COPD-related Events Research Articles

COPD Pathogenesis and Alterations in the Oral, Lung, and Gut Microbiomes

Chronic obstructive pulmonary disease (COPD) is a respiratory and systemic disease affecting more than 300 million people globally every year, and it also becomes a substantial economic burden. COPD is commonly comorbid with various underlying diseases such as cancer, cardiovascular diseases, cerebrovascular diseases, diabetes mellitus, osteoporosis, etc. It has been shown that statins can improve a significant decline in pulmonary function among COPD patients due to their pleiomorphic effect. Some systematic reviews also reported that statins reduced the risk of COPD-related events such as cancer and cardiovascular events, eventually resulting in more favorable outcomes than for non-statin user COPD patients. However, the physiological mechanism is still elucidated. Recently, it has been reported that statins influence the gut microbial composition with increased relative abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii and act with pleiomorphic effects such as anti-inflammatory and anti-cancer effects through modulating gut dysbiosis. We described this review to focus on whether statins can be a useful preventive option for COPD.

Comprehensive care plans for patients with Chronic Obstructive Pulmonary Disease (COPD): Effect on health services utilization

RATIONALE There is limited real-world evidence on evaluation of chronic disease management initiatives provided by general physicians to patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES We aimed to evaluate changes in COPD-related healthcare resource utilization between COPD patients who had general physician’s provided comprehensive annual care plan (CACP) and those who did not have CACP. METHODS We conducted a retrospective cohort study using health administrative data (Alberta) from 2009 to 2016. COPD patients who received a CACP were identified and matched with two control patients based on age, sex, provider, date of service and qualifying comorbidities. Controlled interrupted-time series analysis was used to evaluate changes in COPD-specific hospitalizations, emergency department (ED) visits, physician visits and claims for pulmonary function test (PFT). Immediate and temporal changes were calculated for the difference in outcomes 1 year before and 1 year after receiving the CACP for the intervention group and matched controls. RESULTS Eligible patients (N = 88,002), of whom 35,847 had received CACPs were matched to a total of 52,155 controls. In 1 year after the CACPs implementation the number of COPD-related hospitalization visits significantly increased by 105.33 (95% CI 58.17-152.49), ED visits increased by 172.65 (95% CI 168.09–177.20), general practitioners (GP) visits increased by 359.53 (95% CI 247.64–471.41), specialist visits increased by 77.21 (95% CI 31.58–122.85) and PFT claims increased by 50.82 (95% CI 35.33–66.30) when compared to the controls who did not receive CACP per 10,000 patients per month. However, only increase in ED and specialist visits was confirmed by the sensitivity analysis. CONCLUSIONS Annual care plans provided by physicians were found to be associated with a statistically significant increase in COPD-related events (including ED visits) in the following year; however, clinical significance was minimal.

Association between chronic obstructive pulmonary disease and periodontal disease: a systematic review and meta-analysis

ObjectivesStudies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study was to determine whether PD increased the...

BURDEN OF ILLNESS IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO COPD IN US ADMINISTRATIVE CLAIMS DATA

BURDEN OF ILLNESS IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO COPD IN US ADMINISTRATIVE CLAIMS DATA

Discriminative Accuracy of FEV1:FVC Thresholds for COPD-Related Hospitalization and Mortality

According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial. To determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016. Presence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN). The primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach. Among 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, -0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models. Defining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.

Albuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study.

Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD. To test whether albuminuria was associated with lung function decline and incident CLRDs. Six U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications. Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV1 decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV1/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease. Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.

A Cohort Study of the Impact of Tooth Loss and Periodontal Disease on Respiratory Events among COPD Subjects: Modulatory Role of Systemic Biomarkers of Inflammation

