PEDIATRICS Vol. 108 No. 2 August 2001, pp. 277-282

Asthma Symptoms, Morbidity, and Antiinflammatory Use in Inner-City Children

Karen L. Warman, MD, Ellen Johnson Silver, PhD, and Ruth E. K. Stein, MD

From the Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.

	ABSTRACT

Top Abstract Methods Results Discussion Conclusion References

Background.  Asthma is a major cause of morbidity that disproportionately affects inner-city children. For children with persistent asthma, defined as having asthma symptoms 3 or more days per week or 3 or more nights per month, national guidelines recommend the use of daily antiinflammatory agents. Despite these recommendations, antiinflammatory agents remain underused, particularly in inner-city children with high asthma morbidity.

Objectives.  The objectives of our study were to determine: 1) whether persistent asthma symptoms in inner-city children are related to acute care utilization and to the frequency of acute exacerbations; 2) whether children with persistent asthma are receiving recommended daily antiinflammatory agents; and 3) whether antiinflammatory medication use relates to sociodemographic factors, caretaker self-efficacy, the frequency of primary care visits, and/or measures of quality asthma care.

Design and Methods.  A 64-item telephone survey was administered between July 1996 and June 1997 to 219 parental caretakers of 2- to 12-year-old children who had been hospitalized with asthma at an inner-city medical center between January 1995 and February 1996. Persistent asthma symptoms were assessed by inquiring about the frequency of daily and nocturnal asthma symptoms over the last 4 weeks. Children's asthma severity was classified by applying the 1997 National Asthma Education and Prevention Program (NAEPP) Asthma Guidelines' severity classification scheme based on the frequency of asthma symptoms. Asthma morbidity was defined as the frequency of acute asthma exacerbations, emergency department visits and hospitalizations. Daily antiinflammatory medication use was compared by sociodemographic factors, caretaker self-efficacy, frequency of primary care visits, and measures of quality asthma home management.

Results.  In this sample, quantifying persistent asthma symptoms and applying the NAEPP symptom criteria identified 17% of the children with mild intermittent asthma, 27% with mild persistent asthma and 56% with moderate to severe persistent asthma. There were no differences in the age of the children in the 3 groups (mean age: 6 years). Asthma morbidity, as measured by the number of asthma exacerbations in the last 6 months, was significantly higher in the children with moderate to severe persistent asthma compared with children with mild intermittent asthma (9.8 vs 3.5) or mild persistent asthma (9.8 vs 4.5). In addition, there were significantly more emergency department visits in the moderate to severe group than in the mild persistent (3.05 vs 1.69) or mild intermittent group (3.05 vs 1.76). Lastly, as asthma symptom frequency increased, there were trends toward more hospitalizations and more days hospitalized. Overall, 35% of the 219 families reported giving daily antiinflammatory medications to their child (mostly cromolyn sodium). Of the 181 children (83%) who met NAEPP symptom criteria for persistent asthma, only 39% were receiving daily antiinflammatory treatment. Of the children with symptoms of moderate to severe asthma, only 15% were receiving inhaled steroids in contrast to the guidelines' recommendations.Use of antiinflammatory agents was not related to caretaker sociodemographic factors or self-efficacy scores. Measures of quality asthma home management, which included use of mattress covers, written plans, and peak flow meters, correlated positively with use of antiinflammatory agents. Children whose families reported using daily antiinflammatory medications had more primary care visits in the last 6 months than those children not receiving antiinflammatory medications.

Conclusion.  Questioning parents about the frequency of their child's asthma symptoms is an important, inexpensive, and readily accessible bedside and office tool that may aid in the detection of persistent symptoms and help direct therapy. Our study suggests that classifying asthma severity by quantifying persistent asthma symptoms, as defined in the NAEPP Guidelines, is a clinically useful tool that relates to asthma morbidity. In our sample of previously hospitalized children with asthma, 83% met 1997 NAEPP symptom criteria for persistent asthma, and yet only 35% were receiving daily antiinflammatory agents. Use of antiinflammatory agents correlated positively with other indicators of quality asthma home management. Additional work is necessary to increase appropriate use of antiinflammatory agents in this population, and in particular, to increase inhaled steroid use for children with moderate or severe symptoms.  Key words:  inner-city children, asthma severity, persistent asthma, guidelines, morbidity, antiinflammatory therapy, inhaled steroids, symptom days.

