Aerosol-derived Airway Morphometry Research Articles

Growth of the small airways and alveoli from childhood to the adult lung measured by aerosol-derived airway morphometry

Understanding the human development of pulmonary air spaces is important for calculating the dose from exposure to inhaled materials as a function of age. We have measured, in vivo, the air space caliber of the small airways and alveoli at their natural full distension [total lung capacity (TLC)] by aerosol-derived airway morphometry in 53 children of age 6-22 yr and 59 adults of age 23-80 yr. Aerosol-derived airway morphometry utilizes the gravitational settling time of inhaled inert particles to infer the vertical distance necessary to produce the observed loss of particles to the airway surfaces at sequential depths into the lung. Previously, we identified anatomical features of the lung: the caliber of the transitional bronchioles [transitional effective air space dimension (EADtrans)]; the mean linear dimension of the alveoli (EADmin); and a measure of conducting airway volume [volumetric lung depth (VLDtrans)]. In the present study, we found that EADmin increased with age, from 184 microm at age 6 to 231 microm at age 22, generally accounting for the increase in TLC observed over this age range. EADtrans did not increase with TLC, averaging 572 microm, but increased with subject age and height when the entire age range of 6-80 yr is included {EADtrans (microm)=0.012[height (cm)]x[age (yr)]+508; P=0.007}. VLDtrans scaled linearly with lung volume, but VLDtrans relative to TLC did not change with age, averaging 7.04+/-1.55% of TLC. The data indicate that from childhood (age of 6 yr) to adulthood a constant number of respiratory units is maintained while both the smallest bronchioles and alveoli expand in size to produce the increased lung volume with increased age and height.

Quantitative computed tomography and aerosol morphometry in COPD and 1-antitrypsin deficiency

Relative area of emphysema below -910 Hounsfield units (RA-910) and 15th percentile density (PD15) are quantitative computed tomography (CT) parameters used in the diagnosis of emphysema. New concepts for noninvasive diagnosis of emphysema are aerosol-derived airway morphometry, which measures effective airspace dimensions (EAD) and aerosol bolus dispersion (ABD). Quantitative CT, ABD and EAD were compared in 20 smokers with chronic obstructive pulmonary disease (COPD) and 22 patients with alpha1-antitrypsin deficiency (AAD) with a similar degree of airway obstruction and reduced diffusion capacity. In both groups, there was a significant correlation between RA-910 and PD15 and pulmonary function tests (PFTs). A significant correlation was also found between EAD, RA-910 and PD15 in the study population as a whole. Upon separation into two groups, the significance disappeared for the smokers with COPD and strengthened for those with AAD, where EAD correlated significantly with RA-910 and PD15. ABD was similar in the two groups and did not correlate with PFT and quantitative CT in either group. In conclusion, based on quantitative computed tomography and aerosol-derived airway morphometry, emphysema was significantly more severe in patients with alpha1-antitrypsin deficiency compared with patients with usual emphysema, despite similar measures of pulmonary function tests.

Can aerosol-derived airway morphometry detect early, asymptomatical lung emphysema?

The aerosol-derived airway morphometry technique (ADAM) can be used to assess non-invasively peripheral airspace dimensions. It has been shown that this technique can identify permanent peripheral airspace enlargement in patients with lung emphysema, but it is yet unknown if early stages of emphysema can be detected. In this study, 89 aluminum welders were investigated. Although all (except two subjects) showed normal spirometry, in 29% of the subjects visual signs of early emphysema were observed with high-resolution computed tomography (HRCT) in a previous study. Using the ADAM technique, 28% of the subjects showed increased peripheral airspace dimensions. However, both groups with positive findings overlapped only in about half of the cases. Peripheral airspace dimensions correlated significantly with the mean lung density calculated from the HRCT scans, and lung density was significantly decreased in the group with increased airspace dimensions. The poor overlap of the positive findings observed with both techniques can be explained if it is considered that the visual HRCT technique and ADAM focus on different aspects of emphysematous changes in the lungs. Whereas visual HRCT is a powerful tool to identify focal changes in lung density but cannot detect mild homogeneous emphysema, ADAM delivers a measure for homogeneously distributed emphysema but cannot detect focal emphysema or regions with emphysema which are badly ventilated. Since ADAM is easy to perform, non-invasive, and can be repeatedly applied to human subjects without radiological concerns, this technique might become a useful tool for the detection and monitoring of lung emphysema in occupational medicine, epidemiology, and pharmaceutics.

