mismatch between asthma symptoms and spirometry

Mismatch between Asthma Symptoms and Spirometry: Implications for Managing Asthma in Children Elizabeth D Schifano, PhD1, Jessica P Hollenbach, PhD2, and Michelle M Cloutier, MD2 Objectives To examine the concordance between spirometry and asthma symptoms in assessing asthma severity and beginning therapy by the general pediatrician Study design Between 2008 and 2012, spirometry testing was satisfactorily performed in 894 children (ages 5-19 years) whose asthma severity had been determined by their pediatrician using asthma guideline-based clinical criteria Spirometry-determined asthma severity using national asthma guidelines and clinician-determined asthma severity were compared for concordance using weighted Kappa coefficients Results Thirty percent of participants had clinically determined intermittent asthma; 32%, 33%, and 5% had mild, moderate, and severe, persistent asthma, respectively Increasing disease severity was associated with decreases in the forced expiratory volume in second/forced vital capacity (FVC) ratio (P < 001), the forced expiratory volume in second/FVC% predicted (P < 0001), and the FVC% predicted (P < 01) In 319 children (36%), clinically determined asthma severity was lower than spirometry-determined severity Concordance was 0.16 (95% CI 0.10, 0.23), and when adjusted for bias and prevalence, was 0.20 (95% CI 0.17, 0.23) When accounting for age, sex, exposure to smoke, and insurance type, only spirometry-determined asthma severity was a significant predictor of agreement (P < 0001), with worse agreement as spirometry-determined severity increased Conclusions Concordance between spirometry and asthma symptoms in determining asthma severity is low even when guideline-based clinical assessment tools are used Because appropriate therapy reduces asthma morbidity and is guided by disease severity, results from spirometry testing could better guide pediatricians in determining appropriate therapy for their patients with asthma (J Pediatr 2014;-: -) F or the million children in the US with asthma, treatment is guided by the assignment of an asthma severity category, which assesses the frequency of asthma-related symptoms (impairment) and the risk for an adverse outcome.1 To determine asthma severity and assess asthma control, the 2007 National Asthma Education and Prevention Program Expert Panel Report-3 (NAEPP-EPR3) recommends spirometry testing Although this recommendation is based primarily upon expert panel consensus,1 abnormal spirometry test results (ie, decreased forced expiratory volume in second [FEV1]) have been associated with increased risk of an asthma attack in the subsequent year,2 consistent with the recommendation Despite wide dissemination of the NAEPP guidelines, asthma continues to be underdiagnosed, undertreated, and inadequately followed,3-6 and spirometry testing continues to be underused.7,8 Pediatricians have raised concerns about the sensitivity of spirometry in children,9 about the need for testing, and about their qualifications to perform and interpret the tests10-13—concerns also expressed by specialists.7 Underestimating asthma severity, however, results in suboptimal treatment and increased morbidity3,14,15 and decreased quality of life.16 Easy Breathing is a disease management program for primary care clinicians and is based upon the national asthma guidelines.17 Easy Breathing uses a systematic, standardized approach to the diagnosis of asthma,18 to the determination of asthma severity,19 and to the creation of a severity-specific asthma treatment plan that is consistent with current national asthma guidelines Beginning in 2008, spirometry testing was offered to all clinicians participating in Easy Breathing The goal of this study was to examine the concordance between the systematic assignment of asthma severity using impairment and risk by pediatricians participating in Easy Breathing with the results from spirometry testing in order to determine the contribution of spirometry in assigning asthma severity From the 1Department of Statistics, University of Connecticut, Storrs; and 2Department of Pediatrics, School of Medicine, University of Connecticut Health Center, Connecticut Children’s Medical Center, Hartford, CT ETS FEV1 FVC NAEPP-EPR3 Environmental tobacco smoke Forced expiratory volume in second Forced vital capacity National Asthma Education and Prevention