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.
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.
Authors: X J Chen; L W Hedlund; H E Möller; M S Chawla; R R Maronpot; G A Johnson Journal: Proc Natl Acad Sci U S A Date: 2000-10-10 Impact factor: 11.205
Authors: G Peces-Barba; J Ruiz-Cabello; Y Cremillieux; I Rodríguez; D Dupuich; V Callot; M Ortega; M L Rubio Arbo; M Cortijo; N Gonzalez-Mangado Journal: Eur Respir J Date: 2003-07 Impact factor: 16.671
Authors: Michael Salerno; Eduard E de Lange; Talissa A Altes; Jonathon D Truwit; James R Brookeman; John P Mugler Journal: Radiology Date: 2002-01 Impact factor: 11.105
Authors: Dmitriy A Yablonskiy; Alexander L Sukstanskii; Jason C Leawoods; David S Gierada; G Larry Bretthorst; Stephen S Lefrak; Joel D Cooper; Mark S Conradi Journal: Proc Natl Acad Sci U S A Date: 2002-02-26 Impact factor: 11.205
Authors: Priya Ravikumar; D Merrill Dane; Paul McDonough; Cuneyt Yilmaz; Aaron S Estrera; Connie C W Hsia Journal: J Appl Physiol (1985) Date: 2010-11-25
Authors: Kinjal Maniar-Hew; Candice C Clay; Edward M Postlethwait; Michael J Evans; Justin H Fontaine; Lisa A Miller Journal: Am J Respir Cell Mol Biol Date: 2013-11 Impact factor: 6.914
Authors: Laura L Walkup; Robert P Thomen; Teckla G Akinyi; Erin Watters; Kai Ruppert; John P Clancy; Jason C Woods; Zackary I Cleveland Journal: Pediatr Radiol Date: 2016-08-05
Authors: Manjith Narayanan; John Owers-Bradley; Caroline S Beardsmore; Claudia E Kuehni; Michael Silverman Journal: Am J Respir Crit Care Med Date: 2014-02-15 Impact factor: 21.405
Authors: Carlos A Camargo; G R Scott Budinger; Gabriel J Escobar; Nadia N Hansel; Corrine K Hanson; Gary B Huffnagle; A Sonia Buist Journal: Ann Am Thorac Soc Date: 2014-04
Authors: Manjith Narayanan; Caroline S Beardsmore; John Owers-Bradley; Cristian M Dogaru; Marius Mada; Iain Ball; Ruslan R Garipov; Claudia E Kuehni; Ben D Spycher; Michael Silverman Journal: Am J Respir Crit Care Med Date: 2013-05-15 Impact factor: 21.405
Authors: Robert V Cadman; Robert F Lemanske; Michael D Evans; Daniel J Jackson; James E Gern; Ronald L Sorkness; Sean B Fain Journal: J Allergy Clin Immunol Date: 2012-12-11 Impact factor: 10.793