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Airway Hyper-Responsiveness and Small Airway Function in Children with Well-Controlled Asthma

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Airway Hyper-Responsiveness and Small Airway Function in Children with Well-Controlled Asthma nature publishing group Clinical Investigation Articles Airway hyper-responsiveness and small airway function in children with well-controlled asthma Jianfeng Huang1, Mingzhi Zhang1, Xiaobo Zhang1 and Libo Wang1 BACKGROUND: Airway hyper-responsiveness (AHR) and display condition of the disease. But, the evaluation of AHR small airway function are critical to children with asthma. Little is not popular in pediatric clinic. In areas without this means, is known about the role of the small airway in well-controlled how can we do next? subjects with AHR. We aimed to evaluate AHR and small airway Asthma is an inflammatory airway disorder that involves function in children with well-controlled asthma, and to inves- also the small airways (defined as the peripheral membra- tigate the association between them. nous bronchioles <2 mm in diameter) (3). Two decades METHODS: We studied 116 cases of children with well-con- ago, Wagner et al. (4) demonstrated a more than sevenfold trolled asthma (group A), 46 cases healthy children as con- increase in small airway resistance in asymptomatic asthma trols (group C). Spirometry, impulse oscillometry (IOS), and with normal spirometry (FEV1 and forced vital capacity methacholine challenge test (MCT) were conducted on all the (FVC)). The contribution of the small airways to the devel- children. opment of the clinical features and functional impairment RESULTS: (i) Group A and group C had no differences in forced in asthma is incompletely understood (5). Study suggested expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity that asthmatics with AHR have more severe small airways (FVC) ratio (P > 0.05). Forced expiratory flow between 25 and obstruction, but little is known about the role of the small air- 75% of vital capacity (FEF25–75) and reactance at 5 Hz (X5) in ways in asymptomatic subjects with AHR. Therefore, the aim group A were significantly lower than those in group C. (ii) One of our study was to evaluate AHR and small airway function hundred and five cases (90.5%) of group A proved positive to in children with well-controlled asthma (group A) compared MCT. (iii) FEF25–75 in group A proved positive to MCT but were to healthy control (group C), and to investigate the associa- lower than those proved negative (P < 0.05). tion between them. CONCLUSION: AHR persisted in majority of children with well-controlled asthma. Among children with well-controlled RESULTS asthma, small airway function was lower in those with AHR The participants in this study were 116 children with well-con- than those without AHR. trolled asthma (80 boys and 36 girls), 46 age-matched control subjects (30 boys and 16 girls). Proportion of family history of atopy or asthma, eczema, and allergic rhinitis were more in sthma is the most common chronic lower respiratory group A than in group C (Table 1). Adisease in childhood throughout the world. The new- All participants underwent spirometric tests, impulse est Global Initiative for Asthma guidelines, as well as inter- oscillometry (IOS), and methacholine inhalation challenge national consensus on pediatric asthma suggested that, after safely. There were no significant differences in FVC, 1FEV , initial severity assessment, ongoing care should include con- FEV1/FVC, resistance at 5 Hz (R5), R5 -R20 between two tinual assessment of the patient’s asthma control in terms of groups. Forced expiratory flow between 25 and 75% of vital real-life activities (1,2). This approach uses a cycle of detailed capacity (FEF25–75) of predicted and reactance at 5 Hz (X5) assessment and intervention to achieve and maintain asthma in group A were significantly lower than those in group C control. The level of control is defined by frequency of asthma (Table 2). symptoms, and the degree of lung function (forced expiratory One hundred and five of 116 in group A proved positive volume in 1 s (FEV1), peak expiratory flow). But in some cases to methacholine challenge, and 12 of 46 in healthy group C. called “well controlled asthma” with no disease activity and Results of methacholine challenge test (MCT) had significant normal lung function, how can we evaluate and manage them? differences between the two groups (Figure 1). Airway hyper-responsiveness (AHR) is a clinical feature of FEF25–75 in group A displayed positive results to metha- asthma and is often in proportion to the underlying severity of choline challenge and were significantly lower than those in the disease. AHR of children with well-controlled asthma can the same group displayed negative results to methacholine 1Department of Respiratory, Children’s Hospital of FuDan University, ShangHai, China. Correspondence: Jianfeng Huang ([email protected]) Received 12 July 2014; accepted 17 November 