12
CONTRIBUTING FACULTY Faculty Perspectives Kristy Pezzino, PharmD Director of Pharmacy Health Alliance Medical Plans Champaign, IL The development and publication of this article has been supported by TEVA. TEVA provided the idea for this article and a Medical Accuracy review. The views and opinions expressed are from the authors and not necessarily those of TEVA. THE PEER-REVIEWED FORUM FOR REAL-WORLD EVIDENCE IN BENEFIT DESIGN FOR PAYERS, PURCHASERS, POLICYMAKERS, AND OTHER HEALTHCARE STAKEHOLDERS PHARMACY & CLINICS TRANSFORMING RETAIL PHARMACIES INTO HEALTHCARE DELIVERY COMPANIES TM © 2015 Novellus Healthcare Communications, LLC Prevalence, Burden, Epidemiology, and Pathophysiology of Asthma James F. Donohue, MD Professor of Medicine and Division Chief of Pulmonary and Critical Care Medicine University of North Carolina at Chapel Hill School of Medicine Chapel Hill, NC Ross M. Miller, MD, MPH Medical Advisor California Department of Health Care Services Los Angeles, CA PART 1 OF A 4-PART SERIES an affiliate of Respiratory

Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

  • Upload
    others

  • View
    6

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

CONTRIBUTING FACULTY

Faculty Perspectives™

Kristy Pezzino, PharmDDirector of Pharmacy

Health Alliance Medical PlansChampaign, IL

The development and publication of this article has been supported by TEVA. TEVA provided the idea for this article and a Medical Accuracy review. The views and opinions expressed are from the authors and not necessarily those of TEVA.

THE PEER-REVIEWED FORUM FOR REAL-WORLD EVIDENCE IN BENEFIT DESIGN™

FOR PAYERS, PURCHASERS, POLICYMAKERS, AND OTHER HEALTHCARE STAKEHOLDERS

PHARMACY & CLINICS

TRANSFORMING RETAIL PHARMACIES INTO HEALTHCARE DELIVERY COMPANIES

TM

© 2015 Novellus Healthcare Communications, LLC

Prevalence, Burden, Epidemiology, and Pathophysiology of Asthma

James F. Donohue, MDProfessor of Medicine and Division Chief of Pulmonary and Critical Care Medicine

University of North Carolina at Chapel Hill School of Medicine

Chapel Hill, NC

Ross M. Miller, MD, MPHMedical Advisor

California Department of Health Care Services

Los Angeles, CA

PART 1 OF A 4-PART SERIES

an affiliate of 81

Business units G4

Projects G2

Corporate PG3

Geographical B4

Europe B.V.

Exchange

Americas Generics Italy

TAPI Sicor Biotech UAB

Intranet

Respiratory

Customer Service

Human ResourcesR&DResearch and Development

TGOTeva Global Operations

Page 2: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

2 n January 2015

PUBLISHING STAFFSenior Vice President, Sales & Marketing

Philip Pawelko [email protected]

Vice President/Group PublisherJohn W. Hennessy

[email protected] Directors

Dalia Buffery [email protected]

Frederique H. Evans [email protected]

Strategic EditorRobert E. Henry

Senior Associate EditorLilly Ostrovsky

Associate EditorLara J. LortonCopyeditorHina Khaliq

Editorial AssistantCara Guglielmon

Production ManagerMelissa Lawlor

The Lynx GroupPresident/CEOBrian Tyburski

Chief Operating OfficerPam Rattananont Ferris

Vice President of FinanceAndrea Kelly

Human ResourcesJennine Leale

Director, Strategy & Program DevelopmentJohn Welz

Director, Quality ControlBarbara Marino

Quality Control AssistantTheresa Salerno

Director, Production & ManufacturingAlaina Pede

Director, Creative & DesignRobyn Jacobs

Creative & Design AssistantsLora LaRocca

Wayne WilliamsDirector, Digital Media

Anthony RomanoJr Digital Media Specialist

Charles Easton IVWeb Content Manager

Anthony TreveanDigital ProgrammerMichael Amundsen

Meeting & Events PlannerLinda Mezzacappa

Senior Project ManagersAlyson Bruni

Jini GopalaswamyProject ManagerDeanna Martinez

Project CoordinatorMike KodadaIT ManagerKashif Javaid

Administrative Team LeadersRachael Baranoski

Allison IngramAdministrative Assistant

Amanda HedmanOffice Coordinator

Robert SorensenNovellus Healthcare Communications, LLC

1249 South River Road - Ste 202A Cranbury, NJ 08512

phone: 732-992-1895 fax: 732-992-1881

TABLE OF CONTENTS

Asthma Epidemiology, Burden, and Pathophysiology .......................................................... 3Matthew Wendling, MPH

Stakeholders’ PerspectivesPrevalence, Burden, Epidemiology, and Pathophysiology of Asthma ....................................... 7James F. Donohue, MD

Asthma and the Role of Managed Care Pharmacy ........................................................... 8Kristy Pezzino, PharmD

Trends in Asthma Management................................ 9Ross M. Miller, MD, MPH

Faculty Perspectives™

EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, Novellus Healthcare Communications, LLC, 1249 South River Rd, Suite 202A, Cranbury, NJ 08512. E-mail: [email protected]. POSTMASTER: CORRESPONDENCE REGARDING SUBSCRIPTIONS OR CHANGE OF ADDRESS should be directed to CIRCULATION DIRECTOR, Novellus Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Correspondence re garding permission to reprint all or part of this activity should be addressed to REPRINT PERMISSIONS DEPARTMENT, Novellus Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. The ideas and opinions expressed in Faculty Perspectives™ do not necessarily reflect those of the Advisory Board, the Editorial Director, or the Publisher. Readers are encouraged to contact the manufacturer with questions about the features or limita-tions of the products mentioned. Neither the Advisory Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. Please convey any errors to the Editorial Director.

