Low-density areas on high-resolution computed tomograms in chronic pediatric asthma

doi:10.1067/mpd.2002.125006

The Journal of Pediatrics

Volume 141, Issue 1, July 2002, Pages 104-108

https://doi.org/10.1067/mpd.2002.125006 Get rights and content

Abstract

Objective: In children with chronic persistent asthma, we evaluated whether the presence of increased residual volume (RV) after anti-inflammatory treatment correlates with the detection of low-density areas on high-resolution computed tomography (HRCT), similar to those in emphysema. Methods: Children with a confirmed diagnosis of asthma (n = 32) were enrolled in a prospective study. All patients had reduction of airflow in the peripheral airways, increased RV, and increased serum eosinophil cationic protein (ECP) values indicating airway inflammation. All the children were treated with salmeterol (50 μg twice daily) and fluticasone (250 μg twice daily) for a 3-month period. Results: At the end of treatment, peripheral eosinophil counts, serum ECP, forced expiratory volume in 1 second (FEV₁), mean forced expiratory flow during the middle half of forced vital capacity (FEF_25-75), RV, and total lung capacity values improved in all the patients. HRCT was normal in 22 children (68.8%); in the remaining 10 subjects, low-density areas were found despite normalization of FEV₁, FEF_25-75, and significant reduction in ECP. A significant correlation was found between persistence of RV values >150% predicted and the presence of low-density areas on HRCT (r = 0.84, P <.0001). Conclusions: Structural changes similar to emphysema are also present in asthmatic children. Our findings suggest that the persistence of increased RV may be used to identify subjects with low-density areas on HRCT. (J Pediatr 2002;141:104-8)

Section snippets

Subjects

Thirty-two children (23 boys, 9 girls), 8 to 14 years of age (mean ± SD, 11.6 ± 1.7 years), were enrolled. Inclusion criteria were diagnosis of chronic persistent asthma according to the American Thoracic Society,¹³ reduction of airflow in the peripheral airways mean forced expiratory flow during the middle half of forced vital capacity (FEF_25-75, <70% predicted), and increased RV (>150% predicted). Children were required to have serum ECP values >12 μg/L, indicating ongoing allergic

Results

All the patients had detectable specific IgE levels for house dust mite; 18 children were sensitive to cat and 25 to grass pollen. A minority also had specific IgE for dog and other seasonal allergens. There was no specific relation between sensitivity to a specific allergen and the presence of low-density areas on HRCT. HRCT images in 22 (68.8%) subjects obtained a 0 score. In 5 (15.6%) children, the score was 1, and in 5 (15.6%) patients, the score was 2. Therefore, 10 (31.2 %) children

Discussion

Low-density areas on HRCT were observed in 31% of our asthmatic children. This percentage could have been higher if we had performed HRCT scans at enrollment. However, the aim of our study was to assess whether morphologic changes were associated with persistent functional alterations after anti-inflammatory and bronchodilator treatment.¹⁵ Therefore, it did not appear ethically justified to subject pediatric patients to a baseline study that would have doubled their radiation exposure.

