How to Avoid Underdiagnosed Asthma/Chronic Obstructive Pulmonary Disease?

The prevalence of asthma and chronic obstructive pulmonary disease (COPD) is rising in most countries, including the Netherlands. It has been suggested that a majority of these cases of (self-reported) symptoms related to asthma/COPD are not diagnosed in general practice. We compared a population screening for underdiagnosed asthma/COPD with a high-risk approach by a questionnaire form with specified questions about asthma/COPD-related symptoms. A case-controlled study including a record review was performed of cases and controls. The results of a population screening were used to classify patients as (a) asthma/COPD, (b) at risk for asthma/COPD, or (c) no asthma/COPD. Eleven hundred fifty-five patients were screened. One hundred fifty-five patients reported previous asthma/COPD-related care (cases). The difference between number of cases and controls in asthma/COPD diagnosis was chosen as main outcome measure. The population screening revealed 85 subjects with a diagnosis of asthma/COPD and 154 subjects with an increased risk. Nineteen diagnoses could be made in cases, and eight diagnoses in controls. The chart review showed that only seven cases and two controls were known to the general practitioner. From this study it can be concluded that in order to reduce the number of un- and underdiagnosed patients, all listed patients in general practice should be screened. However, if screening of all patients is not feasible, active case finding by asking a few questions about shortness of breath or wheezing to all patients in the group of listed individuals is recommended.     

Predicting Chronic Obstructive Pulmonary Disease Hospitalizations Based on Concurrent Influenza Activity

Abstract

Although influenza has been associated with chronic obstructive pulmonary disease (COPD) exacerbations, it is not clear the extent to which this association affects healthcare use in the United States. The first goal of this project was to determine to what extent the incidence of COPD hospitalizations is associated with seasonal influenza. Second, as a natural experiment, we used influenza activity to help predict COPD admissions during the 2009 H1N1 influenza pandemic. To do this, we identified all hospitalizations between 1998 and 2010 in the Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project (HCUP) during which a primary diagnosis of COPD was recorded. Separately, we identified all hospitalizations during which a diagnosis of influenza was recorded. We formulated time series regression models to investigate the association of monthly COPD admissions with influenza incidence. Finally, we applied these models, fit using 1998–2008 data, to forecast monthly COPD admissions during the 2009 pandemic. Based on time series regression models, a strong, significant association exists between concurrent influenza activity and incidence of COPD hospitalizations (p-value < 0.0001). The association is especially strong among older patients requiring mechanical ventilation. Use of influenza data to predict COPD admissions during the 2009 H1N1 pandemic reduced the mean-squared prediction error by 29.9%. We conclude that influenza activity is significantly associated with COPD hospitalizations in the United States and influenza activity can be exploited to more accurately forecast COPD admissions. Our results suggest that improvements in influenza surveillance, prevention, and treatment may decrease hospitalizations of patients diagnosed with COPD.     

Measurement of Blood Eosinophils in Asthma and Chronic Obstructive Pulmonary Disease

Eosinophils are important effector cells in airway inflammation, as pleiotropy and heterogeneity can be linked to various pathophysiologies in asthma and chronic obstructive pulmonary disease (COPD). Sputum eosinophils can reflect the heterogeneity of airway inflammation, and owing to their traits, blood eosinophils can be a surrogate and potential biomarker for managing both conditions. Blood eosinophils are activated via the stimulation of type 2 cytokines, such as interleukin (IL)-5, IL-4/13, granulocyte-macrophage colony-stimulating factor, IL-33, and thymic stromal lymphopoietin. There is sufficient evidence to support the relationship between the blood eosinophil count and clinical outcomes, including pulmonary function decline, exacerbations, all-cause mortality, and treatment response to inhaled corticosteroids and biologics. Thus, there is growing interest in the use of blood eosinophils for the management of these diseases. Compiling recent evidence, we herein review the significance of measuring blood eosinophils in asthma and COPD.     