Aerosol-Derived Airway Morphometry and Aerosol Bolus Dispersion in Patients With Lung Fibrosis and Lung Emphysema

Patients with lung emphysema show increased aerosol-derived dimensions of peripheral airspaces and increased aerosol bolus dispersion (AD). To apply these tests in epidemiologic studies, the objective of this pilot study was to investigate whether morphometric changes caused by lung fibrosis can be distinguished from those caused by emphysema. This study was designed as a cross-sectional study in which airspace dimensions and AD in patients with emphysema and in patients with fibrosis were compared. Forty patients participated in the study: 20 patients had high-resolution CT (HRCT)-proved lung emphysema and 20 patients had HRCT-proved lung fibrosis. All patients underwent conventional lung function tests, aerosol-derived airway morphometry (ADAM), and AD measurements. Patients with lung emphysema showed normal dimensions of small airways but enlarged airspace dimensions in the lung periphery. Patients with fibrosis showed in all lung depths increased airspace dimensions. AD was increased in patients with emphysema but was normal in patients with fibrosis. These results show that when using ADAM and AD, morphometric changes caused by emphysema can be distinguished from those caused by fibrosis with high sensitivity and specificity.

Aerosol Bolus Dispersion and Aerosol-Derived Airway Morphometry: Assessment of Lung Pathology and Response to Therapy, Part 2

ABSTRACT This review discusses the potential utility of two methods using inhaled aerosol to detect and diagnose lung disease. Part 1, published earlier,(1) focused upon aerosol bolus dispersion, which measures convective gas mixing. Here, Part 2 focuses upon aerosol-derived airway morphometry (ADAM), which assesses the diameters of airways and acini. This method is discussed in terms of its validity, ability to detect known interventions and diseases, and reproducibility (administering and performing this procedure were already discussed(1). With ADAM, airway and acinar diameters are expressed in terms of the effective airway diameter (EAD), which can be measured as a function of volumetric depth in the lungs. Evidence that ADAM is valid is provided by studies showing EAD agrees well with morphometric indices of airway and acinar size, especially once the distribution of aerosol is accounted for, and changes appropriately in response to known interventions and several diseases. Of particular note is the ...

Aerosol bolus dispersion and aerosol-derived airway morphometry: assessment of lung pathology and response to therapy, Part 1.

review discusses the potential utility of two methods using inhaled aerosols to detect and diagnose lung disease and to evaluate the efficacy of therapy. Aerosol bolus dispersion measures convective gas mixing; aerosol-derived airway morphometry assesses the calibers of airway and airspaces. These two methods are discussed in terms of their ease of use (simplicity and acceptability) and current data regarding their validity, reproducibility, specificity, sensitivity, and detection of lung improvement with therapy. Part 1 of this review focuses upon aerosol bolus dispersion; Part 2(1) focuses upon aerosol-derived airway morphometry. Aerosol bolus dispersion has many features that make it clinically attractive. It is simple to administer and patients can successfully perform the maneuvers. It detects known alterations in the lungs. It is reproducible and has high specificity and sensitivity. However, every lung disease or condition known to be detected by aerosol bolus dispersion is also detected by spirometery, maximal expiratory flow-volume curves, or another conventional lung function test. This, aerosol bolus dispersion appears best reserved as a specialized method to supplement conventional lung function tests and to characterize convective gas transport.

