Factors contributing to medication nonadherence among patients with chronic obstructive pulmonary disease (COPD) are poorly understood.
To identify patient characteristics that are predictive of adherence to inhaled medications for COPD and, for patients on multiple inhalers, to assess whether adherence to one medication class was associated with adherence to other medication classes.
Cohort study using data from Veteran Affairs (VA) electronic databases.
This study included 2,730 patients who underwent pulmonary function testing between 2003 and 2007 at VA facilities in the Northwestern United States, and who met criteria for COPD.
We used pharmacy records to estimate adherence to inhaled corticosteroids (ICS), ipratropium bromide (IP), and long-acting beta-agonists (LABA) over two consecutive six month periods. We defined patients as adherent if they had refilled medications to have 80 % of drug available over the time period. We also collected information on their demographics, behavioral habits, COPD severity, and comorbidities.
Adherence to medications was poor, with 19.8 % adherent to ICS, 30.6 % adherent to LABA, and 25.6 % adherent to IP. Predictors of adherence to inhaled therapies were highly variable and dependent on the medication being examined. In adjusted analysis, being adherent to a medication at baseline was the strongest predictor of future adherence to that same medication [(Odds ratio, 95 % confidence interval) ICS: 4.79 (3.22–7.12); LABA: 6.60 (3.92–11.11); IP: 14.13 (10.00–19.97)], but did not reliably predict adherence to other classes of medication.
Among patients with COPD, past adherence to one class of inhaled medication strongly predicted future adherence to the same class of medication, but only weakly predicted adherence to other classes of medication.
medication adherence; pulmonary diseases; health behavior; veterans
Although oral hypoglycemic agents (OHAs) are an essential element of therapy for the management of type 2 diabetes, OHA adherence is often suboptimal. Pharmacists are increasingly being integrated into primary care as part of the move towards a patient-centered medical home and may have a positive influence on medication use. We examined whether the presence of pharmacists in primary care clinics was associated with higher OHA adherence.
This retrospective cohort study analyzed 280,603 diabetes patients in 196 primary care clinics within the Veterans Affairs healthcare system. Pharmacists presence, number of pharmacist full-time equivalents (FTEs), and the degree to which pharmacy services are perceived as a bottleneck in each clinic were obtained from the 2007 VA Clinical Practice Organizational Survey—Primary Care Director Module. Patient-level adherence to OHAs using medication possession ratios (MPRs) were constructed using refill data from administrative pharmacy databases after adjusting for patient characteristics. Clinic-level OHA adherence was measured as the proportion of patients with MPR >= 80%. We analyzed associations between pharmacy measures and clinic-level adherence using linear regression.
We found no significant association between pharmacist presence and clinic-level OHA adherence. However, adherence was lower in clinics where pharmacy services were perceived as a bottleneck.
Pharmacist presence, regardless of the amount of FTE, was not associated with OHA medication adherence in primary care clinics. The exact role of pharmacists in clinics needs closer examination in order to determine how to most effectively use these resources to improve patient-centered outcomes including medication adherence.
Pharmacist; Medication adherence; Diabetes mellitus; Oral hypoglycemic agent; Patient-centered medical home
It is unclear if primary care physicians are following guidelines or using other patient characteristics and factors to determine when to perform spirometry in patients at risk for COPD. It is also unclear to what degree a diagnosis of COPD is accurately reflected by spirometry results.
To examine characteristics associated with use of spirometry in primary care for patients with increased risk for COPD and to determine the accuracy of COPD diagnosis in patients with spirometry.
Retrospective cohort study.
A cohort that met the following criteria was identified: ≥35 years of age; ≥ 2 primary care visits in internal medicine clinic in 2007; at least one respiratory or smoking cessation medication, or diagnosis of COPD or shortness of breath or dyspnea in 2007.
Medical records of all primary care physician visits prior to the time of inclusion in 2007 were reviewed. Data on patient demographics, co-morbidities, respiratory medication use, presence of symptoms, history of tobacco use, and pulmonary function tests were extracted.
