Future Exacerbations Research Articles

Inhaled Steroids, Circulating Eosinophils, Chronic Airway Infection, and Pneumonia Risk in Chronic Obstructive Pulmonary Disease. A Network Analysis.

Rationale: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS) is controversial, because it can reduce the risk of future exacerbations of the disease at the expense of increasing the risk of pneumonia.Objectives: To assess the relationship between the presence of chronic bronchial infection (CBI), reduced number of circulating eosinophils, ICS treatment, and the risk of pneumonia in patients with COPD.Methods: This was a post hoc long-term observational study of an historical cohort of 201 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV) who were carefully characterized (including airway microbiology) and followed for a median of 84 months. Results were analyzed by multivariate Cox regression and network analysis.Measurements and Main Results: Mean age was 70.3 years, 90.5% of patients were male, mean FEV1 was 49%, 71.6% of patients were treated with ICS, 57.2% of them had bronchiectasis, and 20.9% had <100 blood eosinophils/μl. Pathogenic microorganisms were isolated in 42.3% of patients, and 22.4% of patients fulfilled the definition of CBI. During follow-up, 38.8% of patients suffered one or more episodes of pneumonia, with CBI (hazard ratio [HR], 1.635) and <100 eosinophils/μl (HR, 1.975) being independently associated with the risk of pneumonia, particularly when both coexist (HR, 3.126). ICS treatment increased the risk of pneumonia in those patients with <100 eosinophils/μl and CBI (HR, 2.925).Conclusions: Less than 100 circulating eosinophils/μl combined with the presence of CBI increase the risk of pneumonia in patients with COPD treated with ICS.

Enhancing pulmonary rehabilitation enrollment study (PRESS III)

RATIONALE: Pulmonary rehabilitation (PR) is recommended in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) to reduce the risk of future exacerbations. Previous review in this health region demonstrated 9% of inpatients with AECOPD were being referred to PR following discharge, and 4% were attending, none within 30 days post-discharge. OBJECTIVE Evaluate referral and attendance rates to PR after implementation of a physician-led recruitment method. MEASUREMENTS AND MAIN RESULTS: All inpatients admitted to medicine wards were systematically screened for AECOPD utilizing a Drug Use Evaluation report for prescribed inhalers/nebulizers. Investigators met with identified eligible patients, delivered education and provided a pre-booked appointment card to attend PR within 4 weeks of discharge. PR attendance and barriers to attendance were documented. A total of 296 patients receiving inhalers/nebulizers were screened: 135 patients did not have clinical COPD. Of the remaining 161 patients, 50 were deemed eligible for the intervention. Reasons for exclusion included significant co-morbid conditions (n = 71), distance (n = 34) and preexisting attendance (n = 6). Of eligible patients, 12 declined referral with the main reason being lack of transportation; 38 patients accepted referral to PR, with 16 attending their first appointment. CONCLUSION A physician-led referral strategy improved PR referral rates, with 24% of patients admitted with “clinical COPD” being formally referred to PR compared to only 9% with prior clinical practice. Moreover, physician-led recruitment increased PR attendance to 10% from prior 4%. Of the patients with clinical AECOPD, only 31% were eligible for referral to PR, and of those, only 32% attended their first appointment.

C-Reactive Protein Concentration in Steady-State Bronchiectasis: Prognostic Value of Future Severe Exacerbations. Data From the Spanish Registry of Bronchiectasis (RIBRON)