Asthma is a major cause of morbidity that disproportionately affects inner-city children.¹ Current understanding of asthma is that it is a chronic inflammatory disorder of the lungs that involves complex interactions between mast cells, eosinophils, T-lymphocytes, neutrophils, epithelial cells, and cellular mediators.² Inflammation in the lungs of patients with asthma leads to airway obstruction and increased bronchial hyperresponsiveness to a variety of stimuli. Untreated, inflammation in the lungs of patients with asthma can lead to persistent asthma symptoms, such as chronic cough or wheeze, and frequent recurrence of asthma exacerbations. Chronic inflammation may also lead to persistent abnormalities in lung function that are attributable, in part, to subbasement membrane fibrosis and lung remodeling.³

Long-term control of persistent asthma is accomplished by the use of daily antiinflammatory agents and avoidance of irritants. Antiinflammatory medications have been shown to reduce symptoms and may help prevent progression of the disease.^4-6 Inhaled steroids can reduce hyperresponsiveness⁷ and bronchoconstriction. Other available long-term control medications, such as cromolyn sodium, nedocromil, and/or antileukotrienes, are less effective in controlling airway inflammation than inhaled steroids.² Mounting evidence suggests that early aggressive therapy can reduce recurrence of symptoms and speculation exists that early use of antiinflammatory agents may prevent lung remodeling.^4,5,8 Despite an increasing understanding of the importance of recognizing and treating inflammation to control asthma and reduce morbidity,⁹ there continues to be an overreliance on short-term control agents, such as -agonists, and under-use of antiinflammatory agents.¹⁰

In 1997, The National Asthma Education and Prevention Program (NAEPP) issued revised guidelines for the diagnosis and management of asthma. These guidelines introduced a classification scheme for asthma severity, which distinguishes between mild intermittent asthma and 3 categories of persistent asthma: mild, moderate, and severe. Treatment is based on severity classification. Classification can be accomplished by formal pulmonary function testing or by assessing frequency of asthma symptoms. Patients are placed into the highest category for which they meet a single criterion. In terms of the frequency of reported symptoms, mild persistent asthma is defined as a patient having 3 or more days per week with asthma symptoms or 3 nights per month with asthma symptoms; whereas, severe persistent asthma is defined as continual daytime symptoms and frequent nighttime symptoms. This classification scheme was based on consensus opinion, and is not evidence-based¹¹; as of yet, the clinical significance of the symptom-based classification scheme has not been validated.

The guidelines recommend daily antiinflammatory agents to control all categories of persistent asthma with increasing doses of medications to match severity. For children with mild persistent asthma, the guidelines suggest low-dose inhaled steroids, cromolyn sodium, or nedocromil. For moderate and severe persistent asthma, the guidelines recommend higher doses of inhaled steroids with the addition of long-acting -agonists as needed. Doses are adjusted to control symptoms and may be started higher to gain control and then reduced. Pharmacological therapy should be accompanied by asthma education and trigger reduction.

The objectives of our study were to determine: 1) whether persistent asthma symptoms in inner-city children are related to acute care utilization and to the frequency of acute exacerbations; 2) whether children with persistent asthma symptoms are receiving recommended daily antiinflammatory agents; and 3) whether antiinflammatory medication use relates to sociodemographic factors, caretaker self-efficacy, the frequency of primary care visits, and/or measures of quality asthma care.

	METHODS

Top Abstract Methods Results Discussion Conclusion References

Participants

Study participants were 220 parental caretakers of 2 to 12-year-old children with asthma-related hospitalizations who were recruited as part of a randomized controlled trial to evaluate the effectiveness of the Asthma Passport Program, a primary care-based asthma educational intervention.¹² This analysis is of baseline data gathered at enrollment before intervention assignment.

