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.

1Background Children born preterm or with a small-size-for-gestational-age are at increased 2

Functional residual capacity (FRC) is the only static lung volume that can be measured routinely in infants. It is important for interpreting volume-dependent pulmonary mechanics such as airway resistance or forced expiratory flows, and for defining normal lung growth. Despite requiring complex equipment, the plethysmographic method for measuring FRC is very simple to apply and, unlike the gas dilution techniques, enables repeat measures of lung volume to be obtained within a few minutes. This method has the further advantage that with suitable adaptations to the equipment, simultaneous measurements of airway resistance can also be obtained.The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for plethysmographic measurements in infants. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that meaningful comparisons can be made between data collected in different centres or with different equipment. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis and reporting of results and also highlight areas where further research is needed before consensus can be reached.

Rationale: Histologic data from fatal cases suggest that extreme prematurity results in persisting alveolar damage. However, there is new evidence that human alveolarization might continue throughout childhood and could contribute to alveolar repair. Objectives: To examine whether alveolar damage in extreme-preterm survivors persists into late childhood, we compared alveolar dimensions between schoolchildren born term and preterm, using hyperpolarized helium-3 magnetic resonance. Methods: We recruited schoolchildren aged 10-14 years stratified by gestational age at birth (weeks) to four groups: (1) term-born (37-42 wk; n ¼ 61); (2) mild preterm (32-36 wk; n ¼ 21); (3) extreme preterm (,32 wk, not oxygen dependent at 4 wk; n ¼ 19); and (4) extreme preterm with chronic lung disease (,32 wk and oxygen dependent beyond 4 wk; n ¼ 18). We measured lung function using spirometry and plethysmography. Apparent diffusion coefficient, a surrogate for average alveolar dimensions, was measured by helium-3 magnetic resonance. Measurements and Main Results: The two extreme preterm groups had a lower FEV 1 (P ¼ 0.017) compared with term-born and mild preterm children. Apparent diffusion coefficient was 0.092 cm 2 /second (95% confidence interval, 0.089-0.095) in the term group. Corresponding values were 0.096 (0.091-0.101), 0.090 (0085-0.095), and 0.089 (0.083-0.094) in the mild preterm and two extreme preterm groups, respectively, implying comparable alveolar dimensions across all groups. Results did not change after controlling for anthropometric variables and potential confounders. Conclusions: Alveolar size at school age was similar in survivors of extreme prematurity and term-born children. Because extreme preterm birth is associated with deranged alveolar structure in infancy, the most likely explanation for our finding is catch-up alveolarization.Keywords: alveolar structure; lung acinus; bronchopulmonary dysplasia; neonatal chronic lung disease Advances in preterm care have led to increased survival of extremely premature babies, with increasing numbers reaching adulthood. This has shifted the focus of research from survival toward long-term sequelae of prematurity (1, 2). Infants born extremely preterm are known to have arrested alveolar development, manifesting as fewer and larger alveoli (3, 4). Schoolage and adult survivors of extreme preterm birth are known to have long-term respiratory problems, particularly decreased forced expiratory volumes and increased residual lung volumes, suggesting airway damage (5, 6). There are insufficient data regarding structure and development of the periphery of the lung in long-term survivors of preterm birth because studies on this cohort have relied on traditional lung function tests that only provide an overall estimate of function.The short-and long-term outcomes described previously correlate with gestational age (GA) at birth and the presence of chronic lung disease of prematurity (CLD), one of the early pulmonary sequelae of extreme preterm birth (6-8). Most evidence regard...

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.