Extrathoracic Region Research Articles

An in vitro technique for calculating the regional dosages of drugs delivered by an ultrasonic nebulizer

This study describes an in vitro technique for calculating the dosages of drug delivered to the different regions of the human lung by an ultrasonic nebulizer. The technique uses phase Doppler anemometry to measure particle sizes. Tidal breathing is simulated with a reciprocating pump. Inhalation is divided into an interval in which the sizes of the particles are nearly independent of the relative humidity (RH) of the inlet ambient air and a second interval in which the particles have evaporated. The numerical hygroscopic lung deposition model of Stapleton, Finlay, and Zuberbuhler ( J. Aerosol Med. 7, 325, 1994) is used to calculate the regional dosages. The methodology is applied to the DeVilbiss Aerosonic® ultrasonic nebulizer for 2.5 ml nebules of 1 mg ml −1 Ventolin®. The dosage of drug delivered to the extrathoracic, bronchial, and pulmonary regions is 0.42, 0.10, and 0.22 mg, respectively, at an inlet RH of 95% and 20°C. The corresponding values for RH = 3% are 0.39, 0.097, and 0.22 mg.

Size distributions and lung deposition of submicrometer particles from metered dose inhalers

The size distributions of the submicrometer particles generated from ten metered dose inhalers (MDIs) were determined by a high resolution particle sizer, which could measure the particles in the size range of 0.01 μm to 1 μm. The particle sizer contains a differential mobility analyzer (TSI 3071) and a condensation particle counter (TSI 3022). The median diameters ranged from 0.06-0.10 μm with a geometric standard deviation of 2. In addition, the surface median diameters and volume median diameters were found to be 0.30 μm and 0.45 μm, respectively. Moreover, none of the size distributions of the generated submicrometer particles fits log-normal distributions. The deposition probabilities of the submicrometer particles in the airways were evaluated. It was observed that the average deposition percentages of the particles in the alveolar, tracheobronchial, and extrathoracic regions are 32%, 4%, and 4%, respectively. Understanding the deposition of submicrometer particles from MDIs should benefit the clinical practice in inhalation therapy.

An in vitro method for determining regional dosages delivered by jet nebulizers.

A methodology for determining the regional dosages delivered to the respiratory tract by a jet nebulizer is presented and applied to the DeVilbiss PulmoNeb disposable nebulizer delivering a 2.5 ml nebule of Ventolin (1 mg/ml salbutamol sulphate). Results are obtained both with tapping of the nebulizer, which enhances nebulizer performance, and without tapping. The nebulizer output is characterised by measuring the total mass and the mass of solids leaving the nebulizer per minute, and performing a control volume analysis of the nebulizer. Particle size distributions are determined by phased Doppler anemometry. Deposition probabilities are calculated using a semi-empirical model for the deposition of hygroscopic aerosol particles in healthy adult Caucasian males. Deposition probabilities are then converted to regional dosages using the measured nebulizer output characteristics. The regional dosages (% of initial dose in nebulizer) of Ventolin delivered to the extrathoracic, bronchial, and alveolar regions of the respiratory tract are 0.248 +/- 0.005 mg (9.9%), 0.034 +/- 0.001 mg (1.4%), and 0.071 +/- 0.002 mg (2.8%) respectively when the nebulizer was tapped during operation, and 0.184 +/- 0.005 mg (7.4%), 0.025 +/- 0.001 mg (1.0%), and 0.052 +/- 0.002 mg (2.1%) when tapping was not used. This methodology provides a well controlled and rapid means of comparing the effectiveness of different nebulizers for use in aerosol therapy.

Sampling and chemical characterization of aerosols in workplace air

Abstract

Disposition of Mulberry Pollen in the Human Respiratory System: A Mathematical Model

Abstract Inhaled particle deposition sites must be identified to effectively treat human airway diseases. We have determined distribution patterns of a selected aeroallergen, mulberry pollen, among human extrathoracic (ET: i.e., oronasopharyngeal) regions and the lung. A predictive model validated by inhalation exposure data from human subjects was utilized. Deposition locations were primarily functions of (1) mulberry particle parameters (geometric size, 11–18 μm; shape, spherical; and density, 1.14 g cm−3), and (2) mode of breathing. In the general population, two styles of inhalation are prevalent, normal augmentors (NAs) and mouth breathers (MBs). Their clinical definitions are based on intra-ET airflow divisions. For a NA-mode breathing sedentary (minute ventilation = VE = 10 L min−1) adult, 93% of inhaled mulberry pollen was removed by the ET compartment and 7% collected within the lung. For a MB, the respective deposition efficiencies were 75% and 25%. To apply the model, we used a daily springtime...