Recruitment occurred at a municipal hospital that serves a predominantly inner-city, low-income patient population. Names of 2- to 12-year-old children who had asthma-related hospitalizations between January 1995 and September 1996 were obtained from the hospital medical records database. Children with other chronic illnesses affecting the lungs were excluded. Eligibility requirements included that the caretakers be English- and/or Spanish-speaking residents of the Bronx, New York. In addition, caretakers had to report interest in having their child receive their medical care at the hospital's outpatient clinic and not be prohibited by their managed care plan or health maintenance organization (HMO) affiliation so that they would be eligible for randomization to the intervention. We enrolled only 1 child per family.

All potentially eligible families were mailed information regarding the study and a consent form approved by our institutional review board, together with a stamped, self-addressed return envelope. Approximately 1 week after sending the letter, trained research assistants contacted families by phone to screen for eligibility. Of 947 potentially eligible subjects, 591 (62%) were successfully contacted and screened for eligibility. Reasons for not screening families included incorrect or disconnected telephone numbers (48% and 34%, respectfully), no listed phone number (10%), or no response (8%). Of the 591 contacted, 318 met eligibility requirements. The remainder were excluded for the following reasons: 5 had other chronic illness affecting the lungs (eg, pulmonary tuberculosis and bronchopulmonary dysplasia); 98 belonged to an HMO or managed care group not accepted by our institution; 93 did not want to attend our hospital-based outpatient program; 20 were already enrolled in another asthma study; 1 had a sibling already enrolled in the study; 2 had parents unable to complete the telephone survey (1 deaf, 1 mentally ill); and 53 had ongoing relationships with clinicians who were not participating in our study. Of the 318 eligible respondents, 220 (69%) agreed to participate in the longitudinal study. All of the 220 who consented to the study completed the baseline interview. One survey was missing data so it was not included in this analysis. The average time from the last hospitalization to the interview was 7.5 months (range: 0-21 months).

Measures

Baseline study data were obtained by 30-minute telephone interviews between July 1996 and June 1997 by research assistants trained in questionnaire administration. Caretakers were given the option of being interviewed in English or Spanish and were paid $10 for the interview. Spanish was the language used for 19.6% of the interviews.

The data collection instrument was the Asthma Self-management Awareness Program Questionnaire. The survey assessed sociodemographic factors, asthma severity, asthma morbidity, asthma home management, and primary care practices. The Spanish language version was created by translation and back translation into English by 2 native Spanish speakers.

Persistent asthma symptoms were assessed by asking a series of questions regarding daytime and nighttime symptoms over the last 4 weeks. To help families, a probe was used asking whether symptoms were once a week, twice a week, etc. Medication use was assessed by asking open-ended questions regarding use of syrups, "pumps", pills, or nebulizer machines. Parents were asked the names of the medications and how many days in the last 4 weeks each was given. Steroids, cromolyn sodium, and nedocromil were classified as antiinflammatory agents. Antileukotrienes were not yet in use at the time of the study.

Asthma severity was determined by applying the 1997 NAEPP criteria for persistent asthma based on symptom days to the data obtained form parental report. We extrapolated from the NAEPP use of symptom days per week to report symptom days per month. For nocturnal symptoms, the guidelines measure symptoms per month so no modification was necessary (Table 1). In keeping with the guidelines, children were placed into the highest category for which they had day or night symptoms. Children with either 9 or more days per month and/or 3 or more nights per month with asthma symptoms were categorized as having persistent asthma; whereas, those with less frequent symptoms were categorized as having mild. intermittent asthma. Children with daily symptoms and/or 8 or more nights per month of nighttime symptoms were classified as moderate to severe persistent asthma. Because we could not differentiate children with daily symptoms or continual symptoms, we combined the children with moderate and severe persistent asthma into one group.

Morbidity measures included the frequency of asthma exacerbations in the last 6 months, emergency department (ED) visits during the last 6 months, and hospitalizations because of asthma during the last 12 months. Asthma exacerbations were referred to as "asthma attacks" and defined as "episodes of coughing, wheezing or difficulty breathing."

Assessment of primary care practices included whether the caretaker had a regular doctor for their child, the frequency of primary care visits, and the usual place of care. Measures of quality of asthma care included having a written asthma action plan, a peak flow meter, and having a zippered plastic mattress cover (for dust-mite control).