Program Expert Panel Report-3 Funded by Department of Public Health, State of Connecticut (Contract numbers 2008-0025 and 2010-0025) The authors declare no conflicts of interest 0022-3476/$ - see front matter Copyright ª 2014 Elsevier Inc All rights reserved http://dx.doi.org/10.1016/j.jpeds.2014.07.026 THE JOURNAL OF PEDIATRICS  Methods All children with asthma who were 5-19 years of age and were referred to the Spirometry and Aeroinhalant Allergy Testing Clinic at Connecticut Children’s Medical Center between 2008 and 2012 by an Easy Breathing participating clinician were eligible for inclusion Participants were instructed to withhold all bronchodilator use for a minimum of hours prior to testing and all long-acting bronchodilator therapy for 12 hours prior to testing All eligible children were enrolled in the Easy Breathing program, which has been previously described.20 In brief, parents complete an Easy Breathing survey, which consists of validated questions used to aid the clinician in diagnosing asthma, question about medical services utilization for exacerbations in the prior 12 months, and questions related to family history, demographics, and exposure history.18 For children with asthma, the clinician completes a provider assessment, which consists of questions validated for the clinical determination of asthma severity19 or asthma control and then uses an Asthma Treatment Selection Guide, which lists treatments specific for different asthma severities according to insurance coverage to create a field-tested Asthma Treatment Plan, which is given to the parent This Plan outlines the child’s daily, sick, and emergency treatment for asthma Spirometry Testing Spirometry testing was performed by either a pulmonologist (M.C.) or an asthma nurse educator who was trained in the performance of spirometry testing in children Testing was performed using a standard handheld spirometer (Easy One; Medical Technologies, Andover, Massachusetts) with a digital ultrasonic flow measurement and graphic display with automated coaching messages and quality control This spirometer meets the American Thoracic Society Standard and uses up to date predicted values (National Health and Nutrition Examination Survey III) based upon age, sex, ethnicity, height, and weight.21,22 Testing was performed before and after administration of puffs of albuterol using a holding chamber and with the children standing and wearing nose clips Three reproducible tests were obtained before and 10-15 minutes after bronchodilator administration Spirometry quality was graded using established criteria.23 An acceptable test had or more acceptable maneuvers with 95% reproducibility for FEV1 and forced vital capacity (FVC) Using absolute change, this represents a less than 0.20 L difference between the highest and second highest value for FVC and FEV1 The best FEV1 and the best FVC (even if from different curves) were used to determine percent predicted values Normative values for the FEV1/ FVC ratio based upon age were >0.85.24 A child with unsatisfactory quality testing was invited back to re-test Tests were interpreted by a board-certified pediatric pulmonologist (M.C.), and results were used to determine asthma severity based upon the NAEPP-EPR3 recommendations The addition of spirometry testing results could result in either no Vol -, No - www.jpeds.com change in asthma severity if test results were normal or an increase in the asthma severity category if test results were abnormal but they could not decrease asthma severity This study was exempt as determined by the Institutional Review Board at Connecticut Children’s Medical Center Statistical Analyses All statistical procedures were performed in SAS v 9.3 (SAS Institute Inc, Cary, North Carolina) or R25 v 3.0.1, and all P values and 95% CI were 2-sided unless otherwise stated A P value less than or equal to 05 was considered statistically significant Patient characteristics were compared across groups (ie, age group or completion status) by Wilcoxon rank sum and c2 tests The association between spirometric measures and clinical severity was assessed using linear regression models, adjusted for age, sex, insurance status, and exposure to environmental tobacco smoke (ETS); the arcsine square root transformation was used for the FEV1/ FVC analysis to achieve approximate normality Because spirometry results are normal in children with intermittent