Asthma: Understanding the Problem and Learning How it can be Controlled Carol J. Blaisdell, M.D. Pediatric Pulmonolog

1. Asthma: Understanding the Problem and Learning How it can be Controlled Carol J. Blaisdell, M.D.Pediatric Pulmonology/AllergyUniversity of Maryland

2. SLIDE 1.3.3 Asthma is the most common chronic illness of childhood1. Asthma is the highest-ranking chronic condition causing hospitalization in children2. Eighty-seven percent of asthmatic children had unscheduled physician visits in the prior year3. Asthma is the number one chronic illness resulting in school absences4. Children with asthma have three times the school absences of children without asthma5. Forty percent of children with asthma have sleep disturbance (1 to 2 nights/week)2. So even if the child is not absent from school, he or she may have reduced school performance due to sleep disturbances. Seventy-eight percent of parents of asthmatics report that asthma has a negative impact on the family4. Thirty-six percent of parents of asthmatics missed work in the prior year4. 1Number of selected reported chronic conditions, by age: United States, 1994. In: Adams PF, Marano MA. Current estimates from the National Health Interview Survey, 1994. National Center for Health Statistics. Vital Health Stat. 1995;10(193):93-94. DHHS Publication No. (PHS) 96-1521. 2CDC. Surveillance for Asthma--United States, 1960-1995 (CDC Surveillance Summaries). MMWR. 1998;47(SS-1):1-26). 3Grant et al. Prevalence and burden of illness for asthma and related symptoms among kindergarteners Chicago public schools. Ann Allergy Asthma Immunol. 1999;83:113-120. 4American Lung Association. Pediatric Asthma: A Growing Health Threat. Available at: http://www.lungusa.org/asthma/merck_pediatric.html. Accessed July 9, 1999. 5Fowler et al. School functioning of US children with asthma. Pediatrics. 1992;90:939-944. SLIDE 1.3.3 Asthma is the most common chronic illness of childhood1. Asthma is the highest-ranking chronic condition causing hospitalization in children2. Eighty-seven percent of asthmatic children had unscheduled physician visits in the prior year3. Asthma is the number one chronic illness resulting in school absences4. Children with asthma have three times the school absences of children without asthma5. Forty percent of children with asthma have sleep disturbance (1 to 2 nights/week)2. So even if the child is not absent from school, he or she may have reduced school performance due to sleep disturbances. Seventy-eight percent of parents of asthmatics report that asthma has a negative impact on the family4. Thirty-six percent of parents of asthmatics missed work in the prior year4. 1Number of selected reported chronic conditions, by age: United States, 1994. In: Adams PF, Marano MA. Current estimates from the National Health Interview Survey, 1994. National Center for Health Statistics. Vital Health Stat. 1995;10(193):93-94. DHHS Publication No. (PHS) 96-1521. 2CDC. Surveillance for Asthma--United States, 1960-1995 (CDC Surveillance Summaries). MMWR. 1998;47(SS-1):1-26). 3Grant et al. Prevalence and burden of illness for asthma and related symptoms among kindergarteners Chicago public schools. Ann Allergy Asthma Immunol. 1999;83:113-120. 4American Lung Association. Pediatric Asthma: A Growing Health Threat. Available at: http://www.lungusa.org/asthma/merck_pediatric.html. Accessed July 9, 1999. 5Fowler et al. School functioning of US children with asthma. Pediatrics. 1992;90:939-944.