Caretaker self-efficacy was assessed using the 7-item Ilfeld Self-Efficacy Scale, which measures the degree of mastery that a person believes he or she has over life situations.¹³ Respondents used a 4-point Likert scale to indicate how much they agree or disagree that each of the 7 statements describes how they feel about themselves. To create the self- efficacy score, the items are summed with higher scores indicating greater efficacy.

Data Analysis

All data analyses were conducted using SPSS/PC+ Version 5.0 (SPSS Inc, Chicago, IL). Bivariate analyses were conducted to examine whether severity based on symptom days was related to morbidity and whether child and/or caretaker characteristics, health service variables, or severity of illness were related to use of daily antiinflammatory medications. Differences between the groups were evaluated using: 1) cross-tabulation and ² tests for categorical dependent variables (eg, sex, ethnicity, insurance status) and 2) 1-way analysis of variance for continuous variables (ie, age). Two-sided tests were used, and P values  .05 were considered significant.

To control for seasonal biases, we compared the relationship between asthma severity classification and measures of morbidity for participants who completed surveys during 4 nonoverlapping, 3-month intervals.

	RESULTS

Top Abstract Methods Results Discussion Conclusion References

Sample Characteristics

The caretakers were overwhelmingly mothers (92%); the remainder were foster parents (5%), grandparents (2%), and fathers (1%). The caretakers were primarily Hispanic (42.3% Puerto Rican, 17% other) or 33% black (25.5% African American, 7.7% West Indian, 0.5% other); 1.4% were white, and 6.8% other racial/ethnic groups. Additional characteristics of the caretakers and children are included in Table 2.

Asthma Severity and Morbidity

Table 1 contains the classification scheme we applied to define asthma severity. Table 3 shows the results of applying this classification scheme to the children in the study: 17% met the criterion for mild intermittent asthma, 27% for mild persistent asthma, and 56% for moderate-severe persistent asthma. There was no difference in the age of the children in the 3 groups (mean age: 6 years). Table 3 also compares asthma morbidity across the 3 groups of asthma severity. There were significantly more asthma attacks in the last 6 months in the moderate-severe group than in either the mild intermittent group (9.8 vs 3.5; P < .05) or the mild persistent group (9.8 vs 4.5; P < .05). In addition, there were significantly more ED visits in the last 6 months in the moderate-severe group than in the mild persistent or mild intermittent group (3.05 vs 1.69 or 1.76; P < .05). Lastly, as asthma symptom frequency increased, there were trends toward more hospitalizations and more days hospitalized.

The relationship between asthma severity classification and morbidity measures did not change when we controlled for the season of the year in which the survey was completed.

Use of Daily Antiinflammatory Agents

In the overall sample, we found that 35% of the 219 families reported giving daily antiinflammatory medications to their child; of these, 83% gave cromolyn sodium alone. We then examined reported antiinflammatory use for the subset of children identified with persistent asthma for which the guidelines recommend starting or increasing antiinflammatory agents. In our sample, 83% of the children (N = 181) met this criterion. Of these children, 70 (39%) were receiving daily antiinflammatory agents and 111 (61%) were not.

Table 4 shows daily antiinflammatory use as reported by parents for children with differing levels of asthma severity. In the mild persistent group, 69% were not receiving any daily antiinflammatory agents; 29% were receiving cromolyn sodium alone; and 1.7% was receiving inhaled steroids alone. In the moderate-severe group: 58% were not receiving any daily antiinflammatory agent in strong contrast to the NAEPP recommendations; 27% were on cromolyn sodium alone, and only 16% were on inhaled steroids (6% inhaled steroids alone and 10% inhaled steroids in combination with cromolyn sodium). There were also some families that reported giving inhaled antiinflammatory agents in the last 4 weeks, but not on a daily basis: 10% of the intermittent group, 21% of the mild persistent group, and 15% of the moderate-severe group. Reported use of antiinflammatory agents did not vary by children's ages within severity groups.

Child and Caretaker Characteristics, Primary Care Practices, and Asthma Home Management.

