of successful trial delivery; and (4) careful study design, incorporating outcomes of value to patients, HCPs, policymakers and payers, and using pre-planned analyses to address scientifically valid research hypotheses to ensure robustness of the trial data. Electronic supplementary material The online version of this article (10.1007/s12325-019-01192-1) contains supplementary material, which is available to authorized users.

BACKGROUND: Whether risk of exacerbations of chronic obstructive pulmonary disease (COPD) is influenced by severity of symptoms and maintenance treatment is unclear.OBJECTIVE: We hypothesized that in addition to history of exacerbations of COPD, the severity of dyspnoea and use of maintenance medications are associated with risk of future exacerbations.METHODS: We included 96,462 adults from the Copenhagen General Population Study and assessed risk of moderate and severe exacerbations from 2003 to 2013 according to exacerbation history, dyspnoea score (mMRC), and presence/absence of maintenance treatment with inhaled long-acting bronchodilators and/or inhaled corticosteroids.FINDINGS: Among 13,380 individuals with COPD, we observed 1543 moderate and 348 severe exacerbations. In treatment naïve individuals and in those on maintenance treatment, history of previous exacerbations and to a smaller degree also dyspnoea were associated with a higher risk of future exacerbations; 32% of the treatment naïve individuals with mMRC≥2 and a single moderate exacerbation in the previous year experienced a moderate exacerbation during the following year compared with only 3% in the individuals with similar severity of dyspnoea but no exacerbations in the previous year yielding an adjusted hazard ratio of 6.26 (95% confidence interval, 3.70-10.58).INTERPRETATION: This observational study of the general population suggests that in addition to exacerbation history also the severity of dyspnoea predicts the risk of future COPD exacerbations. In subjects with severe dyspnoea, a history of a single moderate exacerbation is associated with a high risk of future exacerbations, suggesting that this subgroup needs special attention in order to prevent these events.

COPD exacerbation; Coagulation; Cross-linked fibrin degradation Exacerbación de la EPOC; Coagulación; Degradación de fibrina reticulada Exacerbació de la MPOC; Coagulació; Degradació de fibrina reticulada Cardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65–1.48), VWF-N: HR 1.56 (95% CI 1.07–2.27), and VWF-A: HR 0.78 (95% CI 0.52–1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population. This study was funded by the Danish Regions Medical Fund (grant no. 5894/16), the Danish Council for Independent Research (grant no. 6110-00268B), and the Novo Nordisk foundation (grant no. NNF20OC0060657). Author D.D.M. received personal funding from the Danish National Research Foundation (DNRF126).

This meta-analysis explored the safety and effectiveness of mucolytics as an add-on treatment for chronic obstructive pulmonary disease (COPD) exacerbations. Based on a pre-registered protocol and following Cochrane methods, we systematically searched for relevant randomised or quasi-randomised controlled trials (RCTs). We used the Risk of Bias v2 tool for appraising the studies and performed random-effect meta-analyses when appropriate. We assessed certainty of evidence using GRADE. This meta-analysis included 24 RCTs involving 2192 patients with COPD exacerbations, entailing at least some concerns of methodological bias. We demonstrated with moderate certainty that mucolytics increase the rate of treatment success (relative risk 1.37, 95% CI 1.08–1.73, n=383), while they also exert benefits on overall symptom scores (standardised mean difference 0.86, 95% CI 0.63–1.09, n=316), presence of cough at follow-up (relative risk 1.93, 95% CI 1.15–3.23) and ease of expectoration (relative risk 2.94, 95% CI 1.68–5.12). Furthermore, low or very low certainty evidence suggests mucolytics may also reduce future risk of exacerbations and improve health-related quality of life, but do not impact on breathlessness, length of hospital stay, indication for higher level of care or serious adverse events. Overall, mucolytics could be considered for COPD exacerbation management. These findings should be validated in further, rigorous RCTs.

BackgroundStudies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort.MethodsPatients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis.ResultsOf 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses.ConclusionThis analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.

Chronic obstructive pulmonary disease is a prevalent condition in the UK, associated with high morbidity and mortality. Hospital physicians manage a significant portion of acute chronic obstructive pulmonary disease admissions to hospital and readmissions after discharge. Optimal management of exacerbations requires controlled oxygen therapy and ventilatory support where necessary, and careful administration of bronchodilators, steroids and antibiotics. Holistic care for these patients includes nutritional supplementation and palliative support for those with advanced disease. To reduce the chance of readmission, chronic obstructive pulmonary disease care bundles can be used, along with a review of inhaled and oral therapies. Where available, hospital-at-home discharge schemes can safely facilitate early discharge. Most importantly, high quality evidence-based smoking cessation support must be offered to smokers. Exercise improves the physiological and psychological condition of people with chronic obstructive pulmonary disease and should be encouraged, with referral to a pulmonary rehabilitation service if available.