BackgroundIn COPD patients, fatal and non-fatal respiratory-related events are influenced by age, severity of respiratory disease, and comorbidities.ObjectivesAnalyze the effects of edentulism, periodontal disease and systemic biomarkers of inflammation on the occurrence of serious fatal and non-fatal respiratory-related events among subjects with COPD.MethodsCases were identified from Dental Atherosclerosis Risk in Communities study. Edentulism was defined as study participants without any natural teeth or implants. Participants with one or more natural teeth (comprising 11,378 subjects) were studied as dentate subjects. Periodontal disease status among dentate individuals was determined using the consensus definitions published by the joint Center for Disease Control/American Association of Periodontology working group). Adjusted Hazard Models are developed to evaluate the relationship between edentulism/periodontal disease and COPD Related Events. Models were then stratified by GOLD Stage I, II and III/IV. Serum biomarkers were also evaluated to explore the effect of systemic inflammation.ResultsA statistically significant association was found between oral health status and COPD-related events, even adjusting for conditions such as hypertension, smoking and diabetes. Edentulous individuals who had been diagnosed with COPD had a higher incidence and were at greater risk of having a COPD related event (hospitalization and death) than individuals who had teeth and whose mouths had healthy periodontal status. However, being edentulous did not convey excess risk for COPD-related events for those study participants who were classified as GOLD III/IV at baseline. Finally, we showed that individuals who had levels of serum IL-6 in the highest two quartiles were at even higher risk for COPD-related events.ConclusionsThese findings suggest that the risk for COPD-related events after adjusting for potential confounders may be attributable to both edentulism and elevated serum IL-6 levels.

Risk of hospitalizations/emergency department visits and treatment costs associated with initial maintenance therapy using fluticasone propionate 500 µg/salmeterol 50 µg compared with ipratropium for chronic obstructive pulmonary disease in older adults

Background: Cost-effective treatments for chronic obstructive pulmonary disease (COPD) are needed to reduce the burden on the Medicare system. Objectives: The objectives of this retrospective study were to compare the effects of fluticasone propionate 500 µg/salmeterol 50 µg (FSC 500/50) with those of ipratropium (IPR) in older adult patients with COPD on the following factors: (1) the risk of all-cause and COPD-related hospitalization and emergency department (ED) visits; and (2) all-cause and COPD-related treatment costs. Methods: This retrospective, observational cohort study assessed commercially insured patients aged ≥65 years (Medicare eligible) with COPD-related medical costs ( International Classification of Diseases, Ninth Revision, Clinical Modification codes 490.xx, 491.xx, 492.xx, or 496.xx), 18 months of continuous enrollment (12 months' pre-study and 6 months' poststudy), and ≥1 prescription claim (ie, the index event) for FSC 500/50 or IPR between January 2, 2001, and August 12, 2003. Exacerbation events (hospitalizations/ED visits) were assessed using Cox proportional hazards regression models controlling for baseline factors and preindex events. Treatment costs were estimated using multivariate generalized linear models to adjust for baseline characteristics and preindex utilization and costs. A propensity-matched comparison was conducted as a sensitivity analysis. Results: A total of 1051 patients (540 women, 511 men) were identified: 952 in the IPR group (mean age, 74.26 years) and 99 in the FSC 500/50 group (mean age, 72.38 years). Treatment with FSC 500/50 was not associated with a reduction in the risk of all-cause hospitalization or ED visit compared with IPR (adjusted hazards ratio [HR], 0.913 [95% CI, 0.673-1.238]); however, FSC 500/50 was associated with a significantly lower risk (45%) of a COPD-related event (adjusted HR, 0.547 [95% CI, 0.301-0.995]). Although treatment with FSC 500/50 was associated with significantly lower annual mean all-cause medical costs compared with IPR ($18,642 vs $25,556, P < 0.05), the use of FSC 500/50 was also associated with significantly higher annual all-cause pharmacy costs ($2813 vs $2244, P < 0.05). Compared with the IPR cohort, the FSC 500/50 cohort had lower mean annual COPD-related medical costs (-$464 [ P = NS]) and higher COPD-related pharmacy costs ($260 [ P < 0.01]). However, increased pharmacy costs may be compensated for by decreased medical costs in both all-cause and COPD-related services. Results from the sensitivity analysis with the propensity score-matched sample of 194 patients were similar. Conclusions: Compared with the IPR cohort, the FSC 500/50 cohort was 45% less likely to have a COPD-related exacerbation event and had similar medical costs. FSC 500/50 was a more effective initial maintenance therapy than IPR for this Medicare population, and, despite the $260 increase in COPD-related pharmacy costs, there was no significant difference in COPD-related medical costs.