U.S. Regulatory Perspective on the Minimal Clinically Important Difference in Chronic Obstructive Pulmonary Disease

This paper outlines the regulatory issues surrounding the determination and use of minimally clinically important differences (MCID) in assessing measures of outcomes from treatments of chronic obstructive pulmonary disease (COPD). To place this discussion in context, it is important to understand the current state of approved therapies for COPD, as well as newer directions in therapy. This paper discusses the currently available, approved drug therapies for COPD in the United States and how they were approved. This is followed by an overview on the use of MCID for assessing outcomes in therapies for COPD, as well the more general experience with MCID from the U.S. regulatory perspective.     

Assessment of the Inhalation Technique in Outpatients with Asthma or Chronic Obstructive Pulmonary Disease Using a Metered-Dose Inhaler or Dry Powder Device

Inhaled medication is commonly prescribed for the treatment of asthma and chronic obstructive pulmonary disease (COPD), but is often not properly used by patients. A total of 316 patients suffering from asthma or COPD took part in a study that evaluated how patients utilized their metered-dose inhaler (MDI) or dry powder inhaler, using a standardized inhaler checklist. Two hundred eighty-one patients (88.9%) made at least one mistake in the inhalation technique. The mistakes were classified into skill and nonskill mistakes. Two hundred patients made one or more skill mistakes and 81 patients only made one or more nonskill mistakes. The most common skill error was “not continuing to inhale slowly after activation of the canister” (69.6%). The nonskill item most patients had difficulties with was “exhale before the inhalation” (65.8%). Patients who used an MDI made significantly fewer nonskill mistakes than patients using a dry powder device. Older patients had more difficulty with the correct use of the inhaler than younger patients. There was no difference in errors between men and women. In this patient sample, most patients failed to use their inhaler correctly. Regular instructions and checkups of inhalation technique are the responsibility of the physician and should be a standard and routine procedure.     

Red Blood Cell Distribution and Survival in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Background: Cardiovascular disease (CVD) contributes significantly to mortality in chronic obstructive pulmonary disease (COPD). Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity that is largely overlooked, is a newly recognized mortality marker in patients with established CVD. It is unknown whether RDW is associated with mortality in COPD patients.

Aims: To study the prognostic value of RDW in patients with COPD and to compare the value of this measurement with cardiac, respiratory, and hemotological status. Method: We performed retrospective analyses of 270 patients stable with COPD who were admitted to our hospital between January 2007 and December 2009. Demographic, clinical, echocardiographic, and laboratory characteristics were registered and recorded COPD deaths were registered as outcomes. Results: In the overall patients, the RDW level had a mean value of 15.1 ± 2.4. RDW was positively correlated with C-reactive protein (CRP) (p = 0.008, r = 0.21), right ventricular dysfunction (RVD) (p < 0.001, r = 0.25), and pulmonary arterial hypertension (PAH) (p = 0.03, r = 0.14). Variables (p < 0.1) included in the univariate survival analysis were forced expiratory volume in 1 second (FEV1% predicted), RDW levels, age, PaCO2, albumine and CRP levels, presence of CVD, presence of anemia, presence of RVD, and presence of PAH. Subsequent multivariate analysis suggested that RDW levels (1.12; 95% CI, 1.01 to 1.24; p = 0.01), and presence of RVD (2.6; 95% CI, 1.19 to 5.8; p = 0.01) were independently related to mortality. Conclusion: Elevated RDW levels were associated with increased mortality risk in stable COPD patients.     

