Alveolar Size Research Articles

Electronic cigarette power affects count concentration and particle size distribution of vaping aerosol.

IntroductionElectronic cigarettes (EC) have evolved rapidly toward higher powered devices that produce more vaping aerosol and a more satisfying vaping experience. This research characterized the particle size distribution and estimated the mass concentration of vaping aerosols produced at power outputs spanning the operating range typical of second generation variable voltage EC devices.MethodsEC aerosol was characterized from a single coil atomizer powered by a variable voltage EC battery at the minimum and maximum dial settings (3.3, 11.2 Watts, W), and a lab controlled power supply (3–11.9 W). Aerosol particle size distribution was measured by a Scanning Mobility Particle Sizer and Aerodynamic Particle Sizer, spanning 16 nm to 19.8 μm. A mouth puff was simulated using a 100 mL glass syringe.ResultsConsistent with prior studies, sub-micron EC aerosol size distributions were bimodal, with peaks at 40 and 200 nm, however a previously unreported third mode was observed at approximately 1000 nm. The ~1000 nm mode accounted for 7-20x the aerosol mass of the smaller modes. Increasing atomizer power decreased count concentration of particles <600 nm but increased particle count >600 nm. Particle mass distribution shifted toward micron sized particles with increasing power and increased the respirable fraction of aerosol, likely due to increased coagulation and condensation around nano-sized particles.ConclusionsVaping power greatly affects EC aerosol count and mass distribution. Mouth puffed EC aerosol spans a much wider particle size range than previously reported, although the major portion of the mass is still well within the alveolar size range the larger particles will deposit within the oro-pharyngeal cavity at 2-3x greater efficiency than in alveoli. These observations have major clinical implications, as aerosol particle size distribution determines deposition sites along the respiratory tract. The results of this experiment stress the need for further research to inform the design, regulation and use of e-cigarette products.

New fossils, systematics, and biogeography of the oldest known crown primate Teilhardina from the earliest Eocene of Asia, Europe, and North America

Omomyiform primates are among the most basal fossil haplorhines, with the oldest classified in the genus Teilhardina and known contemporaneously from Asia, Europe, and North America during the Paleocene–Eocene Thermal Maximum (PETM) ∼56 mya. Characterization of morphology in this genus has been limited by small sample sizes and fragmentary fossils. A new dental sample (n = 163) of the North American species Teilhardina brandti from PETM strata of the Bighorn Basin, Wyoming, documents previously unknown morphology and variation, prompting the need for a systematic revision of the genus. The P4 of T. brandti expresses a range of variation that encompasses that of the recently named, slightly younger North American species ‘Teilhardina gingerichi,’ which is here synonymized with T. brandti. A new partial dentary preserving the alveoli for P1-2 demonstrates that T. brandti variably expresses an unreduced, centrally-located P1, and in this regard is similar to that of T. asiatica from China. This observation, coupled with further documentation of variability in P1 alveolar size, position, and presence in the European type species T. belgica, indicates that the original diagnosis of T. asiatica is insufficient at distinguishing this species from either T. belgica or T. brandti. Likewise, the basal omomyiform ‘Archicebus achilles’ requires revision to be distinguished from Teilhardina. Results from a phylogenetic analysis of 1890 characters scored for omomyiforms, adapiforms, and other euarchontan mammals produces a novel clade including T. magnoliana, T. brandti, T. asiatica, and T. belgica to the exclusion of two species previously referred to Teilhardina, which are here classified in a new genus (Bownomomys americanus and Bownomomys crassidens). While hypotheses of relationships and inferred biogeographic patterns among species of Teilhardina could change with the discovery of more complete fossils, the results of these analyses indicate a similar probability that the genus originated in either Asia or North America.

Unilateral lung hypoplasia presenting in seventh decade of life: a rare case report

Pulmonary hypoplasia is a bronchopulmonary foregut anomaly in which gross morphology of the lung is preserved but there is decrease in the number or size of airways, vessels, and alveoli. Unilateral pulmonary hypoplasia is a rare clinical condition and most patients reported in the literature are newborns and infants, but patients may remain asymptomatic until late adolescent or till adulthood 65 years old male with parkinsonism was referred to our department with complaints of recent chest symptoms. Clinical examination revealed loss of lung volume in left hemithorax. CT scan thorax and bronchoscopy confirmed the diagnosis of left sided pulmonary hypoplasia. This case report highlights the possibility of pulmonary hypoplasia as one of the differential diagnoses in adult patients presenting with loss of lung volume and to the best of our knowledge he is the eldest patient so far reported.

