Lung morphometry: a fallacy in the use of the counting principle.

Hansen, James E.; Ampaya, E. P.

doi:10.1152/jappl.1974.37.6.951

Cited by 27 publications

(7 citation statements)

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“…The respiratory zone is made up of functional units (some 15,000 or so in the lungs (Hansen & Ampaya 1974)). Each unit consists of a terminal bronchiole, a respiratory bronchiole, alveolar ducts and alveolar sacs: collectively referred to as the acinus.…”

Section: Pulmonary Defense Mechanismsmentioning

confidence: 99%

Scope and relevance of a pulmonary biopharmaceutical classification system AAPS/FDA/USP Workshop March 16-17th, 2015 in Baltimore, MD

Hastedt

Bäckman

Clark³

et al. 2016

AAPS Open

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The Biopharmaceutics Classification System (BCS), developed in the 1990s for oral immediate release drugs, is utilized by R&D scientists and regulators to streamline product development and regulatory approval timelines. This elegant, science-based approach is based on three in vitro parameters representing a combination of drug substance physicochemical and physiological properties with respect to oral administration; specifically a dose number, dissolution number, and absorption number. Interest in applying similar principles to pulmonary drug products is increasing. To date the focus has been on dissolution of drugs in the lung. A workshop co-sponsored by the AAPS, FDA, and USP was held in March 2015 in Baltimore to evaluate if a systematic framework to classify pulmonary drugs could be established, and the scope and relevance of such a classification scheme. The focus of the workshop was to address factors influencing drug delivery and action in the lungs rather than the development of a specific model or system. Presentations included: the history and evolution of the oral BCS (described as the "giBCS" by Gordon Amidon), lung physiology and the fate of inhaled drugs, regional aerosol deposition and dose, macroscopic clearance mechanisms, particle dissolution, drug permeability, absorption and their interplay with pharmacokinetics and pharmacodynamics. Background discussions were followed by three separate breakout sessions each focused on the BCS concepts of dose, dissolution, and absorption numbers as they would apply to pulmonary drug delivery. The workshop concluded that a classification system, if fully developed, would be a useful tool for formulators and discovery chemists. The scope of such a system, at this point in time, would not include aspects relevant to regulatory relief. The goals of the workshop were met by identifying an opportunity to develop a model to classify pulmonary drugs based on physicochemical attributes specific to lung physiology and drug delivery.

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Section: Pulmonary Defense Mechanismsmentioning

confidence: 99%

Scope and relevance of a pulmonary biopharmaceutical classification system AAPS/FDA/USP Workshop March 16-17th, 2015 in Baltimore, MD

Hastedt

Bäckman

Clark³

et al. 2016

AAPS Open

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“…This may be partly due to the problems inherent to the alveolar counting procedures-it is extremely difficult to properly define alveoli in histological sections. Three-dimensional reconstructions of lung parenchyma have proven that large errors could be made by misinterpretation of alveolar ducts and alveoli in light-microscopic sections (160). Also from a theoretical point of view alveolar counting is unreliable if alveoli alter their shape (67), which certainly happens during alveolar formation.…”

Section: Structural Features Of Adaptive Responsementioning

confidence: 99%

Development and Growth of the Human Lung

Burri

1985

Comprehensive Physiology

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“…For each lung lobe 2 sections were randomly chosen. The mean alveolar area of all alveoli which were posi tioned immediately subjacent to the visceral pleura (so as to avoid inclusion of alveolar ducts [21]), within a square field and at a standard magnification of 540X for 5 fields per section was determined.…”

Section: Methodsmentioning

confidence: 99%

Autoradiographic Localization and Effects of Exogenous Radioactively Labelled Surfactant in the Lung of the Prematurely Delivered Fetal Rabbit

Winter¹,

Mr³

et al. 1991

Neonatology

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Adult rabbit lung surfactant was radioactively labelled with [³H]palmitate and isolated by centrifugation. This material was instilled into the trachea of fetal rabbits prematurely delivered on the 27th gestational day. A similar preparation of unlabelled surfactant was used to measure the effects on pressure-volume characteristics in lungs of 27th day fetuses. Tissue sections were prepared from the lungs of all animals and morphometric and autoradiographic determinations made. Surfactant instillation improved pressure-volume relationships in fetal rabbit lungs. Histologically, although only the middle right lobe seemed to show significant qualitative improvement in expansion after surfactant treatment, quantitative assessment indicated that the surfactant preparation had significantly increased the mean alveolar cross-sectional areas in all three lobes of right lungs. In addition, distribution of autoradiographic grains indicated that 8–25% were located over the alveolar spaces while approximately half this percentage was present over tissue at the level of the alveolus. These results indicate that intratracheal instillation of surfactant supplements the endogenous surfactant at the level of the alveolus.

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Lung morphometry: a fallacy in the use of the counting principle.

Cited by 27 publications

References 0 publications

Scope and relevance of a pulmonary biopharmaceutical classification system AAPS/FDA/USP Workshop March 16-17th, 2015 in Baltimore, MD

Scope and relevance of a pulmonary biopharmaceutical classification system AAPS/FDA/USP Workshop March 16-17th, 2015 in Baltimore, MD

Development and Growth of the Human Lung

Autoradiographic Localization and Effects of Exogenous Radioactively Labelled Surfactant in the Lung of the Prematurely Delivered Fetal Rabbit

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