and mild, persistent asthma, results for these categories were combined for analysis The similarity in the clinicalbased asthma severity classification and the spirometrybased asthma severity classification was initially assessed by weighted Kappa statistic (kw) using the Fleiss-Cohen specification.26,27 The unweighted Kappa statistic (k) was additionally computed to examine how often the spirometry result disagreed with the clinical-based disease severity accounting for chance Overall bias was assessed using McNemar test,28 and subsequently prevalence- and bias-adjusted Kappa statistic was also computed to account for imbalances in the numbers of patients observed in the cross-classified clinical and spirometry-based severity categories.29 General characteristics and results on agreement were compared for factors likely to impact the results, including age, sex, insurance type, exposure to ETS, and asthma severity using logistic regression models for observed concordance and also the Cochran-Mantel-Haenszel30,31 and Breslow-Day32 tests Results Between 2008 and 2012, a total of 949 children 5-19 years of age with newly diagnosed asthma were referred for spirometry testing by participating Easy Breathing clinicians in the greater Hartford, Connecticut area and 894 children (94%) with asthma produced interpretable results There was no difference in the proportion of younger (5-12 years) compared with older (12-19 years) children, in sex or in asthma severity between those children who satisfactorily performed spirometry and those who did not When used as a continuous variable, however, younger children were less likely to perform satisfactory spirometry than older children (P < 001) Participants were evenly distributed between boys and girls with more children who were younger (512 years) compared with older (12-19 years) children (Table I) Most of the referred children were low-income, Schifano, Hollenbach, and Cloutier - 2014 ORIGINAL ARTICLES Table I Demographic information for participants by age* Female Ethnicity African American Asian or Pacific Islander Caribbean/Virgin Islander Hispanic Puerto Rican Hispanic: Other Other White/Caucasian Asthma severity† Intermittent Mild, persistent Moderate, persistent Severe, persistent Exposure to tobacco smoke Yes Unknown Age 5-11+ y (n = 631) Age 12-19+ y (n = 263) Combined (n = 894) 294 46.6 137 52.1 431 48.2 90 407 61 15 51 14.3 0.6 0.0 64.5 9.7 2.4 8.1 36 170 14 30 13.7 0.8 1.5 64.6 5.3 2.3 11.4 126 577 75 21 81 14.1 0.7 0.4 64.5 8.4 2.3 9.1 177 224 204 26 28.1 35.5 32.3 4.1 93 58 95 17 35.4 22.1 36.1 6.5 270 282 299 43 30.2 31.5 33.4 4.8 198 79 31.4 12.5 96 28 36.5 10.6 294 107 32.9 12.0 Percentages not add to 100% because of rounding and missing data *Values reported as No and % of total †P < 001 for comparing proportions in the groups; P = 132 for comparing proportions in groups (Intermittent and Mild, Persistent combined) Medicaid insured (62%), and belonged to an ethnic or racial minority group (88%) This is consistent with the economic and ethnic/racial distribution of residents in this area Thirtythree percent of the children with asthma reported exposure to tobacco smoke at home, and 70% of the children had clinically determined persistent asthma Baseline spirometry results demonstrated decreases in the FVC% predicted (P < 01), the FEV1% predicted (P < 0001), and the ratio of FEV1/FVC (P < 001) with increasing clinically determined asthma severity (Table II) Decreases in peak expiratory flow rate and the forced expiratory flow rate between 25% and 75% of the vital capacity with increasing severity were also observed (data not shown; P < 01 and P < 0001, respectively) There were no differences in the changes in these spirometric values with increasing severity between the younger and older children The FEV1/FVC and the FEV1% predicted varied by sex (P < 0001 and P = 02, respectively) with boys with asthma having lower values than Table II Spirometry testing results by clinically determined severity category and age Clinical severity Age 5-11+ n 631 Mean Intermittent 177 Mild, persistent 224 Moderate, persistent 204 Severe, persistent 26 FVC percent predicted FEV1 percent predicted SD Mean SD Mean SD 0.08 0.08 0.09 0.10 95.0 95.0 90.3 84.5 19.1 16.8 18.8 20.5 89.1 89.2 83.1 74.4 17.3 18.2 18.9 19.2 FEV1/FVC 0.85 0.85 0.83 0.80 Age 12-19+ 263 Mean SD Mean SD Mean SD Intermittent Mild, persistent Moderate, persistent