3. SLIDE 1.3.4 Asthma deaths have doubled for 0- to 14-year-olds from 1979 to 1995, with the 5 to 14 year olds driving the rise in mortality1. In a population-based study by Robertson and colleagues2, the majority of patients aged 0 to 20 years who died due to asthma could not be classified as �high risk�: Of 51 deaths: 33% were judged to have had a history of trivial or mild asthma 32% had no previous hospital admission for asthma. Death occurred outside the hospital in 78% of subjects. Thus, some of the patients who died had apparently mild disease, though many were felt in retrospect to have had inadequate assessment or therapy of prior asthma. 1CDC. Surveillance for Asthma--United States, 1960-1995 (CDC Surveillance Summaries). MMWR. 1998;47(SS-1):1-26. 2Robertson et al., Pediatric asthma deaths in Victoria: The mild are at risk. Pediatr Pulmonol 1992;13:95-100. SLIDE 1.3.4 Asthma deaths have doubled for 0- to 14-year-olds from 1979 to 1995, with the 5 to 14 year olds driving the rise in mortality1. In a population-based study by Robertson and colleagues2, the majority of patients aged 0 to 20 years who died due to asthma could not be classified as �high risk�: Of 51 deaths: 33% were judged to have had a history of trivial or mild asthma 32% had no previous hospital admission for asthma. Death occurred outside the hospital in 78% of subjects. Thus, some of the patients who died had apparently mild disease, though many were felt in retrospect to have had inadequate assessment or therapy of prior asthma. 1CDC. Surveillance for Asthma--United States, 1960-1995 (CDC Surveillance Summaries). MMWR. 1998;47(SS-1):1-26. 2Robertson et al., Pediatric asthma deaths in Victoria: The mild are at risk. Pediatr Pulmonol 1992;13:95-100.

5. SLIDE 1.2.2 Asthma is a chronic inflammatory disorder: Airway inflammation underlies the airway hyperresponsivenessto asthma triggers. The airway hyperresponsiveness leads to airway obstructionthat is usually fully reversible. Obstruction leads to the classic symptoms of asthma: cough, wheeze, and dyspnea. It should be noted that while symptoms are easily appreciated, symptoms are not the fundamental aspect of asthma. National Asthma Education and Prevention Program. Highlights of the Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD., May 1997. NIH Publication No. 97-4051A. SLIDE 1.2.2 Asthma is a chronic inflammatory disorder: Airway inflammation underlies the airway hyperresponsivenessto asthma triggers. The airway hyperresponsiveness leads to airway obstructionthat is usually fully reversible. Obstruction leads to the classic symptoms of asthma: cough, wheeze, and dyspnea. It should be noted that while symptoms are easily appreciated, symptoms are not the fundamental aspect of asthma. National Asthma Education and Prevention Program. Highlights of the Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD., May 1997. NIH Publication No. 97-4051A.

6. SLIDE 1.2.3 With asthma, what we see is the tip of the iceberg, the symptoms. At the base of the iceberg is the airway inflammation. This inflammation underlies the bronchial hyperresponsiveness of asthma. Airflow obstruction results from bronchoconstriction, bronchial edema, mucus hypersecretion and inflammatory cell recruitment including eosinophils, a key inflammatory cell. The culmination of the inflammatory process is the tip of the iceberg, the symptoms. SLIDE 1.2.3 With asthma, what we see is the tip of the iceberg, the symptoms. At the base of the iceberg is the airway inflammation. This inflammation underlies the bronchial hyperresponsiveness of asthma. Airflow obstruction results from bronchoconstriction, bronchial edema, mucus hypersecretion and inflammatory cell recruitment including eosinophils, a key inflammatory cell. The culmination of the inflammatory process is the tip of the iceberg, the symptoms.

7. SLIDE 1.2.4 The photomicrograph on the left shows normal human airway mucosa, with the airspace above, pseudostratified respiratory epithelium, and rather bland sub-epithelial tissue. On the right, this photomicrograph shows infiltration of numerous eosinophils and other inflammatory cells into the submucosal tissue. Sub-basement membrane thickening is apparent, but most striking is the desquamation of airway epithelium, with numerous eosinophils within the denuded epithelium. This epithelial damage may predispose the patient with asthma to a greater sensitivity to airway triggers (i.e. airway hyperresponsiveness). SLIDE 1.2.4 The photomicrograph on the left shows normal human airway mucosa, with the airspace above, pseudostratified respiratory epithelium, and rather bland sub-epithelial tissue. On the right, this photomicrograph shows infiltration of numerous eosinophils and other inflammatory cells into the submucosal tissue. Sub-basement membrane thickening is apparent, but most striking is the desquamation of airway epithelium, with numerous eosinophils within the denuded epithelium. This epithelial damage may predispose the patient with asthma to a greater sensitivity to airway triggers (i.e. airway hyperresponsiveness).

