Caroline S. Beardsmore

Alveolarization Continues during Childhood and Adolescence: New Evidence from Helium-3 Magnetic Resonance

RATIONALE The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals. OBJECTIVES We reexamined the current hypothesis using helium-3 ((3)He) magnetic resonance (MR) to assess alveolar size noninvasively between 7 and 21 years, during which lung volume nearly quadruples. If new alveolarization does not occur, alveolar size should increase to the same extent. METHODS Lung volumes were measured by spirometry and plethysmography in 109 healthy subjects aged 7-21 years. Using (3)HeMR we determined two independent measures of peripheral airspace dimensions: apparent diffusion coefficient (ADC) of (3)He at FRC (n = 109), and average diffusion distance of helium (X(rms)) by q-space analysis (n = 46). We compared the change in these parameters with lung growth against a model of lung expansion with no new alveolarization. MEASUREMENTS AND MAIN RESULTS ADC increased by 0.19% for every 1% increment in FRC (95% confidence interval [CI], 0.13-0.25), whereas the expected change in the absence of neoalveolarization is 0.41% (95% CI, 0.31-0.52). Similarly, increase of (X(rms)) with FRC was significantly less than the predicted increase in the absence of neoalveolarization. The number of alveoli is estimated to increase 1.94-fold (95% CI, 1.64-2.30) across the age range studied. CONCLUSIONS Our observations are best explained by postulating that the lungs grow partly by neoalveolarization throughout childhood and adolescence. This has important implications: developing lungs have the potential to recover from early life insults and respond to emerging alveolar therapies. Conversely, drugs, diseases, or environmental exposures could adversely affect alveolarization throughout childhood.

Reference equations for specific airway resistance in children: the Asthma UK initiative

Plethysmographic specific airway resistance (sRaw) is a useful research method for discriminating lung disease in young children. Its use in clinical management has, however, been limited by lack of consensus regarding equipment, methodology and reference data. The aim of our study was to collate reference data from healthy children (3–10 yrs), document methodological differences, explore the impact of these differences and construct reference equations from the collated dataset. Centres were approached to contribute sRaw data as part of the Asthma UK initiative. A random selection of pressure–flow plots were assessed for quality and site visits elucidated data collection and analysis protocols. Five centres contributed 2,872 measurements. Marked variation in methodology and analysis excluded two centres. sRaw over-read sheets were developed for quality control. Reference equations and recommendations for recording and reporting both specific effective and total airway resistance (sReff and sRtot, respectively) were developed for White European children from 1,908 measurements made under similar conditions. Reference sRaw data collected from a single centre may be misleading, as methodological differences exist between centres. These preliminary reference equations can only be applied under similar measurement conditions. Given the potential clinical usefulness of sRaw, particularly with respect to sReff, methodological guidelines need to be established and used in prospective data collection.

Early growth characteristics and the risk of reduced lung function and asthma : A meta-analysis of 25,000 children

BACKGROUND Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

Lung function in infants with cystic fibrosis.

Lung function was measured in 28 infants with cystic fibrosis and repeated in 17 of the infants during the first year of life. Thoracic gas volume (TGV) and specific airway conductance (sGaw) were measured plethysmographically and maximum forced expiratory flow at functional residual capacity (VmaxFRC) was derived from the partial expiratory flow-volume curve. At the time of the initial evaluation respiratory function was correlated with the clinical condition of the infants but not with age. There was a good correlation between sGaw and VmaxFRC when both were expressed as percentages of the predicted normal values. On the basis of the normal range for sGaw the infants were divided into two groups. Group A (n = 9), who had normal sGaw, were younger and had a lower clinical score and normal VmaxFRC and TGV values. Group B (n = 19), who had low sGaw, had increased TGV and decreased VmaxFRC. There was no correlation with age for any measure of lung function for the population as a whole. Repeat testing was undertaken at intervals in 17 representative infants. In most of these infants the relation between sGaw and VmaxFRC was maintained; there was no evidence that VmaxFRC was affected before sGaw. There was no functional evidence that the earliest changes in cystic fibrosis occur in small airways, as reflected by changes in VmaxFRC in infancy.

Are ethnic differences in lung function explained by chest size

Background: Ethnic differences in lung function (LF) are recognised in adults and children. Most prediction equations for LF are derived from whites, so non-whites are at risk of erroneous assessment. It was hypothesised that differences in chest dimensions would explain differences in LF between Asian (Indian) and white schoolchildren. Aims: To quantify the impact of chest dimensions on LF, which would inform our understanding of ethnic differences that have implications for health care. Methods: Children aged 6–11 were studied in school. A questionnaire provided information on ethnicity and respiratory health. Spirometry was used to record FVC, FEV1, FEF25–75, and PEF. Weight, height, sitting height, and chest dimensions (chest height, circumference, antero-posterior and transverse diameters) were measured. Results: Data were obtained from 294 healthy children. Standing height was the most important predictor of LF. Ethnicity was an independent predictor for all LF measures except PEF, where the effect was marginal. FVC in whites was 13.4% bigger than in Asians of the same height, and the FEV1 was 10.6% greater in whites. The influence of chest dimensions on lung function was trivial. Body mass index was smaller in Asians but did not explain differences in LF. Conclusions: Differences in chest dimensions did not explain the substantial effect of ethnicity on LF. Mechanisms whereby ethnicity exerts its influence may include differences in inspiratory muscle strength or lung compliance but remain speculative. Nevertheless it remains imperative that ethnic differences are recognised when interpreting LF tests.

Breastfeeding and lung function at school age: does maternal asthma modify the effect?