We used

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Computer analysis of high-resolution CT (HRCT) scans may improve the assessment of structural lung injury in children with cystic fibrosis (CF). The goal of this cross-sectional pilot study was to validate automated, observer-independent image analysis software to establish objective, simple criteria for bronchiectasis and air trapping.
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The number of total, central, and peripheral airways on inspiratory images and LAD (%) on expiratory images were significantly higher in children with CF compared with control subjects. Among subjects with CF, peripheral airway counts correlated strongly with Brody bronchiectasis scores by two raters (r = 0.86, P < .0001; r = 0.91, P < .0001), correlated negatively with lung function, and were positively associated with sputum free neutrophil elastase activity. LAD (%) correlated with Brody air trapping scores (r = 0.83, P < .0001; r = 0.69, P < .0001) but did not correlate with lung function or sputum inflammatory markers.
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Citation Excerpt :
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Children who are referred to specialist care with asthma that does not respond to treatment (problematic severe asthma) are a heterogeneous group, with substantial morbidity. The evidence base for management is sparse, and is mostly based on data from studies in children with mild and moderate asthma and on extrapolation of data from studies in adults with severe asthma. In many children with severe asthma, the diagnosis is wrong or adherence to treatment is poor. The first step is a detailed diagnostic assessment to exclude an alternative diagnosis (“not asthma at all”), followed by a multidisciplinary approach to exclude comorbidities (“asthma plus”) and to assess whether the child has difficult asthma (improves when the basic management needs, such as adherence and inhaler technique, are corrected) or true, therapy-resistant asthma (still symptomatic even when the basic management needs are resolved). In particular, environmental causes of secondary steroid resistance should be identified. An individualised treatment plan should be devised depending on the clinical and pathophysiological characterisation. Licensed therapeutic approaches include high-dose inhaled steroids, the Symbicort maintenance and reliever (SMART) regimen (with budesonide and formoterol fumarate), and anti-IgE therapy. Unlicensed treatments include methotrexate, azathioprine, ciclosporin, and subcutaneous terbutaline infusions. Paediatric data are needed on cytokine-specific monoclonal antibody therapies and bronchial thermoplasty. However, despite the interest in innovative approaches, getting the basics right in children with apparently severe asthma will remain the foundation of management for the foreseeable future.
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Le contrôle de l’asthme est total si l’enfant ne présente pas de symptôme clinique et si sa fonction respiratoire est normale. L’objectif du travail est d’analyser l’intérêt de la pléthysmographie (PCT) dans le suivi de l’enfant asthmatique. Étude rétrospective portant sur 100 enfants asthmatiques (cinq à 16 ans) ayant bénéficié d’une PCT en plus de la courbe débit-volume (CDV). Nous avons considéré comme obstructifs tous les enfants qui ont un VEMS/CVF inférieur à 80 % et comme distendus ceux dont le rapport VR/CPT est supérieur à 30 % et/ou le VR est supérieur à 120 % des valeurs théoriques. Un test de réversibilité est systématiquement réalisé. Tous les enfants sont étudiés en état stable à distance de toute manifestation asthmatique aiguë. Il y a une corrélation significative entre les valeurs du rapport VR/CPT et le VEMS (p < 0,001, R = −0,374), le rapport VEMS/CV (p = 0,07, R = −0,182) et le DEM 25-75 (p = 0,03, R = −0,216). Les enfants distendus (n = 40) ont plus de symptômes diurnes (30 sur 40, p = 0,05), un poids (33,9 kg vs 41,8 kg, p < 0,05) et un indice de masse corporelle plus bas que les non distendus (n = 60) (16,9 kg/m² vs 18,4 kg/m², p < 0,01). Quarante-neuf pour cent des enfants obstrués sont également distendus. Vingt-trois enfants ont une CDV strictement normale, mais une augmentation significative du rapport VR/CPT. Ils sont plus jeunes au diagnostic (3,9 ± 1,9 vs 6,2 ± 3,1, p = 0,004), et ont un poids légèrement plus faible (31 ± 10 kg vs 40 ± 11 kg, p = 0,04) que les autres. La recherche d’une distension par PCT apporte des éléments complémentaires pour l’appréciation phénotypique d’un asthme.
In asthmatic children, control of the disease is perfect when no symptoms occur and lung function is normal. The aim of this study is to analyse the role of plethysmography in the follow-up of asthmatic children. We present the results of a retrospective study of lung function (plethysmography and forced expiratory flow) in about 100 asthmatic children aged five to 16 years. FEV1/FVC less than 80% predicted was considered as pathological (airflow obstruction). The ratio RV/TLC was considered pathological if greater than 30% and RV was considered pathological if greater than 120% (lung hyperinflation). Bronchodilator reversibility was performed in all patients. All patients were studied in a stable condition. None had developed any asthmatic exacerbations during the past month. We found a significant correlation between the residual volume/total lung capacity (RV/TLC) ratio and, on one hand: FEV1 (p < 0.0001, R = −0.374), and on the other hand FEV1/FVC (p = 0.07, R = −0.182) or forced expiratory flow 25-75 (p = 0.03, R = −0.216). When comparing children with (n = 40) and without (n = 60) lung hyperinflation, we noticed more diurnal symptoms (30/40 vs 10/60, p = 0.05), lower weight (33.9 kg vs 41.8 kg, p < 0.05) and lower body mass index (16.9 kg/m² vs 18.4 kg/m², p < 0.01). Among the children with defined airway obstruction, 49% also had lung hyperinflation. Twenty-three children had normal forced expiratory ratios but an increase of the ratio RV/TLC or of RV. When compared with children without lung hyperinflation, the age at diagnosis was significantly lower (3.9 ± 1.9 years vs 6.2 ± 3.1 years, p < 0.01) and weight slightly lower (31 ± 10 kg vs 40 ± 11 kg, p = 0.04). In conclusion, the use of plethysmography and thus the evaluation of pulmonary hyperinflation contributed to a better appreciation of the asthmatic phenotype in children.
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Citation Excerpt :
Only 2 studies in children have addressed the question of small airway disease evaluation; both suggested that quantitative HRCT scans may be a useful tool. Pifferi et al17 carried out HRCT scans of 32 children with asthma after a 3-month period of treatment with salmeterol and fluticasone. HRCT scans were obtained in maximal inspiratory and expiratory modes, and areas of low density were analyzed qualitatively.
Computed tomography (CT) scans are usually performed in children with asthma to exclude alternative diagnoses. Technical improvements of high-resolution CT (HRCT) scans have increased the spatial resolution sufficiently for the theoretical quantification of bronchial wall thickening of the proximal airways and the assessment of small airway disease by the extent and degree of low attenuation areas, which are believed to represent air trapping. In contrast with adults, very few studies have been performed in children. The results suggest that the HRCT scan might be useful as a noninvasive technique for airway inflammation and airway remodeling. In the future, the potential use of HRCT scans for determining optimal treatment should be evaluated. However, several issues remain to be resolved, including the validity of algorithm reconstruction, the imaging parameters to be used, and the application of this technique to young children. Furthermore, because of its cost and the irradiation involved, this examination is highly unlikely to be used routinely for the management and follow-up of all children with asthma but will likely be restricted to patients with severe asthma.
Small airways response to naturalistic cat allergen exposure in subjects with asthma
2006, Journal of Allergy and Clinical Immunology
Citation Excerpt :
We chose changes in lung attenuation on HRCT after allergen as our primary outcome because previous studies suggest that this technique is more sensitive for detecting small airways obstruction, as well as changes therein, than most existing physiologic tests. For example, in a pediatric asthma population, Pifferi et al23 showed the presence of qualitatively assessed low attenuation areas on HRCT as well as an RV >150% predicted after inhaled salmeterol/fluticasone therapy even after normalization of FEV1 and FEF25-75. Furthermore, our group demonstrated that use of an extrafine inhaled corticosteroid for 4 weeks (beclomethasone dipropionate hydrofluoroalkane [BDP-HFA]) resulted in improved small airways obstruction in subjects with asthma measured by shifts in lung attenuation on HRCT but not by changes in FEV1 or FEF25-75.24
It is currently unclear whether the small airways (diameter <2 μm) contribute significantly to late asthmatic reactions to inhaled allergen.
We sought to determine whether naturalistic exposure to cat allergen induced late responses in the small airways as measured by pulmonary function testing and high-resolution computed tomography (HRCT) of the chest performed at end-expiration.
In a group of 10 subjects with cat-induced asthma, physiologic studies (spirometry and lung volumes, including closing volume) and HRCT were performed before and 6 and 23 hours after a cat room challenge that caused a 20% or greater acute fall in FEV₁.
There was no significant decline in FEV₁ at 6 or 23 hours after cat exposure. Forced expiratory flow at 25% to 75% of forced vital capacity was significantly decreased at 6 hours after the challenge and returned to normal by 23 hours. HRCT image analysis as well as closing volume demonstrated increased air trapping from baseline at both 6 and 23 hours after the challenge. In addition, image analysis demonstrated a significant increase in small airways hyperresponsiveness to methacholine at 23 hours after the challenge. No significant mean changes were noted in lung volumes at either 6 or 23 hours or in PC₂₀ FEV₁ at 23 hours postchallenge.
These findings demonstrate that naturalistic exposure to cat allergen results in significant small airways obstruction and hyperresponsiveness persisting for at least 23 hours, at which time these changes cannot be detected by conventional physiologic measures.
Physiologically silent distal lung inflammation persists after an antigenic challenge.