Evidence of Normal Alveolar Size in Pediatric Generalized Lymphatic Anomaly.

Evidence of Normal Alveolar Size in Pediatric Generalized Lymphatic Anomaly.

Preemptive Mechanical Ventilation Based on Dynamic Physiology in the Alveolar Microenvironment: Novel Considerations of Time-Dependent Properties of the Respiratory System.

The acute respiratory distress syndrome (ARDS) remains a serious clinical problem with the current treatment being supportive in the form of mechanical ventilation. However, mechanical ventilation can be a double-edged sword; if set properly, it can significantly reduce ARDS associated mortality but if set improperly it can have unintended consequences causing a secondary ventilator induced lung injury (VILI). The hallmark of ARDS pathology is a heterogeneous lung injury, which predisposes the lung to a secondary VILI. The current standard of care approach is to wait until ARDS is well established and then apply a low tidal volume (LVt) strategy to avoid over-distending the remaining normal lung. However, even with the use of LVt strategy, the mortality of ARDS remains unacceptably high at ~40%. In this review, we analyze the lung pathophysiology associated with ARDS that renders the lung highly vulnerable to a secondary VILI. The current standard of care LVt strategy is critiqued as well as new strategies used in combination with LVt to protect the lung. Using the current understanding of alveolar mechanics (i.e. the dynamic change in alveolar size and shape with tidal ventilation) we provide a rationale for why the current protective ventilation strategies have not further reduced ARDS mortality. New strategies of protective ventilation based on dynamic physiology in the micro-environment (i.e. alveoli and alveolar ducts) are discussed. Current evidence suggests that alveolar inflation and deflation is viscoelastic in nature, with a fast and slow phase in both alveolar recruitment and collapse. Using this knowledge, a ventilation strategy with a prolonged time at inspiration would recruit alveoli and a brief release time at expiration would prevent alveolar collapse, converting heterogeneous to homogeneous lung inflation significantly reducing ARDS incidence and mortality.

Deposition of bolus and continuously inhaled aerosols in rhythmically moving terminal alveoli

The particle dynamics in an oscillating alveolus under tidal breathing can be dramatically different from those in a static alveolus. Despite its close relevance to pulmonary drug delivery and health risk from airborne exposure, quantifications of alveolar deposition are scarce due to its inaccessibility to in vivo measurement instruments, tiny size to replicate in vitro, and dynamic wall motions to model. The objective of this study is to introduce a numerical method to quantify alveolar deposition with continuous particle release in a rhythmically oscillating alveolus by integrating the deposition curves for bolus aerosols and use this method to develop correlations applicable in assessing alveolar drug delivery efficiency or dosimetry of inhaled toxicants. An idealized blind-end terminal alveolus model was developed with rhythmically moving alveolar boundary conditions in phase with tidal breathing. The dynamic wall expansion mode and magnitude were based on experimentally measured chest wall motions and tidal volumes. A well-validated Lagrangian tracking model was used to simulate the transport and deposition of inhaled micrometer particles. Large differences were observed between dynamic and static alveoli in particle motion, deposition onset, and final alveolar deposition fraction. Alveolar deposition of bolus aerosols is highly sensitive to breath-holding duration, particle release time, and alveolar dimension. For 1 µm particles, there exists a cut-off release time (zero bolus deposition), which decreases with alveolar size (i.e., 1.0 s in a 0.2-mm-diameter alveolus and 0.56 s in a 0.8-mm-diameter alveolus). The cumulative alveolar deposition was predicted to be 39% for a 0.2-mm-diameter alveolus, 22% for a 0.4-mm-diameter alveolus, and 10% for a 0.8-mm-diameter alveolus. A cumulative alveolar deposition correlation was developed for inhalation delivery with a prescribed period of drug release and the second correlation for the time variation of alveolar deposition of ambient aerosols, both of which captured the relative dependence of the particle release time and alveolar dimension.

Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype.