We then examined whether use of daily antiinflammatory agents was related to sociodemographic characteristics of the children and/or their caretakers. In our inner-city sample, for the 181 children with persistent asthma, we found no differences in antiinflammatory use based on the child's age or gender, or the caretaker's race, educational level, insurance, or receipt of public assistance. We also found no difference in caretaker self-efficacy scores¹³ between caretakers who reported giving antiinflammatory agents and those who did not. (Data available on request).

We examined whether other aspects of asthma care were related to antiinflammatory use. Seventy-eight percent of the overall sample could identify a primary care provider, and of these families, 84% reported phone access to the clinician. The usual source of care for the children was: 51% outpatient clinic, 25% private doctor, 9% no usual source of care, and 4% an ED. Families who attended an outpatient clinic were more likely to be giving daily antiinflammatory medications than those who went to a private doctor, the ED, or had no usual place of care (P < .04). The children averaged 3.1 visits to their clinicians in the last 6 months (median: 2, range: 0-52) including 1.9 visits with asthma symptoms (median: 1, range: 0-52). Families who were giving their child a daily antiinflammatory medication had more mean visits to their primary care provider than those who were not (4.5 vs 2.5; P < .01) and more visits with asthma symptoms (3.2 vs 1.4; P < .02).

The relationships between daily antiinflammatory medication use and other aspects of asthma home management for children with persistent asthma are shown in Table 5. As the odds ratios indicate, families who had a primary care provider for their child and those who knew how to reach their child's doctor were each twice as likely to report that their child was receiving daily antiinflammatory agents than those who did not. In addition, families who reported having a written asthma plan, a peak flow meter, or a zippered mattress cover (dust mite control) were also twice as likely to report that their child was receiving daily antiinflammatory medications than those without these items.

	DISCUSSION

Top Abstract Methods Results Discussion Conclusion References

In this study, we quantified persistent asthma symptoms and applied the NAEPP symptom criteria to classify asthma severity in children and compared asthma morbidity and medication use among children with different levels of asthma severity. We found significant relationships between the frequency of reported persistent asthma symptoms and the frequency of both asthma exacerbations and ED visits. As asthma severity increased, there were also trends toward more hospitalizations. The majority of children meeting criteria for persistent asthma were not receiving appropriate antiinflammatory therapy.

To our knowledge, this is the first study that compares the NAEPP guidelines' symptom-based classification scheme to morbidity outcomes. The use of symptom frequency to classify asthma severity was originally proposed by Aas in 1981¹⁴ and recent studies have supported its use. In 1999, the interreliability of the guidelines' symptom based criteria and objective measures of lung function were compared.¹⁵ Poor correlation between the variables, including pulmonary function testing, was found; a single variable, nocturnal symptoms, determined to a large extent overall categorization. Additional support for the significance of chronic symptoms was published by Droste et al¹⁶ who found that chronic cough and exercise-induced wheeze were significant predictors of decreased lung function in 7- and 8-year-old children. Recently, the relationship between asthma severity classification to airway inflammation, as defined by modification of the Global Initiative for Asthma Guidelines,¹⁷ was examined using induced sputum samples. A severity-related increase in sputum eosinophilia and eosinophil cationic protein was found.¹⁸

Although biological markers may prove to be more sensitive indicators of asthma severity and heterogeneity, questioning children and their parents about the frequency of symptoms is an important, inexpensive, and readily accessible bedside and office tool that may aid in the detection of persistent symptoms and help direct therapy.

In this study, we found that the majority of children (83%) in our sample of previously hospitalized inner-city children with asthma met the NAEPP criteria for persistent asthma. In contrast to the guidelines' recommendation for use of daily antiinflammatory agents, only 35% of the children were receiving daily antiinflammatory treatment. In the moderate to severe group, in strong contrast to the guidelines' recommendations, only 15% were receiving daily inhaled steroids.