Comparison of hospitalizations, emergency department visits, and costs in a historical cohort of Texas Medicaid patients with chronic obstructive pulmonary disease, by initial medication regimen

Limited information is available on the relative outcomes and treatment costs of various pharmacotherapies for chronic obstructive pulmonary disease (COPD) in a Medicaid population. This study compared the effects of initial medication regimens for COPD on COPD-related and all-cause events (hospitalizations and/or emergency department [ED] visits) and COPD-related and all-cause costs. The study population was a historical cohort of Texas Medicaid beneficiaries aged 40 to 64 years with COPD-related medical costs (International Classification of Diseases, Ninth Revision, Clinical Modification codes 491.xx, 492.xx, 496.xx), 24 months of continuous Medicaid enrollment (12 months before and after the index prescription), and at least 1 prescription claim (index) for a combination product containing fluticasone propionate + salmeterol, an inhaled corticosteroid, salmeterol, or ipratropium between April 1, 2001, and March 31, 2003. The analyses of events employed Cox proportional hazards regression, controlling for baseline factors and preindex events. The analyses of costs used a 2-part model with logistic regression and generalized linear model to adjust for baseline characteristics and preindex utilization and costs. The study population included 6793 patients (1211 combination therapy, 968 inhaled corticosteroid, 401 salmeterol, and 4213 ipratropium). Only combination therapy was associated with a significantly lower risk for any COPD-related event (hazard ratio [HR] = 0.733; 95% CI, 0.650-0.826) and any all-cause event (HR = 0.906; 95% CI, 0.844-0.972) compared with ipratropium. COPD-related prescription costs were higher in all cohorts compared with the ipratropium cohort, but COPD-related medical costs were lower, offsetting the increase in prescription costs. For all-cause costs, prescription costs were higher in the combination-therapy cohort (+$415; P < 0.05) and the salmeterol cohort (+$247; P < 0.05) compared with the ipratropium cohort, but significant reductions in all-cause medical costs in the combination-therapy cohort (-$1735; P < 0.05) and salmeterol cohort (-$1547; P < 0.05) more than offset the increase in prescription costs. In this historical population of Texas Medicaid beneficiaries, the combination-therapy cohort was 27% less likely to have a COPD-related event than the ipratropium cohort, 10% less likely to have any all-cause event, had similar COPD-related costs, and had reduced all-cause costs. Thus, compared with the ipratropium cohort, the combination-therapy cohort had an improvement in outcomes (based on the decreased time to a hospitalization or ED visit), with similar or decreased direct medical costs. Future research is needed in other patient groups.

RISK OF HOSPITALIZATIONS AND/OR EMERGENCY DEPARTMENT VISITS FOR MEDICAID PATIENTS WITH COPD: COMPARISON OF CONTROLLERS

PURPOSE: To compare the risk of hospitalizations and/or emergency department (ED) visits among Medicaid COPD patients prescribed various medications. This study analyzed both COPD-related events and all-cause events.

Comparison of the efficacy and tolerability of mepifylline oral solution versus inhaled ipratropium bromide in patients with stable chronic obstructive pulmonary disease: A randomized, active-controlled, open-label study

Background: Inhaled ipratropium bromide, through a metered-dose inhaler (MDI), is a first-line treatment for the prevention of exacerbations of chronic obstructive pulmonary disease (COPD). However, MDIs are often used incorrectly by patients, and the efficacy of inhaled medications may be affected as a result. Objective: The purpose of this study was to compare the efficacy and tolerability of inhaled ipratropium bromide versus oral mepifylline in the prevention of medical events among patients with COPD. Methods: This was an open-label, randomized, parallel-group, active-controlled study. Patients with stable COPD were randomly assigned to receive 75 mg mepifylline by the oral route every 8 hours or 0.04 mg ipratropium bromide inhaled every 6 hours, for 6 months. A medical event was defined as any unanticipated, COPD-related event requiring extra medical care. Secondary end points were pulmonary function, intensity of dyspnea on the Borg scale, distance on the 6-minute walking test (and intensity and subjective feelings of dyspnea before and/or after the test), blood gas and inspiratory pressures, and use of any type of medication to control COPD symptoms. Results: A total of 134 patients were enrolled. After 6 months of treatment, oral mepifylline and inhaled ipratropium bromide were equally effective in preventing medical events. Forced expiratory volume in 1 second (FEV 1) and forced vital capacity (FVC) decreased slightly but significantly versus baseline ( P = 0.018). In both groups, a decrease in dyspnea ( P = 0.054) and an increase in the distance covered in the walking test were observed. The subjective feeling of dyspnea after the 6-minute walking test decreased significantly among the patients treated with mepifylline ( P = 0.01 vs baseline), but not among those treated with ipratropium bromide ( P = 0.172 vs baseline). The need for rescue medication decreased throughout the study, with no differences between treatment groups. A significantly greater number of gastrointestinal adverse events were seen in the mepifylline group ( P = 0.003). Conclusion: Mepifylline is as effective as ipratropium bromide in controlling symptoms and preventing medical events in patients with COPD, and can be considered a good therapeutic alternative to inhaled ipratropium bromide.