8. SLIDE 1.4.4 In a population-based study in Rochester MN conducted from 1964 to 1983, medical records that met explicit predetermined diagnostic criteria for asthma were used to calculate incidence rates. Across all ages, the median age of onset was 3 years for males and 8 years for females. The lower median age in males was due to higher incidence rates early in life. Through the age of 14, the incidence among males was higher than that for females. Also of interest in this study (published by researchers at Mayo Clinic), the two-decade timespan allowed comparisons of asthma incidence rates within the time period of the study. Annual incidence rates were relatively constant through the 1960s, then gradually increased through 1983 (i.e., through the end of the data collection period). After adjusting for age and sex, total incidence of asthma rose from 183 per 100,000 to 284 per 100,000. The increase in incidence rates from 1964 to 1983 occurred only in children and adolescents (i.e., increased in patients aged 1 to 14 years only) Yunginger JW et al. A community-based study of the epidemiology of asthma: incidence rates, 1964�1983. Am Rev Respir Dis. 1992;146:888-894. SLIDE 1.4.4 In a population-based study in Rochester MN conducted from 1964 to 1983, medical records that met explicit predetermined diagnostic criteria for asthma were used to calculate incidence rates. Across all ages, the median age of onset was 3 years for males and 8 years for females. The lower median age in males was due to higher incidence rates early in life. Through the age of 14, the incidence among males was higher than that for females. Also of interest in this study (published by researchers at Mayo Clinic), the two-decade timespan allowed comparisons of asthma incidence rates within the time period of the study. Annual incidence rates were relatively constant through the 1960s, then gradually increased through 1983 (i.e., through the end of the data collection period). After adjusting for age and sex, total incidence of asthma rose from 183 per 100,000 to 284 per 100,000. The increase in incidence rates from 1964 to 1983 occurred only in children and adolescents (i.e., increased in patients aged 1 to 14 years only) Yunginger JW et al. A community-based study of the epidemiology of asthma: incidence rates, 1964�1983. Am Rev Respir Dis. 1992;146:888-894.

9. SLIDE 1.4.5 The natural history and prognosis of pediatric asthma is incompletely understood. Most children �don�t grow out of asthma�1. Instead, the �loss� of symptoms may actually be related simply to growth of the lungs and not due to a change of airway hyperresponsiveness. The �loss� of symptoms may thus represent a period of time when the disease goes through a silent, asymptomatic period only to recur later in life2. 1Martinez, FD. In: Barnes PJ, Leff AR, Grunstein MM, Woolcock AJ., eds. Asthma. Philadelphia PA: Lippincott - Raven; 1997:121-128. 2 Weiss ST, Environmental risk factors in childhood asthma. Clin Exp Allergy. 1998;28(suppl 5):29-34. SLIDE 1.4.5 The natural history and prognosis of pediatric asthma is incompletely understood. Most children �don�t grow out of asthma�1. Instead, the �loss� of symptoms may actually be related simply to growth of the lungs and not due to a change of airway hyperresponsiveness. The �loss� of symptoms may thus represent a period of time when the disease goes through a silent, asymptomatic period only to recur later in life2. 1Martinez, FD. In: Barnes PJ, Leff AR, Grunstein MM, Woolcock AJ., eds. Asthma. Philadelphia PA: Lippincott - Raven; 1997:121-128. 2 Weiss ST, Environmental risk factors in childhood asthma. Clin Exp Allergy. 1998;28(suppl 5):29-34.

10. SLIDE 1.4.7 Lung function frequently remains altered even when patients are asymptomatic1. Many children who become symptom-free still have persistent airway obstruction2 and nonspecific airway hyperresponsiveness3. Finally, airway inflammation exists even in patients with mild asthma4. 1National Asthma Education and Prevention Program. Highlights of the Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD., May 1997. NIH Publication No. 97-4051A. 2Godden et al. Outcome of wheeze in childhood. Symptoms and pulmonary function 25 years later. Am J Respir Crit Care Med. 1994;149:106-112. 3Phelan PD. Hyperresponsiveness as a determinant of the outcome in childhood asthma. Am Rev Resp Dis. 1991;143:1463-1466. 4Beasley et al. Cellular events I the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis. 1989;139:806-817. SLIDE 1.4.7 Lung function frequently remains altered even when patients are asymptomatic1. Many children who become symptom-free still have persistent airway obstruction2 and nonspecific airway hyperresponsiveness3. Finally, airway inflammation exists even in patients with mild asthma4. 1National Asthma Education and Prevention Program. Highlights of the Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD., May 1997. NIH Publication No. 97-4051A. 2Godden et al. Outcome of wheeze in childhood. Symptoms and pulmonary function 25 years later. Am J Respir Crit Care Med. 1994;149:106-112. 3Phelan PD. Hyperresponsiveness as a determinant of the outcome in childhood asthma. Am Rev Resp Dis. 1991;143:1463-1466. 4Beasley et al. Cellular events I the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis. 1989;139:806-817.