BackgroundBoth systemic inflammation and exacerbations have been associated with greater severity of bronchiectasis. Our objective was to analyze the prognostic value of the peripheral concentration of C-reactive protein (CRP) for the number and severity of exacerbations in patients with bronchiectasis. MethodsPatients from the Spanish Bronchiectasis Registry (RIBRON) with valid data on their CRP value (in a clinically stable phase) and valid data on exacerbations during the first year of follow-up were included. A logistic regression analysis was used to evaluate the prognostic value of the CRP concentration (divided into tertiles) with the presence of at least one severe exacerbation or at least two mild-moderate exacerbations during the first year of follow-up. Results802 patients (mean age: 68.1 [11.1 years], 65% female) were included. Of these, 33.8% and 13%, respectively, presented ≥2 mild-moderate exacerbations or at least one severe exacerbation during the first year of follow-up. The mean value of the CRP was 6.5 (17.6mg/L). Patients with a CRP value between 0.4 and 2.7mg/L (second tertile) and ≥2.7mg/L (third tertile) presented a 2.9 (95%CI: 1.4–5.9) and 4.2 (95%CI: 2.2–8.2) times greater probability, respectively, of experiencing a severe exacerbation than those with <0.4mg/L (control group), regardless of bronchiectasis severity or a history of previous exacerbations. However, the CRP value did not present any prognostic value for the number of mild-moderate exacerbations. ConclusionsThe CRP value was associated with a greater risk of future severe exacerbations but not with mild or moderate exacerbations in patients with steady-state bronchiectasis.

Association of Guideline-Recommended COPD Inhaler Regimens With Mortality, Respiratory Exacerbations, and Quality of Life: A Secondary Analysis of the Long-Term Oxygen Treatment Trial

Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vslow) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. The trial enrolled 738 patients (73.4%men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95%CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64%higher risk of pneumonia (incidence rate ratio, 1.64; 95%CI, 1.01-2.66). Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.

Predictive value of control of COPD for risk of exacerbations: An international, prospective study.

The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18-month follow-up period. A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1 % = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow-up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). Control status, defined by easy-to-obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.

Future exacerbation of hot and dry summer monsoon extremes in India

Summer monsoon (June-September) precipitation is crucial for agricultural activities in India. Extremes during the monsoon season can have deleterious effects on water availability and agriculture in the region. Here, we show that hot and dry extremes during the summer monsoon season significantly impact food production in India and find that they tend to occur during El Niño years during the observed record of 1951–2018. We then use an ensemble of climate simulations for the historic (1971–2000) and future (2006–2100) that capture this coupling between El Niño and the Indian monsoon to show that the frequency of concurrent hot and dry extremes increases by a factor of 1.5 under continued greenhouse warming during the 21st century. Despite projections of summer monsoon intensification on the order of ~10%, the rise in surface air temperatures as well as increase in rainfall variability contributes to more severe hot and dry monsoon extremes over India, thereby posing a substantial challenge to future food security in India.

Latent Class Analysis of School-Age Children at Risk for Asthma Exacerbation

Factors responsible for asthma exacerbations in children are complex and may differ from those that drive asthma severity. To identify latent classes of children at risk for asthma exacerbation and determine whether latent class assignment is useful in the prediction of future exacerbation. Latent class analysis was performed on 513 children aged 6 to 17 years at risk for asthma exacerbation, with 31 variables encompassing demographics, medical history, treatment, symptoms, lung function, sensitization, and type 2 inflammation. Primary and secondary outcomes included exacerbation occurrence by 12 months and time to first exacerbation, respectively. Four latent classes were identified with differing demographic features, sensitization and type 2 inflammatory markers, prior exacerbation severity and health care utilization, and lung function. Exacerbations occurred in 22.4% of class 1 ("lesser sensitization with normal lung function"), 27.9% of class 2 ("lesser sensitization with prior severe exacerbation and normal lung function"), 45.3% of class 3 ("multiple sensitization with reversible airflow limitation"), and 64.3% of class 4 ("multiple sensitization with partially reversible airflow limitation") (P < .001). Time to exacerbation also followed similar trends and was shortest in the latent classes with multiple sensitization and airflow limitation (P < .001). Outcomes were driven largely by children with exacerbation-prone asthma (defined as ≥3 exacerbations in the prior year), who were present in each class but most strongly represented in classes 3 and4. Children at risk for asthma exacerbation are a heterogeneous group. Sensitization, prior exacerbation severity, and lung function variables may be particularly useful in identifying children at greatest risk for future exacerbation.

