Kourtney J. Davis

American Cancer Society guidelines for the early detection of cancer.

This issue of CA inaugurates a yearly report on American Cancer Society guidelines for early detection of cancer in asymptomatic individuals.

Lung function decline and outcomes in an elderly population

Objective: To determine the risk factors for and outcomes associated with the rapid decline in lung function in a cohort of elderly US adults. Methods: Data from 4923 adult participants aged 65 years and older at baseline in the Cardiovascular Health Study were analysed. Subjects were classified using a modification of the GOLD criteria for chronic obstructive pulmonary disease (COPD) and a “restricted” category (FEV1/FVC ⩾70% and FVC <80% predicted) was added. Cox proportional hazard models were used to determine the risk of lung function decline over 4 years on subsequent mortality and COPD hospital admissions after adjusting for age, race, sex, smoking status, and other factors. Results: Of the participants in the initial cohort, 3388 (68.8%) had spirometric tests at the year 4 visit. Participants with GOLD stages 3 or 4 COPD at baseline were less likely than normal subjects to have follow up spirometric tests (52.7% v 77.9%, p<0.01) and were more likely to be in the most rapidly declining quartile of FEV1 (28.2% v 21.3%, p<0.01) with an annual loss of FEV1 of at least 3.5%. Overall, being in the most rapidly declining quartile of FEV1 from baseline to year 4 was associated with an increased risk of admission to hospital for COPD (adjusted hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.3 to 2.0) and all-cause death (adjusted HR 1.5, 95% CI 1.2 to 1.7) over an additional 7 years of follow up. Conclusion: More rapid decline in lung function is independently associated with a modest increased risk of hospital admissions and deaths from COPD in an elderly cohort of US participants.

Lung function impairment, COPD hospitalisations and subsequent mortality

Background Hospitalisations and their sequelae comprise key morbidities in the natural history of chronic obstructive pulmonary disease (COPD). A study was undertaken to examine the associations between lung function impairment and COPD hospitalisation, and COPD hospitalisation and mortality. Methods The analysis included a population-based sample of 20 571 participants with complete demographic, lung function, smoking, hospitalisation and mortality data, with 10-year median follow-up. Participants were classified by prebronchodilator lung function according to the modified Global Initiative on Obstructive Lung Disease (GOLD) criteria. Hospitalisations were defined by the presence of a COPD discharge diagnosis (ICD-9 codes 490–496). Incidence rate ratios (IRR) of COPD admissions and hazard ratios (HR) of mortality with respective 95% CI were calculated, adjusted for potential confounders. Results The prevalence of modified GOLD categories was normal (36%), restricted (15%), GOLD stage 0 (22%), GOLD stage 1 (13%), GOLD stage 2 (11%) and GOLD stages 3 or 4 (3%). Adjusted IRRs (and 95% CI) indicated an increased risk of COPD hospitalisation associated with each COPD stage relative to normal lung function: 4.7 (3.7 to 6.1), 2.1 (1.6 to 2.6), 3.2 (2.6 to 4.0), 8.0 (6.4 to 10.0) and 25.5 (19.5 to 33.4) for the restricted, GOLD stage 0, GOLD stage 1, GOLD stage 2 and GOLD stages 3 or 4, respectively. Hospitalisation for COPD increased the risk of subsequent mortality (HR 2.7, 95% CI 2.5 to 3.0), controlling for severity, number of prior hospitalisations and other potential confounders. The increase in mortality associated with admission was very similar across the modified GOLD stages. Conclusions COPD severity was associated with a higher rate of severe exacerbations requiring hospitalisation, although severe exacerbations at any stage were associated with a higher risk of short-term and long-term all-cause mortality.