Populations with COPD demonstrate higher survival in overweight and obese compared with normal weight; the “obesity paradox”. Relationships in less-severe COPD are unclear, as is the impact of cardiovascular risk, and few studies include individuals at extremes of obesity. We examined the relationship between body mass index (BMI; defined as underweight: 40 kg·m−2, suggesting that obesity may not remain protective at the extremes in this population., In a population with moderate COPD, at heightened cardiovascular risk and containing a substantial proportion of individuals with BMI ≥40 kg/m2, BMI and mortality demonstrate a U-shaped (rather than J-shaped) relationship https://bit.ly/3hDztI6

BackgroundIndividual susceptibility to exacerbations in chronic obstructive pulmonary disease (COPD) is likely influenced by genetic factors; however, most such variance is unexplained. We hypothesised that β2-adrenergic receptor genotypes, Gly16Arg (rs1042713, c.46G>A) and Gln27Glu (rs1042714, c.79C>G) influence risk of severe exacerbations in COPD.MethodsAmong 96 762 individuals in the Copenhagen General Population Study, we identified 5262 with COPD (forced expiratory volume in one second divided by forced vital capacity, FEV1/FVC, below 0.7, FEV1 less than 80% of predicted value, age above 40 years and no asthma) who had genotyping performed. Severe exacerbations were defined as acute admissions due to COPD during 5 years of follow-up (mean 3.4 years). 923 individuals with COPD diagnosed similarly in the Copenhagen City Heart Study (CCHS) were used for replication analyses.ResultsWe recorded 461 severe exacerbations in 5262 subjects. The HRs for severe exacerbations were 1.62 (95% CI 1.30 to 2.03, p=0.00002) for 16Gly/Arg heterozygotes and 1.41 (1.04 to 1.91, p=0.03) for 16Arg homozygotes, compared with 16Gly homozygotes. HRs were 1.35 (1.03 to 1.76, p=0.03) for 27Gln/Glu heterozygotes and 1.49 (1.12 to 1.98, p=0.006) for 27Gln homozygotes, compared with 27Glu homozygotes. Similar trends were observed in the CCHS. Among 27Gln homozygotes only, HRs were 5.20 (1.81 to 14.9, p=0.002) for 16Gly/Arg heterozygotes and 4.03 (1.40 to 11.6, p=0.01) for 16Arg homozygotes, compared with 16Gly homozygotes.ConclusionCommon β2-adrenergic receptor genotypes influence risk of severe exacerbations in COPD, potentially mainly by genetic influence of the 16Arg allele in rs1042713.

Background The relationship between respiratory diseases and individual cardiovascular diseases, and the impact of cardiovascular diseases on mortality in patients with respiratory disease, are unclear. Objectives This study sought to determine the relationship between chronic obstructive pulmonary disease (COPD), asthma and interstitial lung disease (ILD), and individual cardiovascular diseases, and evaluate the impact of individual cardiovascular diseases on all-cause mortality in respiratory conditions. Methods The authors conducted a cohort study of all patients admitted to 7 National Health Service hospitals across the North West of England, between January 1, 2000, and March 31, 2013, with relevant respiratory diagnoses, with age-matched and sex-matched control groups. Results A total of 31,646 COPD, 60,424 asthma, and 1,662 ILD patients were included. Control groups comprised 158,230, 302,120, and 8,310 patients, respectively (total follow-up 2,968,182 patient-years). COPD was independently associated with ischemic heart disease (IHD), heart failure (HF), atrial fibrillation, and peripheral vascular disease, all of which were associated with all-cause mortality (e.g., odds ratio for the association of COPD with HF: 2.18 [95% confidence interval (CI): 2.08 to 2.26]; hazard ratio for the contribution of HF to mortality in COPD: 1.65 [95% CI: 1.61 to 1.68]). Asthma was independently associated with IHD, and multiple cardiovascular diseases contributed to mortality (e.g., HF hazard ratio: 1.81 [95% CI: 1.75 to 1.87]). ILD was independently associated with IHD and HF, both of which were associated with mortality. Patients with lung disease were less likely to receive coronary revascularization. Conclusions Lung disease is independently associated with cardiovascular diseases, particularly IHD and HF, which contribute significantly to all-cause mortality. However, patients with lung disease are less likely to receive coronary revascularization.