COPD exacerbations: finally, a more than ACCEPTable risk score

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with substantial respiratory morbidity, including major deterioration in functional status, accelerated decline of lung function, and mortality. Prevention of these exacerbations is imperative. To date, the strongest identified risk factor for future exacerbations seems to be history of previous exacerbations. However, this information does not provide any warning of a first exacerbation, which in many individuals can be a sentinel event in their disease course.

A rational approach to the treatment of bronchial asthma in children: what can we do to control the disease?

Bronchial asthma is the most common among chronic bronchopulmonary diseases with heterogeneity in symptom profiles. Despite the delivery of baseline anti-inflammatory iGCS therapy, including the subsequent staged addition of other controlling treatment methods, symptoms of the disease persist in 40% of patients. Lack of asthma control results in high morbidity, mortality and treatment costs, which justifies the search for new therapeutic options to improve control and reduce the risk of future exacerbations. Tiotropium, a long-acting anticholinergic bronchodilator, can be a good alternative in the therapeutic treatment of poorly controlled asthma in both adults and children. Several clinical studies showed the efficacy and safety of Tiotropium Respimat Soft Mist Inhaler at a dose of 5 mg in various asthma treatment options in children at 6 years old and over, who do not achieve asthma control with iGCS monotherapy at medium/high doses or with iGCS/LABA combination at medium/high doses. All asthma studies in children were conducted using Respimat Soft Mist Inhalers that generate an aerosol with a larger number of small particles, which ensures effective drug distribution and deposition in the lungs. The aerosol cloud velocity at the nozzle outlet of the inhaler is just 0.8 m/s, and the time period over which the aerosol is released is extended to 1.5 s. Moving slowly, aerosol particles more often avoid colliding with the posterior pharyngeal wall and tongue, which reduces the drug deposition in the oral cavity, significantly increasing the amount of active substance delivered to the air ways. 55% of the dose of tiotropium bromide is released in the form of particles with an optimal aerodynamic diameter, which guarantees a high level of lung deposition - 52% of the ex-valve dose.

Heterogeneity of Mild to Moderate Persistent Asthma in Children: Confirmation by Latent Class Analysis and Association with 1-Year Outcomes

Compared with adults, phenotypic characterization of children with asthma is still limited and it remains difficult to predict which children with asthma are at highest risk for poor outcomes. To identify latent classes in a large population of treatment-adherent children with mild to moderate asthma enrolled in clinical trials and determine whether latent class assignment predicts future lung function abnormalities and exacerbation rate. Latent class analysis was performed on 2593 children with mild to moderate asthma aged 5 18 years, with 19 variables encompassing demographic characteristics, medical history, symptoms, lung function, allergic sensitization, and type 2 inflammation. Outcomes included lung function and the annualized exacerbation rate at 12 months of follow-up. Five latent classes were identified with differing demographic features, asthma control, sensitization, type 2 inflammatory markers, and lung function. Exacerbation rates were 1.30 ± 0.12 for class 1 (multiple sensitization with partially reversible airflow limitation), 0.90 ± 0.05 for class 2 (multiple sensitization with reversible airflow limitation), 0.87 ± 0.08 for class 3 (lesser sensitization with reversible airflow limitation), 0.87 ± 0.05 for class 4 (multiple sensitization with normal lung function), and 0.71 ± 0.06 for class 5 (lesser sensitization with normal lung function). Lung function abnormalities persisted in class 1 at 12 months. Children with mild to moderate asthma are a heterogeneous group. Allergic sensitization and lung function may be particularly useful in identifying children at the greatest risk for future exacerbation. Additional studies are needed to determine whether latent classes correspond to meaningful phenotypes for the purpose of personalized treatment.

Characteristics of Chronic Obstructive Pulmonary Disease Patients with Pulmonary Hypertension Assessed by Echocardiography in a Three-Year Observational Cohort Study.