Previous work has shown an over-reliance on episodic treatment with -agonists.¹⁹ This study shows not only that preventive therapy is underused, but also more specifically that inhaled steroids, the most effective therapy currently available for long-term control of asthma, are underused. The vast majority of children receiving daily antiinflammatory treatment in this study were receiving cromolyn sodium. Cromolyn sodium is widely used because of its excellent safety profile and availability in a nebulized form, but it is effective for some, but not all, and is less effective than inhaled steroids.²⁰ In addition, adherence to cromolyn sodium can be difficult because initial treatment requires at least 3-times-a-day dosing. Because evidence suggests early aggressive treatment of inflammation may help prevent progression of disease and reduce symptoms, we may be wise to shift practice patterns to use inhaled steroids more often as a first-line approach.

This study did not address the respective contributions of physician prescribing practices and of parental adherence to the current underuse of antiinflammatory agents for children with persistent asthma. It may be that some doctors are failing to recognize symptoms of persistent asthma and to prescribe appropriate therapy. In addition, many parents are afraid of giving their child a daily medication and/or may not prioritize giving preventive medications to their children amid a variety of other demands on their time. Of interest, reported use of antiinflammatory agents was higher in families who could identify a usual clinician for their child, knew how to reach their clinician, and had written plans and peak flow meters. In addition, families who were informed about the importance of allergy mattress covers and had obtained them were more likely to be giving their child preventive medications. Physicians' skills in increasing parental adherence to medications can be augmented by training regarding implementation of the asthma guidelines and self-regulation.²¹ Increasing physicians and patient discussion about the importance of long-term control agents is an important area for future work.

There were several limitations to our study. First, we relied on parental recall to assess symptom frequency and did not include objective measures of lung function. In addition, we classified some children already on medications. The guideline's classification of severity is based on clinical features of untreated patients. These children might have been in a higher classification if surveyed before therapy. Children with asthma can vary in symptoms over time and therefore change classifications, especially in the face of untreated allergic rhinitis, sinusitis, or an intercurrent illness.

In addition, parents who report frequent daily symptoms may be more likely to report frequent exacerbations. Furthermore, the line between cough, wheeze, and asthma exacerbation is not distinct. We do, however, believe our families were able to distinguish acute exacerbations, "asthma attacks," from chronic symptoms because the number of exacerbations reported in a 6-month period is far smaller than the number of reported daily symptoms if we were to extrapolate symptoms days for the same time interval. A larger, prospective study that includes data on morbidity from a heath care system database may help to validate the relationship between symptom frequency and other measures of morbidity.

Finally, we chose children who had been hospitalized for asthma within the last 2 years. This sample may represent a more severe population or select for children with poorer outpatient management. In addition, we restricted our study to English or Spanish speakers and excluded families who belonged to an outside HMO, and we do not know how these factors affected our study.

	CONCLUSION

Top Abstract Methods Results Discussion Conclusion References

Symptom criteria are a clinically useful tool to classify asthma severity and identify children at differential risk for asthma morbidity. In this sample of previously hospitalized inner-city children with asthma, children with persistent asthma were not receiving antiinflammatory agents as recommended in the 1997 NAEPP Guidelines. Inhaled steroids, in particular, were infrequently used to control moderate to severe asthma.

Additional research is necessary to validate and refine methods of classifying asthma severity. Clinicians, parents, and the children they collectively care for may benefit by increasing awareness regarding the significance of recognizing persistent asthma symptoms and using antiinflammatory therapy, especially inhaled steroids, to reduce inflammation.

	ACKNOWLEDGMENTS

This work was supported by a grant from The Fan Fox and Leslie R. Samuels Foundation.

	FOOTNOTES

Portions of this article were presented at the 38th Annual Meeting of the Ambulatory Pediatric Association; May 1998; New Orleans, LA.

Received for publication Apr 25, 2000; accepted Nov 13, 2000.

Address correspondence to Karen L. Warman, MD, Department of Pediatrics, Albert Einstein College of Medicine/Children's Hospital at Montefiore, 1621 Eastchester Rd, Bronx, NY 10461.

	ABBREVIATIONS

NAEPP, National Asthma Education and Prevention Program; HMO, health maintenance organization; ED, emergency department.