Relationship between lung function impairment and incidence or recurrence of cardiovascular events in a middle-aged cohort

Introduction: Lung function impairment may be a risk factor for cardiovascular disease (CVD) events. Objective: To determine the relationship between the severity of airflow obstruction based on modified Global Initiative on Obstructive Lung Disease (GOLD) criteria and the prevalence and incidence or recurrence of CVD in a cohort of US adults, aged 45–64 years, from 1987 to 2001. Methods: We analysed data from 14 681 adults using logistic regression to determine the cross sectional association between lung function impairment and prevalent CVD at baseline and Cox regression to examine the prospective association of lung function impairment at baseline with CVD over 15 years of follow-up. Models were adjusted for age, sex, race, smoking, comorbid hypertension and diabetes, cholesterol levels and fibrinogen level. Results: At baseline, the crude prevalence of CVD was higher among subjects with GOLD 2 (OR 2.9, 95% CI 2.4 to 3.6) and GOLD 3 or 4 chronic obstructive pulmonary disease (COPD) (OR 3.0, 95% CI 2.0 to 4.5), compared with normal subjects. These relative risks were greatly reduced after adjusting for covariates (OR 1.4, 95% CI 1.1 to 1.8 for GOLD 2 and OR 1.3, 95% CI 0.8 to 2.1 for GOLD 3 or 4). Similarly, the association between COPD and risk of incident or recurrent CVD was much stronger in the unadjusted models (hazard ratio (HR) 2.4, 95% CI 2.1 to 2.7 for GOLD 2 and 2.9, 95% CI 2.2 to 3.9 for GOLD 3 or 4) than in the adjusted ones (HR 1.2, 95% CI 1.03 to 1.4 for GOLD 2 and 1.5, 95% CI 1.1 to 2.0 for GOLD 3 or 4). Conclusion: We observed a crude association between lung function impairment and prevalent and incident or recurrent CVD that was greatly reduced after adjusting for covariates, including age, sex, race, smoking, comorbid hypertension and diabetes, cholesterol levels and fibrinogen level. These data suggest that this association may be, in part, mediated through established CVD risk factors included in our adjusted models.

The natural history of community-acquired pneumonia in COPD patients: a population database analysis.

BACKGROUND Patients with Chronic Obstructive Pulmonary Disease (COPD) are at higher risk of developing Community-Acquired Pneumonia (CAP) than patients in the general population. However, no studies have been performed in general practice assessing longitudinal incidence rates for CAP in COPD patients or risk factors for pneumonia onset. METHODS A cohort of COPD patients aged ≥ 45 years, was identified in the General Research Practice Database (GPRD) between 1996 and 2005, and annual and 10-year incidence rates of CAP evaluated. A nested case-control analysis was performed, comparing descriptors in COPD patients with and without CAP using conditional logistic regression generating odds ratios (OR) and 95% confidence intervals (CI). RESULTS The COPD cohort consisted of 40,414 adults. During the observation period, 3149 patients (8%) experienced CAP, producing an incidence rate of 22.4 (95% CI 21.7-23.2) per 1000 person years. 92% of patients with pneumonia diagnosis had suffered only one episode. Multivariate modelling of pneumonia descriptors in COPD indicate that age over 65 years was significantly associated with increased risk of CAP. Other independent risk factors associated with CAP were co-morbidities including congestive heart failure (OR 1.4, 95% CI 1.2-1.6), and dementia (OR 2.6, 95%CI 1.9-3.). Prior severe COPD exacerbations requiring hospitalization (OR 2.7, 95% CI 2.3-3.2) and severe COPD requiring home oxygen or nebulised therapy (OR 1.4, 95% CI 1.1-1.6) were also significantly associated with risk of CAP. CONCLUSION COPD patients presenting in general practice with specific co-morbidities, severe COPD, and age >65 years are at increased risk of CAP.

Trends and Cardiovascular Co-morbidities of COPD Patients in the Veterans Administration Medical System, 1991–1999

Persons with Chronic Obstructive Pulmonary Disease (COPD) are at risk for developing other smoking-related complications, including cardiac and vascular diseases. Information about the prevalence and incidence of these conditions is needed to anticipate their occurrence in clinical research. We conducted a cohort study using longitudinal administrative data to describe the prevalence and incidence of cardiovascular (CV) diseases among COPD patients treated by the Veterans Administration Medical System. The COPD cohort included all persons with a diagnosis of COPD admitted to a Veterans Administration Medical System hospital (N = 70,679) or seen in a outpatient clinic (N = 314,209) in fiscal year 1998. Each COPD patient was matched to a Veteran of the same age and gender who did not have a COPD diagnosis, creating a non-COPD cohort for comparison. Among all hospitalized Veterans, the prevalence of COPD steadily increased from 1991 to 1999, although the total number of Veterans hospitalized during this time period decreased by more than one-third. Among COPD patients hospitalized in 1998, the prevalence of coronary artery disease, congestive heart failure, and atrial fibrillation were very high (33.6%, 24.4%, and 14.3%, respectively) and significantly higher than those seen among the matched non-COPD cohort (27.1%, 13.5%, and 10.4%; p < 0.001). Among COPD outpatients, increased complications were found in every CV disease category with rate ratios that were greater than observed among inpatients. We conclude that CV diseases are remarkably prevalent among Veterans with COPD, and their incidence is likely to increase as the Veteran population ages.

Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)

Objectives The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. Setting 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. Primary outcome measure The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. Results 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5–92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7–94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2–44.4%). Conclusions Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004.

Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012-2013

Purpose The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999–2000. Materials and methods Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples. Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments. Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale. Results Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey. COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%–9%. In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%–14%) than among women (range 5%–11%). A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries. Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment. Conclusion This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey. A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey.

The Influence of Variation in Type and Pattern of Symptoms on Assessment in Pediatric Asthma

OBJECTIVE. We conducted a national, population-based survey to examine the asthma-related health burden of US children. METHODS. A telephone-based survey was conducted in 2004 of children 4 to 18 years of age with current asthma in the United States. In 41433 households screened, 1089 children reported current asthma; 801 interviews were completed by parents of children aged 4 to 15 years and by children themselves aged 16 to 18 years. The survey included questions about symptoms, perceived level of control, activity limitations, health care use, medicines, disease management, and knowledge. Global asthma symptom burden, derived from the National Asthma Education and Prevention Program guidelines, was composed of 3 components: short-term symptom burden (4-week recall), long-term symptom burden (past year), and functional impact (activity limitation). RESULTS. The majority of children were classified with mild intermittent disease on the basis of recent daytime symptoms alone (80%); yet, when report of nighttime symptoms was included, the proportion of children classified as having mild intermittent symptoms decreased (74%). When asthma burden was assessed on the basis of the global symptom burden construct, only a minority (13%) of individuals was classified as having an asthma symptom burden consistent with mild intermittent disease; the majority (62%) was classified as having moderate/severe disease. In addition, the impact of asthma on the daily activities is substantial; avoiding exertion (47%) and staying inside (34%) are common approaches to improve control of asthma symptoms. CONCLUSIONS. The goals of therapy for asthma, based on the National Asthma Education and Prevention Program guidelines, have not been achieved for the majority of children. In addition, parents and children overestimate the childs asthma control and commonly restrict activities to control asthma symptoms. Deficiencies in the control of asthma may be related to the underestimation of the burden of disease.

Asthma Management in Pregnancy

Background Asthma is common during pregnancy, however research is limited regarding the extent and timing of changes in asthma management associated with pregnancy. Objective To determine the prevalence of asthma during pregnancy and identify changes in treatment and asthma exacerbation rates associated with pregnancy, while controlling for seasonal influences. Methods Pregnant women with asthma were identified from the UK General Practice Research Database between 2000 and 2008. For each woman asthma medication prescribed during the study period was identified; for each product combination the British Thoracic Society medication-defined asthma treatment step was identified. Asthma exacerbations were identified during pregnancy and in the corresponding 12 months prior. Analyses of changes in asthma treatment and exacerbation rates during pregnancy relative to the corresponding period 12 months prior, to control for seasonality, were stratified by trimester and asthma treatment intensity level. Results The prevalence of treated asthma in pregnancies resulting in a delivery was 8.3%. From 14,141 pregnancies, in 12,828 women with asthma, 68.4% received prescriptions for a short-acting β2-agonist and 41.2% for inhaled corticosteroids; 76.5% were managed with asthma treatment Step 1 or 2. Poor persistence to inhaled corticosteroids, defined as a gap of up to 60 days between prescriptions, was common. In 45.0% of pregnancies, an increase in average treatment step was observed whereas in 25.6% the treatment step decreased. Treatment intensity remained the same in 29.5% of pregnancies. Exacerbations occurred in 4.8% of pregnancies compared to 5.9% in the same season the year before (p<0.001). Conclusion Exacerbation rates during pregnancy were slightly lower than in the year before. However, treatment patterns and exacerbation rates in this study suggest asthma control during pregnancy is variable, and women may require close monitoring especially in those with evidence of poor control before pregnancy.