Specific airway resistance in 3-year-old children: a prospective cohort study

doi:10.1016/S0140-6736(02)08781-0

The Lancet

Volume 359, Issue 9321, 1 June 2002, Pages 1904-1908

https://doi.org/10.1016/S0140-6736(02)08781-0 Get rights and content

Summary

Background

The development of a method to assess lung function in young children may provide new insight into asthma development. Plethysmographic measurement of specific airway resistance (sR_aw) is feasible in this age group. We aimed to identify risk factors associated with low lung function in early childhood in a prospective birth cohort.

Methods

Children were prenatally assigned to risk group according to parental atopic status (high risk, both parents atopic; medium risk, one parent atopic; low risk, neither parent atopic) and followed prospectively until age 3 years. We measured sR_aw in 503 symptom-free children using whole-body plethysmography during tidal breathing.

Findings

803 of 868 children attended the clinic, of whom 503 obtained satisfactory sR_aw readings. 200 who wheezed at least once during first 3 years of life had significantly higher sR_aw than the 303 who had never wheezed (mean difference 5·8%, 95% CI 2·2–9·3, p=0·002). For children who had never wheezed there were significant differences in sR_aw between risk groups (p<0·001). Children at high risk (n=87) had a higher sR_aw (geometric mean 1·17 kPa/s, 1·12–1·22) than children at medium risk (n=162; 1·02 kPa/s, 1·00–1·05) and at low risk (54; 1·04 kPa/s, 0·99–1·11). Atopic children (n=62) had significantly higher sR_aw (1·15 kPa/s, 1·09–1·21) than those who were not atopic (232; 1·05 kPa/s, 1·02–1·07, p=0·002). For non-atopic children, those at high risk (58) had higher sR_aw (1·13 kPa/s, 1·07–1·18) than those at medium risk (125, 1·01 kPa/s, 0·98–1·05) or at low risk (49, 1·04 kPa/s, 0·97–1·10, p=0·003). We showed a significant interaction between history of maternal asthma and child's atopic status (p=0·006).

Interpretation

Even in the absence of respiratory symptoms, children of atopic parents and those with personal atopy have impaired lung function in early life.

Introduction

The assessment of lung function in young children may have major implications for our understanding of respiratory health and disease, especially in view of the association between lung function in early life and lung disease in adulthood.¹ Techniques that measure lung function in sedated infants allow assessment of lung function in preterm infants and those aged less than 18 months.2, 3, 4, 5, 6, 7 Factors affecting lung function very early in life (eg maternal smoking, maternal asthma, and sex) have therefore been established.8, 9, 10, 11

However, lung function cannot be measured in preschool children (aged 5 years and younger) with standard tests, because most cannot produce adequate forced breathing manoeuvres. Between ages 2 and 6 years, children are generally too young to cooperate and too old to sedate. Specific airway resistance (sR_aw) can be measured during normal tidal breathing with a single-step procedure without the measurement of thoracic gas volume, so that panting manoeuvres against a closed shutter are unnecessary.¹² sR_aw can also be measured with the child, accompanied by an adult, inside a plethysmograph,¹³ which makes it a potentially useful respiratory measurement in young children.

As part of the National Asthma Campaign Manchester Asthma and Allergy Study (^NACMAAS)14, 15, 16 we did sR_aw measurements in children at age 3 years. We aimed to investigate factors that determine pulmonary function in early childhood: parental atopic status, sex, wheeze, maternal smoking, maternal asthma, and child's atopic status.

Section snippets

Study population

^NACMAAS is a prospective cohort study, described in detail elsewhere.14, 15, 16 All mothers were screened for eligibility at antenatal visits in the 8–10th week of pregnancy. Both parents were skin prick tested with extracts of the four most common inhalant allergens (Dermatophagoides pteronyssinus, cat, dog, pollen) and interviewed about history of asthma and allergy. Children were identified as at high, medium, or low risk of allergic disease, according to parental skin test results and

Results

Figure 1 shows the flow chart for study participants. Of the 996 children who attended the review clinic, 503 met the criteria to take part in the study.