GWAS have repeatedly mapped susceptibility loci for emphysema to genes that modify hedgehog signaling, but the functional relevance of hedgehog signaling to this morbid disease remains unclear. In the current study, we identified a broad population of mesenchymal cells in the adult murine lung receptive to hedgehog signaling, characterized by higher activation of hedgehog surrounding the proximal airway relative to the distal alveoli. Single-cell RNA-sequencing showed that the hedgehog-receptive mesenchyme is composed of mostly fibroblasts with distinct proximal and distal subsets with discrete identities. Ectopic hedgehog activation in the distal fibroblasts promoted expression of proximal fibroblast markers and loss of distal alveoli and airspace enlargement of over 20% compared with controls. We found that hedgehog suppressed mesenchymal-derived mitogens enriched in distal fibroblasts that regulate alveolar stem cell regeneration and airspace size. Finally, single-cell analysis of the human lung mesenchyme showed that segregated proximal-distal identity with preferential hedgehog activation in the proximal fibroblasts was conserved between mice and humans. In conclusion, we showed that differential hedgehog activation segregates mesenchymal identities of distinct fibroblast subsets and that disruption of fibroblast identity can alter the alveolar stem cell niche, leading to emphysematous changes in the murine lung.

Targeting transglutaminase 2 partially restores extracellular matrix structure but not alveolar architecture in experimental bronchopulmonary dysplasia.

The generation, maturation and remodelling of the extracellular matrix (ECM) are essential for the formation of alveoli during lung development. Alveoli formation is disturbed in preterm infants that develop bronchopulmonary dysplasia (BPD), where collagen fibres are malformed, and perturbations to lung ECM structures may underlie BPD pathogenesis. Malformed ECM structures might result from abnormal protein cross-linking, in part attributable to the increased expression and activity of transglutaminase 2 (TGM2) that have been noted in affected patient lungs, as well as in hyperoxia-based BPD animal models. The objective of the present study was to assess whether TGM2 plays a causal role in normal and aberrant lung alveolarization. Targeted deletion of Tgm2 in C57BL/6J mice increased septal thickness and reduced gas-exchange surface area in otherwise normally developing lungs. During aberrant lung alveolarization that occurred under hyperoxic conditions, collagen structures in Tgm2-/- mice were partially protected from the impact of hyperoxia, where normal dihydroxylysinonorleucine and hydroxylysylpiridinoline collagen cross-link abundance was restored; however, the lung alveolar architecture remained abnormal. Inhibition of transglutaminases (including TGM2) with cysteamine appreciably reduced transglutaminase activity in vivo, as assessed by Nε -(γ-l-glutamyl)-l-lysine abundance and TGM catalytic activity, and restored normal dihydroxylysinonorleucine and hydroxylysylpiridinoline collagen cross-link abundance under pathological conditions. Furthermore, a moderate improvement in alveoli size and gas-exchange surface density was noted in cysteamine-treated mouse lungs in which BPD was modelled. These data indicate that TGM2 plays a role in normal lung alveolarization, and contributes to the formation of aberrant ECM structures during disordered lung alveolarization.

Acute lung injury: how to stabilize a broken lung

The pathophysiology of acute respiratory distress syndrome (ARDS) results in heterogeneous lung collapse, edema-flooded airways and unstable alveoli. These pathologic alterations in alveolar mechanics (i.e. dynamic change in alveolar size and shape with each breath) predispose the lung to secondary ventilator-induced lung injury (VILI). It is our viewpoint that the acutely injured lung can be recruited and stabilized with a mechanical breath until it heals, much like casting a broken bone until it mends. If the lung can be “casted” with a mechanical breath, VILI could be prevented and ARDS incidence significantly reduced.

AMD3100 ameliorates cigarette smoke-induced emphysema-like manifestations in mice.

We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPCs). To investigate whether a limited availability of HPCs may contribute to CS-induced lung injury, we used a Food and Drug Administration-approved antagonist of the interactions of stromal cell-derived factor 1 (SDF-1) with its chemokine receptor CXCR4 to promote intermittent HPC mobilization and tested its ability to limit emphysema-like injury following chronic CS. We administered AMD3100 (5mg/kg) to mice during a chronic CS exposure protocol of up to 24 wk. AMD3100 treatment did not affect either lung SDF-1 levels, which were reduced by CS, or lung inflammatory cell counts. However, AMD3100 markedly improved CS-induced bone marrow HPC suppression and significantly ameliorated emphysema-like end points, such as alveolar airspace size, lung volumes, and lung static compliance. These results suggest that antagonism of SDF-1 binding to CXCR4 is associated with protection of both bone marrow and lungs during chronic CS exposure, thus encouraging future studies of potential therapeutic benefit of AMD3100 in emphysema.