Trends in Outcomes,Financial Burden,and Mortality for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) in the United States from 2002 to 2010

Chronic obstructive pulmonary disease (COPD) is the cause of substantial economic and social burden. We evaluated the temporal trends of hospitalizations from acute exacerbation of COPD and determined its outcome and financial impact using the National (Nationwide) Inpatient Sample (NIS) databases (2002–2010). Individuals aged ≥ 18 years were included. Subjects who were hospitalized with primary diagnosis of COPD exacerbation and those who were admitted for other causes but had underlying acute exacerbation of COPD (secondary diagnosis) were captured by International Classification of Diseases-Ninth Revision (ICD-9) codes. The hospital outcomes and length of stay were determined. Multivariate logistic regression was used to identify the independent predictors of inpatient mortality. Overall acute exacerbation of COPD-related hospitalizations accounted for nearly 3.31% of all hospitalizations in the year 2002. This did not change significantly to year 2010 (3.43%, p = 0.608). However, there was an increase in hospitalization with secondary diagnosis of COPD. Elderly white patients accounted for most of the hospitalizations. Medicare was the primary payer source for most of the hospitalizations (73–75%). There was a significant decrease in inpatient mortality from 4.8% in 2002 to 3.9% in 2010 (slope –0.096, p < 0.001). Similarly, there was a significant decrease in average length of stay from 6.4 days in 2002 to 6.0 days in 2010 (slope –0.042, p < 0.001). Despite this, the hospitalization cost was increased substantially from $22,187 in 2002 to $38,455 in 2010. However, financial burden has increased over the years.     

The Relationship between Particulate Matter (PM10) and Hospitalizations and Mortality Of Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Abstract

Background: Numerous studies have reported variable associations between ambient particulate matter (PM) and chronic obstructive pulmonary disease (COPD) hospitalizations and mortality. Objective: To conduct a systematic study assessing the associations between hospitalizations and mortality from COPD and ambient PM₁₀ (particulate matter with aerodynamic diameters ≤ 10 μm, PM₁₀). Methods: Systematic searches were conducted in 6 common electronic databases. A meta-analysis was performed to estimate the odds ratio (OR) to evaluate the relationship between PM₁₀ and COPD hospitalizations and mortality. Publication bias and heterogeneity of samples were tested by Begg funnel plot and Egger test, respectively. Study findings were analyzed using random-effect model and fixed-effect model. Results: The search yielded 31 studies suitable for the meta-analysis during the period from Jan 1, 2000 to Oct 31, 2011. A 10μg/m³ increase in PM₁₀ was associated with a 2.7% (95%CI = 1.9%-3.6%) increase in COPD hospitalizations with an OR of 1.027 (95%CI: 1.019–1.036), and a 1.1% (95%CI: 0.8%–1.4%) increase in COPD mortality with an OR of 1.011 (95%CI: 1.008–1.014). Conclusions: Ambient PM₁₀ is associated with increased COPD hospitalizations and mortality. Further research is needed to elucidate whether this association is causal and to clarify its mechanisms.     

Levels of IL-32 in Serum,Induced Sputum Supernatant,and Bronchial Lavage Fluid of Patients with Chronic Obstructive Pulmonary Disease

Interleukin-32 (IL-32) is a newly described cytokine which is expected to have an important role in autoimmune disorders. It was shown that chronic obstructive pulmonary disease (COPD) has a component of autoimmunity, though the role of IL-32 in its pathogenesis is not known. The aim of this study was to estimate IL-32 concentrations in serum, induced sputum (IS) supernatant and bronchoalveolar lavage (BAL) fluid from patients with COPD, and to compare asthma patients with and healthy subjects. Outpatients with COPD (63.7 ± 8.4 years, n = 51), asthma (58.3 ± 12.4 years, n = 31), and healthy subjects (59.8 ± 8.2 years, n = 9) were studied. The levels of IL-32 in serum, BAL fluid, and IS supernatant samples were analyzed by ELISA. Concentrations of IL-32 were higher in all the studied materials from patients with COPD (BAL 22.46 ± 2.48 pg/ml, IS 19.66 ± 1.69 pg/ml, serum 26.77 ± 2.56 pg/ml) in comparison with patients with asthma (BAL 6.25 ± 1.08 pg/ml, IS 5.82 ± 1.15 pg/ml, serum 6.09 ± 1.16 pg/ml, p < 0.05 respectively) as well as healthy subjects (BAL 4.21 ± 1.13 pg/ml, IS 3.59 ± 0.66 pg/ml, serum 4.63 ± 1.03 pg/ml, p < 0.05 respectively). Moreover, the level of IL-32 was higher in COPD smokers than in COPD ex-smokers in investigated respiratory tissue compartments and serum, and correlated with smoking history. Increased level of IL-32 in serum, IS supernatant, and BAL fluid from patients with COPD in comparison with asthma patients and healthy subjects suggest that IL-32 may play an important role in the pathogenesis of COPD, which depends on the smoking history.     