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^☆: Reprint requests: Massimo Pifferi, MD, Department of Pediatrics, University of Pisa, Via Roma 67, 56100 Pisa, Italy.

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Original ArticlesLow-density areas on high-resolution computed tomograms in chronic pediatric asthma☆

Abstract

Section snippets

Subjects

Results

Discussion

Chest

Chest

Chest

Chest

Chest

Chest

Clin Radiol

Mucosal inflammation in asthma

Am Rev Respir Dis

Eosinophilic inflammation in asthma

N Engl J Med

Clinical value of monitoring eosinophil activity in asthma

Arch Dis Child

The use of serum eosinophil cationic protein (ECP) in the management of steroid therapy in chronic asthma

Clin Exp Allergy

Asthma from bronchoconstriction to airways inflammation and remodeling

Am J Respir Crit Care Med

Computed tomography of the lungs in asthma: influence of disease severity and etiology

Am J Respir Crit Care Med

Significance of emphysema observed on computed tomography scan in asthma

Eur Respir J

Measurement of CT lung density in patients with chronic asthma

Eur Respir J

Chest radiography and high resolution computed tomography of the lungs in asthma

Am Rev Respir Dis

Definitions and classification of chronic bronchitis, asthma and emphysema

Am Rev Respir Dis

Original Articles
Low-density areas on high-resolution computed tomograms in chronic pediatric asthma☆