Prevalence of atopy, maternal smoking, and maternal asthma did not differ between children who successfully completed the lung function testing and those who did not. However, children who successfully completed testing were significantly more likely to have wheezed (40%) than those who were unable to do so (31%, p=0·02). Differences in sR_aw

Discussion

Our results have shown that lung function at age 3 years was worse in children who had wheezed than in those who had never wheezed. Children who had never wheezed in the first 3 years of life had significantly higher sR_aw if they were atopic, or were at high risk of atopy (ie, if both parents were atopic). Additionally, although having a mother with asthma did not significantly increase the child's sR_aw, if the child was atopic there was a significant increase in sR_aw in the offspring of

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Cited by (137)

Beyond the Skin: Reduced Lung Function Associated With Atopic Dermatitis in Infants
2023, Journal of Allergy and Clinical Immunology: In Practice
Very few studies have examined lung function parameters using tidal breath analysis (TBA) in atopic dermatitis (AD) with its high potential for progression to asthma.
To measure lung functions using TBA in infants with AD and in healthy controls (HCs), and to investigate the effects of disease severity, food sensitivity, and history of recurrent wheezing on TBA parameters in infants with AD.
Two hundred thirty infants were included in this prospective cross-sectional study, including an AD group (n = 150) and an HC group (n = 80). Food sensitivity was assessed by means of food-specific IgE or the skin prick test. The severity of the disease was evaluated using the SCORing Atopic Dermatitis. Lung function was assessed using TBA.
The following TBA parameters were significantly lower in the AD group than in the HC group (P < .05): time to peak tidal expiratory flow, exhaled volume to peak tidal expiratory flow, ratio of time to peak tidal expiratory flow to expiratory time, ratio of exhaled volume to peak tidal expiratory flow to total expiratory volume, expiratory flow when 25% of tidal volume remains in the lungs, respiratory rate, and minute ventilation. No difference was observed in the AD group when TBA parameters were compared according to disease severity, food sensitivity, and history of recurrent wheezing (P > .05). The receiver-operating characteristic curve demonstrated by the ratio of time to peak tidal expiratory flow to expiratory time yielded an area under the curve of 0.826 (CI, 0.772-0.879), with a cutoff value of 31.65 or higher in differentiating AD, with a sensitivity of 78.7% and a specificity of 77.5%.
TBA curves can be a useful tool for demonstrating expiratory airway obstruction in AD and for providing objective information for the clinician. Bronchial obstruction was detected in young children with AD irrespective of the severity of the disease, food sensitivity, and history of recurrent wheezing.
Atopic march in children with early-onset atopic dermatitis: A retrospective study
2022, Revue Francaise d'Allergologie
Atopic march is a term that describes the progression of atopic disorders, from atopic dermatitis in young infants and toddlers to allergic rhinitis and asthma in later childhood. The aim of this study was to elucidate the course of allergic diseases between 3-7 years of age in patients with atopic dermatitis in the first 2 years of life.
A total of 211 children have been analyzed in this retrospective study. The atopic dermatitis group consisted of 119 children diagnosed with atopic dermatitis between the ages of 0–2 in 2013 and the control group consisted of 92 children aged 0-3 months who had a hearing test for screening in the same year. The diagnoses of wheezing, atopic dermatitis, and allergic rhinitis in both groups below 2 years old and between 3-7 years old were examined from the hospital database and government e-health service.
The frequency of at least one wheezing attack (28.6% vs. 29.3%), at least three wheezing attacks (15.1% vs. 9.8%) and allergic rhinitis (22.7% vs. 22.8%) were not significantly different between atopic dermatitis and control groups in children between 3 and 7 years old. However, in the atopic dermatitis group, the frequency of at least one wheezing attack (42.6% vs. 19.4%, P = 0.006), at least three wheezing attacks (25.6% vs. 8.3%, P = 0.011), and allergic rhinitis (38.3% vs. 12.5%, P = 0.001) were significantly higher in children with food sensitization than individuals without food sensitization.
