The Journal of Allergy and Clinical Immunology
Volume 118, Issue 1 , Pages 280-282, July 2006

Normal lung function in children with mild to moderate persistent asthma well controlled by inhaled corticosteroids

From Princess Amalia Children's Clinic, Isala Klinieken, Zwolle, The Netherlands

published online 28 May 2006.

Article Outline

 

To the Editor:

International guidelines on the diagnosis and management of childhood asthma emphasize the importance of assessing its severity with objective measures of lung function.1 More specifically, FEV1 and its reversibility after a bronchodilator are proposed as measures for the severity of childhood asthma, both at initial assessment and during follow-up.1 Inclusion criteria for many clinical trials in asthma usually include a certain reduction of FEV1% predicted, along with an improvement of >12% in FEV1 after bronchodilator.2, 3 Several studies have shown that FEV1 levels may improve considerably during treatment with inhaled corticosteroids (ICSs),4 and that normal levels of lung function may be attained during ICS treatment.5, 6, 7 We tested the hypothesis that children with mild to moderate persistent asthma well controlled on ICS therapy have normal FEV1 levels and little or no bronchodilator response (BDR), unless they are experiencing a symptomatic episode at the moment of lung function testing, or when their adherence to treatment is poor.

In this study, we retrospectively reviewed all lung function data collected during scheduled follow-up visits of children 5 to 17 years of age with chronic persistent asthma at our pediatric asthma clinic between January 1, 2002, and December 31, 2004. Children with any other chronic pulmonary disease were excluded from the analysis. The diagnosis of asthma had been made by pediatric chest physicians according to Global Initiative for Asthma guidelines. All children had had asthma for more than 12 months and were on ICS maintenance therapy. Each patient performed lung function measurements at least once a year. Full expiratory flow-volume loops were recorded before and after 800 μg salbutamol on a Jaeger Masterlab system (Erich Jaeger GmbH, Würzburg, Germany). The measurements were performed following European Respiratory Society/American Thoracic Society guidelines. Results were expressed as percentage of predicted.8 BDR was expressed as the percentage improvement of FEV1 compared with the prebronchodilator value.

A standard procedure in our practice is to evaluate clinical status by reviewing symptoms of wheeze and examining the patient for tachypnea, poor air entry, and wheeze on auscultation, and to record these findings in the chart. At each follow-up visit, the importance of adherence to maintenance therapy was emphasized, and inhalation technique was checked and corrected when needed. Patients were asked how often they forgot to take their maintenance medication. This was also recorded in the chart.9 Based on this information in the chart, but irrespective of the patient's lung function, patients were categorized as clinically stable (no symptoms of wheeze, tachypnea, poor air entry, or wheezing on auscultation) or clinically unstable. Only patients who were clinically stable, who had not received oral steroids during 4 weeks before lung function measurement, and who stated that they took their maintenance medication on most or all days were categorized as the stable group; patients who were clinically unstable or poorly adherent to therapy made up the unstable group. Data were analyzed with SPSS for Windows, version 12 (SPSS Inc, Chicago, Ill).

A total of 301 children (191 boys) with mild to moderate persistent asthma were included in this analysis. In 86 of these patients (29%), the flow-volume curve did not show a concave pattern on visual inspection, and an FEV1 > 100% predicted was found. In these patients, we refrained from repeating the flow-volume curves after bronchodilator. The remaining 215 children also recorded flow-volume loops 20 minutes after inhaling salbutamol. In the entire population, the mean prebronchodilator FEV1 was just over 100% predicted (mean, 100.6%; SD, 15.6), and mean BDR was 7.8% (SD, 10.3). There were 253 patients in the stable group and 48 in the unstable group. The frequency distribution of prebronchodilator FEV1% predicted in these 2 groups is presented in Fig 1. Prebronchodilator FEV1 was on average normal in the stable group (mean, 104.9%; SEM, 0.8%) but considerably lower in the unstable group (mean, 77.9%; SEM, 1.5%; P < .001; 95% CI for difference, 23% to 31%). This difference was comparable when only children who performed lung function both before and after bronchodilator were analyzed (95% CI for difference, 23% to 32% predicted). Conversely, the BDR was significantly lower in the stable (mean, 5.7%; SEM, 0.5%) than in the unstable group (mean, 17.3%; SEM, 2.7%; P < .001; 95% CI for difference, 8% to 14%; Fig 2). In the stable group, only 0.8% of the children had an FEV1% predicted of ≤80%, compared with 52.1% in the unstable group (P < .001). Only 10% of the children in the stable group had a BDR > 12%, compared with 48% in the unstable group (P < .001). Despite normal levels of FEV1% predicted and absence of BDR in most children with stable, controlled asthma, an midexpiratory flow at 50% of exhaled vital capacity (MEF50) of less than 80% of predicted was encountered in 42.3% of children in this group. The mean MEF50 in the stable group was 87.1% (SEM, 1.3%), compared with 45.7% (SEM, 1.9%) in the unstable group (P < .001; 95% CI for difference, 35% to 48%). The mean improvement of MEF50 after bronchodilator was 20.4% (SD, 20.8) in the stable group, compared with 53.2% (SD, 53.4) in the unstable group (P < .001; 95% CI for difference, 25% to 45%).