11. SLIDE 1.6.1 Factors predictive of persistent asthma include: family history (more important on the maternal than on the paternal side), atopy (elevated IgE and presence of other atopic diseases), viral infections (particularly with Respiratory Syncytial Virus [RSV]), male gender, smoking (whether passive or active). Also, the severity of asthma in childhood is a factor that can predict persistent asthma. Ehrlich et al. Risk Factors for childhood asthma and wheezing. Am J Resp Crit Care Med. 1996;154:681-688. Martinez FD et al. Asthma and wheezing in the first 6 years of life. N Engl J Med 332:133-8, 1995. von Mutius E and Martinez FD. In: Murphy S and Kelly HW., eds. Pediatric Asthma: Marcel Dekkar; 1999:17-25. SLIDE 1.6.1 Factors predictive of persistent asthma include: family history (more important on the maternal than on the paternal side), atopy (elevated IgE and presence of other atopic diseases), viral infections (particularly with Respiratory Syncytial Virus [RSV]), male gender, smoking (whether passive or active). Also, the severity of asthma in childhood is a factor that can predict persistent asthma. Ehrlich et al. Risk Factors for childhood asthma and wheezing. Am J Resp Crit Care Med. 1996;154:681-688. Martinez FD et al. Asthma and wheezing in the first 6 years of life. N Engl J Med 332:133-8, 1995. von Mutius E and Martinez FD. In: Murphy S and Kelly HW., eds. Pediatric Asthma: Marcel Dekkar; 1999:17-25.

12. The Goals of Asthma Therapy Are Inadequately Realized As is evident in these results from the Asthma in America survey, the goals of asthma therapy are not being met. Nearly one third of all patients reported having their sleep disturbed at least once a week in the previous 4 weeks, and nearly one third missed school or work in the previous year. Nearly half of all patients reported being unable to fully participate in recreational activities due to asthma, and nearly one quarter required emergency room care for their asthma during the previous year. In addition, the survey demonstrated that most patients with asthma overestimate the level of control of their underlying disease. As is evident in these results from the Asthma in America survey, the goals of asthma therapy are not being met. Nearly one third of all patients reported having their sleep disturbed at least once a week in the previous 4 weeks, and nearly one third missed school or work in the previous year. Nearly half of all patients reported being unable to fully participate in recreational activities due to asthma, and nearly one quarter required emergency room care for their asthma during the previous year. In addition, the survey demonstrated that most patients with asthma overestimate the level of control of their underlying disease.

13. Shifting Focus of Asthma Therapy

14. SLIDE 2.4.6 Underdiagnosis of asthma is a frequent problem in children who wheeze with respiratory infection. These patients may be labeled with diagnoses other than asthma. It is important to suspect asthma if a patient has repeated diagnoses of wheezy bronchitis, asthmatic bronchitis, recurrent bronchiolitis, or reactive airway disease, or even chronic cough. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999. SLIDE 2.4.6 Underdiagnosis of asthma is a frequent problem in children who wheeze with respiratory infection. These patients may be labeled with diagnoses other than asthma. It is important to suspect asthma if a patient has repeated diagnoses of wheezy bronchitis, asthmatic bronchitis, recurrent bronchiolitis, or reactive airway disease, or even chronic cough. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.