Faculty Perspectives™ is published by Novellus Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Telephone: 732-992-1895. Fax: 732-992-1881. Copyright © 2015 by Novellus Healthcare Communications, LLC. All rights reserved. Faculty Perspectives is a trademark of Novellus Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.

NOV361-1

To obtain a digital version, download a free QR code app on your SmartPhone and then scan this code.

Page 3: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

Faculty Perspectives n 3

ASTHMA EPIDEMIOLOGY, BURDEN, AND PATHOPHYSIOLOGY

Asthma is a chronic inflammatory disorder of the air-ways characterized by airflow obstruction, height-ened bronchial response, and underlying inflamma-

tion.1,2 The acute manifestations of the disorder, often called “asthma attacks,” are periodic, recurrent episodes caused by chronically hyperactive and inflamed airways, leading to air-flow obstruction.2

For most patients, asthma onset begins in childhood, with patterns of inflammation and disease persistence determined by early, recognizable risk factors, including parental history of asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4

During an acute exacerbation, individuals may experience wheezing, coughing, chest tightness, chest pain, or shortness of breath. The severity of asthma attacks varies from mild to moderate to severe. In extreme cases, attacks may be life- threatening and require immediate medical attention.1,2,5

There is no known cure for asthma.6 However, it can be controlled with appropriate medical care, and by avoiding exposures (particularly environmental exposures that may trigger an attack), exacerbations can be lessened and severe exacerbations should be rare.7

Epidemiology and Risk FactorsAsthma is a significant public health issue, affecting about

300 million people worldwide.8 In 2009, it was estimated that 1 in 12 people (approximately 25 million) had asthma in the United States alone.9 Asthma prevalence has been on the rise, increasing from 3.1% in 1980 to 5.5% in 1996 and 7.3% in 2001 to 8.4% in 2010.10

Race and ethnicity may play a role in asthma preva-lence, as evidenced by data from 2001 through 2010. Higher rates of asthma were observed among blacks than whites and Hispanics, whereas Hispanics had lower rates than either group (Figure 1).10

In addition to race/ethnicity, asthma prevalence var-ies by a number of modifiable and nonmodifiable risk factors, including weight, tobacco use, age, socioeco-nomic status, and geography.11 Overall, it is more prev-alent in children than adults. In terms of gender, asthma is more prevalent in women than men; however, among children, boys have a higher prevalence (11.3%) than girls (7.9%). Not surprisingly, the prevalence of asthma is higher among families living in poverty compared

with those who have incomes above the federal poverty level.1

Asthma prevalence also varies from state to state, as shown by Behavioral Risk Factor Surveillance System data (Figure 2).12

Obesity has been receiving increasing attention as a risk factor for asthma. In a study published last year, Zhang and colleagues reported a high prevalence of asthma among obese (10.2%, 95% confidence interval [CI], 10.0-10.3) and mor-bidly obese (18.2%, 95% CI, 17.7-18.7) persons, concluding that the ongoing obesity epidemic could be contributing to an increased prevalence of asthma among adults in some states.11

Economic Burden of AsthmaIn 2007, the total societal cost of asthma was estimated at

$56 billion. Most of this total ($50.1 billion) was attributed to medical expenses, whereas loss of productivity resulting from missed schooldays or workdays and premature death accounted for the remainder.13 By 2008, working adults who experienced 1 or more asthma attacks during the previous 12 months missed

Asthma Epidemiology, Burden, and PathophysiologyMatthew Wendling, MPH

Figure 1. Asthma prevalence by race/ethnicity in the United States (2001-2010).

Source: Centers for Disease Control and Prevention: Asthma Prevalence in the US 2014.

14

12

10

8

6

4

2

0

US

Pop

ula

tio

n (

%)

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Whites Blacks Hispanics

The severity of asthma attacks varies from mild to moderate to severe. In extreme

cases, attacks may be life-threatening and require immediate medical attention.