A total 1052 patients were identified. Dyspnea on exertion (Adjusted odds ratio (AOR) 1.52 [95% CI 1.06–2.18]) and chronic cough (AOR 1.71 [1.07–2.72]) were the only chronic symptoms associated with use of spirometry. Current (AOR 1.54 [0.99–2.40]) or past smoking (AOR 1.09 [0.72–1.65]) status were not associated with use of spirometry. Of the 159 patients with a diagnosis of COPD, 93 (58.5%) met GOLD criteria and 81(50.9%) met lower limit of normal (LLN) criteria for COPD.
Clinicians use spirometry more often among patients with symptoms suggestive of COPD but not more often among patients with current or past tobacco use. For patients who had a spirometry and a diagnosis of COPD, primary care physicians were accurate in their diagnosis only half of the time.
chronic disease; diagnosis; health care delivery; chronic obstructive pulmonary disease; spirometry; quality of care
Chronic obstructive pulmonary disease affects millions worldwide. It is America’s third leading cause of death, and results in significant morbidity and cost. Although many therapies exist and are being developed to alleviate symptoms and decrease morbidity and mortality in chronic obstructive pulmonary disease, most have only been studied in placebo-controlled efficacy studies in highly selected populations. Comparative effectiveness and translational research in chronic obstructive pulmonary disease will require the development of infrastructures to support collaboration between researchers and the stakeholders who generate, disseminate and use new knowledge. Methodologies need to evolve to both prioritize research questions and to conduct collaborative comparative effectiveness research studies. Given the impracticality of testing every clinical intervention in comparative pragmatic trials for comparative effectiveness research in chronic obstructive pulmonary disease, we advocate expanding methodology that includes the use of observational databases with serially performed effectiveness analyses and quasi-experimental designs that include following healthcare changes longitudinally over time to assess benefit, harm, subgroups and cost.
chronic obstructive pulmonary disease; comparative effectiveness research; data warehouse; emphysema; health services research; outcome research; quasi-experimental design; registry; translational research
The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed.
randomized controlled trials; observational studies; implementation; study designs; methodology
There is little data about the combined effects of COPD and obesity. We compared dyspnea, health-related quality of life (HRQoL), exacerbations, and inhaled medication use among patients who are overweight and obese to those of normal weight with COPD.
We performed secondary data analysis on 364 Veterans with COPD. We categorized subjects by body mass index (BMI). We assessed dyspnea using the Medical Research Council (MRC) dyspnea scale and HRQoL using the St. George's Respiratory Questionnaire. We identified treatment for an exacerbation and inhaled medication use in the past year. We used multiple logistic and linear regression models as appropriate, with adjustment for age, COPD severity, smoking status, and comorbidities.
The majority of our population was male (n=355, 98%) and either overweight (n=115, 32%) or obese (n=138, 38%). Obese and overweight subjects had better lung function (obese: mean FEV1 55.4% ±19.9% predicted, overweight: mean FEV1 50.0% ±20.4% predicted) than normal weight subjects (mean FEV1 44.2% ±19.4% predicted), yet obese subjects reported increased dyspnea [adjusted OR of MRC score ≥2= 4.91 (95% CI 1.80, 13.39], poorer HRQoL, and were prescribed more inhaled medications than normal weight subjects. There was no difference in any outcome between overweight and normal weight patients.
Despite having less severe lung disease, obese patients reported increased dyspnea and poorer HRQoL than normal weight patients. The greater number of inhaled medications prescribed for obese patients may represent overuse. Obese patients with COPD likely need alternative strategies for symptom control in addition to those currently recommended.
Obesity; COPD; health-related quality of life; symptoms; inhaled medications; exacerbations
Disparities in treatment exist for non-white and Hispanic patients with non-small-cell lung cancer, but little is known about disparities in the use of staging tests or their underlying causes.
Prospective, observational cohort study of 3638 patients with newly diagnosed non-small-cell lung cancer from 4 large, geographically-defined regions, 5 integrated health care systems and 13 VA health care facilities.
