Prognostic models for mortality and hospitalisation risk in a contemporary Australian chronic obstructive pulmonary disease cohort.

Case-finding and improving patient outcomes for chronic obstructive pulmonary disease in primary care: the BLISS research programme including cluster RCT

Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire-based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). Nomograms built from these models can assist clinicians in the decision-making process of COPD care.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and "asthma-like" features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.

There are limited to no data regarding the use of immune checkpoint inhibitors (ICIs) in patients who have preexisting organ dysfunction because these patients are frequently excluded from clinical trials. The authors' objective was to evaluate the effects of ICIs in patients with chronic kidney disease (CKD), cirrhosis, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). Data were obtained retrospectively for patients older than 18 years with solid organ malignancies who received at least one dose of an ICI between January 1, 2015, and January 1, 2021, and had either CKD (n=90), cirrhosis (n=20), COPD (n=142), or CHF (n=82) before ICI initiation at the authors' institution. Descriptive statistics were used to summarize patient characteristics, treatment characteristics, immune-related adverse events (IrAEs), and outcomes. An independent samples t-test or the Wilcoxon rank-sum test was used to assess differences in continuous variables; the χ2 test or the Fisher exact test was used to assess differences in categorical variables between patients with and without IrAEs. Progression-free survival (PFS) was assessed using Kaplan-Meier curves, and the log-rank test was used to assess differences in PFS. In all four cohorts, there were no statistically significant differences in patient characteristics, treatment characteristics, or outcomes, such as the number of hospitalizations and PFS, among those who experienced IrAEs compared with those who did not. In the CKD cohort, patients with IrAEs were significantly less likely to die than those without IrAEs (52% vs. 81% [p=.009] for all patients; 53% vs. 83% [p=.008] for patients with stage II/III disease who received no definitive local treatment and patients with stage IV disease); this difference was not observed in the cirrhosis, COPD, or CHF cohorts. There was no statistically significant difference in the number of heart failure and COPD exacerbations during the receipt of ICIs in the CHF and COPD cohorts, respectively. The incidence and time to onset of IrAEs in this study appeared to be similar to those reported previously in clinical trials that excluded patients with significant comorbidities. The current results demonstrate that ICIs are well tolerated by patients who have preexisting organ dysfunction.

BackgroundThe anti-inflammatory pneumoprotein club cell secretory protein-16 (CC-16) is associated with the clinical expression of chronic obstructive pulmonary disease (COPD). We aimed to determine if there is a causal effect...

Patients with chronic obstructive pulmonary disease (COPD) had higher risk of atrial fibrillation (AF). The treatment of AF includes medicines to control heart rate and reduce the risk of stroke, and procedures such as cardioversion to restore normal heart rhythm. To reduce the stroke, patients with AF may prescribe some type of antithrombotic medication (such as warfarin, one of the new non-vitamin K antagonist oral anticoagulants [NOACs] - dabigitran, apixaban, rivoraxaban, or edoxaban) or maybe aspirin. The aim of our study was to exam the prescription pattern in patients with COPD and AF. We selected COPD population in Taiwan older than 40 years and less than 90 years old with an COPD diagnosis at least two outpatient claims or at least one inpatient claim coded and also need at least one prescription of bronchodilators. We followed this COPD cohort until they have AF and their prescription pattern. We included 267,740 patients with COPD who meet the inclusion and exclusion criteria and 6,582 patients concomitant with COPD and AF. The mean age was 75 years, and about 77% of the patients were older than 70 years. Three-fourths of patients with COPD were male. The common comorbidities were hypertension (17.58%), diabetes (7.47%), ischemic heart disease (4.66%), and dyslipidemia (3.68%). we found that most patients received aspirin which accounting for 31%, followed by coumadin (8.22%) and clopidogrel. Prescribing NOAC within 30 days after AF diagnosis was low in patients with COPD and the percentage of NOAC usage was also lower than warfarin.

BackgroundDepression is a common and mostly undertreated problem in patients with chronic diseases. However, population-based studies on the association between chronic obstructive pulmonary disease (COPD) and subsequent depression are limited in Asian populations. This study evaluated the incidence and risk factors of depression for patients with COPD in Taiwan.MethodsUsing the claims data from the National Health Insurance of Taiwan, we identified 38,010 COPD patients newly diagnosed in 2000–2004 and 38,010 subjects without COPD frequency, matched by sex, age and index date. The incidence rate and hazard ratio for depression were estimated by the end of 2008.ResultsThe incidence rate of depression was 1.88 folds higher in the COPD cohort than in the non-COPD cohort (12.2 versus 6.47 per 1,000 person-years, p < 0.0001). The depression risk was the greatest within the first year following COPD diagnosis and tended to decline with follow-up time. Among COPD patients, multivariate analysis showed that younger women and low-income patients were at higher risk of depression. Hospitalization and comorbidities such as hypertension, arthritis, cancer, and heart disease were also significant predictors for depression risk.ConclusionThis population-based cohort study demonstrated a strong relationship between COPD and subsequent depression. These findings could assist healthcare providers to pinpoint individuals with a higher predisposition to having depression, which could then facilitate the provision of culturally appropriate rehabilitation within the first year after the diagnosis of COPD.

