Measuring alveolar dimensions at total lung capacity by aerosol-derived airway morphometry

A technique based on particle sedimentation, aerosol-derived airway morphometry (ADAM), was modified to investigate the morphometry of human lung airspaces at full inflation in 54 subjects with normal lung function, ages 18 to 69 years. The technique compares the recovered concentrations of monodisperse aerosol particles after gravitational settling during breath holds to determine effective airspace diameters (EADs) as a function of volumetric lung depth. The method is simple and non-invasive, requiring only several inhalations of aerosol to total lung capacity, breath holds at end inhalation and exhalation to residual volume (RV). The method is sensitive enough to detect differences in the smallest observed airspaces (EADmin) due to normal aging of healthy lungs when older subjects are compared to younger subjects. The average EADmin was larger (p = 0.009) for the oldest adults (293 +/- 54 um, s.d., 50-70 years, n = 13) at the deepest volumetric lung depth (near 40% of TLC into the lung) when compared to the youngest adults (250 +/- 38 um, s.d., 18-40 years, n = 22). The two groups had similar EADs at a depth of 5% of TLC. No gender difference in EADmin was found when comparing all males and females. No correlation was found between EADs and TLC implying number of alveolar airspaces rather than airspace size determines lung volume. The effects of changing the aerosol inhalation volume to TLC ratio was also investigated. Compared to the dichotomous Weibel morphometric model, the average EADs of 22 18-40 year old subjects were found to be equivalent near 1% TLC and 40% TLC, but were larger in size than the model between those extremes with a maximum difference occurring at approximately 3% TLC. This method appears to be extremely sensitive to in vivo changes in airspace dimensions and may prove useful in determining changes in these dimensions associated with normal lung development and early disease states.