BackgroundPulmonary hypertension (PH) is a major comorbidity of chronic obstructive pulmonary disease (COPD). However, the association of PH detected by echocardiography and COPD-related outcome in longitudinal follow-up has not been elucidated. In this study, we aimed to investigate the relationship between clinical characteristics of COPD patients with PH detected by echocardiography and various outcome parameters such as COPD exacerbation and health status over a three-year observation period.MethodsIn this observational study, we analyzed patients with COPD who underwent chest computed tomography and echocardiography at baseline (n = 183).ResultsThe prevalence of PH was 21.9% (40 patients). The median estimated systolic pulmonary artery pressure in patients with PH was 38.8 mmHg. COPD patients with PH were older, had a lower body mass index, scored worse in the COPD Assessment Test and St. George’s Respiratory Questionnaire, and exhibited a lower diffusing capacity of the lung for carbon monoxide in comparison to patients without PH. In computed tomography images, the percentages of low-attenuation areas (LAA%) and interstitial abnormalities were higher in COPD patients with PH than in those without PH. Higher values for LAA% (LAA ≥ 30%) and interstitial abnormalities independently increased the risk of PH. The ratio of main pulmonary diameter to aortic artery diameter was significantly correlated with estimated systolic pulmonary artery pressure. In the follow-up analysis, the frequency of exacerbations in three years was significantly higher in patients with PH compared to patients without PH.ConclusionIn this study, we identified the clinical characteristics of COPD patients with PH detected by echocardiography. The presence of PH assessed by echocardiography was related to future COPD exacerbations and closely related to radiographical emphysema.

A242 EXERCISE AND PHYSICAL ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND RECOMMENDATIONS

Abstract Background Inflammatory bowel disease (IBD) is a chronic life-long condition affecting 0.25% of the North American population. Childhood onset IBD is particularly aggressive, with disease often characterised by poor growth, severe unpredictable abdominal pain and frequent school absences. Treatment involves lifelong medications, which do not always resolve symptoms and carry increased cumulative risks of infections, malignancy, or other adverse effects. Exercise has been suggested as a method of ameliorating some of the symptoms associated with IBD. To date, few studies have investigated the role of exercise and physical activity in paediatric IBD patients. Aims We conducted a systematic review assessing the role of exercise and physical activity in paediatric IBD. Methods This Level III systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. An electronic database search of Pubmed, Google Scholar, and Cochrane used the search terms “(physical activity or exercise), (Inflammatory Bowel Disease), and (children or paediatric)”. Of the 1458 articles identified during the two rounds of review, only 21 articles met final inclusion criteria. Results Three main themes emerged from the review: 1) prescriptive exercise and physical activity ameliorated symptoms IBD and improved physical well-being, 2) patients who actively engage in exercise and physical activity show improved markers of inflammation and decreased future risk of disease, 3) exercise and physical activity improves the mental health and well-being of paediatric IBD patients. The results recommended 30–60 minutes, 6 times per week of mild to moderate aerobic exercise activity. It was noted that vigorous and high intensity exercise was well-tolerated by most IBD patients. Further, exercise prescription should be tailored to individual needs. Conclusions Exercise and physical activity improves mental and physical health and well-being of paediatric IBD patients, including decreasing the risk of future disease exacerbation in patients with mild to moderate disease activity. Clinicians and practitioners should consider actively prescribing exercise and physical activity to IBD patients as part of a standard treatment algorithm. Funding Agencies None

COPD clinical control as a predictor of future exacerbations: concept validation in the SPARK study population

The concept of chronic obstructive pulmonary disease (COPD) control has been proposed to guide treatment decisions in COPD. In this study, we aimed to validate the prospective value of this...