177 Effects of Metabolizable Protein Level on Mammary Gland Vascularity, Proliferation, and Alveoli Size during Late Gestation in Sheep.

177 Effects of Metabolizable Protein Level on Mammary Gland Vascularity, Proliferation, and Alveoli Size during Late Gestation in Sheep.

Stereological analysis of individual lung lobes during normal and aberrant mouse lung alveolarisation.

The quantitative assessment of the lung architecture forms the foundation of many studies on lung development and lung diseases, where parameters such as alveoli number, alveolar size, and septal thickness are quantitatively influenced by developmental or pathological processes. Given the pressing need for robust data that describe the lung structure, there is currently much enthusiasm for the development and refinement of methodological approaches for the unbiased assessment of lung structure with improved precision. The advent of stereological methods highlights one such approach. However, design-based stereology is both expensive and time-demanding. The objective of this study was to examine whether 'limited' stereological analysis, such as the stereological analysis of a single mouse lung lobe, may serve as a surrogate for studies on whole, intact mouse lungs; both in healthy lungs and in diseased lungs, using an experimental animal model of bronchopulmonary dysplasia (BPD). This served the dual-function of exploring BPD pathobiology, asking whether there are regional (lobar) differences in the responses of developing mouse lungs to oxygen injury, by examining each mouse lung lobe separately in the BPD model. Hyperoxia exposure resulted in decreased alveolar density, alveoli number, and gas-exchange surface area in all five mouse lung lobes, and increased the arithmetic mean septal thickness in all mouse lung lobes except the lobus cardialis. The data presented here suggest that - in healthy developing mice - a single mouse lung lobe might serve as a surrogate for studies on whole, intact mouse lungs. This is not the case for oxygen-injured developing mouse lungs, where a single lobe would not be suitable as a surrogate for the whole, intact lung. Furthermore, as the total number of alveoli can only be determined by an analysis of the entire lung, and given regional differences in lung structure, particularly under pathological conditions, the stereological assessment of the whole, intact lung remains desirable.

Design of biomimetic substrates for long-term maintenance of alveolar epithelial cells.

There is a need to establish in vitro lung alveolar epithelial culture models to better understand the fundamental biological mechanisms that drive lung diseases. While primary alveolar epithelial cells (AEC) are a useful option to study mature lung biology, they have limited utility in vitro. Cells that survive demonstrate limited proliferative capacity and loss of phenotype over the first 3-5 days in traditional culture conditions. To address this limitation, we generated a novel physiologically relevant cell culture system for enhanced viability and maintenance of phenotype. Here we describe a method utilizing e-beam lithography, reactive ion etching, and replica molding to generate poly-dimethylsiloxane (PDMS) substrates containing hemispherical cavities that mimic the architecture and size of mouse and human alveoli. Primary AECs grown on these cavity-containing substrates form a monolayer that conforms to the substrate enabling precise control over cell sheet architecture. AECs grown in cavity culture conditions remain viable and maintain their phenotype over one week. Specifically, cells grown on substrates consisting of 50 μm diameter cavities remained 96 ± 4% viable and maintained expression of surfactant protein C (SPC), a marker of type 2 AEC over 7 days. While this report focuses on primary lung alveolar epithelial cells, our culture platform is potentially relevant and useful for growing primary cells from other tissues with similar cavity-like architecture and could be further adapted to other biomimetic shapes or contours.

Determination of a potential quantitative measure of the state of the lung using lung ultrasound spectroscopy

B-lines are ultrasound-imaging artifacts, which correlate with several lung-pathologies. However, their understanding and characterization is still largely incomplete. To further study B-lines, lung-phantoms were developed by trapping a layer of microbubbles in tissue-mimicking gel. To simulate the alveolar size reduction typical of various pathologies, 170 and 80 µm bubbles were used for phantom-type 1 and 2, respectively. A normal alveolar diameter is approximately 280 µm. A LA332 linear-array connected to the ULA-OP platform was used for imaging. Standard ultrasound (US) imaging at 4.5 MHz was performed. Subsequently, a multi-frequency approach was used where images were sequentially generated using orthogonal sub-bands centered at different frequencies (3, 4, 5, and 6 MHz). Results show that B-lines appear predominantly with phantom-type 2. Moreover, the multi-frequency approach revealed that the B-lines originate from a specific portion of the US spectrum. These results can give rise to significant clinical applications since, if further confirmed by extensive in-vivo studies, the native frequency of B-lines could provide a quantitative-measure of the state of the lung.