Severe, persistent 93 58 95 17 0.86 0.84 0.83 0.78 0.08 0.08 0.09 0.11 93.3 93.5 92.2 91.1 14.3 16.6 14.4 17.7 89.9 87.8 85.8 78.4* 14.3 17.5 16.9 18.2* *n = 16 girls even when controlling for age group, insurance type, clinical severity, and exposure to ETS Mean values for the FEV1/FVC for boys were 0.83 Ỉ 0.09 (mean Ỉ SD) compared with 0.85 Ỉ 0.08 for girls and for FEV1% predicted were 85.4 Ỉ 19.0% for boys and 88.1 Ỉ 16.6% for girls An age by sex interaction for both FEV1/FVC (age >12 vs #12, P = 324) and FEV1% predicted (age >12 vs #12, P = 107) was not significant when controlling for insurance type, clinical severity, and exposure to ETS The concordance between clinically determined asthma severity and asthma severity determined by spirometry was poor (k = 0.08, 95% CI 0.03, 0.13; kw = 0.16, 95% CI 0.10, 0.23) Thirty-six percent of the participants had a greater asthma severity determined by spirometry compared with their severity determined using clinical criteria alone (Table III) This imbalance reflected a significant bias (P < 0001), but the concordance remained poor even after accounting for bias, as well as the differing severity prevalences (prevalence- and bias-adjusted Kappa = 0.20, 95% CI 0.17, 0.23) The distribution of severity changed using clinical criteria alone vs clinical and spirometric criteria (Figure) The observed proportion of children with lower asthma severity determined clinically compared with asthma severity determined using spirometry testing did not vary by age (34% vs 40% for 5- to 12-year-olds and older than 12-year-olds, respectively, even after adjusting for exposure to ETS; P = 16) Spirometry after bronchodilator inhalation was satisfactorily performed in 95% of the children Of these 848 children, the FEV1 increased more than 12% in 153 children (18%) and the FVC increased more than 10% in 124 (15%) children There was a greater likelihood of an increase in FEV1 with lower baseline percent predicted values for FEV1 (P < 10À6) After adjusting for age group, sex, exposure to ETS, and type of insurance (Medicaid vs private), the observed concordance rates between clinical and spirometry-determined asthma severity were significantly lower in children with more severe spirometry-determined asthma classifications (P < 0001) Discussion In this study, 894 children with asthma and clinically determined asthma severity underwent spirometry testing using standard procedures Using the spirometry testing results would have resulted in an assignment of a higher asthma severity category in 36% of these children This compared clinically determined asthma severity by general pediatricians using a standard, evidence-based state-of-the-art approach to spirometry-determined severity and suggests that spirometry testing could aid general pediatricians in determining asthma severity and thus, appropriate asthma therapy The Easy Breathing participating clinicians used a set of questions based upon the NAEPP guidelines for asthma severity1 and tested previously to assign asthma severity.19 Clinicians in the program were trained to choose the greatest asthma severity with any symptom frequency and to increase Mismatch between Asthma Symptoms and Spirometry: Implications for Managing Asthma in Children THE JOURNAL OF PEDIATRICS  www.jpeds.com Table III Contingency table of severity ratings for all participants* Clinical severity Spirometric severity Intermittent/mild, persistent Moderate, persistent Severe, persistent Total Intermittent/ mild Moderate, Severe, persistent persistent persistent Total 307 163 82 552 135 90 74 299 12 11 20 43 454 264 176 894 *The (unweighted) proportion of observed agreement, po, is 0.466 The absolute bias and prevalence index for less severe vs more severe asthma are 0.110 and 0.125, respectively asthma severity in the presence of increased risk (ie, emergency department visits for asthma or hospitalization) but often used the responses to these questions as a guide that was combined with their clinical judgment and knowledge of the child Whatever the clinically determined asthma severity, the clinician then prescribed therapy appropriate to that asthma severity If treatment was not consistent with their clinical designation of disease severity, clinicians were provided feedback and recommendations for changes to the therapy by the Easy Breathing program The overall adherence to asthma-severity guided treatment in