A systematic review of methodology used in the development of prediction models for future asthma exacerbation

BackgroundClinical prediction models are widely used to guide medical advice and therapeutic interventions. Asthma is one of the most common chronic diseases globally and is characterised by acute deteriorations. These exacerbations are largely preventable, so there is interest in using clinical prediction models in this area. The objective of this review was to identify studies which have developed such models, determine whether consistent and appropriate methodology was used and whether statistically reliable prognostic models exist.MethodsWe searched online databases MEDLINE (1948 onwards), CINAHL Plus (1937 onwards), The Cochrane Library, Web of Science (1898 onwards) and ClinicalTrials.gov, using index terms relating to asthma and prognosis. Data was extracted and assessment of quality was based on GRADE and an early version of PROBAST (Prediction study Risk of Bias Assessment Tool). A meta-analysis of the discrimination and calibration measures was carried out to determine overall performance across models.ResultsTen unique prognostic models were identified. GRADE identified moderate risk of bias in two of the studies, but more detailed quality assessment via PROBAST highlighted that most models were developed using highly selected and small datasets, incompletely recorded predictors and outcomes, and incomplete methodology. None of the identified models modelled recurrent exacerbations, instead favouring either presence/absence of an event, or time to first or specified event. Preferred methodologies were logistic regression and Cox proportional hazards regression.The overall pooled c-statistic was 0.77 (95% confidence interval 0.73 to 0.80), though individually some models performed no better than chance. The meta-analysis had an I2 value of 99.75% indicating a high amount of heterogeneity between studies. The majority of studies were small and did not include internal or external validation, therefore the individual performance measures are likely to be optimistic.ConclusionsCurrent prognostic models for asthma exacerbations are heterogeneous in methodology, but reported c-statistics suggest a clinically useful model could be created. Studies were consistent in lacking robust validation and in not modelling serial events. Further research is required with respect to incorporating recurrent events, and to externally validate tools in large representative populations to demonstrate the generalizability of published results.

Chitotriosidase Activity in Plasma and COPD Exacerbations.

This study aimed to determine the association between plasma chitotriosidase activity and the clinical characteristics and exacerbation rate of COPD patients. The study comprised 97 patients with COPD. Their clinical characteristics and a history of exacerbations in the last 12months were noted. Plasma chitotriosidase activity was determined. Patients were followed up for 12months, and the number of moderate and severe exacerbations during this period was recorded. Chitotriosidase activity positively correlated with patient age (rho = 0.217, p = 0.036) and inversely with CAT (rho = - 0.240, p = 0.020). There was no correlation with lung function. Chitotriosidase activity was significantly lower in patients with a history of ≥ 2 exacerbations compared to patients without a history of exacerbations (93 [38-312] vs. 264 [168-408] nmol/h/mL, p = 0.033). Overall, there was no difference in chitotriosidase activity between patients with or without observed exacerbations. Patients with a history of ≥ 1 exacerbation and ≥ 1 observed exacerbation had higher chitotriosidase activity compared to patients without further exacerbations (240 [144-456] vs. 52 [39-240] nmol/h/mL, p = 0.035). Multivariate analysis identified FEV1 (HR 0.976, 95% CI 0.956-0.996, p = 0.016) and blood eosinophil percentage (HR 1.222, 95% CI 1.048-1.424, p = 0.011) as independent predictors of future exacerbations in the total patient population, while in patients with a history of ≥ 1 exacerbation ,the only independent predictor was chitotriosidase activity (HR per 10nmol/h/mL 1.028, 95% CI 1.002-1.055, p = 0.037). While mixed associations between chitotriosidase activity and clinical outcomes were seen, chitotriosidase activity could be a predictor of future exacerbations in patients with a history of ≥ 1 exacerbation in the past 12months.

Test for respiratory and asthma control in preschool kids in the emergency department as a predictor of wheezing exacerbations.