RATIONALE The evidence for an effect of breastfeeding on lung function is conflicting, in particular whether the effect is modified by maternal asthma. OBJECTIVES To explore the association between breastfeeding and school-age lung function. METHODS In the Leicestershire Cohort Studies we assessed duration of breastfeeding (not breastfed, ≤3 months, 4-6 months, and >6 months), other exposures, and respiratory symptoms by repeated questionnaires. Post-bronchodilator FVC, FEV(1), peak expiratory flow (PEF), forced midexpiratory flow (FEF(50)), and skin prick tests were measured at age 12 years. We performed multivariable linear regression and tested potential causal pathways (N = 1,458). MEASUREMENTS AND MAIN RESULTS In the entire sample, FEF(50) was higher by 130 and 164 ml in children breastfed for 4 to 6 months and longer than 6 months, respectively, compared with those not breastfed (P = 0.048 and 0.041), with larger effects if the mother had asthma. FVC and FEV(1) were associated with breastfeeding only in children of mothers with asthma (P for interaction, 0.018 and 0.008): FVC was increased by 123 and 164 ml for those breastfed 4 to 6 months or longer than 6 months, respectively (P = 0.177 and 0.040) and FEV(1) was increased by 148 and 167 ml, respectively (P = 0.050 and 0.016). Results were unchanged after adjustment for respiratory infections in infancy and asthma and atopy in the child. CONCLUSIONS In this cohort, breastfeeding for more than 4 months was associated with increased FEF(50) and, in children of mothers with asthma, with increased FEV(1) and FVC. It seems that the effect is not mediated via avoidance of early infections or atopy but rather through a direct effect on lung growth.

Does Inhaling Menthol Affect Nasal Patency or Cough

There is widespread use of menthol in over‐the‐counter medications, despite scant information on any beneficial effects. Our aim was to assess the effect of menthol on nasal air flow, perception of nasal patency and cough challenge testing.

Pulmonary sequelae of neonatal respiratory distress in very low birthweight infants: a clinical and physiological study.

Twenty infants, mechanically ventilated in the neonatal period for respiratory distress syndrome, were compared with 15 healthy controls, matched for birthweight(less than 1501 g) but greater in mean gestational age. Clinical features and lung mechanics (by whole body plethysmography) were recorded at 6-monthly intervals until about one year. THe neonatal course of the mechanically ventilated infants was commonly complicated by tracheobronchial hypersecretion and the later course by a fairly high incidence of lower respiratory tract illness. In this group, thoracic gas volume, dynamic compliance, pulmonary and airways conductance were all abnormal during the middle 4 months of the first year and reverted towards normal towards the end of the first year. The control group had normal lung mechanics. Early lung function tests were of limited value in predicting later lower respiratory tract illness, which was more common in boys, after neonatal mechanical ventilation for longer than 24 hours or raised ambient oxygen for longer than 5 days. There were few predictive physical signs. In this group of very low birthweight infants, respiratory distress syndrome of sufficient severity to require mechanical ventilation led to significant physiological and clinical disturbances of lung function which lasted into the second 6 months of life and which were particularly severe in those who had recurrent lower respiratory tract illness.

Nasal flow limitation in children

Nasal congestion due to the common cold may be exacerbated in small children because of their small nasal passages. Our aims were 1) to test the hypothesis that smaller children have relatively larger nasal airways compared to the intrathoracic airways, and 2) to examine the effect of stenting and a decongestant on nasal patency and nasal flow. During oral forced vital capacity (FVC) maneuvers, expiratory flow is limited by intrathoracic airways. During nasal FVC, flow at high volumes is limited by the nose. The point where the nasal flow–volume curve becomes superimposable on the oral curve (%Sup) depends on the relative resistance of nasal and intrathoracic airways. Fifty‐four healthy children (28 male), median age 9.5 years (range 5.9–16.0), performed full forced respiratory maneuvers through: 1) the mouth, 2) the nose, 3) the nose after application of an external stent (Breathe Right® (BR) strip), and 4) the nose following instillation of xylometazoline. Peak inspiratory and expiratory flow (PIF and PEF), and mid‐inspiratory and expiratory flow (MIF50 and MEF50) all showed a significant decrease from the oral to the nasal baseline maneuver. Mean (SD) %Sup of the nasal baseline was 35.6 (13.7)% and was unrelated to height. PIF and MIF50 increased with the BR strip (P < 0.05). Xylometazoline also caused a significant increase in all measured flows (P < 0.05). Mean (SD) %Sup of the nasal maneuver after application of xylometazoline increased to 53.3 (14.0)%. We conclude that there is no evidence that relative resistance of nasal and intrathoracic airways change with height. The %Sup is easy to obtain and may prove a useful index of nasal patency. Pediatr Pulmonol. 1999; 27:32–36.

Airway function in infants with vascular rings: preoperative and postoperative assessment.

Aortic arch anomalies in infancy often cause intrathoracic airway obstruction. Airway function was assessed as part of the diagnostic evaluation in six symptomatic infants both by plethysmography and using a chest compression technique to obtain partial flow-volume loops. Two infants had normal intrathoracic airway function and their symptoms were unrelated to aortic arch abnormalities. The remaining four had complete vascular rings (three double aortic arch, one pulmonary sling) and had increased expiratory airway resistance (Raw) (mean Raw = 700% predicted) and greatly decreased maximum flow rates at functional residual capacity (VmaxFRC; mean VmaxFRC = 34% predicted) with gross shape abnormalities of the flow-volume loop. Postoperatively airway function was substantially improved (mean Raw = 175% predicted, VmaxFRC = 79% predicted) but some abnormality of flow-volume loop shape remained, suggesting that tracheal dynamics were not completely normal in the early postoperative period.