Easy Breathing is 94% This consistent approach to the determination of asthma severity and treatment has resulted in a 3-fold increase in prescriptions for inhaled corticosteroid therapy for children with persistent asthma and a 34% and 27% reduction in hospitalizations and emergency department visits respectively for Easy Breathing participants in Hartford and throughout Connecticut.20,33 Easy Breathing began offering spirometry testing and allergy skin testing to participating practices upon referral beginning in 2008 This testing was begun at the request of the Easy Breathing practices that wanted to better understand lung function and the allergy status of their patients but were not performing their own testing The clinic provided a readily available resource for general pediatric practices and Figure Distribution of asthma severity using clinical criteria alone or clinical and spirometric criteria Vol -, No their patients without requiring consultation by a specialist The children referred for spirometry testing were not different from other children enrolled in the program although more children with persistent disease were referred which is consistent with the NAEPP-EPR3 recommendations The observed concordance between clinically determined asthma severity and spirometry-determined asthma severity was lower for children with higher spirometrydetermined severity This is not surprising, given that 20% of the children were classified as severe, persistent based on spirometry criteria, and only 5% of the children were classified as severe, persistent clinically (Table III and Figure) Bronchodilator responsiveness in this population was also low, but this could be a reflection of the ethnic/racial composition of our study participants who were predominantly Puerto Rican or African American Puerto Rican children and adults and African American children with moderate to severe asthma demonstrate low bronchodilator responsiveness overall.34 Though clinician determined asthma severity in our study population is systematic and standardized, the variability in perception of asthma symptoms reported by patients35 may have contributed to the discordance between clinician determined and spirometry determined severity The unreliability of patient symptom perception further supports the usefulness of objective assessment of lung function in determining asthma severity Asthma severity is the intrinsic severity of the disease and is best assessed in the absence of therapy.1 The clinically determined severity was assigned prior to any therapy and, thus, it reflects asthma severity Participating children with persistent disease, however, were receiving some controller therapy at the time of the pulmonary function testing It is possible that this therapy might have altered the spirometry results which, in the presence of therapy, reflect asthma control Whether the use of controller therapy at the time of the testing changes the distribution of asthma severity is not known The goal of therapy is normalization of pulmonary function, and because all of the children were clinically stable and “well” at the time of testing, their pulmonary function should have been “normalized.” A priori we decided that pulmonary function test results could not decrease asthma severity but could only assign a greater severity when test results were not consistent with the clinically determined severity In the presence of abnormal test results, even on therapy, the NAEPP recommendation is to increase treatment and that treatment would have increased the disease severity category for these children.1 Despite the relatively low agreement between clinically and spirometry-determined asthma severity, decreases in the FEV1/FVC ratio and in the FEV1% predicted were observed with increasing clinically determined severity These results also varied by sex and are thought to be due to sex differences in lung growth velocity.36 The usefulness of spirometry in the determination of asthma severity has been demonstrated in other studies including a large field study of children,23 in children cared for in an urban health center,37 in children Schifano, Hollenbach, and Cloutier - 2014 with asthma referred to an asthma specialist,38 as part of asthma clinical trials,39,40 and in children participating in the studies of inner city asthma.41 This study of a large number of children whose asthma severity was clinically