The test for respiratory and asthma control in kids (TRACK score) is a standardized questionnaire tool validated to identify poor symptom control in children with stable preschool wheeze. This study determined if TRACK score measured within 5 days of an Emergency Department (ED) visit for acute wheezing predicts a subsequent wheezing exacerbation requiring an ED visit and/or treatment with systemic corticosteroids within 3 months. This was a single-center prospective cohort study of children aged 36 to 71 months who presented to the ED with an acute episode of wheezing and had TRACK score measured at a clinic visit within 5 days of the index ED encounter, focused on information about symptoms occurring before the onset of the current acute episode. The outcomes were the independent association of a repeat wheezing exacerbation with the overall TRACK score (primary) and with mutually uncorrelated TRACK items (secondary), adjusted for sex and atopy. We enrolled 102 children; median age 52.3 (44.1, 59.9) months, 59% males. Of these, 33 (32.4%) had further wheezing exacerbations. For each 10 unit decrease in TRACK, the odds of a future exacerbation was 1.38 (95% CI, 1.10-1.75); male sex demonstrated OR, 5.13 (1.84-14.33). A model that included TRACK items reflecting more than equal to 1 awakenings for wheezing in the past 4 weeks, receipt of more than equal to 2 courses of corticosteroids in the last year and male sex was predictive of wheezing exacerbations: OR, 6.43 (2.18-19.00). In preschoolers with acute wheezing episodes in the ED, we have identified the TRACK score components which, together with male sex, can be used to identify children at risk of future exacerbations requiring referral for specialized care. These results need to be confirmed and validated in other populations enrolled at multiple sites before they can be implemented in practice.

Modified and simplified clinically important deterioration: multidimensional indices of short-term disease trajectory to predict future exacerbations in patients with chronic obstructive pulmonary disease.

Background and aims:Various prediction indices based on the single time point observation have been proposed in chronic obstructive pulmonary disease (COPD), but little was known about disease trajectory as a predictor of future exacerbations. Our study explored the association between disease trajectory and future exacerbations, and validated the predictive value of the modified and simplified short-term clinically important deterioration (CID).Methods:This study was a multicenter, prospective observational study. Patients with COPD were recruited into our study and followed up for 18 months. The modified CID (CID-C) was defined as a decrease of 100 mL in forced expiratory volume in 1 second (FEV1), or suffering exacerbations, or increase of 2 units in COPD Assessment Test (CAT) during the first 6 months follow-up. Simplified CID was defined when excluding CAT from the CID-C model.Results:A total of 127 patients were enrolled in our final analysis. Compared with patients without exacerbations during the period of the 6th to the 18th month, patients with exacerbations were more likely to have frequent short-term exacerbations in the first 6 months (2.14 versus 0.21, p < 0.001). The short-term exacerbations were the best predictor for future exacerbations [odds ratio (OR): 13.25; 95% confidence interval: 5.62–34.67; p < 0.001], followed by the history of exacerbation before study entry, short-term changes in FEV1 and CAT. CID-C and Simplified CID were both significantly associated with exacerbations (OR: 7.14 and 9.74, both p < 0.001). The receiver operating characteristic curves showed that the Simplified CID had slightly better predictive capacity for future exacerbation than CID-C (0.754 versus 0.695, p = 0.02).Conclusion:Disease trajectory, including both the CID-C and the Simplified CID had significant predictive value for future exacerbations. The reviews of this paper are available via the supplemental material section.

Validation and Assessment of the COPD Treatment Ratio as a Predictor of Severe Exacerbations.