Median age was 69 years, 62% were men, 26% were Hispanic or non-white, 68% graduated high school, 50% had private insurance, and 41% received care in the VA or another integrated health care system. After adjustment, PET use was 13% lower among non-whites and Hispanics than non-Hispanic whites (RR 0.87, 95% CI 0.77 to 0.97), 13% lower among those with Medicare than those with private insurance (RR 0.87, 95% CI 0.76 to 0.99), and 24% lower among those with an elementary school education than those with a graduate degree (RR 0.76, 95% CI 0.57 to 0.98). Disparate use of PET was not observed among patients who received care in an integrated health care setting, but the association between race/ethnicity and PET use was similar in magnitude across all other subgroups. Further analysis showed that income, education, insurance and health care setting do not explain the association between race/ethnicity and PET use.
Hispanics and non-whites with non-small-cell lung cancer are less likely to receive PET imaging. This finding is consistent across subgroups and not explained by differences in income, education, or insurance coverage.
lung neoplasms; carcinoma; non-small-cell lung; neoplasm staging; tomography; emission-computed; healthcare disparities
Lung cancer is the leading cause of cancer death in the United States. Identifying factors associated with stage of diagnosis can improve our understanding of biologic and behavioral pathways of lung cancer development and detection. We used data from a prospective cohort study to evaluate associations of demographic, health history, and health behaviors with early versus late stage at diagnosis of non-small cell lung cancer (NSCLC).
We calculated odds ratios (ORs) for the association of patient-level characteristics with advanced stage of diagnosis for NSCLC. The OR's were then adjusted for age, gender, race/ethnicity, smoking status, income, education, chronic obstructive pulmonary disease, and a comorbidity index.
We identified 612 cases of NSCLC among 77,719 adults, aged 50 to 76 years from Washington State recruited in 2000-2002, with followup through December 2007. In univariate analyses, subjects who quit smoking <10 years (OR 2.56, 95% CI 1.17 - 5.60) and were college graduates (OR 1.67, 95% CI, 1.00 - 2.76) had increased risks of being diagnosed with advanced stage NSCLC, compared to never smokers and non-college graduates, respectively. Receipt of sigmoidoscopy/colonoscopy, compared to no receipt, was associated with a decreased risk of advanced stage (OR 0.65, 95% CI, 0.43 - 0.99). The adjusted OR for receipt of sigmoidoscopy/colonoscopy was 0.55 (95% CI, 0.36 - 0.86). There was evidence that increasing the number of screening activities was associated with a decreased risk of advanced stage NSCLC (P for trend = 0.049).
Smoking status, education, and a screening activity were associated with stage at diagnosis of NSCLC. These results may guide future studies of the underlying mechanisms that influence how NSCLC is detected and diagnosed.
Lung cancer is the leading cause of cancer-related mortality among women. The role of hormone replacement therapy (HRT) in lung cancer development is unclear.
Patients and Methods
We evaluated a prospective cohort of 36,588 peri- and postmenopausal women aged 50 to 76 years from Washington State recruited in 2000 to 2002 (Vitamins and Lifestyle [VITAL] Study). Lung cancer cases (n = 344) were identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry during 6 years of follow-up. Hazard ratios (HRs) associated with use and duration of specific HRT formulations were calculated for total incident lung cancer, specific morphologies, and cancer by stage at diagnosis.
After adjusting for smoking, age, and other potential confounders, there was an increased risk of incident lung cancer associated with increasing duration of estrogen plus progestin (E+P) use (HR = 1.27 for E+P use 1 to 9 years, 95% CI, 0.91 to 1.78; and HR = 1.48 for E+P use ≥ 10 years, 95% CI, 1.03 to 2.12; P for trend = .03). There was no association with duration of unopposed estrogen use. Duration of E+P use was associated with an advanced stage at diagnosis (P for trend = .03).
Use of E+P increased the risk of incident lung cancer in a duration-dependent manner, with an approximate 50% increased risk for use of 10 years or longer. These findings may be helpful for informing women of their risk of developing lung cancer and delineating important pathways involved in hormone metabolism and lung cancer.
Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.
Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria.
4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).
Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.
Lung cancer is the most common cause of cancer-related mortality. Smoking cessation is crucial to decrease risk but additional prevention modalities are needed. Use of non-steroidal anti-inflammatory drugs (NSAIDs) may be promising.