Gas Exchange in the Prone Posture.

The prone posture is known to have numerous effects on gas exchange, both under normal conditions and in patients with ARDS. Clinical studies have consistently demonstrated improvements in oxygenation, and a multi-center randomized trial found that, when implemented within 48 h of moderate-to-severe ARDS, placing subjects in the prone posture decreased mortality. Improvements in gas exchange occur via several mechanisms: alterations in the distribution of alveolar ventilation, redistribution of blood flow, improved matching of local ventilation and perfusion, and reduction in regions of low ventilation/perfusion ratios. Ventilation heterogeneity is reduced in the prone posture due to more uniform alveolar size secondary to a more uniform vertical pleural pressure gradient. The prone posture results in more uniform pulmonary blood flow when compared with the supine posture, due to an anatomical bias for greater blood flow to dorsal lung regions. Because both ventilation and perfusion heterogeneity decrease in the prone posture, gas exchange improves. Other benefits include a more uniform distribution of alveolar stress, relief of left-lower-lobe lung compression by the heart, enhanced secretion clearance, and favorable right-ventricular and systemic hemodynamics.

The native frequency of B-lines artifacts may provide a quantitative measure of the state of the lung

B-lines are ultrasound-imaging artifacts, which correlate with several lung-pathologies. However, their understanding and characterization is still largely incomplete. To further study B-lines, ten lung-phantoms were designed. A layer of microbubbles was trapped in tissue-mimicking gel. To simulate the alveolar size reduction typical of various pathologies, 166 and 80-micrometer bubbles were used for phantom-type 1 and phantom-type 2, respectively. A normal alveolar diameter is around 280 micrometer. A LA332 linear-array connected to the ULA-OP platform was used for imaging. Standard ultrasound imaging at 4.5 MHz was performed. Next, a multi-frequency approach was used: images were sequentially generated using orthogonal sub-bands centered at different frequencies (3, 4, 5, and 6MHz). Results show that B-lines appear predominantly with the phantom-type 2, suggesting a link between increased artifact formation and the reduction of the alveolar size. Moreover, the multifrequency approach revealed that the B-lines have a native frequency: B-lines appeared with significantly stronger amplitude in one of the 4 images, and spectral-analysis confirmed B-lines to be centered at specific frequencies. These results can find relevant clinical application since, if confirmed by in-vivo studies, the native frequency of B-lines could serve as a quantitative-measure of the state of the lung.

Physiology in Medicine: Understanding dynamic alveolar physiology to minimize ventilator-induced lung injury.

Acute respiratory distress syndrome (ARDS) remains a serious clinical problem with the main treatment being supportive in the form of mechanical ventilation. However, mechanical ventilation can be a double-edged sword: if set improperly, it can exacerbate the tissue damage caused by ARDS; this is known as ventilator-induced lung injury (VILI). To minimize VILI, we must understand the pathophysiologic mechanisms of tissue damage at the alveolar level. In this Physiology in Medicine paper, the dynamic physiology of alveolar inflation and deflation during mechanical ventilation will be reviewed. In addition, the pathophysiologic mechanisms of VILI will be reviewed, and this knowledge will be used to suggest an optimal mechanical breath profile (MBP: all airway pressures, volumes, flows, rates, and the duration that they are applied at both inspiration and expiration) necessary to minimize VILI. Our review suggests that the current protective ventilation strategy, known as the “open lung strategy,” would be the optimal lung-protective approach. However, the viscoelastic behavior of dynamic alveolar inflation and deflation has not yet been incorporated into protective mechanical ventilation strategies. Using our knowledge of dynamic alveolar mechanics (i.e., the dynamic change in alveolar and alveolar duct size and shape during tidal ventilation) to modify the MBP so as to minimize VILI will reduce the morbidity and mortality associated with ARDS.