Population-based risk assessments are needed to identify individuals who may benefit from chronic obstructive pulmonary disease (COPD) management programs for preventing exacerbations. This study compared the validated COPD treatment ratio (CTR) versus other COPD exacerbation predictors: prior exacerbation and rescue and maintenance medication use. A retrospective observational study using medical and pharmacy claims data among Medicare Advantage with Part D beneficiaries with COPD (January 2011-August 2016). Unadjusted and adjusted logistic regression models tested the predictive performance (C-statistic) of potential exacerbation predictors for future severe exacerbations. The unadjusted association between exacerbation predictors and severe exacerbation was examined in 60,776 patients: baseline severe exacerbation had the highest C-statistic (0.668), then number of rescue units dispensed (0.651), CTR (0.619), and number of controller units dispensed (0.562). During the at-risk period, baseline CTR was inversely associated with severe exacerbation (odds ratio, <1.0); other predictors were positively associated with a severe exacerbation (odds ratio, >1.0). Adjusting for age, geographic region, chronic oxygen, and nebulizer use, the severe exacerbation odds were 0.90 (95% confidence interval [CI], 0.89-0.91) lower per 0.10 change in CTR (C-statistic, 0.710). The C-statistic was 0.734 when baseline exacerbation was added to the model. The CTR is an effective tool for identifying patients diagnosed with COPD who are at increased risk of severe exacerbation. Although CTR does not predict future exacerbation as well as prior severe exacerbation history, it has the advantage of being applicable in predicting future exacerbations in patients without an exacerbation history, or in databases limited to pharmacy claims only. In addition, the significant reduction in risk has been observed with incremental increases in the ratio: the ratio can be monitored to assess COPD health improvements over time.

Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts

Rationale: Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux.Objectives: To determine the value of adding blood biomarkers to clinical variables to predict exacerbations.Methods: Subjects from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) (n = 1,544) and COPDGene (Genetic Epidemiology of COPD) (n = 602) cohorts had 90 plasma or serum candidate proteins measured on study entry using Myriad-RBM multiplex panels. We defined total exacerbations as subject-reported worsening in respiratory health requiring therapy with corticosteroids and/or antibiotics, and severe exacerbations as those leading to hospitalizations or emergency room visits. We assessed retrospective exacerbations during the 12 months before enrollment and then documented prospective exacerbations in each cohort. Exacerbations were modeled for biomarker associations with negative binomial regression including clinical covariates (age, sex, percent predicted FEV1, self-reported gastroesophageal reflux, St. George's Respiratory Questionnaire score, smoking status). We used the Stouffer-Liptak test to combine P values for metaanalysis.Measurements and Main Results: Between the two cohorts, 3,471 total exacerbations (1,044 severe) were reported. We identified biomarkers within each cohort that were significantly associated with a history of exacerbation and with a future exacerbation, but there was minimal replication between the cohorts. Although established clinical features were predictive of exacerbations, of the blood biomarkers only decorin and α2-macroglobulin increased predictive value for future severe exacerbations.Conclusions: Blood biomarkers were significantly associated with the occurrence of exacerbations but were not robust between cohorts and added little to the predictive value of clinical covariates for exacerbations.

Hyperuricemia Is Not Predictive of Long-Term Outcome in Patients with Stable Chronic Obstructive Pulmonary Disease.

BackgroundAlthough the association of hyperuricemia with an increased risk of mortality has been demonstrated in the context of acute exacerbation of chronic obstructive pulmonary disease (COPD), the long-term outcomes of hyperuricemia have not been studied in the case of stable COPD.MethodsWe retrospectively analyzed baseline data of 240 men with stable COPD enrolled in the Korea Obstructive Lung Disease cohort. We evaluated associations between serum uric acid levels and clinical parameters, risk factors for all-cause mortality, and acute exacerbation of COPD.ResultsThe mean age of subjects was 66.4 ± 7.7 years, and the median follow-up time was 5.9 years. We identified no significant difference in terms of lung function or laboratory findings between patients with hyperuricemia and those without. Serum uric acid level was negatively associated with systemic inflammation indicated by neutrophil–lymphocyte ratio (r = −0.211, P = 0.001). Univariate Cox regression analysis revealed hyperuricemia to not be associated with an increased risk of all-cause mortality in men with stable COPD (hazard ratio [HR], 0.580; 95% confidence interval [CI], 0.250–1.370; P = 0.213). In the multivariate Cox regression model, hyperuricemia was not an independent predictor of acute exacerbation (HR, 1.383; 95% CI, 0.977–1.959; P = 0.068).ConclusionAmong men with stable COPD, hyperuricemia is not an independent predictor of all-cause mortality or future acute exacerbation of COPD. These results differ from those of previous studies on patients with acute exacerbation of COPD.