Deposition and cellular interaction of cancer-inducing particles in the human respiratory tract: Theoretical approaches and experimental data

Our plain-English summary of Deposition and cellular interaction of cancer-inducing particles in the human respiratory tract: Theoretical approaches and experimental data, by R. Sturm (Thoracic Cancer, 2010).

The study

• Author: R. Sturm
• Journal: Thoracic Cancer
• Published: 2010;1(4):141-152
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhaled particles that are deposited on the epithelial surface of the human respiratory tract (HRT) may act as serious health hazards, in the worst case inducing the development of various types of lung cancer. In the past, several particle types, such as asbestos fibers, hard wood dust and cigarette smoke were identified and classified as human carcinogens. Due to their different physical and chemical properties these particles are characterized by remarkable discrepancies concerning their transport, deposition, and epithelial interaction in the HRT. In order to continuously increase the knowledge on carcinogenic particle behavior in the HRT, theoretical models describing single stages of particulate action in the lung airways were developed over the last few decades. With the help of these mathematical approaches physical characteristics of aerosolized drugs as well as protocols of inhalative therapies for the treatment of lung diseases could be significantly optimized. In addition, new experimental setups for the enlightenment of possible mechanisms underlying particle-lung interaction were, among other things, founded upon the results of theoretical computations. This review summarizes the efforts and advances of theoretical lung modeling from the early 1970s till today, thereby mainly directing the attention to the simulation of carcinogenic particle behavior in the HRT.

© Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.

In plain English

This was an invited review by a single author at the University of Salzburg, Austria. It covered mathematical models and experiments, from the early 1970s to 2010, on how inhaled cancer-causing particles settle in and are cleared from the human respiratory tract. It reported no new asbestos data. Citing earlier work, it named asbestos fibers among recognized carcinogens, with the highest cancer risk given for crocidolite. The review explained that long, thin fibers can have a greatly reduced aerodynamic diameter, which affects where they deposit. In the data it reviewed, total deposition was lowest for particles of about 0.5 to 1 micrometre. Nose breathing raised deposition above the chest by 7 to 50% compared with mouth breathing. Intermediate-sized particles reached the deepest parts of the lung. Slow bronchial clearance half-times were given as five to 20 days, and alveolar half-times as 50 to 300 days. The author concluded that a particle's cancer potential depends partly on how much deposits, where, and how long removal takes. The author noted that clearance experiments used only spherical test particles.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Invited narrative review of theoretical (mathematical) models and experimental data on particle deposition and clearance in the human respiratory tract
• Who was studied: No study population. The review covered models and experimental data on carcinogenic particle behavior in the human airways and alveoli, published from the early 1970s to 2010.
• Exposure: Inhaled carcinogenic particles in general: asbestos fibers (crocidolite cited from earlier work as carrying the highest cancer risk), respirable crystalline silica, hard wood dusts, ambient particulate matter, ultrafine particles and airborne radionuclides. No asbestos doses or exposed groups were studied.
• Main results:
  • For long but thin fibers, the volume-equivalent diameter can lower the calculated aerodynamic diameter by a large amount. The review states such particles often deposit on airway walls through collisions with air molecules.
  • Total deposition in the respiratory tract followed a U-shaped curve, lowest for aerodynamic diameters between 0.5 and 1 micrometre (printed as 'mm' in the text).
  • Nose breathing produced extrathoracic deposition (nose, throat, larynx) 7 to 50% higher than mouth breathing.
  • Intermediate-sized particles (0.05 to 1 micrometre, printed as 'mm') penetrated to the most terminal parts of the lung. Ultrafine and large particles not filtered above the chest mainly deposited in the bronchial airways.
  • The fraction of particles still in the lungs 24 hours after exposure peaked at about 80%, for particles around 0.1 micrometre. Very small and large particles had values around 25% (a comparison symbol is lost in the text).
  • Clearance mechanisms needed between 10 and 70 hours to remove half of the particles deposited in the bronchial airways and alveoli.
  • Half-times used in clearance models were five to 20 days for slow bronchial clearance and 50 to 300 days for alveolar clearance.
• The authors' conclusion: The author concluded that the potential of inhaled particles to act as carcinogens depends, among other things, on three factors: their ability to deposit in sufficient quantities, where in the respiratory tract they deposit, and the time needed to remove them. Distally deposited, intermediate-sized particles undergo slow clearance, which the author said enhances their chance to act as carcinogens.
• Limitations the authors state:
  • Clearance experiments were carried out only with spherical test particles.
  • The dependence of clearance mechanisms on particle size had been addressed only by theoretical considerations.
  • Shape factors and aerodynamic diameters of irregular aggregates rest on more or less reliable approximation formulae.
  • Knowledge of how particles interact with lung fluids, cells and tissues was still basic.

Topics

Medical terms in this study, explained in our Lexicon: Deposition, Lung Cancer, Carcinogenic.

Related studies

• Human and experimental data on translocation of asbestos fibers through the respiratory system — J. Bignon, G. Monchaux, et al. (1979)
• Estimation of fibrous aerosol deposition in upper bronchi based on experimental data with model bifurcation — T. Myojo, M. Takaya (2001)
• Studies on the deposition of inhaled fibrous material in the respiratory tract of the rat and its subsequent clearance using radioactive tracer techniques. 1. UICC crocidolite asbestos — J.C. Evans, R.J. Evans, et al. (1973)
• Studies on the deposition of inhaled fibrous material in the respiratory tract of the rat and its subsequent clearance using radioactive tracer techniques — A. Morgan, J.C. Evans, et al. (1975)
• Deposition of inhaled asbestos and man-made mineral fibres in the respiratory tract — A. Morgan (1995)
• In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts — B.T. Mossman (1983)

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