Membrane and Capillary Components of Lung Diffusion in Infants with Bronchopulmonary Dysplasia.

RATIONALE: Autopsied lungs of infants with bronchopulmonary dysplasia (BPD) demonstrate impaired alveolar development with larger and fewer alveoli, which is consistent with our previous physiologic findings of lower pulmonary diffusing capacity of the lung for carbon monoxide (DL(CO)) in infants and toddlers with BPD compared with healthy controls born at full term (FT). However, it is not known whether the decreased DL(CO) in infants with BPD results from a reduction in both components of DL(CO): pulmonary membrane diffusing capacity (D(M)) and Vc. OBJECTIVES: We hypothesized that impairment of alveolar development in BPD results in a decrease in both D(M) and Vc components of DlCO but that the D(M)/Vc ratio would not differ between the BPD and FT groups. METHODS: DL(CO) was measured under conditions of room air and high inspired oxygen (90%), which enabled D(M) and Vc to be calculated. MEASUREMENTS AND MAIN RESULTS: D(M) and Vc increased with increasing body length; however, infants with BPD had significantly lower D(M) and Vc than FT subjects after adjustment for race, sex, body length, and corrected age. In contrast to D(M) and Vc, the D(M)/Vc ratio remained constant with increasing body length and did not differ for infants with BPD and FT subjects. CONCLUSIONS: Our findings are consistent with infants with BPD having impaired alveolar development with fewer but larger alveoli, as well as a reduced Vc.

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

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.

An alternative method to measure the diffusing capacity of the lung for carbon monoxide in infants.

BACKGROUND: Lung diffusion assessed by the uptake of carbon monoxide (DLCO ) and alveolar volume (VA ) by inert gas dilution are readily assessed in cooperative older subjects; however, obtaining these measurements in infants has been much more difficult. Our laboratory has measured DLCO and VA in sleeping infants using a mass spectrometer, which continuously measures gas concentrations, and demonstrated that infants with bronchopulmonary dysplasia (BPD) have lower DLCO , but no difference in VA compared to full-term controls. The mass spectrometer is expensive and lacks portability; therefore, we evaluated whether measurement of end-expiratory alveolar gas concentrations using a gas chromatograph would provide an alternative approach. METHODS: (1) Using our previously digitized data for infants with BPD and full-term controls, DLCO and VA were calculated at end-expiration rather than between 60 and 80% of expired volume, as previously reported. (2) In a new group of infants, DLCO and VA were measured using gas concentrations obtained at end-expiration with a mass spectrometer and a gas chromatograph. RESULTS: (1) Using end-expiratory concentrations, infants with BPD (n = 49) had significantly lower DLCO , but similar VA compared to healthy controls (n = 34) (DLCO : 4.2 vs 4.6 mL/min/mmHg, P = 0.047; VA : 614 vs 608 mL, P = 0.772). (2) Among newly evaluated infants (n = 28), DLCO and VA obtained with a mass spectrometer and a gas chromatograph were highly correlated (R2 = 0.94 and 0.99, respectively), and were not significantly different for the two analyzers. CONCLUSION: Measuring DLCO and VA at end-expiration using a gas chromatograph can provide an effective assessment of gas exchange in sleeping infants.

Lung parenchymal development in premature infants without bronchopulmonary dysplasia.

RATIONALE: While infants who are born extremely premature and develop bronchopulmonary dysplasia (BPD) have impaired alveolar development and decreased pulmonary diffusion (DLCO), it remains unclear whether infants born less premature and do not develop BPD, healthy premature (HP), have impaired parenchymal development. In addition, there is increasing evidence that pro-angiogenic cells are important for vascular development; however, there is little information on the relationship of pro-angiogenic cells to lung growth and development in infants. OBJECTIVE: and Methods Determine among healthy premature (HP) and fullterm (FT) infants, whether DLCO and alveolar volume (VA) are related to gestational age at birth (GA), respiratory support during the neonatal period (mechanical ventilation [MV], supplemental oxygen [O2], continuous positive airway pressure [CPAP]), and pro-angiogenic circulating hematopoietic stem/progenitor cells (CHSPCs). We measured DLCO, VA, and CHSPCs in infants between 3-33 months corrected-ages; HP (mean GA = 31.7 wks; N = 48,) and FT (mean GA = 39.3 wks; N =88). RESULT: DLCO was significantly higher in HP than FT subjects, while there was no difference in VA , after adjusting for body length, gender, and race. DLCO and VA were not associated with GA, MV and O2; however, higher values were associated with higher CHSPCs, as well as treatment with CPAP. CONCLUSION: Our findings suggest that in the absence of extreme premature birth, as well as BPD, prematurity per se, does not impair lung parenchymal development.