15. SLIDE 2.5.3 This is an encapsulated view of the classification of asthma severity. The four severity levels are listed on the left, with the accompanying quantification of daytime and nighttime symptoms. For children who are >5 years of age and can use a spirometer or peak flow meter, the expected measures of FEV1 or peak flow, and peak flow variability are listed on the right. The bold line that is near the bottom of the table marks an important separation: It divides intermittent disease from persistent disease. It also divides those patients who can be managed with short-acting beta agonist alone -- the �intermittent� patients -- from those patients who require long-term controller therapy -- the �persistent� patients. Mild persistent asthma is characterized by more than two days per week of symptoms, OR three to four nights per month of symptoms. Although symptoms do not occur daily, these patients are still defined as having persistent disease and require daily controller (i.e., preventive) therapy. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999. SLIDE 2.5.3 This is an encapsulated view of the classification of asthma severity. The four severity levels are listed on the left, with the accompanying quantification of daytime and nighttime symptoms. For children who are >5 years of age and can use a spirometer or peak flow meter, the expected measures of FEV1 or peak flow, and peak flow variability are listed on the right. The bold line that is near the bottom of the table marks an important separation: It divides intermittent disease from persistent disease. It also divides those patients who can be managed with short-acting beta agonist alone -- the �intermittent� patients -- from those patients who require long-term controller therapy -- the �persistent� patients. Mild persistent asthma is characterized by more than two days per week of symptoms, OR three to four nights per month of symptoms. Although symptoms do not occur daily, these patients are still defined as having persistent disease and require daily controller (i.e., preventive) therapy. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.

16. SLIDE 2.5.4 Goals of asthma therapy that should reasonably be expected for any given child with asthma include: Minimal, and ideally no, symptoms during the day or at night Minimal, and ideally no, asthma episodes Minimal use (meaning less than daily) of a short-acting beta-agonist A peak flow rate that is at least 80% of the child�s personal best Minimal, and ideally no, adverse effects from medications And, very importantly, the patient should be able to pursue normal activities Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999. SLIDE 2.5.4 Goals of asthma therapy that should reasonably be expected for any given child with asthma include: Minimal, and ideally no, symptoms during the day or at night Minimal, and ideally no, asthma episodes Minimal use (meaning less than daily) of a short-acting beta-agonist A peak flow rate that is at least 80% of the child�s personal best Minimal, and ideally no, adverse effects from medications And, very importantly, the patient should be able to pursue normal activities Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.

17. US Patients Overestimate Their Asthma Control Of patients who report symptoms that meet NIH criteria for moderate-persistent asthma 61% still consider their asthma to be �well controlled� or �completely controlled� Of patients who report symptoms that meet NIH criteria for severe-persistent asthma 32% still consider their asthma to be �well controlled� or �completely controlled� As shown in this slide, 61% of patients in the survey whose level of symptoms classified them as having moderate persistent asthma actually considered their asthma to be �well controlled� or �completely controlled� in the previous 4 weeks. Of greater concern, 32% of patients who had severe persistent asthma actually considered their asthma to be �well controlled� or �completely controlled� in the previous 4 weeks. The fact that patients overestimate their level of asthma control serves as an impediment to actually improving asthma control in these patients, since they accept suboptimal symptom control as normal. These data indicate that asthma remains undertreated in many patients, and that patients do not fully realize the level of disease control achievable. Thus, there is a potentially significant patient population which could benefit from improved control of their asthma. Advair Diskus provides a new treatment option in these patients for whom combination therapy is appropriate.As shown in this slide, 61% of patients in the survey whose level of symptoms classified them as having moderate persistent asthma actually considered their asthma to be �well controlled� or �completely controlled� in the previous 4 weeks. Of greater concern, 32% of patients who had severe persistent asthma actually considered their asthma to be �well controlled� or �completely controlled� in the previous 4 weeks. The fact that patients overestimate their level of asthma control serves as an impediment to actually improving asthma control in these patients, since they accept suboptimal symptom control as normal. These data indicate that asthma remains undertreated in many patients, and that patients do not fully realize the level of disease control achievable. Thus, there is a potentially significant patient population which could benefit from improved control of their asthma. Advair Diskus provides a new treatment option in these patients for whom combination therapy is appropriate.

20. SLIDE 2.6.4 With regard to drug therapy, medications to treat asthma have been categorized into two groups. �Quick-relief� medications act to treat asthma symptoms and signs once they have occurred. This group includes short-acting inhaled beta-agonists and inhaled anticholinergics. Systemic corticosteroids are grouped here because they can be used acutely -- e.g., intravenous steroids in an emergency room -- when other quick-relief medication has been insufficiently effective. �Long-term control� medications can be thought of as �preventative� medications that should be used to prevent asthma symptoms before they occur. This group includes corticosteroids (inhaled and oral), cromolyn sodium and nedocromil, long-acting beta-agonists, theophylline, and the leukotriene modifiers. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999. SLIDE 2.6.4 With regard to drug therapy, medications to treat asthma have been categorized into two groups. �Quick-relief� medications act to treat asthma symptoms and signs once they have occurred. This group includes short-acting inhaled beta-agonists and inhaled anticholinergics. Systemic corticosteroids are grouped here because they can be used acutely -- e.g., intravenous steroids in an emergency room -- when other quick-relief medication has been insufficiently effective. �Long-term control� medications can be thought of as �preventative� medications that should be used to prevent asthma symptoms before they occur. This group includes corticosteroids (inhaled and oral), cromolyn sodium and nedocromil, long-acting beta-agonists, theophylline, and the leukotriene modifiers. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.