Page 4: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

ASTHMA EPIDEMIOLOGY, BURDEN, AND PATHOPHYSIOLOGY

4 n January 2015

a combined total of 14.2 million days of work due to asthma.1 In 2010, asthma accounted for 3404 deaths; 439,400 hos-

pitalizations; 1.8 million emergency department visits; and 14.2 million physician office visits.14 It was estimated that from 2002 to 2007, the value of productivity loss attributable to asthma was $2.03 billion because of morbidity and $2.37 billion because of mortality, per year. In addition, asthma was responsible for incremental direct medical costs of $3259 per person per year.13 In terms of healthcare utiliza-tion, asthma is responsible for an estimated 15.0 million outpatient visits per year.15

Pathophysiology Although the root causes of the inflammatory process lead-

ing to asthma are yet to be fully explained, the development of asthma appears to involve the interaction between genetic and environmental factors that take place at a critical point in the development of the immune system.2,16

The pathophysiology of asthma is complex and involves mechanisms of adaptive and nonadaptive immunity that re-sult in airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness.2,17 Evidence indicates that patterns of inflammation vary according to phenotypic differences, which are identifiable clusters of demographic, clinical, or pathophysiological characteristics, including al-lergic asthma, nonallergic asthma, late-onset asthma, asthma with fixed airflow limitation, and asthma with obesity.3 Al-though some phenotype-guided treatments are available for

patients with severe asthma, thus far, phenotypes have not correlated strongly with specific pathological pro-cesses or treatment responses.3

In allergic asthma—the most common form of the disease—T helper type 2 (TH2) lymphocytes produce interleukin (IL)-4, IL-5, IL-9, and IL-13 in response to airborne allergens. These cytokines regulate the aller-gen-specific synthesis of immunoglobulin E (IgE) from B cells, promote the growth and differentiation of mast cells and eosinophils and the recruitment and activa-tion of basophils, and directly cause airway hyperreac-tivity, a hallmark characteristic of asthma.17,18

Airway InflammationIn asthma, the mechanism of inflammation varies

from acute to subacute to chronic.19 Most patients have chronic inflammation, which persists over many years. In addition to ongoing chronic inflammation, patients may also experience acute inflammatory episodes, or exacerbations, of asthma.19,20

Airway inflammation is characterized by varying de-grees of mucus hypersecretion, desquamation of the ep-ithelium, smooth muscle hyperplasia, and airway re-modeling.19 The degree of airway hyperresponsiveness is usually correlated with the clinical severity of asthma.21

Chronic inflammation of the airways is associated with in-creased bronchial hyperresponsiveness, which leads to bron-chospasm and typical symptoms of wheezing, shortness of breath, and coughing following exposure to triggers such as allergens, environmental irritants, or viruses. In some patients with chronic asthma, airflow limitation may be only partially reversible because of airway remodeling, which is character-ized by hypertrophy and hyperplasia of smooth muscle, subep-ithelial fibrosis, injury to epithelial cells, and angiogenesis.2

Several cell types are involved in the inflammatory process, including mast cells, macrophages, eosinophils, epithelial cells, endothelial cells, and activated T lymphocytes. Patients with asthma have elevated numbers of mast cells in the smooth muscle lining the airways. Mast cells play a role in initiating the acute bronchoconstrictor responses to allergens and other stimuli,20 and are thought to be an important con-

Figure 2. Adult self-reported asthma prevalence rates in the United States.

Source: Centers for Disease Control and Prevention 2010. www.cdc.gov/asthma/brfss/2010/current/ mapC1.htm.

The pathophysiology of asthma is complex and involves mechanisms of adaptive and nonadaptive immunity that result in airway

inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness.

Page 5: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

Faculty Perspectives n 5

ASTHMA EPIDEMIOLOGY, BURDEN, AND PATHOPHYSIOLOGY

tributor in cases of severe asthma. A greater proportion of chymase-positive mast cells in the airways and increased pros-taglandin D2 levels have been identified as important predic-tors of severe asthma.22

Macrophages are thought to be activated by IgE recep-tors present on allergenic cells and cell components, and may both increase and decrease inflammation, depending on the stimulus.20

Eosinophils are also thought to play a central role in asthma pathophysiology. The presence of elevated eosinophil counts are linked to airway hyperresponsiveness. In animal studies, activated eosinophils have shown direct inflammatory chang-es in the airway.20 Enhanced eosinophilic activity is mediated by TH2 cells, which activates vascular cell adhesion mole-cule-1 to facilitate the preferential movement of circulating eosinophils to the airways.20,23

Structural cells of the airways, including epithelial and endo-thelial cells, are thought to be an important source of inflamma-tory mediators, such as cytokines and lipid mediators. Moreover, epithelial cells may have a key role in translating inhaled envi-ronmental signals into an airway inflammatory response.20

Neutrophils may also be involved in patients with certain asthma phenotypes. Elevated neutrophil activity has been found in patients with sudden-onset, fatal asthma exacerba-tions, in cases of occupational asthma, and in patients who smoke tobacco. However, it has not been determined whether neutrophils have a causative role in these fatal exacerbations.2,20,24

Two additional cell types, invariant natural killer T (iNKT) cells and innate lymphoid cells (ILCs), have been found to produce cytokines that mediate the inflammatory process in asthma, independently of adaptive immunity and conventional antigens. Although the specific roles of iNKT cells and ILCs in immunity are still being defined, these cells respond to environmental triggers important in clinical asth-ma and may function independently and in conjunction with adaptive immunity to shape immunity environmental trig-gers, including specific allergens, microbes, and foods.17