The Size of Fibrous Aerosols

Abstract The deposition of fibrous aerosols in the human respiratory tract is an important subject in view of the health effects associated with the inhalation of the fibers. The estimation of the regional deposition of compact aerosols uses aerodynamic equivalent diameter as the size parameter. In the case of fibers, the four deposition mechanisms, impaction, interception, sedimentation, and diffusion, are not unique functions of one size parameter, in that each deposition mechanism involves the aspect ratio of the fibers. In this article, a simple, single relationship between the fiber diameter and aspect ratio is sought for the characterization of fibers in terms of deposition in the respiratory tract. The comparisons of deposition predictions are made by using the equations that describe deposition compact particles in the extra-thoracic, tracheobronchial, and pulmonary regions of the human respiratory tract in conjunction with different fiber size definitions including equivalent aerodynamic, impacti...

Dosimetry Model for Bronchial and Extrathoracic Tissues of the Respiratory Tract

The Task Group to Review the Lung Model for the International Commission on Radiological Protection (ICRP) is proposing to revise the dosimetry model for the respiratory tract on the basis of the relative sensitivities of the various tissue components. If all tissues within the lung were to receive the same radiation dose, it is considered that approximately 80% of fatal lung cancers would arise in the bronchi, about 15% in the bronchioles. and only about 5% in alveolar - interstitial tissue, with a very small fraction of cancers (less than 0.1%) in lymph nodes. Tissues in the nose, nasopharynx, mouth, oral pharynx, and larynx are less sensitive than the bronchi or bronchioles, but their contribution to the radiation detriment would not necessarily be negligible if they were to receive a higher equivalent dose than the thoracic airways or other organs. This paper outlines the model proposed by the task group to evaluate doses received by presumed target cells in the various epithelial tissues, to take account of non-uniform irradiation by a.ß. positron and electron emitters, and to derive and equivalent dose for the lung and the extrathoracic region of the respiratory tract for use in ICRPs recommended system of dose limitation. Examples are given of equivalent doses to the respiratory tract that are calculated for several types of a.ß emitter. These new values are compared with the equivalent doses calculated using the ICRP Publication 30 lung model. It is emphasised that the current version of the lung model described here is still provisional.

Deposition patterns of ragweed pollen in the human respiratory tract

Abstract Inhaled particle deposition sites must be identified to effectively treat human airway diseases. We have determined distribution patterns of a selected aeroallergen, ragweed pollen, among human extrathoracic (ET: i.e., oro-nasopharyngeal) regions and the lung. A predictive model validated by inhalation exposure data from human subjects was utilized. Deposition locations were primarily functions of 1. ragweed particle parameters (size: 14–20 μm, shape: spherical, and density: 1.14 g cm-3) and 2. mode of breathing. In the general population, two styles of inhalation are prevalent: normal augmentors (NAs), and mouth breathers (MBs), their clinical definitions are based on intra-ET airflow divisions. For a NA-mode breathing, sedentary (10 L min-1) adult, 88% of inhaled ragweed pollen was removed by the ET compartment and 7% collected within the lung. For a MB, the respective deposition efficiencies were 68% and 25%. To apply the model, we used a daily springtime ragweed pollen concentration of 300 gr...

The Current Approach of the ICRP Task Group for Modeling Doses to Respiratory Tract Tissues

For radiation protection purposes, the International Commission on Radiological Protection (ICRP) Task Group proposes to apportion radiation risk within the respiratory tract according to the tumor mortality rates observed in the different anatomical regions. This approach requires that doses absorbed by extrathoracic tissues must be considered, in addition to those in the lung. For the extrathoracic region, the tissues at highest potential risk are the pharyngeal parts of the nasopharynx and oropharynx and a part of the larynx. In the lung, all tissues are potentially at risk, and it is necessary to consider doses absorbed by bronchial tissues, the lung parenchyma, and lymph nodes. This paper outlines the methods proposed by the Task Group to evaluate the heterogeneous doses absorbed by sensitive cells in these tissues from radioactive decays of alpha-emitters. The objective is to evaluate doses to broad regions of the respiratory tract, where the regions are defined to reflect substantial differences in potential risk when taking into account deposition and clearance behavior. The Task Group proposes to represent the respiratory tract by three generic regions: an extrathoracic region and two thoracic regions, one clearing fast and one slowly. The models of aerosol deposition and clearance applied for each region are outlined. To illustrate the use of the model, doses are evaluated for the key cases of short-lived radionuclides and long-lived insoluble alpha-emitters and are discussed with regard to current ICRP recommendations.

Human respiratory tract model for radiological protection: a revision of the ICRP Dosimetric Model for the Respiratory System.