21. In school aged children, beta agonists represent 65% of prescriptions

22. SLIDE 2.6.5 Greater use of beta-agonists has been associated with a greater risk of hospitalization for asthma in children. This retrospective cohort study (from an HMO in Massachusetts) illustrates an association between the use of beta-agonists and the relative risk of hospitalizations due to asthma. Patients with no beta-agonist use were assigned a relative risk of one. In this study, concomitant use of controller medication (such as inhaled steroids and cromolyn) conferred protection against exacerbations of asthma that lead to hospitalizations. The relative risk of hospitalizations due to asthma increased dramatically in those asthmatics 0 to 17 years of age who were relying heavily on beta-agonists alone to treat the symptoms of asthma. Patients who used more than eight beta-agonist prescriptions per year had a greater than five-fold increase in risk of hospitalization due to asthma. Note that eight prescriptions per year comes out to less than one canister per month. Similar results were demonstrated in asthmatics 18 to 44 years of age. Donahue JG et al. JAMA 1997;277:887-891. SLIDE 2.6.5 Greater use of beta-agonists has been associated with a greater risk of hospitalization for asthma in children. This retrospective cohort study (from an HMO in Massachusetts) illustrates an association between the use of beta-agonists and the relative risk of hospitalizations due to asthma. Patients with no beta-agonist use were assigned a relative risk of one. In this study, concomitant use of controller medication (such as inhaled steroids and cromolyn) conferred protection against exacerbations of asthma that lead to hospitalizations. The relative risk of hospitalizations due to asthma increased dramatically in those asthmatics 0 to 17 years of age who were relying heavily on beta-agonists alone to treat the symptoms of asthma. Patients who used more than eight beta-agonist prescriptions per year had a greater than five-fold increase in risk of hospitalization due to asthma. Note that eight prescriptions per year comes out to less than one canister per month. Similar results were demonstrated in asthmatics 18 to 44 years of age. Donahue JG et al. JAMA 1997;277:887-891.

26. Effects of Inhaled Corticosteroids on Inflammation

27. SLIDE 2.6.7 One of the biggest challenges facing physicians treating patients with a chronic condition may be compliance -- more recently referred to as medication adherence. While many medications show efficacy in the ideal setting of a controlled clinical trial, the real effectiveness of a medication for chronic asthma is likely to be complicated by a variety of issues including route of administration1, dosing frequency2, perceived potential for side effects, patient�s cost, effectiveness of patient education, perceived onset of action, and inhalation technique3. Data have demonstrated that poor compliance (otherwise termed �poor medication adherence�) to controller medication is associated with an increased need for courses of oral steroid rescue4. It has been suggested that effectiveness of medication is dependent on the drug�s efficacy in combination with the patient�s adherence to therapy -- in other words, �Effectiveness = Efficacy x Adherence�. An otherwise efficacious drug may not provide full effectiveness if not taken in an adherent manner5,6,7. 1Kelloway et al. Arch Intern Med 1994;154:1349. 2Coutts et al. Arch Dis Child. 1992;67:332. 3Rand CS. Eur Respir Rev. 1998;8(56):270-274. 4Milgrom et al. J All Clin Immunol. 1996:98:1051-1057. 5Fletcher et al. Clinical Epidemiology: The Essentials. 1988: p. 132, 153. 6Simon et al., J Clin Epidemiol 1995;48(3):363-373. 7Sacristan et al. Clin Ther 1997;19:1510-1517. SLIDE 2.6.7 One of the biggest challenges facing physicians treating patients with a chronic condition may be compliance -- more recently referred to as medication adherence. While many medications show efficacy in the ideal setting of a controlled clinical trial, the real effectiveness of a medication for chronic asthma is likely to be complicated by a variety of issues including route of administration1, dosing frequency2, perceived potential for side effects, patient�s cost, effectiveness of patient education, perceived onset of action, and inhalation technique3. Data have demonstrated that poor compliance (otherwise termed �poor medication adherence�) to controller medication is associated with an increased need for courses of oral steroid rescue4. It has been suggested that effectiveness of medication is dependent on the drug�s efficacy in combination with the patient�s adherence to therapy -- in other words, �Effectiveness = Efficacy x Adherence�. An otherwise efficacious drug may not provide full effectiveness if not taken in an adherent manner5,6,7. 1Kelloway et al. Arch Intern Med 1994;154:1349. 2Coutts et al. Arch Dis Child. 1992;67:332. 3Rand CS. Eur Respir Rev. 1998;8(56):270-274. 4Milgrom et al. J All Clin Immunol. 1996:98:1051-1057. 5Fletcher et al. Clinical Epidemiology: The Essentials. 1988: p. 132, 153. 6Simon et al., J Clin Epidemiol 1995;48(3):363-373. 7Sacristan et al. Clin Ther 1997;19:1510-1517.