The study was a prospective cohort of 77,125 men and women aged 50–76 years from Washington State recruited in 2000–2002 (the VITAL study). Lung cancer cases were identified through the Seattle-Puget Sound SEER cancer registry during 5 years of follow-up. Hazard ratios (HRs) associated with 10 year average use of total NSAIDs (excluding low-dose aspirin) and specific categories of NSAIDs were calculated for total incident lung cancer and specific morphologies.
665 lung cancer cases were identified. After adjusting for smoking, age, gender, and acetaminophen use, there was a borderline-significant inverse trend with total NSAID use (>4.2 days/week over 10 years vs. none, HR 0.82, 95% CI, 0.64–1.04, P for trend 0.05). The association was strongest for adenocarcinoma (HR 0.59, 95% CI, 0.37–0.94, P for trend 0.01) and appeared to be limited to men (HR 0.66, 95% CI, 0.47–0.92, P for trend 0.01) and to long-term (≥ 10 years) former smokers (HR 0.65, 95% CI, 0.44–0.96, P for trend 0.04). There were no appreciable differences by NSAID type.
Total NSAID use was associated with a small reduced risk of lung cancer which was strongest for adenocarcinoma, men, and long-term former smokers. These findings are supported by known lung carcinogenesis mechanisms, and suggest that NSAIDS may be useful for chemoprevention.
lung cancer; adenocarcinoma; non-steroidal anti-inflammatory drugs; cyclooxygenase-2; chemoprevention
Smoking cessation has been demonstrated to reduce the rate of loss of lung function and mortality among patients with mild to moderate chronic obstructive pulmonary disease (COPD). There is a paucity of evidence about the effects of smoking cessation on the risk of COPD exacerbations.
We sought to examine whether smoking status and the duration of abstinence from tobacco smoke is associated with a decreased risk of COPD exacerbations.
We assessed current smoking status and duration of smoking abstinence by self-report. Our primary outcome was either an inpatient or outpatient COPD exacerbation. We used Cox regression to estimate the risk of COPD exacerbation associated with smoking status and duration of smoking cessation.
We performed a cohort study of 23,971 veterans who were current and past smokers and had been seen in one of seven Department of Veterans Affairs (VA) primary care clinics throughout the US.
MEASUREMENTS AND MAIN RESULTS
In comparison to current smokers, ex-smokers had a significantly reduced risk of COPD exacerbation after adjusting for age, comorbidity, markers of COPD severity and socio-economic status (adjusted HR 0.78, 95% CI 0.75–0.87). The magnitude of the reduced risk was dependent on the duration of smoking abstinence (adjusted HR: quit <1 year, 1.04; 95% CI 0.87–1.26; 1–5 years 0.93, 95% CI 0.79–1.08; 5–10 years 0.84, 95% CI 0.70–1.00; ≥10 years 0.65, 95% CI 0.58–0.74; linear trend <0.001).
Smoking cessation is associated with a reduced risk of COPD exacerbations, and the described reduction is dependent upon the duration of abstinence.
chronic obstructive pulmonary disease; exacerbation; smoking cessation
Rationale: Lung cancer is the leading cause of cancer-related mortality in the United States. Although supplements are used by half the population, limited information is available about their specific effect on lung cancer risk.
Objectives: To explore the association of supplemental multivitamins, vitamin C, vitamin E, and folate with incident lung cancer.
Methods: Prospective cohort of 77,721 men and women aged 50–76 years from Washington State in the VITAL (VITamins And Lifestyle) study. Cases were identified through the Seattle–Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry.
Measurements and Main Results: Hazard ratios (HRs) for incident lung cancer according to 10-year average daily use of supplemental multivitamins, vitamin C, vitamin E, and folate. A total of 521 cases of lung cancer were identified. Adjusting for smoking, age, and sex, there was no inverse association with any supplement. Supplemental vitamin E was associated with a small increased risk of lung cancer (HR, 1.05 for every 100-mg/d increase in dose; 95% confidence interval [CI], 1.00–1.09; P = 0.033). This risk of supplemental vitamin E was largely confined to current smokers (HR, 1.11 for every 100-mg/d increase; 95% CI, 1.03–1.19; P < 0.01) and was greatest for non–small cell lung cancer (HR, 1.07 for every 100-mg/d increase; 95% CI, 1.02–1.12; P = 0.004).
