Membrane and capillary components of lung diffusion and pro-angiogenic cells in infants

Abstract

Angiogenesis is a critical determinant of alveolarisation, which increases alveolar surface area and pulmonary capillary blood volume in infants; however, our understanding of this process is very limited. The purpose of our study was to measure the pulmonary membrane diffusion capacity (DM) and pulmonary capillary blood volume (VC) components of the diffusing capacity of the lung for carbon monoxide (DLCO) in healthy infants and toddlers, and evaluate whether these components were associated with pro-angiogenic circulating haematopoietic stem/progenitor cells (pCHSPCs) early in life.21 healthy subjects (11 males), 3-25 months of age, were evaluated. DLCO was measured under normoxic and hyperoxic conditions, and DM and VC were calculated. From 1 mL venous blood, pCHSPCs were quantified by multiparametric flow cytometry.DM and VC increased with increasing body length; however, membrane resistance as a fraction of total resistance to pulmonary diffusion remained constant with somatic size. In addition, DLCO and VC, but not DM, increased with an increasing percentage of pCHSPCs.The parallel increase in the membrane and vascular components of pulmonary diffusion is consistent with alveolarisation during this period of rapid lung growth. In addition, the relationship between pCHSPCs and VC suggest that pro-angiogenic cells may contribute to this vascular process. @ERSpublications Vascular components of pulmonary diffusion are associated with circulating pro-angiogenic cells in infants and toddlers

Lung parenchymal development in premature infants without bronchopulmonary dysplasia

“…Among our study population, a higher pCHSPC:nCHSPC ratio was associated with a higher DL CO , which suggests that a pro‐angiogenic environment is associated with greater lung development. We previously found in infants born full term that increasing pCHSPC:nCHSPC ratio was associated with increasing DL CO , which was secondary to the increasing pulmonary capillary blood volume, which more directly associates these pro‐angiogenic cells to vascular development . Our current study extends these findings from infants born full term to infants born prematurely.…”

Standing on shoulders

“…A large interindividual variability in the number of alveoli was recognised decades ago [12][13][14] and one can speculate that this is partly due to biological variation in the numbers and/or ratio of pro-and non-angiogenic CHSPCs. Also the greater capillary volume found in males compared to females in infancy [1], fits very well with the larger numbers of alveoli found in males compared to females [13,14].…”

“…A contemporary meaning of this would be: one who discovers by building on discoveries made by predecessors. And in this issue of the European Respiratory Journal, CHANG et al [1] have done exactly that. Appreciating and using the ideas of a classical physiological study [2], and combining this with the results of modern molecular biology they demonstrate how, at the crossroads of two completely different scientific fields, an added value is created that brings us forward in understanding one of the most fascinating phenomena in respiratory medicine: lung growth and repair.…”

“…However, the study by CHANG et al [1] is far more advanced because it introduces new applications of novel infant lung function techniques and incorporates these with classic physiological concepts [2], while combining them with advanced subtyping of progenitor cells.…”

“…In addition, the authors observed that the ratio of pro-angiogenic to nonangiogenic circulating haematopoietic stem/progenitor cells (CHSPCs) was related to a higher pulmonary diffusion capacity, as well as a higher pulmonary capillary vascular volume [1].…”