28. SLIDE 2.6.8 If the patient is not doing well, and before increasing medications, it is important to assess possible reasons for poor asthma control. This includes reviewing the patient�s inhalation technique adherence to medication the possibility of environmental exposures that may have intervened to lead to a current loss of asthma control (e.g., a new pet at home). Other complicating factors should be considered, particularly viral respiratory infections, sinusitis, rhinitis, gastroesophageal reflux, or chemical / irritant exposures (e.g., sulfites in food). Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999. SLIDE 2.6.8 If the patient is not doing well, and before increasing medications, it is important to assess possible reasons for poor asthma control. This includes reviewing the patient�s inhalation technique adherence to medication the possibility of environmental exposures that may have intervened to lead to a current loss of asthma control (e.g., a new pet at home). Other complicating factors should be considered, particularly viral respiratory infections, sinusitis, rhinitis, gastroesophageal reflux, or chemical / irritant exposures (e.g., sulfites in food). Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.

29. SLIDE 2.8.2 It is important to assess and monitor the patient, and to aim for asthma control. Asthma control, particularly as felt by the patient, includes: no coughing, no difficulty in breathing, no waking up at night, and normal activities -- including activities of play, sports, and exercise. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999. SLIDE 2.8.2 It is important to assess and monitor the patient, and to aim for asthma control. Asthma control, particularly as felt by the patient, includes: no coughing, no difficulty in breathing, no waking up at night, and normal activities -- including activities of play, sports, and exercise. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.

30. SLIDE 2.8.3 It is important to assess and monitor the patient, and to aim for asthma control. Other measures of asthma control -- that can be noted by others who are around the patient -- include: no acute episodes requiring urgent care, no absences from school or activities, no missed time from work for caregivers, normal or near-normal lung function, and medication use that is well-tolerated. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999. SLIDE 2.8.3 It is important to assess and monitor the patient, and to aim for asthma control. Other measures of asthma control -- that can be noted by others who are around the patient -- include: no acute episodes requiring urgent care, no absences from school or activities, no missed time from work for caregivers, normal or near-normal lung function, and medication use that is well-tolerated. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.

31. SLIDE 2.8.4 Finally, in addressing the challenges of treating childhood asthma, the expectations of physicians, parents, and patients all should be high. Not only can symptoms can be controlled, but with appropriate management, the disease can be controlled. Activity limitations are not necessary. And, finally, treatment should be associated with minimal to no adverse effects of medication Thus, childhood asthma can and should be well-controlled at minimal risk. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999. SLIDE 2.8.4 Finally, in addressing the challenges of treating childhood asthma, the expectations of physicians, parents, and patients all should be high. Not only can symptoms can be controlled, but with appropriate management, the disease can be controlled. Activity limitations are not necessary. And, finally, treatment should be associated with minimal to no adverse effects of medication Thus, childhood asthma can and should be well-controlled at minimal risk. Pediatric Asthma: Promoting Best Practice, Guide for Managing Asthma in Children. Milwaukee, WI: American Academy of Allergy, Asthma and Immunology (with AAP, NAEPP / NHLBI / NIH), 1999.