Mortality Related to Chronic Obstructive Pulmonary Disease and Co-morbidities in the United States,A Multiple Causes of Death Analysis

ABSTRACT

Chronic obstructive pulmonary disease (COPD) mortality based on the underlying cause of death (UCOD) underestimates disease burden. We aimed to determine the current COPD mortality rate, trends and the distribution of co-morbidities using United States (US) multiple-cause of death (MCOD) records.

All 38,905,575 death certificates of decedents aged ≥45 years in the United States were analyzed for 1999–2015. COPD was defined by ICD–10 codes J40–J44 and J47 based either on the UCOD or up to 20 contributing causes coded. Annual age–standardized COPD death rates were computed by age, gender and race/ethnicity for those with any mention of COPD.

In 2015, COPD was mentioned in 11.59% (292,572 deaths) in MCOD, compared to 11.13% (243,617 deaths) in 1999, a 4% increase. However, it was reported as the UCOD for only 5.56% and 4.97% in 2015 and 1999 respectively, an 11% increase. The most common UCOD in subjects with any mention of COPD was respiratory disorders in 49% of males and 55% of females. The relative change in death rates differed between MCOD and UCOD. For example, among non-Hispanic white females aged 65–74 years the UCOD rate per 100,000 (95% CI) decreased from 163 (160–166) to 147 (145–150), average annual percent decrease (AAPD) –0.26, while the MCOD rate decreased from 308 (304–311) to 263 (260–267), AAPD –0.87.

Statistics based on UCOD understated the burden of COPD in the United States. MCOD rates were twice as high as UCOD rates. The relative change in death percent or rates differed between MCOD and UCOD. MCOD analysis should be repeated periodically to help evaluate the burden of COPD-related mortality.     

Modifying the Course of Chronic Obstructive Pulmonary Disease: Looking Beyond the FEV1

Abstract

COPD is defined by airflow limitation that is not fully reversible and is usually progressive. Thus, airflow obstruction (measured as FEV₁) has traditionally been used as the benchmark defining disease modification with therapy. However, COPD exacerbations and extrapulmonary effects are common and burdensome and generally become more prominent as the disease progresses. Therefore, disease progression should be broader than FEV₁ alone. Interventions that reduce the frequency or severity of exacerbations or ameliorate extrapulmonary effects should also be considered disease modifiers. A narrow focus on FEV₁ will fail to capture all the beneficial effects of therapy on disease modification. Although smoking cessation has been unequivocally demonstrated to slow the rate of FEV₁ decline, inhaled corticosteroid–long-acting bronchodilator therapy may also have modest effects according to post hoc analysis. Maintenance pharmacotherapy with inhaled long-acting anti-muscarinic or ®-adrenergic agents or combined ®-adrenergic—inhaled corticosteroid reduces symptoms, improves lung function, reduces the frequency of exacerbations, and improves exercise capacity and HRQL. Pulmonary rehabilitation reduces symptom burden, increases exercise capacity, improves HRQL, and reduces health care utilization, probably through reducing the severity of exacerbations. Smoking cessation, lung volume reduction surgery, inhaled maintenance pharmacotherapy, and pulmonary rehabilitation administered in the post-exacerbation period may reduce mortality in COPD. These improvements over multiple outcome areas and over relatively long durations suggest that disease modification is indeed possible with existing therapies for COPD. Therefore, therapeutic nihilism in COPD is no longer warranted.     