2014; advance online publication 25 March 2015. doi:10.1038/pr.2015.42 Copyright © 2015 International Pediatric Research Foundation, Inc. Volume 77 | Number 6 | June 2015 Pediatric Research 819 Articles Huang et al. challenge. We did not detect analogous difference in the results demonstrated that airway inflammation persisted in most obtained by IOS in group A (Table 3). well-controlled asthma patients despite the fact that their con- dition was controlled, and therefore, measurement of bron- DISCUSSION chial inflammation seems essential to achieve proper asthma Asthma is the most common chronic lower respiratory disease control. Stojković-Andjelković et al. (7) evaluated AHR in in childhood throughout the world. Therefore, appropriate 106 children randomly selected from general pediatric pop- asthma management may have a major impact on the quality ulation. The prevalence rate of AHR was 18%. Among the of life of patients and their families, as well as on public health asthmatic children who did not show asthma symptoms or outcomes. Recent international guidelines for the assessment did show mild asthma symptoms, bronchial sensitivity, one and monitoring of asthma have defined the concepts of asthma aspect of AHR, remained unchanged after 2 y of treatment by control. Asthma control is the degree to which manifestations Global Initiative for Asthma These results are in line with our of the disease are reduced or removed by therapy. Asthma con- study (105 of 116 asymptomatic subjects in group A remained trol is not intrinsic to the patient and can fluctuate over time. AHR). AHR is a condition of excessive airway irritability and Control categories are quite relevant in clinical practice. By can be a prognostic marker of asthma persistency and sever- appropriate asthma management, we can achieve better con- ity, and is used to monitor long-term treatment effects. AHR trol. Subsequent management in children with well-controlled is reported to decrease through childhood (8). During our asthma is also an important proposition to pediatrician (1,2). research, we detected that the majority of well-controlled Children with well-controlled asthma have no current asthma expressed AHR. AHR persists in children with well- impairment (symptoms, need for rescue medication, limita- controlled asthma, which means airway inflammation exists; tion of activities), and future risk (lung function, no exacer- so, subsequent treatment is required. We should incorpo- bations, no medication side effects). They are asymptomatic rate MCT into management of children with well-controlled with normal spirometry (FEV1 and FVC). Therefore, the asthma in the future, and should survey the recovery period development of reliable and noninvasive methods to assess of AHR with different levels. well-controlled asthma in children remains a priority and is Asthma is an inflammatory disease of the entire airway. The essential for the effective management of asthma, for instance, pathophysiology of asthma involves inflammatory and struc- guide to step down inhaled corticosteroids. Muñoz et al. (6) tural changes that have, for the most part, been described in the large airways (9). Due to technical considerations, it has been considerably easier to sample the large airways in human Table 1. Baseline characteristics of children with well-controlled asthmatic patients, for example, by induced sputum to assess asthma (group A) and healthy controls (group C) 120 Group A Group C 2 (N = 116) (N = 46) P value t/χ 100 Age (year) 8.19 ± 2.10 8.71 ± 2.74 P > 0.05 −1.27 80 Male/female 80/36 30/16 P > 0.05 0.02 Height (cm) 129.2 (121,141) 137.5 (120,150) P > 0.05 −1.515 60 Weight (kg) 29 (24,35) 32 (27,38) P > 0.05 −1.953 Number (n) 40 Family history of 54/62 4/42 P < 0.05 18.92 20 atopy or asthma Parental smoking 34/82 8/38 P > 0.05 1.85 0 Group A Group C Eczema 68/48 7/39 P < 0.05 23.24 Group Allergic rhinitis 70/46 5/41 P < 0.05 30.46 Figure 1. Comparison of methacholine challenge test (MCT) results Current inhaled 16 0 — — between children with well-controlled asthma (group A) and healthy corticosteroids controls (group C). One hundred and five of 116 in group A proved posi- tive to methacholine challenge, and 12 of 46 in healthy group C. Results Current 0 0 — — of methacholine challenge had significant differences between the two montelukast groups (P < 0.05). n, Positive to MCT; , Negative to MCT. Table 2. Summary of spirometry and impulse oscillometry results for children with well-controlled asthma (group A) and healthy controls (group C) FVC (%) FEV1 (%) FEV1/FVC FEF25−75(%) R5(KPa/l/s) R5-R20(KPa/l/s) X5(KPa/l/s) Group A 98.81 ± 8.46 102.97 ± 10.92 87.15 ± 6.12 88.56 ± 20.94 0.39 (0.27, 0.58) 0.07 (0.03, 0.15) −0.21 (−0.32, −0.16) Group C 95.52 ± 12.05 104.74 ± 16.08 89.03 ± 4.88 99.13 ± 22.67 0.51 ± 0.23 0.11 ± 0.09 −0.16 ± 0.1 t/z 1.83 −0.75 −1.86 −2.61 −1.58 −1.20 −4.40 P value 0.068 0.455 0.065 0.01 0.112 0.23 P < 0.001 FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity.
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