Airflow ObstructionAirflow obstruction can be caused by a variety of changes,

including bronchoconstriction, edema, mucus plug formation,

and airway remodeling (Figure 3).25 Acute bronchoconstric-tion, which is the primary manifestation of the early asthmat-ic response, takes place when IgE-dependent mediators are released upon exposure to airbound allergens. Airway edema, which typically occurs 6 to 24 hours following an allergen challenge, constitutes late asthmatic response. Chronic mucus plug formation, which consists of serum proteins and cell de-bris that accumulate in the airways, may take weeks to resolve. The structural changes associated with chronic inflammation may limit the reversibility of airway obstruction, resulting in permanent tissue impairment.26

Airway obstruction causes resistance to airflow and de-creased expiratory flow rates. Over time, patients may experi-ence irreversible decline in lung function because of persistent, chronic pathology that results in thickening of airway walls.26

Bronchial HyperresponsivenessBronchial hyperresponsiveness is an exaggerated reponse to

stimuli, leading to excessive bronchial narrowing.27 Although it is recognized as an important feature in asthma, it does not occur in all patients with the disease.28 Moreover, bronchial hyperresponsiveness is not specific to asthma, and may also be caused by endogenous pathologies such as chronic obstructive pulmonary disease (COPD), viral respiratory infection, and cystic fibrosis as well as exogenous stimuli, including atopy, tobacco smoking, smoke inhalation, and near-drowning.27

Although the precise biochemical mechanisms have not been fully elucidated, the pathogenesis of bronchial hyperre-sponsiveness depends on the underlying pathological process.

Figure 3. Multiple mechanisms of airflow obstruction in asthma.

Source: Doeing DC et al. J Appl Physiol. 2013;114:834-843. Reprinted with permission.

Structural cells of the airways, including epithelial and endothelial cells, are thought to be an important source of inflammatory mediators, such as

cytokines and lipid mediators.

Page 6: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

ASTHMA EPIDEMIOLOGY, BURDEN, AND PATHOPHYSIOLOGY

6 n January 2015

As a result, there are important differences in the pathogene-sis of bronchial hyperresponsiveness in patients with asthma, COPD, or allergic rhinitis.29

Bronchial hyperresponsiveness is associated with the influx of inflammatory cells.28 In asthma, epithelial shedding and subsequent loss of barrier function can contribute to bronchi-al hyperresponsiveness by allowing allergens to penetrate the epithelial barrier. Epithelial damage also results in the loss of enzymes that break down inflammatory mediators, which may exacerbate the inflammatory process.30

The precise pathological mechanisms involved in bron-chial hyperresponsiveness are currently being explored. Researchers have found that the TH2 cytokines IL-4, IL-5, and IL-13 are each associated with worsening of bronchial hyperresponsiveness in animal models. Specific interventions to block each of these cytokines in humans with asthma may warrant further investigation.28

SummaryOverall, it appears that the development of asthma in-

volves an interaction between host factors (particularly genet-ics) and environmental exposures that occur at a crucial point in the development of the immune system.2,16

Atopy, the genetic predisposition for the development of an IgE-mediated response to common airborne allergens, such as mites, animal dander, pollen, mold, and fungi, is the stron-gest identifiable predisposing factor for developing asthma. In addition, viral respiratory infections are one of the most im-portant causes of exacerbations of asthma and may also con-tribute to the development of the disease.31

A variety of other factors have also been linked to asthma or airway hyperreactivity, including exercise, chronic comor-bid conditions (eg, gastroesophageal reflux disease and obe-sity), aspirin or other nonsteroidal anti-inflammatory drugs, beta-blockers, emotional hypersensitivity, tobacco smoke, occupational exposure (eg, cold air, chemical irritants, or air pollution), and stress.31,32

The interaction of the pathophysiological features of asth-ma determines the clinical manifestations and disease sever-ity, as well as the response to treatment.2

Although the critical role of airway inflammation in asthma pathology is clear, considerable variations exist in patterns of inflammation, which suggests that phenotypic differences may influence treatment responses. Further research is warranted

regarding the potential clinical utility of a targeted approach to treatment based on the asthma phenotype profile.2,3

However, since it is a central feature of asthma, mitigating inflammation remains a primary target of treatment. Although current therapeutic approaches are effective in controlling symptoms, reducing airflow limitation, and preventing exacer-bations, they do not appear to prevent progression of the un-derlying disease severity.31 As inflammatory and genetic fac-tors become better understood at the cellular and molecular levels, new therapeutic approaches may be developed that will allow even greater specificity, to tailor treatment to the indi-vidual patient’s needs and circumstances.33 Emerging research that seeks to identify more targeted therapies for asthma will be discussed in more detail in the next issue of this series. n

