• Manjith Narayanan, Caroline S Beardsmore, John Owers-Bradley, Marius Mada, Iain Ball, Claudia E Kuehni, Ben D Spycher, Michael Silverman, Ruslan Garipov, Kuldeep S Panesar, and Sian E Williams.
• Department of Infection, Immunity and Inflammation, University of Leicester, United Kingdom. mn87@leicester.ac.uk
• Am. J. Respir. Crit. Care Med.. 2012 Jan 15;185(2):186-91.

RationaleThe current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals.ObjectivesWe 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.MethodsLung 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 ResultsADC 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.ConclusionsOur 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.

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