Background: Blood eosinophils may predict response to inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) where ICS is recommended in patients at high risk of exacerbations. The proportion of patients who may benefit the most from ICS-based therapy was quantified in a real-world population. Materials and methods: European data from the Adelphi Real World Respiratory Disease Specific Programme™ 2017 survey were collected from consecutive COPD patients by participating physicians. Overall, 1,528 patients were assessable for Global Initiative for COPD (GOLD) 2017 status and were included in the analysis. Results: More GOLD D patients had elevated eosinophil counts compared with GOLD B. The proportions of GOLD D patients with a history of ≥2 exacerbations and eosinophil counts of ≥150, ≥300, and ≥400 cells/µL were 81.2%, 39.4%, and 24.6%, respectively. In total, 10.6% of the patients had ≥300 eosinophils/µL and a history of ≥2 exacerbations. ICS-based therapy was received by 41.5% of GOLD B and 68.0% of GOLD D patients. Conclusion: There was no apparent relation between ICS use and eosinophil blood count. There are differences in the distributions of patients with frequent exacerbations and/or high blood eosinophil counts and the use of ICS in COPD. These data may provide information for the implementation of future treatment recommendations.

Chronic obstructive pulmonary disease (COPD) is characterised by chronic airflow limitation and inflammation of the airways and lung parenchyma. COPD is associated with many comorbidities, especially cardiovascular disease (CVD), which share similar risk factors with COPD [1]., Circulating MFAP4 is a relevant biomarker to identify COPD patients at risk of death and cardiovascular comorbidity after smoking cessation http://ow.ly/6vnL30o8t1g

Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an essential structural protein of the lungs. In this study, we investigated whether elastin degradation products generated by the enzymes proteinase 3, cathepsin G, neutrophil elastase, MMP7 or MMP9/12 were prognostic biomarkers for COPD-related outcomes. The elastin degradome was assessed in a subpopulation (n = 1307) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort with 3 years of clinical follow-up. Elastin degraded by proteinase 3 could distinguish between COPD participants and non-smoking controls (p = 0.0006). A total of 30 participants (3%) died over the 3 years of observation. After adjusting for confounders, plasma levels of elastin degraded by proteinase 3 and cathepsin G were independently associated with mortality outcome with a hazard ratio per 1 SD of 1.49 (95%CI 1.24–1.80, p

Background: SLS COPD was the first open-label randomised controlled trial demonstrating a reduction in moderate/severe COPD exacerbations with once-daily inhaled fluticasone furoate/vilanterol (FF/VI) in everyday clinical practice. Here we report FF/VI effectiveness and safety in predefined patient subgroups. Methods: Patients with COPD, exacerbation history, and receiving maintenance inhaler therapy, were randomised to initiate FF/VI 100/25 μg or continue usual care (UC) with 12 months’ follow-up. Annual rates of moderate/severe exacerbations (primary outcome), selected secondary outcomes, and incidence of pneumonia serious adverse events of special interest (SAESI) were compared between randomisation groups across various patient subgroups/baseline treatment strata. SAESI rates by actual treatment were also assessed. Results: Lower exacerbation rates were observed for FF/VI versus UC across all subgroups/strata, including ICS + LABA therapy subset (8.0% [0.1, 15.4]), except in patients without baseline airflow limitation (−0.5% [–29.8, 22.1]). Larger reductions compared to the overall analysis were observed for patients on ICS-containing regimens (excluding LAMA) before the study (15.6% [3.4, 26.3]), and with baseline CAT score

Purpose It is a challenge to control oxygen saturation (SpO2) in patients with exacerbations of COPD during admission. We tested a newly developed closed-loop system, O2matic®, and its ability to keep SpO2 within a specified interval compared with manual control by nursing staff. Patients and methods We conducted a crossover trial with patients admitted with an exacerbation of COPD and hypoxemia (SpO2 ≤88% on room air). Patients were monitored with continuous measurement of SpO2. In random order, they had 4 hours with manually controlled oxygen and 4 hours with oxygen delivery controlled by O2matic. Primary outcome was time within a prespecified SpO2 target interval. Secondary outcomes were time with SpO2