References1. Akinbami LJ, Moorman JE, Liu X. Asthma Prevalence, Health Care Use, and Mortality: United States, 2005–2009. National health statistics reports; no 32. Hyattsville, MD: National Center for Health Statistics; 2011.2. Expert Panel Report 3 (EPR-3)—Summary Report 2007. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 08-5846. Bethesda, MD: US Department of Health & Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program; 2007.3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention 2014. www.ginasthma.org. Accessed November 7, 2014.4. Merck Manuals Web site. Overview of allergy and atopy. www.merckmanuals.com/professional/immunology_allergic_disorders/allergic_autoimmune_and_other_hypersensitivity_disorders/overview_of_allergy_and_atopy.html. Accessed November 7, 2014.5. Data from the CDC National Asthma Control Program. Asthma’s impact on the nation. www.cdc.gov/asthma/impacts_nation/asthmafactsheet.pdf. Accessed November 7, 2014.6. US Department of Health & Human Services. National Institutes of Health; National Heart, Lung, and Blood Institute. How is asthma treated and controlled? www.nhlbi.nih.gov/health/health-topics/topics/asthma/treatment.html. Accessed November 7, 2014.7. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Revised 2006. www.ginasthma.org. Accessed November 7, 2014.8. Masoli M, Fabian D, Holt S, Beasley R, for the Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy. 2004;59:469-478.9. CDC Web site. Vital signs. www.cdc.gov/vitalsigns. Accessed November 7, 2014.10. CDC. National Center for Environmental Health. Asthma prevalence in the United States [PowerPoint]. June 2014. 11. Zhang X, Morrison-Carpenter T, Holt JB, Callahan DB. Trends in adult current asthma prevalence and contributing risk factors in the United States by state: 2000–2009. BMC Public Health. 2013;13:1156.12. CDC Web site. 2010 adult asthma data: prevalence, tables and maps. www.cdc.gov/asthma/brfss/2010/current/mapC1.htm. Accessed November 7, 2014.13. Barnett SB, Nurmagambetov TA. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011;127:145-152.14. CDC. Asthma Facts—CDC’s National Asthma Control Program Grantees. Atlanta, GA: US Department of Health & Human Services, Centers for Disease Control and Prevention; 2013.15. Dougherty RH , Fahy JV. Acute exacerbations of asthma: epidemiology, biol-ogy and the exacerbation-prone phenotype. Clin Exp Allergy. 2009;39:193-202.16. Subbarao P, Mandhane PJ, Sears MR. Asthma: epidemiology, etiology and risk factors. CMAJ. 2009;18:E181-E190.17. DeKruyff RH, Yu S, Kim HY, Umetsu DT. Innate immunity in the lung reg-ulates the development of asthma. Immunol Rev. 2014;260:235-248.18. Kim HY, DeKruyff RH, Umetsu DT. The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nature Immunol. 2010;11:577-584.19. Busse WW, Calhoun WF, Sedgwick JD. Mechanism of airway inflammation in asthma. Am Rev Respir Dis. 1993;147:S20-S24.20. Barnes PJ. Pathophysiology of asthma. Eur Respir Mon. 2003:23;84-113.21. Olivenstein R, Taha R. Airway hyperresponsiveness. In: Hamid Q, Shannon J,

continued on page 10

In asthma, epithelial shedding and subsequent loss of barrier function can contribute to

bronchial hyperresponsiveness by allowing allergens to penetrate the epithelial barrier.

Page 7: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

Faculty Perspectives n 7

PROVIDER PERSPECTIVE

The prevalence and cost of asthma are considerable. In 2010, an estimated 25.7 million Americans had asth-ma, and direct and indirect costs related to the care

of this disorder totaled a staggering $56 billion in 2007.1,2 According to the 2012 Behavioral Risk Factor Surveillance System, 49% of patients with asthma reported an attack in the past year, 11% reported no symptoms in the past year, and 43% reported no physician visits in the past year. Furthermore, only 27% of patients reported having an asthma management plan, and 33% reported missing work or days of reduced activ-ity.3 Clearly, there is room for improvement when it comes to the management of asthma in the United States.

One of the most important questions facing practitioners when a patient presents with symptoms of cough, wheezing, nocturnal signs, and sleep disruption, is whether the individ-ual has asthma.4 To establish a diagnosis, practitioners should access patient history, and inquire about symptoms to determine if they are consistent with recurrent episodes of airflow obstruction.4

The key signs of asthma include recurrent wheezing, short-ness of breath, chest tightness, and cough that vary over time and intensity.4 Variable expiratory airflow limitation is noted if measurements of peak expiratory flow rates are made. Typically, symptoms are worse at night or in the early morn-ing, and may be triggered by infections, exercise, allergens, weather, and irritants.4

Obesity is an important risk factor for asthma, as it often results in an altered pulmonary physiology and increased air-way resistance. In addition, obesity is associated with more asthma exacerbations, especially in women.5 Patients with asthma who are obese tend to have more airway symptoms and airway inflammation. These patients also respond differ-ently to asthma medications. Therefore, it is imperative to manage obesity in order to improve airway hyperresponsive-ness and inflammation.6-8

Various tools can be used to assess and monitor asthma, such as spirometry, which provides an objective measure of lung function; the forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of >0.75 to 0.80 is consid-ered normal in adult patients.3 Other asthma assessment tools include asthma control questionnaires, asthma control tests, and peak flow meters.9

The clinical symptoms of asthma may vary greatly in terms of severity. Some of the characteristics of severe asthma include chronic airflow obstruction, eosinophilic and/or neu-trophilic asthma, corticosteroid insensitivity, and recurrent exacerbations.9 Given the fact that asthma is heterogenous in terms of the underlying clinical and inflammatory phenotypes involved, the care of patients is moving toward a more person-alized, targeted approach.