ObjectiveChronic obstructive pulmonary disease (COPD) is associated with atherosclerosis. Previous studies including limited sample sizes have shown the prevalence of peripheral arterial occlusive disease (PAOD) among COPD patients. We sought to investigate the incidence of PAOD among COPD patients in Taiwan using a national database.MethodsCOPD patients were collected from the National Health Insurance Research Database of Taiwan from 1996 to 2010. The COPD cohort was propensity score matched according to age, sex, and comorbidities of atrial fibrillation, hypertension, diabetes, hyperlipidemia, cerebrovascular accidents, and chronic liver disease to patients without COPD (the control cohort). We evaluated the incidence of PAOD in COPD patients and the risk of PAOD associated with atrial fibrillation, hypertension, diabetes, hyperlipidemia, cerebrovascular accidents, and chronic liver disease.ResultsThe study included 51,869 COPD patients and 51,869 control patients without COPD. The incidence of PAOD was 1.23-fold higher (95% confidence interval [CI] =1.17–1.29) in the COPD group than in the non-COPD group. Moreover, COPD and atrial fibrillation alone (adjusted hazard ratio (aHR) 2.99; P=0.001), hypertension alone (aHR, 2.05; P<0.001), diabetes alone (aHR, 2.62; P<0.001) and cerebrovascular accidents alone (aHR 2.05; P<0.001), increased the risk of developing PAOD. The significant aHRs increased (from 3.7 to 4.9) when the number of comorbidities increased (from ≥1 to ≥3 comorbidities).ConclusionCOPD patients have a higher incidence and an independently higher risk of PAOD than patients without COPD. The risk of PAOD is markedly elevated in COPD patients with more comorbidities.

Proteinase-activated receptor-1 (PAR-1) plays a key role in mediating the interplay between coagulation and inflammation in response to injury. The aim of this study was to investigate the role of the promoter single-nucleotide polymorphism (SNP) rs2227744G>A in modulating PAR-1/F2R gene expression in the context of chronic obstructive pulmonary disease (COPD) and COPD exacerbations. The function of the rs2227744G>A SNP was investigated by using reporter gene assays. The frequency of the polymorphism in the UK population was assessed by genotyping 8,579 healthy individuals from the Whitehall II and English Longitudinal Study of Ageing cohorts. The rs2227744G>A SNP was genotyped in a carefully phenotyped cohort of 203 COPD cases and matched controls. The results were further replicated in two different COPD cohorts. The minor allele of the rs2227744G>A polymorphism was found to increase F2R expression by 2.6-fold (P < 0.001). The rs2227744G>A SNP was not significantly associated with COPD, or with lung function, in all cohorts. The minor allele of the SNP was found to be associated with protection from frequent exacerbations (P = 0.04) in the cohort of COPD patients for which exacerbation frequency was available. Considering exacerbations as a continuous variable, the presence of the minor allele was associated with a significantly lower COPD exacerbation rate (3.03 vs. 1.98 exacerbations/year, Mann-Whitney U-test P = 0.04). Taken together, these data do not support a role for the rs2227744G>A F2R polymorphism in the development of COPD but suggest a protective role for this polymorphism from frequent exacerbations. Studies in separate cohorts to replicate these findings are warranted.

The diagnosis of depression, a frequent comorbidity of chronic obstructive pulmonary disease (COPD), is often supported by questionnaires, such as the Patient Health Questionnaire 9 (PHQ-9). It is unknown to which extent its single questions are affected by the clinical characteristics of COPD patients.We addressed this question in 2255 GOLD grade 1–4 patients from the COSYCONET (COPD and Systemic Consequences - Comorbidities Network) COPD cohort. The dependence on COPD severity was assessed using symptoms, exacerbation risk (GOLD A-D; modified Medical Research Council dyspnoea scale (mMRC)), and frequent comorbidities as predictors of PHQ-9 results, while including age, gender, body mass index (BMI) and smoking habits as covariates.Symptoms and exacerbation risk were associated with depression in an additive manner, with mean elevations in the PHQ-9 sum score by 2.75 and 1.44 points, respectively. Asthma, sleep apnoea, gastrointestinal disorders, osteoporosis and arthritis were linked to increases by 0.8 to 1.3 points. Overall, the COPD characteristics contributed to the mean PHQ-9 score by increases from 4.5 or 5.2 to 6.3 points, respectively, when either taking GOLD A as reference or the absence of comorbidities. This finding was independent of the diagnosis of mental disorder or the intake of antidepressants. The presence of COPD led to an increase in the proportion of scores indicating depression from 12 to 22%. Single item analysis revealed homogenous effects regarding GOLD groups, but heterogeneous effects regarding GOLD grades.These findings indicate specific effects of COPD severity on the PHQ-9 depression score, especially symptoms and exacerbation risk, explaining the high prevalence of depression in COPD. Alternative explanations like an overlap of COPD severity and PHQ-9 items are discussed. Of note, we also found COPD treatment effects on depression scores.

