Growth of lung parenchyma in infants and toddlers with chronic lung disease of infancy

Abstract

Rationale: The clinical pathology describing infants with chronic lung disease of infancy (CLDI) has been limited and obtained primarily from infants with severe lung disease, who either died or required lung biopsy. As lung tissue from clinically stable outpatients is not available, physiological measurements offer the potential to increase our understanding of the pulmonary pathophysiology of this disease.

Objectives: We hypothesized that if premature birth and the development of CLDI result in disruption of alveolar development, then infants and toddlers with CLDI would have a lower pulmonary diffusing capacity relative to their alveolar volume compared with full-term control subjects.

Methods: We measured pulmonary diffusing capacity and alveolar volume, using a single breath-hold maneuver at elevated lung volume. Subjects with chronic lung disease of infancy (23-29 wk of gestation; n = 39) were compared with full-term control subjects (n = 61) at corrected ages of 11.6 (4.8-17.0) and 13.6 (3.2-33) months, respectively.

Measurements and main results: Alveolar volume and pulmonary diffusing capacity increased with increasing body length for both groups. After adjusting for body length, subjects with CLDI had significantly lower pulmonary diffusing capacity (2.88 vs. 3.23 ml/min/mm Hg; P = 0.0004), but no difference in volume (545 vs. 555 ml; P = 0.58).

Conclusions: Infants and toddlers with CLDI have decreased pulmonary diffusing capacity, but normal alveolar volume. These physiological findings are consistent with the morphometric data obtained from subjects with severe lung disease, which suggests an impairment of alveolar development after very premature birth.

Figure 1.

Alveolar volume, Va (ml), versus body length (cm). Individual data for subjects with chronic lung disease of infancy (CLDI) (solid circles) and control subjects (open squares) are presented, as well as the linear regressions for each group. There was no significant difference in Va when subjects with CLDI were compared with control subjects when adjusted for body length by analysis of covariance (P = 0.58).

Figure 2.

Pulmonary diffusing capacity, Dl_CO (ml/min/mm Hg), versus body length (cm). Individual data for subjects with chronic lung disease of infancy (CLDI) (solid circles) and control subjects (open squares) are presented, as well as the linear regressions for each group. Dl_CO was significantly lower for subjects with CLDI compared with control subjects when adjusted for body length by analysis of covariance (P = 0.0004).

Figure 3.

(A) Pulmonary diffusing capacity, Dl_CO (ml/min/mm Hg), versus alveolar volume, Va (ml). Individual data for subjects with chronic lung disease of infancy (CLDI) (solid circles) and control subjects (open squares) are presented, as well as the linear regressions for each group. Dl_CO was significantly lower for subjects with CLDI compared with control subjects when adjusted for alveolar volume by analysis of covariance (P = 0.0004). (B) Ratio of pulmonary diffusing capacity to alveolar volume, Dl_CO/Va (ml/min/mm Hg/ml), was not related to body length. Individual data for subjects with CLDI (solid circles) and control subjects (open squares) are presented, as well as the average data for each group. Dl_CO/Va was significantly lower for subjects with CLDI compared with control subjects (P = 0.0004).