This study showed that the later allergic respiratory diseases in children with early-onset atopic dermatitis were associated with food sensitization regardless of early wheezing, and the persistence of atopic dermatitis was associated with multiple food sensitizations.
La marche atopique est un terme qui décrit la progression des troubles atopiques, depuis les tout-petits jusqu’à la rhinite allergique et l’asthme plus tard dans l’enfance. Le but de cette étude était d’élucider l’âge de 3 à 7 ans chez les patients atteints de dermatite atopique au cours des 2 premières années de vie.
Au total, 211 enfants ont été analysés dans cette étude rétrospective. Le groupe dermatite atopique était composé de 119 enfants diagnostiqués avec une dermatite atopique âgés de 0 à 2 ans en 2013 et le groupe témoin était composé de 92 enfants âgés de 0 à 3 mois qui avaient passé un test auditif de dépistage la même année. Les diagnostics de respiration sifflante, de dermatite atopique et de rhinite allergique dans les deux groupes de moins de 2 ans et de 3 à 7 ans ont été examinés à partir de la base de données hospitalière et du service de santé en ligne du gouvernement.
La fréquence d’ au moins une crise sifflante (28,6 % vs 29,3 %), au moins trois crises sifflantes (15,1 % vs 9,8 %) et la rhinite allergique (22,7 % vs 22,8 %) n’étaient pas significativement différentes entre les dermatites atopiques et des groupes témoins chez les enfants entre 3 et 7 ans. Cependant, dans le groupe dermatite atopique, la fréquence d’ au moins une crise de respiration sifflante (42,6 % vs 19,4 %, p = 0,006), d’ au moins trois crises de respiration sifflante (25,6 % vs 8,3 %, p = 0,011) et de rhinite allergique (38,3 % contre 12,5 %, p = 0,001) étaient significativement plus élevés chez les enfants avec une sensibilisation alimentaire que chez les individus sans sensibilisation alimentaire.
Cette étude a montré que les maladies respiratoires allergiques tardives chez les enfants atteints de dermatite atopique précoce étaient associées à une sensibilisation alimentaire indépendamment d’une respiration sifflante précoce, et la persistance de la dermatite atopique était associée à de multiples sensibilisations alimentaires.
Pulmonary Function Tests in Infants and Children
2019, Kendig's Disorders of the Respiratory Tract in Children
Lung function testing in early life can provide information on lung growth and development and can help clinicians in the decision making process. However, the techniques available in infants and preschool-age children are usually not adequately validated for these age groups. Understanding the impact of measurement conditions on the data is essential to achieving valid results. Infant lung function tests are still limited to research settings in highly specialized lung function laboratories and are not suited for the everyday clinical use. In contrast, tests in preschoolers are easy to perform; most of the tests only require minimal subject cooperation and can be undertaken as early as 3 years of age with high feasibility. The main limitations of these techniques are that they are more useful at detecting differences between groups of healthy children and children with lung disease, but they are not specific and sensitive enough to be utilized in individuals in the clinical practice. Interpretation of the results also requires comprehensive understanding of respiratory physiology. There are promising techniques in the focus of pediatric respiratory research in recent years that are likely to improve the clinical utility of lung function measurements during these critical years of lung development.
Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies
2018, The Lancet Respiratory Medicine
Maximal lung function in early adulthood is an important determinant of mortality and COPD. We investigated whether distinct trajectories of lung function are present during childhood and whether these extend to adulthood and infancy.
To ascertain trajectories of FEV₁, we studied two population-based birth cohorts (MAAS and ALSPAC) with repeat spirometry from childhood into early adulthood (1046 participants from 5–16 years and 1390 participants from 8–24 years). We used a third cohort (PIAF) with repeat lung function measures in infancy (V'_maxFRC) and childhood (FEV₁; 196 participants from 1 month to 18 years of age) to investigate whether these childhood trajectories extend from early life. We identified trajectories using latent profile modelling. We created an allele score to investigate genetic associations of trajectories, and constructed a multivariable model to identify their early-life predictors.