determined by their pediatrician uses a standard set of criteria However, the results are quite consistent and demonstrate that spirometry changes the asthma severity assignment and should, therefore, change treatment in approximately 30%-35% of individuals.37,38 Thus, these results reflect the added value of spirometry in a general setting when the national guidelines for clinical determination of asthma severity have been used They also suggest that spirometry has added value even when standard clinical criteria are used and support the growing literature in support of the NAEPP-EPR3 guideline recommendations The results also suggest that spirometry testing can be performed in an outpatient referral setting and not necessarily in the clinician’s office This could address the concern about test quality and interpretation familiarity in general practice settings.7 Not all children who were referred for testing were able to satisfactorily perform spirometry Our failure rate of testing (6%), however, is less than what has been reported by others23,42 in large part because many participants with unsatisfactory testing ($15% of the total) returned for testing at a later date and most were subsequently able to satisfactorily perform spirometry Postbronchodilator testing was not successful in 5% of children primarily because of fatigue Another limitation is that participants represented a convenience sample—that is, not all children with asthma cared for in these practices were referred for testing and not all children who were referred for testing completed a visit Nevertheless, the referred children were similar in age and in insurance status to the overall participants in Easy Breathing, although disease severity was greater Because asthma is a clinical diagnosis, it is also possible that some of the children tested might not have had asthma This would not have altered the results because these children should have had normal pulmonary function tests Finally, we assume that the abnormal pulmonary function demonstrated in many of these children is reversible with additional therapy Because this was not examined, it is possible that some of these changes in pulmonary function were not amenable to additional therapy and represented fixed obstruction In conclusion, even when clinical criteria for the determination of asthma severity are used, spirometry testing has added value in the management of childhood asthma One way to assure availability of this testing is through spirometry clinics with professional interpretation offered to the community Increasing access to spirometry testing, whether in the pediatrician’s office or through referral in the community, should be a goal to improve asthma care for children n We thank Katie Ruane, RN, AE-C, for her technical support in performing pulmonary function tests Submitted for publication Jan 30, 2014; last revision received Jun 18, 2014; accepted Jul 11, 2014 ORIGINAL ARTICLES Reprint requests: Michelle M Cloutier, MD, University of Connecticut Health Center, Connecticut Children’s Medical Center, 282 Washington St, Hartford, CT 06106 E-mail: mclouti@connecticutchildrens.org References National Institutes of Health Heart Lung and Blood Institute Guidelines for the diagnosis and management of asthma Washington, DC: NIH; 2007 p 1-60 Publication No 08-5846 Fuhlbrigge AL, Kitch BT, Paltiel AD, Kuntz KM, Neumann PJ, Dockery DW, et al FEV(1) is associated with risk of asthma attacks in a pediatric population J Allergy Clin Immunol 2001;107:61-7 Piecoro LT, Potoski M, Talbert JC, Doherty DE Asthma prevalence, cost, and adherence with expert guidelines on the utilization of health care services and costs in a state Medicaid population Health Serv Res 2001;36:357-71 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Respir Med 2001;95:319-23 17 Cloutier MM, Wakefield DB, Hall CB, Bailit HL Childhood asthma in an urban community: prevalence, care system, and treatment Chest 2002;122:1571-9 18 Hall CB, Wakefield D, Rowe TM, Carlisle PS, Cloutier MM Diagnosing pediatric asthma: validating the Easy Breathing Survey J Pediatr 2001; 139:267-72 19 Cowen MK, Wakefield DB, Cloutier MM Classifying asthma severity: objective versus subjective measures J Asthma 2007;44:711-5 20 Cloutier MM, Hall CB, Wakefield DB, Bailit H Use of asthma guidelines by primary care providers to reduce hospitalizations and emergency Mismatch between Asthma