An experimental study of a rat model of emphysema induced by cigarette smoke exposure and the effect of Survanta therapy

The present study was performed to test the therapeutic effects of Survanta (an exogenous surfactant) on a Wistar rat model of emphysema. Thirty-five adult male Wistar rats were divided randomly into the following groups; control subgroups Ia&b (n=14); emphysematous model subgroups IIa,b&c (n=21) exposed to cigarette smoke (CS), received phosphate buffer solution (PBS) and Survanta respectively. The levels of serum myeloperoxidase (MPO), lung tissue lactate dehydrogenase (LDH), alkaline phosphatase (ALP) as well as antioxidants: catalase (CAT), superoxide dismutase (SOD) and oxidative stress: malondialdehyde (MDA) markers were measured. Immunohistochemical staining of the lung was applied with anti-P53, anti- tumor necrosis factor (TNFα) and anti-proliferating cell nuclear antigen (PCNA) to reveal the changes of the lung structure. The mean linear intercepts (MLI) of alveoli were measured to assess alveolar size. In emphysematous rats, the serum level of MPO and tissue LDH, ALP & MDA were significantly increased while; CAT and SOD were significantly decreased. Pictures analysis for all immunostains was clearly increased. In Survanta treated group, a significant improvement in all previously mentioned findings while; no improvement in alveolar diameter was detected. These results conclusively demonstrate that Survanta administration improves the inflammatory biochemical and histochemical parameters of the emphysematous lung.

Evaluation of pulmonary function in sportsmen playing different games

Background: The type of sports and the training and regular exercises make athletes to have an increase in pulmonary function test (PFT) parameters. Intensity and severity of sports performed by the athletes usually determine the extent of strengthening of the inspiratory muscles and the alveolar size with a resultant increase in the lung functions. Aims and Objectives: The aim of this study is to study the PFTs in male swimmers, marathoners, cricket players, and kabaddi players and to compare the same with matched sedentary control group. Materials and Methods: In this study, PFTs such as forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), maximum voluntary ventilation (MVV), and peak expiratory flow rate (PEFR) parameters were studied in 46 swimmers, marathoners, cricket players, and kabaddi players in the age group of 18-25 years. These parameters were compared with matched apparently normal healthy sedentary medical students using unpaired t-test. Results: In this study, a significant increase was observed in PFT parameters of swimmers, marathoners, cricket players, and kabaddi players than sedentary controls. The study group had a higher mean of percentage value of FVC, FEV1, MVV, and PEFR than controls. However, swimmers (P < 0.0001) had highest pulmonary parameters than marathoners, cricket players, and kabaddi players (

Parenchymal Airspace Profiling: Sensitive Quantification and Characterization of Lung Structure Evaluating Parenchymal Destruction.

Lung morphometry was introduced over 50 years ago to provide quantitative evaluation of the lung structure. The existing parameters, such as mean linear intercept and destructive index, suffer from simplistic data interpretation and a subjective data acquisition process. To overcome these existing shortcomings, parenchymal airspace profiling (PAP) was developed to provide a more detailed and unbiased quantitative method. Following the standard protocols of fixation, embedding, and sectioning, lung micrographs were: (1) marked with nonparenchymal area, preprocessed, and binarized under the researcher's supervision; (2) analyzed with a statistical learning method, Gaussian mixture model, to provide an unbiased categorization of parenchymal airspace compartments, corresponding to a single alveolus, alveolar sac, and ductal/destructive airspace; and (3) further quantified into morphometric parameters, including reference volume, alveolar count, and ductal/destructive fraction (DF) based on stereological principles. PAP was performed on hematoxylin and eosin-stained lung sections from mice and rabbits. Unbiased categorization revealed differences in alveolar size among several mouse strains (NZW/LacJ<AKR/J<A/J<C57BL/6J) and across species (mouse<rabbit). Further quantification indicates that parenchymal destruction, modeled in mouse lungs with 1-month smoke exposure, resulted in decreased alveolar count, increased DF, but no significant differences in mean linear intercept. DF also provides a robust measurement that is not biased by processing artifacts, magnification, or reference volume, which are common limitations in human lung biopsies or data obtained from different laboratories. PAP is a novel approach to lung morphometry that offers more detailed characterization of the lung structure, sensitivity, and robustness than presently used methods for evaluating parenchymal destruction.