We identified four childhood FEV₁ trajectories: persistently high, normal, below average, and persistently low. The persistently low trajectory (129 [5%] of 2436 participants) was associated with persistent wheezing and asthma throughout follow-up. In genetic analysis, compared with the normal trajectory, the pooled relative risk ratio per allele was 0·96 (95% CI 0·92–1·01; p=0·13) for persistently high, 1·01 (0·99–1·02; p=0·49) for below average, and 1·05 (0·98–1·13; p=0·13) for persistently low. Most children in the low V'_maxFRC trajectory in infancy did not progress to the low FEV₁ trajectory in childhood. Early-life factors associated with the persistently low trajectory included recurrent wheeze with severe wheezing exacerbations, early allergic sensitisation, and tobacco smoke exposure.
Reduction of childhood smoke exposure and minimisation of the risk of early-life sensitisation and wheezing exacerbations might reduce the risk of diminished lung function in early adulthood.
None.
Asthma predictive index in relation to respiratory mechanics by impulse oscillometry in recurrent wheezers
2018, Allergologia et Immunopathologia
Citation Excerpt :
Atopy is a risk factor for persistent wheeze.30 Even in the absence of respiratory symptoms, children of atopic parents and those with personal atopy have impaired lung function in early life.29 Lowe et al. showed that in young children a combination of sensitization and exposure to a sensitizing allergen resulted in significant deficits in lung function measured as specific airway resistance in plethysmography.31
The identification of children who will have persistent asthma has become a focus of recent research. The aim of this study was to assess whether impulse oscillometry (IOS) has a diagnostic value to predict modified API (asthma predictive index) in pre-schoolers with recurrent wheezing.
Pre-school children aged 3–6 years with recurrent wheezing were enrolled. The study population was divided into two groups based on mAPI criteria. Lung function was assessed by IOS.
115 children were assessed; 75 (65.2%) of them were male. The median age was 39 months (min: 36, max: 68 months). 64 (55.6%) of the children were mAPI positive. The R5-R20% levels of children with positive mAPI were significantly higher compared to negative mAPI. Also, R5-R20% levels of children with parental asthma and R20% pred and resonant frequency (Fres) levels of children with inhalant sensitization were higher than those without. No significant differences were found in IOS indices between groups based on the presence of atopic dermatitis, food sensitization, eosinophilia, inhaled corticosteroid usage or wheezing without colds. R5-R20% and total IgE values were found to be significantly related to positive mAPI (aOR: 1.40, p = 0.022 and aOR: 1.02, p = 0.001, respectively). In the ROC analysis, R5-R20% levels >14.4 had a sensitivity of 75% and specificity of 53% for predicting a positive mAPI (p = 0.003).
IOS may help clinicians to identify the pre-school wheezers with a high risk of asthma.
Pediatric respiratory diseases
2015, Revue des Maladies Respiratoires Actualites

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ArticlesSpecific airway resistance in 3-year-old children: a prospective cohort study

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Study population

Results

Discussion

Lancet

J All Clin Immunol

Lancet

Lung development and early origins of childhood respiratory illness

Br Med Bull

Infant respiratory function testing

Tidal breath analysis for infant pulmonary function testing

Eur Respir J

Assessment of passive respiratory mechanics in infants: double versus single occlusion?

Eur Respir J

Standards for infant respiratory function testing: the bias flow nitrogen washout technique for measuring the functional residual capacity

Eur Respir J

Standards for infant respiratory function testing: tidal forced expirations

Eur Respir J

Standards for infant respiratory function testing: plethysmographic measurements oflung volume and airway resistance

Eur Respir J

Bronchial responsiveness in the neonatal period as a risk factor for wheezing in infancy

Am J Respir Crit Care Med

Diminished lung function as a predisposing factor for wheezing respiratory illness in infants

N Engl J Med

The influence of a family history of asthma and parental smoking on airway responsiveness in early life

N Engl J Med

A simplified approach to the measurement of specific airway resistance

Paediatr Res

Articles
Specific airway resistance in 3-year-old children: a prospective cohort study