BackgroundICIs (PD-1 inhibitors, PDL-1 inhibitors, CTLA-4 inhibitors) are increasingly used to treat various malignancies. The percentage of cancer patients in the US who may benefit from ICIs has increased from...

The beta2-adrenergic receptors are cell surface receptors playing a central role in the pharmacological targeting asthma and chronic obstructive pulmonary disease [COPD]. Recent studies suggest that patients who are homozygous for one of the two important polymorphisms of the beta2-adrenergic receptor [ADRB2] gene at codon 16 (arginine to glycine) and 27 (glutamine to glutamate) may have a reduced response to ss2-agonists. Since smoking patients who are Gly16 homozygotes have an increased risk of airway obstruction we hypothesized that beta2-adrenoreceptor gene polymorphisms may be also a cofounder for COPD development and disease severity. We investigated 190 COPD patients and 172 healthy volunteers in a case-control study. DNA was isolated from whole blood and beta2-AR gene polymorphisms Arg/Gly16 and Gln/Glu27 were determined using allele-specific polymerase chain reaction [PCR]. In COPD patients with Gly/Gly16 was found more frequently than in healthy smokers [29.47% COPD versus 18.18% controls, p = 0.026]. All other gene polymorphisms of the ADRB2 gene at codon 16 were equally distributed between groups. ss2-adrenoreceptor gene polymorphisms were neither a cofounder for COPD exacerbations [>or= 3 hospitalizations within the last 3 years] nor for disease severity [FEV1 <or= 30% predicted]. Our study suggests that the Gly16 allele of the beta2-AR gene predisposes to COPD development but not for exacerbation rates and disease severity. In contrast, Gln/Glu27 polymorphism was irrelevant in our COPD cohort.

RationaleClinical phenotyping, therapeutic investigations as well as genomic, airway secretion metabolomic and metagenomic investigations can benefit from robust, nonlinear modeling of FEV1 in individual subjects. We demonstrate the utility of measuring FEV1 dynamics in representative cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) populations.MethodsIndividual FEV1 data from CF and COPD subjects were modeled by estimating median regression splines and their predicted first and second derivatives. Classes were created from variables that capture the dynamics of these curves in both cohorts.ResultsNine FEV1 dynamic variables were identified from the splines and their predicted derivatives in individuals with CF (n = 177) and COPD (n = 374). Three FEV1 dynamic classes (i.e. stable, intermediate and hypervariable) were generated and described using these variables from both cohorts. In the CF cohort, the FEV1 hypervariable class (HV) was associated with a clinically unstable, female-dominated phenotypes while stable FEV1 class (S) individuals were highly associated with the male-dominated milder clinical phenotype. In the COPD cohort, associations were found between the FEV1 dynamic classes, the COPD GOLD grades, with exacerbation frequency and symptoms.ConclusionNonlinear modeling of FEV1 with splines provides new insights and is useful in characterizing CF and COPD clinical phenotypes.

Introduction: Although occupational exposure is an important risk factor for development of chronic obstructive pulmonary disease (COPD), it has been little known about the effects of occupations exposures for progression of COPD. Aims and Objectives: To determine the effect of history for occupational exposures on lung function decline in men with COPD. Methods: Subjects were selected from a Korean COPD cohort, prospectively designed observational study and underwent yearly post bronchodilator spirometry. They were included if they underwent the spirometry at least three times. History of occupational exposures was evaluated for metal, asbestos, fiber, cereal, drugs, paper dust, and chemicals. History of occupational exposures was assessed by two blinded experts for each case. The annual decline of FEV1 was analyzed by random-slope and random-intercept mixed linear regression. Results: A total 222 patients with COPD were included, and patients with occupational exposures were 49. The mean age was 65.2 (standard deviation: 7.5) years, the mean smoking amount was 46.3 (28.1) pack-years. There were no significant differences in years of age, smoking amount, quality of life, and emphysema extent on CT, according to the presence of occupation exposures. The annual decline rates in FEV1 (ml per year) were significantly different for groups without occupational exposures of -32.9±21.9 compared to groups with occupational exposures of -25.5±19.9 (p = 0.038). Conclusions: Occupational exposures in men with COPD were associated with slower decline of lung function.

Detection and severity grading of COPD exacerbations using the exacerbations of chronic pulmonary disease tool (EXACT).