Aerosol derived airway morphometry in healthy subjects

Monodisperse aerosol particles can be used to non-invasively probe intrapulmonary airspace dimensions. In this study, the aerosol-derived airway morphometry technique was used to study airspace dimensions in 79 healthy subjects, in order to assess reference data for the future clinical application of aerosol-derived airway morphometry, and to investigate the effect of lung inflation, anthropometric, and lung function parameters on aerosol-derived airway morphometry. Intrapulmonary airspace dimensions were assessed by measuring the deposition of monodisperse, hydrophobic submicron aerosol particles during breathholding. Additionally, measurements of spirometric and body plethysmographic lung function were performed. Airspace dimensions were in good agreement with morphometric lung data. Airspace dimensions increased with increasing lung inflation. Interindividual variation of airspace dimensions was lowest in the lung periphery, at high levels of lung inflation, and when the volumetric lung depth was normalized to the end-inspiratory lung volume. Analysis of variance showed an increase of airspace dimensions with age. The results of this study indicate that aerosol-derived airway morphometry is dependent on the level of lung inflation and the age of the subject. These results suggest that in contrast to conventional lung function techniques, aerosol-derived airway morphometry might be a powerful tool for the detection of small changes in peripheral airway geometry.

Peripheral Airspace Dimensions in Patients With COPD

Monodisperse aerosol particles can be used to assess noninvasively intrapulmonary airspace dimensions. Since emphysematic changes in the peripheral lung are difficult to detect with most of the common lung function tests, aerosol-derived airway morphometry was used to assess the peripheral airspace dimensions (EAD800) in 25 patients with COPD and in 36 healthy volunteers. Spirometric and body plethysmographic measurements were performed in all patients. In ten patients, high-resolution CT-derived mean lung density (MLD) was additionally assessed. In healthy subjects, EAD800 was 0.39 +/- 0.05 mm. In patients, EAD800 was significantly increased (0.82 +/- 0.33 mm). In a subset of nine patients with severe alpha 1-antitrypsin deficiency and clinically severe emphysema, EAD800 was even larger (1.14 +/- 0.32 mm). In patients, EAD800 correlated with MLD (r = 0.82), diffusion capacity (DCO) (r = 0.78), and FEV1 (r = -0.75). Since MLD is considered a valid indicator for lung emphysema, the close correlation between EAD800 and MLD suggests that EAD800 reflects enlarged peripheral airspace dimensions in patients with emphysema.

Accuracy and resolution power of aerosol-derived airway morphometry in a simple lung model.

Aerosol-derived airway morphometry (ADAM) uses sedimentational deposition of monodisperse aerosol particles during breathhold to estimate intrapulmonary air-space dimensions. To determine the accuracy and resolution power of this technique a simple physical lung model comprised of uniform glass beads was investigated. Using the chordlength model, aerosol recovery from this porous medium was calculated by computer simulation of the geometrical structure of air-spaces between glass beads. The results of this calculation were then compared with experimental data: Calculated and measured air-space dimensions differ less than 2% for particles with diameters above about 1 micron. The measured air-space dimension can be described geometrically by the mean chordlength of the porous medium. To estimate the resolution power of ADAM, a defined change in air-space dimensions represented by a horizontal air slit was introduced into the porous medium. This air slit induces a marked increase of measured air-space dimensions. The volumetric width of this increase is the higher the deeper the slit is situated within the medium. Intercomparison of these data with the results of aerosol bolus dispersion measurements suggests that the resolution power of ADAM is decreased by the same mechanisms that increase dispersion of aerosol boluses, demonstrating the close relationship between both methods.

Aerosol Derived Airway Morphometry at Different Levels of Lung Inflation

ABSTRACT Monodisperse aerosol particles can be used to estimate intrapulmonary air-space dimensions. However, effective air-space diameters (EAD) measured by this technique as a function of volumet...

Mechanical factors in distribution of pulmonary ventilation.

Mechanical factors in distribution of pulmonary ventilation.