In the future, we will have phenotype-targeted treatments based on the pathophysiology and biomarkers of asthma.10 Phenotyping patients with asthma with links to pathophysio-logical mechanisms will lead to a more precise, rational way of providing specific treatments to the individual patient. For example, patients with recurrent exacerbations who have sputum or blood eosinophils may be candidates for anti-inter-leukin-5 antibody treatment; and patients with chronic air-flow obstruction, airway wall remodeling, low FEV1 levels, and high serum periostin levels may be candidates for anti-interleukin-13 antibody treatment. In addition, patients with neutrophils in the sputum may be more responsive to macro-lide antibiotics, and patients with eosinophilic asthma may be more responsive to an anti-interleukin-4 receptor.10 n

References1. Akinbami LJ, Moorman JE, Bailey C, et al. Trends in asthma prevalence, health care use, and mortality in the United States, 2001–2010. NCHS Data Brief. 2012;94:1-8.2. Barnett SB, Nurmagambetov TA. Costs of asthma in the United States: 2002-2007. J Allergy Clin Immunol. 2011;127:145-152.3. Centers for Disease Control and Prevention. 2012 BRFSS asthma call-back survey prevalence tables. www.scdhec.gov/Health/DiseasesandConditions/Asthma/ AsthmaFacts/. Accessed November 21, 2014. 4. Global Institute for Asthma. Global strategy for asthma management and pre-vention. Revised 2014. www.ginasthma.org/local/uploads/files/GINA. Accessed November 21, 2014.5. Heacock T, Lugogo N. Role of weight management in asthma symptoms and control. Immunol Allergy Clin North Am. 2014;34:797-808.6. Scott HA, Gibson PG, Garg ML, et al. Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: a randomized trial. Clin Exp Allergy. 2013;43:36-49.7. Dogra S, Kuk JL, Baker J, Jamnik V. Exercise is associated with improved asthma control in adults. Eur Respir J. 2011;37:318-323.8. Mendes FA, Almeida FM, Cukier A, et al. Effects of aerobic training on airway inflammation in asthmatic patients. Med Sci Sports Exerc. 2011;43:197-203.9. National Heart, Lung, and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf. Accessed November 21, 2014.10. Chung KF. New treatments for severe treatment-resistant asthma: targeting the right patient. Lancet Respir Med. 2013;1:639-652.

Prevalence, Burden, Epidemiology, and Pathophysiology of Asthma James F. Donohue, MDProfessor of Medicine and Division Chief of Pulmonary and Critical Care MedicineUniversity of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC

Page 8: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

8 n January 2015

PHARMACIST PERSPECTIVE

Managed care organizations (MCOs) allocate resourc-es to improve the quality of asthma care while controlling asthma-related drug costs. MCOs that

are accredited by the National Committee for Quality Assurance (NCQA) focus on Healthcare Effectiveness Data and Information Set (HEDIS) measures to develop manage-ment strategies for drugs. NCQA-accredited MCOs strive to create and maintain a drug formulary that offers value to the member; value is defined as outcomes relative to costs.1

HEDIS measures are divided into 2 categories: (1) preven-tive care and (2) condition-specific care. The targeted areas for condition-specific care focus on asthma, cardiac condi-tions, chronic obstructive pulmonary disease, depression, dia-betes, mental illness, rheumatoid arthritis, tobacco use, and alcohol and drug abuse.2 The 2015 HEDIS measures for asth-ma include the use of appropriate medications and medication management.3 The HEDIS quality metrics and the overall value of the drug are taken into consideration when managed care pharmacy teams develop utilization management strate-gies to address pharmacy costs.

The main article in this publication provides an excellent update for healthcare professionals regarding asthma and its prevalence, pathophysiology, and economic burden. The prevalence of asthma continues to rise along with treat-ment-related costs. The pathophysiology of asthma remains a complex subject, with treatment still focused on controlling symptoms rather than halting disease progression. Therefore,

managing patients with asthma continues to focus on symp-tom control and avoidance of triggers of an exacerbation.

The economic burden of asthma is well known. Outpatient visits, emergency department visits, and hospitalizations are the key drivers of asthma-related costs. To reduce these costs and improve patient outcomes, MCOs have established disease state management programs that utilize case managers and drug formulary designs, such as Pitney Bowes’s value-based benefit design.4 In order to effectively manage asthma at the health plan level, multiple departments within the organiza-tion need to work together to achieve a common goal.

On the pharmacy side, a managed care’s annual drug spending and patient compliance to medication regimens are monitored, using formulary design and management techniques to provide cost-effective options for patients. Pharmacy departments work with medical management de-partments to identify patients who are over- or underutiliz-ing medications in an effort to reduce exacerbations that lead to hospitalization. Using claims data on the pharmacy and medical side allows the health plan to apply resources in the most effective manner.