In 1984, the International Commission on Radiological Protection (ICRP) appointed a task group of Committee 2 to review and revise, as necessary, the ICRP Dosimetric Model for the Respiratory System. The model was originally published in 1966, modified slightly in Publication No. 19, and again in Publication No. 30 (in 1979). The task group concluded that research during the past 20 y suggested certain deficiencies in the ICRP Dosimetric Model for the Respiratory System. Research has also provided sufficient information for a revision of the model. The task group's approach has been to review, in depth, morphology and physiology of the respiratory tract; deposition of inhaled particles in the respiratory tract; clearance of deposited materials; and the nature and specific sites of damage to the respiratory tract caused by inhaled radioactive substances. This review has led to a redefinition of the regions of the respiratory tract for dosimetric purposes. The redefinition has a morphologic and physiological basis and is consistent with observed deposition and clearance of particles and with resultant pathology. Regions, as revised, are the extrathoracic (E-T) region, comprising the nasal and oral regions, the pharynx, larynx, and upper part of the trachea; the fast-clearing thoracic region (T[f]), comprising the remainder of the trachea and bronchi; and the slow-clearing thoracic region (T[s]), comprising the bronchioles, alveoli, and thoracic lymph nodes. A task group report will include models for calculating radiation doses to these regions of the respiratory tract following inhalation of representative alpha-, beta-, and gamma-emitting particulate and gaseous radionuclides. The models may be implemented as a package of computer codes available to a wide range of users. This should facilitate application of the revised human respiratory tract model to worldwide radiation protection needs.

Extrinsic pathways of the adrenergic innervation of the guinea-pig trachealis muscle.

Origins and extrinsic pathways of the adrenergic innervation of the guinea-pig trachealis muscle were studied using fluorescence histochemical techniques. Bilateral superior cervical ganglionectomy caused a marked reduction in the adrenergic innervation of the extra-thoracic region, which suggests that these ganglia are a major source of adrenergic innervation to this muscle. Combined anterior and posterior transection of the recurrent laryngeal nerves also caused a marked reduction in the density of adrenergic fibres in the extra-thoracic trachealis muscle. Crushing of these nerves revealed adrenergic fibres running both anteriorly and posteriorly. The majority of these adrenergic nerves were lost after superior cervical ganglionectomy and thus the fibres running in both directions originate in the superior cervical ganglion. Antero-posteriorly directed fibres entered the recurrent laryngeal nerve from the superior cervical ganglion via an anastomosis at the level of the cricoid cartilage, while those running postero-anteriorly entered the recurrent laryngeal nerve posteriorly from the vagus nerve and these adrenergic fibres were lost after cervical vagotomy.

Malignant Thymoma with Distant Metastases: A Case Report and Review of the Literature

A patient, a 46-year-old female, with a malignant thymoma spreading to the extrathoracic region is described. She underwent a thoracotomy and received radiation therapy, but the myasthenic symptoms did not disappear. A metastatic thymoma of the right mandibula was removed 9 months after thoracotomy. Further examination revealed metastatic thymomas of the bone and liver. After the operation the patient received combination chemotherapy (vincristine, cyclophosphamide, 6-mercaptopurine, prednisone) and remained asymptomatic for 31 months. She was found to have a metastatic thymoma in the occipital lobe of the brain 3.5 years after thoracotomy, and died from infection of the lung. Distant metastases and chemotherapy in malignant thymoma are reviewed.

Alveolar deposition of inhaled particles in humans.

Total deposition data were used to estimate the efficiency of the alveolar region of the human respiratory tract to collect aerosol particles. When inspired at a flow rate of 250 cm3s-1 (1000 cm3s-1) through the mouth particles of 2.6 micrometers (1.7 micrometer) aerodynamic diameter are the largest particles which pass through the extrathoracic and bronchial region without being deposited. They are deposited in the alveolar region only.

GIANT LYMPH NODE HYPERPLASIA IN EXTRATHORACIC LYMPH NODES‐REPORT OF TWO CASES WITH A REVIEW OF THE LITERATURE

Two cases of giant lymph node hyperplasia occurring in extrathoracic regions are reported, one on the right side of the supra‐and infraclavicular fossa, pectoral muscle and axilla, and the other in the right groin. In both cases enlarged masses were removed several times having arisen from slow growing preexisting smaller masses. The histological features of all masses were identical, although removed at different times during the course of the disease. Both cases were characterized by marked proliferation of lymphoid follicles and capillaries, and infiltration of plasma cells. Fibrous thickening and hyalinization of the capillaries varied somewhat in severity from one case to the other. It is thought that the histogenesis of the lesion is related to chronic inflammation rather than to a hamartoma.