Symptoms and Spirometry: Implications for Managing Asthma in Children THE JOURNAL OF PEDIATRICS 21 22 23 24 25 26 27 28 29 30 31  www.jpeds.com department visits in poor, minority, urban children J Pediatr 2005;146: 591-7 Hankinson J, Odencrantz J, Fedan K Spirometric reference values from a sample of the general U.S population Am J Respir Crit Care Med 1999;159:179-87 American Thoracic Society Standardization of Spirometry, 1994 Update American Thoracic Society Am J Respir Crit Care Med 1995; 152:1107-36 Enright PL, Linn WS, Avol EL, Margolis HG, Gong H Jr, Peters JM Quality of spirometry test performance in children and adolescents : experience in a large field study Chest 2000;118:665-71 National Heart Lung and Blood Institute (National Asthma Education and Prevention Program) Expert Panel Report 3: Guidelines for the diagnosis and management of asthma; 2007 US Dept of Health and Human Service, National Institutes of Health, National Heart, Lung and Blood Institute; NIH Publication Number 085846; October 2007 R Development Core Team R: A Language and Environment for Statistical Computing Vienna, Austria: R Foundation for Statistical Computing; 2013 Cohen J A coefficient of agreement for nominal scales Educ Psychol Measurement 1960;20:37-46 Fleiss JL, Cohen J The equivalence of weighted kappa and the intraclass correlation coefficient as measures of reliability Educ Psychol Measurement 1973;33:613-9 Bishop YM, Fienberg SE, Holland PW Discrete multivariate analysis: Theory and practice Cambridge, MA: MIT Press; 1975 Byrt T, Bishop J, Carlin JB Bias, prevalence and kappa J Clin Epidemiol 1993;46:423-9 Cochran WG Some methods for strengthening the common chisquared tests Biometrics 1954;10:417-51 Mantel N, Haenszel W Statistical aspects of the analysis of data from retrospective studies of disease J Natl Cancer Inst 1959;22:719-48 Vol -, No 32 Breslow N, Day NE Classical methods of analysis of grouped data In: Statistical methods in cancer research: The analysis of case-control studies Lyon, France: International Agency for Research on Cancer; 1980 p 122-59 33 Cloutier MM, Wakefield DB Translation of a pediatric asthma management program into the community in Connecticut Pediatrics 2011;127: 11-8 34 Naqvi M, Thyne S, Choudhry S, Tsai HJ, Navarro D, Castro RA, et al Ethnic-specific differences in bronchodilator responsiveness among African Americans, Puerto Ricans, and Mexicans with asthma J Asthma 2007;44:639-48 35 Kendrick AH, Higgs CM, Whitfield MJ, Laszlo G Accuracy of perception of severity of asthma: patients treated in general practice BMJ 1993;307:422-4 36 Strunk RC, Weiss ST, Yates KP, Tonascia J, Zeiger RS, Szefler SJ Mild to moderate asthma affects lung growth in children and adolescents J Allergy Clin Immunol 2006;118:1040-7 37 Holt EW, Tan J, Hosgood HD The impact of spirometry on pediatric asthma diagnosis and treatment J Asthma 2006;43:489-93 38 Nair SJ, Daigle KL, DeCuir P, Lapin CD, Schramm CM The influence of pulmonary function testing on the management of asthma in children J Pediatr 2005;147:797-801 39 Chipps BE, Spahn JD, Sorkness CA, Baitinger L, Sutton LB, Emmett AH, et al Variability in asthma severity in pediatric subjects with asthma previously receiving short-acting beta2-agonists J Pediatr 2006;148:517-21 40 Arets HG, Kamps AW, Brackel HJ, Mulder PG, Vermue NA, van der Ent CK Children with mild asthma: they benefit from inhaled corticosteroids? Eur Respir J 2002;20:1470-5 41 Stout JW, Visness CM, Enright P, Lamm C, Shapiro G, Gan VN, et al Classification of asthma severity in children: the contribution of pulmonary function testing Arch Pediatr Adolesc Med 2006;160:844-50 42 Schneider A, Gindner L, Tilemann L, Schermer T, Dinant GJ, Meyer FJ, et al Diagnostic accuracy of spirometry in primary care BMC Pulm Med 2009;9:31 Schifano, Hollenbach, and Cloutier ... trained to choose the greatest asthma severity with any symptom frequency and to increase Mismatch between Asthma Symptoms and Spirometry: Implications for Managing Asthma in Children THE JOURNAL... Bailit H Use of asthma guidelines by primary care providers to reduce hospitalizations and emergency Mismatch between Asthma Symptoms and Spirometry: Implications for Managing Asthma in Children... is systematic and standardized, the variability in perception of asthma symptoms reported by patients35 may have contributed to the discordance between clinician determined and spirometry determined