	REFERENCES

Top Abstract Methods Results Discussion Conclusion References

1. Crain EK, Weiss K, Bijur P, Hersh M, Westbrook L, Stein REK An estimate of the prevalence of wheezing among inner-city children. Pediatrics 1994; 94:356-362 [Abstract/Free Full Text]
2. Busse WW, Calhoun WJ, Sedgwick JD Mechanisms of airway inflammation in asthma. Am Rev Respir Dis 1993; 147:S20-S24 [Medline]
3. Roche WR Fibroblasts and asthma. Clin Exp Allergy 1991; 21:545-548 [CrossRef][Medline]
4. Agertoft L, Pedersen S Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994; 88:373-381 [CrossRef][Medline]
5. Laitinen LA, Laitenen A, Haahtela T A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta₂-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double blind, parallel-group controlled trial. J Allergy Clin Immunol 1992; 90:32-42 [Medline]
6. Djukanovic R, Roche WR, Wilson JW, Mucosal inflammation in asthma. Am Rev Respir Dis 1990; 142:434-457 [Medline]
7. van Essen-Sandvliet EE, Hughes MD, Waalkens HJ, Duiverman EJ, Pocock SJ, Kerrebijn KF Effects of 22 months of treatment with inhaled corticosteroids and/or beta-agonists on lung function, airway responsiveness, and symptoms in children with asthma. Am Rev Respir Dis 1992; 146:547-554 [Medline]
8. Djukanovic R, Roche WR, Wilson JW, Mucosal inflammation in asthma. Am Rev Respir Dis 1990; 142:434-57
9. National Asthma Education and Prevention Program. Expert Panel Report II: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD: National Institutes of Health Publication; 1997
10. Lang DM, Sherman MS, Polansky M Guidelines and realities of asthma management. The Philadelphia Story . Arch Intern Med 1997; 157:1193-1199 [Abstract]
11. Berg AO, Moy JG Clinical guidelines and primary care guidelines for the diagnosis and management of asthma. J Am Board Fam Pract 1992; 5:629-634
12. Warman KL, Silver EJ, Esteban-Cruciani N, McCourt MP, Bauman LJ, Stein REK. Can a primary care based asthma intervention affect service use, home management and morbidity for inner-city children? Paper presented at: 39th Annual Meeting of the Ambulatory Pediatric Association; May 1999; San Francisco, CA
13. Ilfeld FW Psychologic status of community residents along major demographic dimensions. Arch Gen Psychiatry 1978; 35:716-724 [Abstract]
14. Aas K Heterogeneity of bronchial asthma. Allergy 1981; 36:3-14 [Medline]
15. Colice GL, Vanden Burgt J, Song J, Stampone P, Thompson PJ Categorizing asthma severity. Am J Respir Crit Care Med 1999; 160:1962-1967 [Abstract/Free Full Text]
16. Droste JHJ, Weiringa MH, Weyler JJ, Nelen VJ, Van Bever HP, Vermeire PA Lung function measures and their relationship to respiratory symptoms in 7- and 8-year-old children. Pediatric Pulmonol 1999; 27:260-266 [Medline]
17. NAEPP/WHO Workshop Report. Global Strategy for Asthma Management and Prevention. Bethesda, MD: National Institutes of Health. National Heart, Lung, and Blood Institute; 1995. Publ. No. 95-3659
18. Louis R, Lau LC, Bron AO, Roldaan AC, Radermecker M, Djukanovic R The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med 2000; 161:9-16 [Abstract/Free Full Text]
19. Goodman DC, Loosen P, Stubble TA, Chang C, Hecht J Has asthma medication use in children become more frequent, more appropriate, or both? Pediatrics 1999; 104:187-194 [Abstract/Free Full Text]
20. Svendsen UG, FrØlund L, Madsen F, Nielsen NH, Holstein-Rathlou N-H, Weeke B A comparison of the effects of sodium cromoglycate and beclomethasone diproprionate on pulmonary function and bronchial hyperreactivity in subjects with asthma. J Allergy Clin Immunol 1987; 80:68-74 [Medline]
21. Clark NM, Gong MM, Schork A, et al. Impact of education for physicians on patient outcomes. Pediatrics. 1998;101:831-836