title: Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance.
abstract: BACKGROUND
  The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, United Kingdom. mn87@leicester.ac.uk
authors.forename: Manjith
authors.initials: M
authors.lastname: Narayanan
authors.forename: John
authors.initials: J
authors.lastname: Owers-Bradley
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Beardsmore
authors.forename: Marius
authors.initials: M
authors.lastname: Mada
authors.forename: Iain
authors.initials: I
authors.lastname: Ball
authors.forename: Ruslan
authors.initials: R
authors.lastname: Garipov
authors.forename: Kuldeep S
authors.initials: KS
authors.lastname: Panesar
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Kuehni
authors.forename: Ben D
authors.initials: BD
authors.lastname: Spycher
authors.forename: Sian E
authors.initials: SE
authors.lastname: Williams
authors.forename: Michael
authors.initials: M
authors.lastname: Silverman
mesh_terms: D000293:Adolescent; D002648:Child; D016001:Confidence Intervals; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006371:Helium; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007554:Isotopes; D008168:Lung / Q000254:growth & development; D008297:Male; D010991:Plethysmography; D011650:Pulmonary Alveoli / Q000254:growth & development*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013147:Spirometry; D055815:Young Adult
chemical_list: D007554:Isotopes; D006371:Helium
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