  • View full-size image.
  • Fig 1. 

    Frequency distributions of prebronchodilator FEV1% predicted in patients without current symptoms and good adherence to maintenance therapy with inhaled corticosteroids (stable group, open bars) and patients with current symptoms or poor adherence to maintenance therapy with inhaled corticosteroids (unstable group, solid bars).

  • View full-size image.
  • Fig 2. 

    Frequency distributions of improvement in FEV1 after high-dose salbutamol, expressed as a percentage of the prebronchodilator value, in patients in the stable group (open bars) and unstable group (solid bars).

The results of this study show that the large majority of children with stable, controlled asthma and good adherence to ICS therapy have normal levels of FEV1. This has also been recently reported by others,3, 4, 5 but the mean value of prebronchodilator FEV1 in our study population of children with stable mild to moderate persistent asthma was even higher (104% of predicted) than those previously published. A possible explanation for this may be that the patients in the other studies had had asthma for several years before ICS therapy was instituted. In the Netherlands, conversely, ICSs have been the standard first-line maintenance treatment of asthma since 1997, both in primary and in secondary care. Recent studies have shown persistent lung function deficits in young adults who had asthma as children in the era when ICSs were not routinely prescribed,10 possibly as a result of airway remodeling. Early diagnosis and ICS treatment may thus contribute to preservation of normal lung function. Our results appear to support this hypothesis.

In the presence of normal prebronchodilator lung function, there is little room for improvement in FEV1 after inhaling a bronchodilator (ceiling effect), and therefore reversibility is limited or absent. Considering the results of the BDR in our population, using a BDR > 12% as an inclusion criterion for clinical trials will result in a highly selected study population of children with either currently symptomatic asthma or poor adherence to controller medication. Consequently, results of studies applying such inclusion criteria will be applicable only to children with unstable asthma or poor treatment adherence. This, clearly, is undesirable. In agreement with others, we feel that reduced FEV1 levels and improvement of FEV1 after bronchodilator are no longer valid inclusion criteria for childhood asthma trials.5, 7

Despite normal levels of FEV1% predicted and absence of BDR, MEF50 was slightly reduced in most children in the stable group. Although this may suggest that midexpiratory flows such as MEF50 might be a more appropriate measure to assess and monitor lung function impairment in children with asthma,7 this requires further study.

In conclusion, most children with persistent asthma well controlled by inhaled corticosteroids have normal lung function and little or no bronchodilator response. This calls into question the use of reduced lung function and presence of bronchodilator response as inclusion criteria for clinical trials in childhood asthma.

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References 

  1. NAEPP Expert Panel . Guidelines for the diagnosis and management of asthma: update on selected topics 2002. Bethesda (MD): National Institutes of Health; 2002;NIH publication #02-5075
  2. Szefler SJ, Philips BR, Martinez FD, Chinchilli VM, Lemanske RF, Strunk RC, et al. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005;115:233–242
  3. Garcia ML, Wahn U, Gilles L, Swern A, Tozzi CA, Polos P. Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC Study. Pediatrics. 2005;116:360–369
  4. Adams NP, Bestall JB, Malouf R, Lasserson TJ, Jones PW. Inhaled beclomethasone versus placebo for chronic asthma. Cochrane Database Syst Rev. 2005;1:CD002738
  5. Spahn JD, Cherniak R, Paull K, Gelfand EW. Is forced expiratory volume in one second the best measure of severity in childhood asthma?. Am J Respir Crit Care Med. 2004;169:784–786
  6. Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF, Sorkness CA. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med. 2004;170:426–432
  7. Paull K, Covar R, Jain N, Gelfand EW, Spahn JD. Do NHLBI lung function criteria apply to children? a cross-sectional evaluation of childhood asthma at National Jewish Medical and Research Center, 1999-2002. Pediatr Pulmonol. 2005;39:311–317
  8. Zapletal A, Samanek M, Paul T. Lung function in children and adolescents: methods, reference values. In:  Zapletal A,  Samanek M,  Paul T editor. Progress in respiration research. Basel, Switzerland: Karger; 1987;p. 114–218
  9. Kamps AW, Brand PL, Kimpen JL, Maille AR, Overgoor-van de Groes AW, Helsdingen-Peek LC, et al. Outpatient management of childhood asthma by paediatrician or asthma nurse: randomised controlled study with one year follow up. Thorax. 2003;58:968–973
  10. Limb SL, Brown KC, Wood RA, Wise RA, Eggleston PA, Tonascia J, et al. Irreversible lung function deficits in young adults with a history of childhood asthma. J Allergy Clin Immunol. 2005;116:1213–1219

 Disclosure of potential conflict of interest: P. Brand and R. Roorda have received grants from GlaxoSmithKline and AstraZeneca. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(06)00656-7

doi:10.1016/j.jaci.2006.03.013

The Journal of Allergy and Clinical Immunology
Volume 118, Issue 1 , Pages 280-282, July 2006

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