Difficulties in the Interpretation of Lung Function Tests in the Diagnosis of Asthma and Chronic Obstructive Pulmonary Disease

Objective. To ascertain differences in the interpretation of spirometry and peak flow measurement between primary care (several practioners and nurses) and specialists in patients with a pre-existing diagnosis of asthma and chronic obstructive pulmonary disease (COPD). Design. A randomized, prospective cohort study of 98 patients with a pre-existing diagnosis of asthma or COPD. Two chest specialists independently interpreted the peak flow and spirometric data and they were also blinded to the primary care results. Results. There was total agreement in interpretation of the data between general practitioners and specialists in only 20 (20.4%). Levels of diagnostic agreement were highest between the two chest specialists (55%) and lowest between the general practice records and the diagnosis assigned by general practitioners (16%). Disagreement between general practitioners and the two chest specialists was consistent (38%) indicating systematic differences in interpretation. Conclusions. This study raises concerns about differences in the interpretation of spirometry and peak expiratory flow rates in general and hospital practice and the guidelines on which these interpretations are based.     

Difficulties in the Interpretation of Lung Function Tests in the Diagnosis of Asthma and Chronic Obstructive Pulmonary Disease

Objective. To ascertain differences in the interpretation of spirometry and peak flow measurement between primary care (several practioners and nurses) and specialists in patients with a pre-existing diagnosis of asthma and chronic obstructive pulmonary disease (COPD). Design. A randomized, prospective cohort study of 98 patients with a pre-existing diagnosis of asthma or COPD. Two chest specialists independently interpreted the peak flow and spirometric data and they were also blinded to the primary care results. Results. There was total agreement in interpretation of the data between general practitioners and specialists in only 20 (20.4%). Levels of diagnostic agreement were highest between the two chest specialists (55%) and lowest between the general practice records and the diagnosis assigned by general practitioners (16%). Disagreement between general practitioners and the two chest specialists was consistent (38%) indicating systematic differences in interpretation. Conclusions. This study raises concerns about differences in the interpretation of spirometry and peak expiratory flow rates in general and hospital practice and the guidelines on which these interpretations are based.     

Medical Utilization and Cost in Patients with Overlap Syndrome of Chronic Obstructive Pulmonary Disease and Asthma

Background: Little information is available regarding medical utilization and cost in patients with overlap syndrome of chronic obstructive pulmonary disease (COPD) and asthma. The purpose of this study is to analyze medical utilization and cost in patients with overlap syndrome and to compare them to COPD patients without asthma. Methods: Using the 2009 Korean National Health Insurance (NHI) database, COPD patients were identified. Medical utilization and costs were also analyzed. Results: Of a total of 185,147 patients identified with COPD, 101,004 patients were classified with overlap syndrome of COPD and asthma and 84,143 patients with COPD without asthma. In 2009, the percentages of emergency room visits, admissions, and intensive care unit admissions were 14.6%, 30.5%, and 0.5%, respectively, in the patients with overlap syndrome group and 5.0%, 14.1%, and 0.2%, respectively, in the COPD patients without asthma group (p < 0.05 for all comparisons). The cost of medical utilization was 790 ± 71 US dollars per person and 3,373 ± 4,628 dollars per person for outpatient and inpatient services, respectively, in the patients with overlap syndrome and 413 ± 512 and 3,010 ± 5,013, respectively, in the COPD patients without asthma (p < 0.05 for all comparisons). Multiple linear regression showed that age, sex, overlap syndrome, hospitalization in the last year, low socioeconomic status, and type of hospital use were significant factors affecting medical utilization and cost. Conclusions: In patients with overlap syndrome, both medical utilization and cost were higher than in COPD patients without asthma.