Asthma disease progression is based on genetic and envi-ronmental factors. By understanding the disease process and identifying allergens that trigger asthma attacks, patients can better manage their symptoms. As novel targeted therapies continue to be developed, health plans are monitoring pipe-line drug development to prepare for potential new therapies that will target asthma disease progression. It is hoped that these advances will lead to improved outcomes for patients with this disorder. n

References1. Porter ME. What is value in health care? N Engl J Med. 2010;363:2477-2481.2. National Quality Measures Clearinghouse. Measure summary. www.quality measures.ahrq.gov/content.aspx?id=47279. Accessed November 26, 2014.3. National Committee for Quality Assurance. Summary table of measures, prod-uct lines and changes. www.ncqa.org/Portals/0/HEDISQM/Hedis2015/List_of_HEDIS_2015_Measures.pdf. Accessed November 26, 2014.4. Mahoney JJ. Value-based benefit design: using a predictive modeling approach to improve compliance. J Manag Care Pharm. 2008;14(6 Suppl B):3-8.

Asthma and the Role of Managed Care PharmacyKristy Pezzino, PharmDDirector of Pharmacy, Health Alliance Medical PlansChampaign, IL

The pathophysiology of asthma remains a complex subject, with treatment still

focused on controlling symptoms rather than halting disease progression.

Page 9: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

Faculty Perspectives n 9

PAYER PERSPECTIVE

Asthma continues to be an important chronic condi-tion for public and private payers, especially given the fact that it ranks as the top pediatric condition

for commercial and managed Medicaid plans.1 From a clinical perspective, asthma management has evolved considerably in the past 2 decades, leading to better self-management and more appropriate use of medications. Perhaps most notably, improvements in asthma control have resulted in improved outcomes and quality of life for patients and their families.

In terms of payer mix, asthma disproportionately affects Medicaid members for 2 reasons. First, asthma is more preva-lent among children than among adults, and the managed Medicaid member base skews toward a younger demographic.2 Second, asthma disproportionately affects those at the lower socioeconomic end of the spectrum, again representing the group frequently served by Medicaid programs.3

From a payer perspective, hospitalizations are the most important component of healthcare utilization in asthma, fol-lowed by emergency department (ED) visits.3 Hospitalizations and ED visits tend to occur more frequently in patients with uncontrolled severe disease who experience frequent exacerba-tions. Furthermore, these patients are frequently nonadherent to their prescribed chronic therapy.

In asthma, pharmacy management focuses on the appropri-ate use of controller medications to help limit acute exacerba-tions (ie, asthma attacks), which can be dangerous and even life- threatening to the patient. These efforts are closely aligned with the national quality initiatives led by the National Committee for Quality Assurance (NCQA), the main accred-iting body for managed care health plans. NCQA evaluates payer performance on 2 core asthma quality measures: (1) use of appropriate medication for individuals with asthma, and (2) medication management for individuals with asth-ma.4 These measures provide specific criteria that allow payers to identify and to report appropriate medication use in patients diagnosed with persistent asthma. They also provide the tools needed to help payers proactively identify and intervene with members who have an elevated high risk of developing exacerbations as a result of the suboptimal use of asthma control medications.

In addition to targeted pharmacy-based programs, payers play an important role in promoting patient self-management and medication adherence through condition-management

initiatives. In asthma, these population-based programs are designed to educate members about their disease, promote awareness of exacerbation triggers, and encourage appropri-ate use of medications.5

Asthma management has also been facilitated by the adop-tion of ED observation units, which allow hospitals to monitor patients for up to 23 hours without inpatient admission. Typically, payers have been supportive of observation units for patients with acute asthma exacerbations under the assump-tion that close monitoring in the outpatient setting will lead to improved quality of care, less hospitalizations, and perhaps fewer recurrences.6 There is evidence to suggest that ED obser-vation units have resulted in improved patient satisfaction and cost-savings; one study found that the cost of monitoring a patient in an observation setting is approximately half of the cost of monitoring the same patient in an inpatient setting.7,8

Overall, advances in asthma management have been positive for payers as well as for patients. The appropriate prescribing of controller medications have led to substantially improved dis-ease control and reduced daily burden for patients. Furthermore, improved adherence to asthma control medications has been shown to reduce healthcare-related utilization and costs.7

Despite improvements in asthma care, however, a number of key unmet needs remain. First, in the clinical practice guidelines promulgated by the National Heart, Lung, and Blood Institute, which have not been revised since 2007 but are due to be updated in 2015, treatment recommendations are based on symptomatology rather than on diagnostic cri-teria.9 This is important because differential diagnoses of respiratory conditions continue to pose a challenge for clini-cians, especially when trying to differentiate between asthma,

Trends in Asthma ManagementRoss M. Miller, MD, MPHMedical Advisor, California Department of Health Care ServicesLos Angeles, CA

In asthma, these population-based programs are designed to educate

members about their disease, promote awareness of exacerbation triggers, and

encourage appropriate use of medications.

Page 10: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

10 n January 2015

PAYER PERSPECTIVE

“chronic bronchitis,” and chronic obstructive pulmonary dis-ease in adults.

In addition, a substantial number of patients are nonadher-ent to their controller medications—as prescribed or at all.7 This is surprising given the minimal financial barriers to drugs in the category because of generic availability; some payers that have implemented value-based insurance designs charge min-imal or zero copays for generic asthma control medications.