Conclusions: Supplemental multivitamins, vitamin C, vitamin E, and folate were not associated with a decreased risk of lung cancer. Supplemental vitamin E was associated with a small increased risk. Patients should be counseled against using these supplements to prevent lung cancer.
bronchial neoplasm; diet; dietary supplements; public health
The title compound, C8H12Br2O4, is a bicyclic ketal in which the two six-membered rings are cis to one another and assume a double-chair conformation. A crystallographic twofold axis bisects the molecule.
Rationale and Objectives: Lung cancer is a frequent cause of death among patients with chronic obstructive pulmonary disease (COPD). We examined whether the use of inhaled corticosteroids among patients with COPD was associated with a decreased risk of lung cancer.
Methods: We performed a cohort study of United States veterans enrolled in primary care clinics between December 1996 and May 2001. Participants had received treatment for, had an International Classification of Disease, 9th edition, diagnosis of, or a self-reported diagnosis of COPD. Patients with a history of lung cancer were excluded. To be exposed, patients must have been at least 80% adherent to inhaled corticosteroids. We used Cox regression models to estimate the risk of cancer and adjust for potential confounding factors.
Findings: We identified 10,474 patients with a median follow-up of 3.8 years. In comparison to nonusers of inhaled corticosteroids, adjusting for age, smoking status, smoking intensity, previous history of non–lung cancer malignancy, coexisting illnesses, and bronchodilator use, there was a dose-dependent decreased risk of lung cancer associated with inhaled corticosteroids (ICS dose < 1,200 μg/d: adjusted HR, 1.3; 95% confidence interval, 0.67–1.90; ICS dose ⩾ 1,200 μg/d: adjusted HR, 0.39; 95% confidence interval, 0.16–0.96). Changes in cohort definitions had minimal effects on the estimated risk. Analyses examining confounding by indication suggest biases in the opposite direction of the described effects.
Interpretation: Results suggest that inhaled corticosteroids may have a potential role in lung cancer prevention among patients with COPD. These initial findings require confirmation in separate and larger cohorts.
chronic obstructive pulmonary disease; pharmacoepidemiology; lung cancer; adherence
Rationale: The role of pulmonary function before stem cell transplant as a potential risk factor for the development of early post-transplant respiratory failure and mortality is controversial. Methods: We conducted a retrospective analysis of the pretransplant pulmonary function of 2,852 patients who received their transplant between 1990 and 2001. Measurements: Pretransplant FEV1, FVC, total lung capacity (TLC), diffusing capacity of carbon monoxide (DLCO), and the alveolar–arterial oxygen tension difference P(A-a)O2 were measured and assessed for association with development of early respiratory failure and mortality in Cox proportional hazard logistic models. Main Results: In multivariate analyses, progressive decrease of all lung function parameters was associated with a stepwise increase in risk of developing early respiratory failure and mortality when assessed in independent models. On the basis of a significant correlation between FEV1 and FVC (r = 0.81), FEV1 and TLC (r = 0.61), and FVC and TLC (r = 0.80), and a lack of correlation between FEV1 and DLCO, we developed a pretransplant lung function score based on pretransplant FEV1 and DLCO to determine the extent of pulmonary compromise before transplant. Multivariate analysis indicated that higher pretransplant lung function scores are associated with a significant increased risk for developing early respiratory failure (category II hazard ratio [HR], 1.4; category III HR, 2.2; category IV HR, 3.1; p < 0.001) and death (category II HR, 1.2; category III HR, 2.2; category IV HR, 2.7; p < 0.005). Conclusions: These results suggest that not only does compromised pretransplant lung function contribute to the risk for development of early respiratory failure and mortality but this risk may be estimated before transplant by grading the extent of FEV1 and DLCO compromise.
bone marrow transplantation; mortality; pretransplant pulmonary function tests; respiratory failure