Maturational changes in airway smooth muscle structure-function relationships

Airways become less compliant with age. When examined at either extreme of the developmental spectrum, airway smooth muscle (ASM) undergoes changes that parallel the trachea: both passive and active stress increase from preterm to adult. To determine how ASM changes throughout maturation, trachealis muscles from sheep airways of five age groups (group 1, <110 d gestation; group 2,110-124 d gestation; group 3,125-140 d gestation; group 4, newborn; and group 5, adult) were separated from their cartilaginous supports and cleaned of their mucosa and serosa. The length at which active stress was optimal was determined and passive and active stress were measured. Concentration-effect curves for acetylcholine (ACh) and KC1 were performed at the length at which active stress was optimal. Morphometric analysis of the muscle was performed by computerized image analysis. At the length at which active stress was optimal, both passive and active stress increased with maturation (p < 0.001). Concentration-effect curves for both ACh and KC1 also showed a significant increase in active stress as a function of dose and of age (p < 0.002), and the ED₅₀ for ACh decreased with maturation (p < 0.005). Although muscle length, thickness, and area increased with age (p< 0.005), the ratio of contractile to connective tissue within the muscle bundle remained constant throughout maturation. These data demonstrate that ASM undergoes a progressive increase in contractility and sensitivity to ACh throughout maturation. The inability of immature ASM to generate as much force as adult ASM may in part explain why preterm infants who require positive-pressure ventilation are at risk to sustain structural central airway injury.