Ultimately, however, asthma management is predominant-ly driven by the patient–provider relationship. Nevertheless, health plans seek to identify high-risk patients who take mul-tiple rescue medications without a controller medication, often referring these patients to outreach programs by case management professionals. In addition, payers also engage in population health efforts, which may include the develop-ment and dissemination of asthma self-management tools for their members with asthma. They may also work with their network providers to raise awareness about validated patient assessment tools.

Similar to other chronic conditions, the future of asthma care will likely bring new opportunities to personalize patient care as more gene-based targeted therapies are developed and commercialized. More efficient, simpler drug delivery systems may also facilitate improved compliance to asthma medica-tions and minimize the burden for patients and their families. To demonstrate value, these technologic and therapeutic enhancements will need to contribute to better cost-effective asthma management and improved patient outcomes. n

References1. Andrews AL, Simpson AN, Basco WT Jr, et al. Asthma medication ratio predicts emergency department visits and hospitalizations in children with asth-ma. Medicare Medicaid Res Rev. 2013;3:E1-E10. 2. Asthma and Allergy Foundation of America. Asthma facts and figures. www.aafa.org/display.cfm?sub=42&id=8. Accessed November 29, 2014.3. Centers for Disease Control and Prevention. Asthma facts: CDC’s national asthma control program grantees. July 2013. www.cdc.gov/asthma/pdfs/asthma_facts_program_grantees.pdf. Accessed November 29, 2014.4. National Committee for Quality Assurance. Summary table of measures, prod-uct lines and changes. www.ncqa.org/Portals/0/HEDISQM/HEDIS2014/List_of_HEDIS_2014_Measures.pdf. Accessed November 29, 2014.5. Erickson CD, Splett PL, Mullett SS, et al. The healthy learner model for stu-dent chronic condition management—part II: the asthma initiative. J Sch Nurs. 2006;22:319-329.6. Downey C. EDTUs (emergency diagnostic and treatment units): last line of defense against costly inpatient stays. Manag Care. 2001;10:44-46.7. National Committee for Quality Assurance. Improving quality and patient experience: the state of health care quality 2013. October 2013. www.ncqa.org/Portals/0/Newsroom/SOHC/2013/SOHC-web_version_report.pdf. Accessed November 29, 2014.8. Baugh CW, Venkatesh AK, Hilton JA, et al. Making greater use of dedicated hospital observation units for many short-stay patients could save $3.1 billion a year. Health Aff (Millwood). 2012;31:2314-2323.9. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (EPR-3 2007). NIH Publication No. 07-4051. Bethesda, MD: US Department of Health & Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program; 2007.

Martin J, eds. Clinical Respiratory Physiology. Hamilton, Ont, Canada: BC Decker; 2005:709-719.22. Balzar S, Fajt ML, Comhair SAA, et al. Mast cell phenotype, location, and activation in severe asthma: data from the severe asthma research program. Am J Respir Crit Care Med. 2011;183:299-309.23. Johansson MW, Han S-T, Gunderson KA, et al. Platelet activation, P-selectin, and eosinophil β1-integrin activation in asthma. Am J Respir Crit Care Med. 2012;185:498-507.24. Lugogo NL, MacIntyre NR. Life-threatening asthma: pathophysiology and management. Respir Care. 2008;53:726-735.25. Doeing DC, Solway J. Airway smooth muscle in the pathophysiology and treatment of asthma. J Appl Physiol. 2013;114:834-843. 26. Sears MR. Consequences of long-term inflammation. The natural history of asthma. Clin Chest Med. 2000;21:315-329.27. Law KW, Ng KK, Yuen KN, Ho CS. Detecting asthma and bronchial hyper-responsiveness in children. Hong Kong Med J. 2000;6:99-104.

28. Grootendorst DC, Rabe KF. Mechanisms of bronchial hyperreactivity in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2004; 1:77-87.29. Antosova M, Strapkova A, Plevkova J. Bronchial hyperreactivity: pathogen-esis and treatment options. Open J Molec Integr Physiol. 2011;1:43-51.30. Kaufman G. Asthma: pathophysiology, diagnosis and management. Nursing Standard. 2011;26:48-56.31. EPR 3—Full Report 2007. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 07-4051. Bethesda, MD: US Department of Health & Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program; August 2007.32. World Health Organization Web site. Chronic respiratory disease. www.who.int/respiratory/asthma/causes/en/. Accessed November 7, 2014.33. Arron JR, Scheerens H, Matthews JG. Redefining approaches to asthma: developing targeted biologic therapies. Adv Pharmacol. 2013;66:1-49.

Asthma Epidemiology, Burden, and Pathophysiologycontinued from page 6

Similar to other chronic conditions, the future of asthma care will likely bring

new opportunities to personalize patient care as more gene-based targeted therapies

are developed and commercialized.

Page 11: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,

Faculty Perspectives n 11

NOTES

Page 12: Prevalence, Burden, Epidemiology, and Pathophysiology of ... · asthma and atopy (a genetic predisposition toward allergic hypersensitivity reactions).3,4 During an acute exacerbation,