Objectives The purposes of this study were to determine why chronic obstructive pulmonary disease (COPD) is associated with heart failure (HF). Specific objectives included whether COPD is associated with myocardial fibrosis, whether myocardial fibrosis is associated with hospitalization for HF and death in COPD, and whether COPD and smoking are associated with myocardial inflammation. Background COPD is associated with HF independent of shared risk factors. The underlying pathophysiological mechanism is unknown. Methods A prospective, multicenter, longitudinal cohort study of 572 patients undergoing cardiac magnetic resonance (CMR), including 450 patients with COPD and 122 age- and sex-matched patients with a median: 726 days (interquartile range: 492 to 1,160 days) follow-up. Multivariate analysis was used to examine the relationship between COPD and myocardial fibrosis, measured using cardiac magnetic resonance (CMR). Cox regression analysis was used to examine the relationship between myocardial fibrosis and outcomes; the primary endpoint was composite of hospitalizations for HF or all-cause mortality; secondary endpoints included hospitalizations for HF and all-cause mortality. Fifteen patients with COPD, 15 current smokers, and 15 healthy volunteers underwent evaluation for myocardial inflammation, including ultrasmall superparamagnetic particles of iron oxide CMR. Results COPD was independently associated with myocardial fibrosis (p

The CORTICO-COP trial showed that eosinophil-guided corticosteroid-sparing treatment for acute exacerbation of chronic obstructive pulmonary disease was non-inferior to standard of care and decreased the accumulated dose of systemic corticosteroids that patients were exposed to by approximately 60%. Smoking status has been shown to affect corticosteroid responsiveness. This post hoc analysis investigated whether eosinophil-guided treatment is non-inferior to conventional treatment in current smokers. The main analysis of current smokers showed no significant difference in the primary endpoint, days alive, and out of hospital within 14 days between the control group (mean, 9.8 days, 95% confidence interval (CI), 8.7–10.8) and the eosinophil-guided group (mean, 8.7 days, 95% CI, 7.5–9.9, p = 0.34). Secondary analyses of the number of exacerbations or deaths, the number of intensive care unit admissions or deaths, lung function improvement, and change in health-related quality of life also showed no significant differences between the two groups. The results of a sensitivity analysis of ex-smokers are consistent with the main analysis. Our results suggest that eosinophil-guided treatment is non-inferior to standard of care in current smokers and ex-smokers. Because data on the impact of smoking status on eosinophil-guided treatments are sparse, more randomised trials are needed to confirm our results.

Background Indoor and outdoor mould exposure can affect respiratory symptoms, but its contribution to COPD outcomes such as exacerbation rates or antibiotics courses is not well defined. Some patients with COPD develop chronic pulmonary aspergillosis (CPA), but the contribution of environmental exposure is not known. Methods We correlated activities or exposures related to mould with COPD outcomes in patients with COPD with or without CPA using a questionnaire. Results One hundred and forty patients were included and 60 had CPA in addition to COPD. Seventy-six were male and mean age was 66.9 years (range 40–87). Thirty-nine (28%) were active cigarette smokers. On multivariate analysis, occupational contact with agricultural resources (p = 0.017), vacuuming once weekly or more often (p = 0.026) and not asking visitors to remove shoes on home entry (p = 0.035) were significantly more common in participants reporting ≥ 4 office visits for COPD symptoms in the last year. Living within one mile of industrial composting sites (p = 0.013), vacuuming once weekly or more often (p = 0.016) and not asking visitors to remove shoes on home entry (p = 0.028) were significantly more common in participants reporting ≥4 antibiotics courses in the last year. Patients with CPA showed a trend for residence within one mile of farms or agricultural areas (P = 0.088, OR 2, 95% CI 0.9–4.4). Conclusion Activities potentially leading to mould exposure were common in a population with COPD with or without CPA and were associated with adverse COPD outcomes. Environmental mould exposure may play a role in the development of CPA in patients with COPD.

Evidence to support clinical decision making must be based on safety data that have been captured, analysed and interpreted in a robust and reliable way. Randomised real-world evidence (RRWE) studies provide the opportunity to evaluate the use of medicines in patients and settings representative of routine clinical practice. However, elements that underpin the design of RRWE studies can have a significant impact upon the analysis, interpretation and implications of safety data. In this narrative review, we use data from the Salford Lung Study; two prospective, 12-month, open-label, parallel-group, phase III randomised controlled trials conducted in primary care in the UK; to highlight the importance of capturing treatment modifications when attempting to evaluate safety events according to actual treatment exposure. We demonstrate that analysing safety data by actual treatment received (i.e. accounting for the treatment modifications that occur routinely in the primary care setting) provides additional insight beyond analysing according to randomised treatment strategy only. It is therefore proposed that understanding of safety data from RRWE trials can be optimised by analysing both by randomised group and by actual treatment received., Using results from the Salford Lung Study, this review demonstrates that the understanding of safety data from randomised real-world evidence studies can be optimised by analysing both actual treatment received and randomisation group https://bit.ly/3p7zPXU