Citing Literature. Volume 26 , Issue 5 1 December Pages Related Information. Close Figure Viewer. Browse All Figures Return to Figure. Previous Figure Next Figure. Email or Customer ID. Forgot password? Old Password. New Password. Password Changed Successfully Your password has been changed. This is what is known as the breathable fraction of an aerosol.
Because particles are transported through the airway by an air current, their trajectories are affected by its characteristics. The air flow in the lungs is determined by the tidal volume and respiratory rate. Sbirlea-Apiou et al. However, the opposite is true in the last generations of the airway, where the deposition of particles is inversely proportional to this flow. This is due to that fact that the increased inspiratory flow reduces the residence time of the particles in the airway, therefore the effects of the severity and of the Brownian movement will be quite lower.
Obviously, a minimal inspiratory flow is necessary to drag the particles toward the interior of the bronchial tree.. The probabilities of particle deposition by impaction increase when the particles themselves are larger, the inspiratory airflow is greater, the angle separating the two branches is wider and the airway is narrower. In pathologies such as chronic bronchitis or asthma, which may alter the lung architecture with the appearance of bronchoconstriction, inflammation or secretion accumulation, the deposition of aerosolized drugs is modified.
The smaller caliber of the airway increases air speed, producing turbulence in places where the flow is usually laminar. The airway obstruction also means that the air tends to be displaced toward unobstructed areas, and therefore the drug will also tend to be deposited mostly in healthy areas of the lung. The particles of aerosolized drugs can be hygroscopic to a greater or lesser extent. Hygroscopicity is the property of some substances to absorb and exhale humidity depending on the setting in which they are found. This means that they can get larger or smaller in size upon entering into the airway, with the consequent modification in the deposition pattern compared to what was initially expected.
The diameter that a particle reaches after hygroscopic growth depends on its initial diameter, the intrinsic properties of the particle, and the environmental conditions in the airways. The mole fraction of water vapor contained in the airway has been demonstrated to be an important factor related with the increase in the MMAD of the aerosol particles. The hygroscopicity of molecules can be used to try to favor the deposition of inhaled drugs. Studies have been developed in which an aerosol was administered with a submicrometric or nanometric MMAD in order to reduce extrathoracic loss, taking advantage of later growth due to hygroscopicity, which enabled the particles to be retained within the lungs.
Once deposited in the airways, the particles can be carried by the mucociliary system, degraded or absorbed into the systemic circulation or the lymph ducts. This biphasic layer of mucus protects the epithelium from dehydration, helping to humidify the air and providing a protective barrier by trapping inhaled particles.
In cystic fibrosis CF , for example, very thick mucus is produced that does not correctly move along with the cilia. This is due to a mutation in the gene that codes the CFTR receptor, which regulates the passage of the chloride ion through the surface of the epithelial cells. The soluble particles are eliminated by absorptive mechanisms.
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The liposoluble molecules cross the respiratory epithelium by passive transport; the hydrosoluble molecules can cross the epithelial barrier either through the intercellular spaces or by active transport by mechanisms of endocytosis and exocytosis. The administration of inhaled drugs presents a series of advantages over systemic administration, making it preferable for the treatment of local diseases. High doses of a drug may be administered and rapidly absorbed through the epithelium of the airways, meaning that the inhaled administration enables a drug to act quickly, while minimizing systemic side effects.
If, however, an aerosolized drug is deposited at a suboptimal dose or in a region of the lung that is not affected by the pathology to be treated, the effectiveness of the treatment will be compromised. In the case of inhaled corticoids, the treatment seems to be more beneficial when more of the drug is dispersed throughout the lungs, as inflammatory cells such as eosinophils, lymphocytes, and macrophages are present throughout the respiratory tract and alveoli in asthma patients.
In the case of CF, there is chronic colonization by Pseudomonas aeruginosa , which tends to grow in the lumen of the airways, with a limited invasion of the pulmonary parenchyma.
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The infection starts in the bronchioles and moves toward more proximal airways 26 ; therefore, the ideal place for deposition of inhaled antibiotics would be throughout all the conducting airways. Mucus accumulations in certain areas can impede the antibiotics being deposited in regions behind the obstruction, which are presumably the most infected areas, and the effectiveness of the treatment is therefore compromised. The treatment of respiratory infections with inhaled steam has been traditionally done for as long as anyone can remember.
In , Schneider and Waltz developed an atomizer for mineral water sprays, but it was also used as an inhaler. The first portable inhaler was created in by Sales-Giron, a physician at a spa. It consisted of a manual liquid atomizer that enabled patients to administer inhaled balsamic infusions at home.
The discovery of adrenalin in by Takamine and Aldrich, and its inhaled administration for the first time in , 28 initiated the search for and administration of new inhaled drugs, leading to improvements in the devices for their administration. The devices currently used for the administration of inhaled drugs can be divided into three types: nebulizers, metered-dose inhalers, and dry powder inhalers.. There are basically two types of nebulizers: jet and ultrasonic. Jet nebulizers are based on the Bernouilli effect, according to which a compressed gas that passes through a narrow orifice creates a low-pressure area upon exiting.
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If at this low-pressure point we connect a tube that has a thin layer of liquid, the low pressure will cause this liquid to be aspirated in small droplets. Ultrasonic nebulizers use piezoelectric crystals that vibrate at a high frequency within the nebulizing chamber, transmitting the vibratory energy to the liquid that is in contact with it, converting said liquid into an aerosol.
Nebulizers can administer high doses of medication in patients who are not able to coordinate or cooperate and they are able to administer several substances mixed together in one same solution. Pulmonary deposition may be increased by modifying the patient's way of inhaling. Most patients inhale by using circulating volume.
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This can be done with ultrasonic nebulizers by making the piezoelectric crystal vibrate at a greater frequency; doing so with jet nebulizers can increase the compressed gas flow. Metered dose inhalers MDI are devices used to administer aerosolized drugs that emit a fixed dose of medication with each pulse.
They have a metallic chamber containing a suspension or solution of the drug with a liquid propellant that, at room temperature and atmospheric pressure, turns to its gaseous phase. A key piece in this system is the dosage valve, which releases at each pulse a controlled, reproducible dose of medication. In the past, the propellant used was chlorofluorocarbons CFC , but due to their harmful effects on the ozone layer, they have been banned by the United Nations. There are currently on the market MDI-HFA with salbutamol, fluticasone, beclomethasone, anticholinergics, and the combination of salmeterol—fluticasone.
One way to avoid the lack of coordination between the patient and the device are to use inhalation chambers that fit on the mouthpiece of the MDI. The aerosol goes into the chamber and the particles that are too big impact against its wall and are retained there, while the smaller particles remain in suspension within the chamber until they are inhaled by the patient. In addition, the space that the chamber provides between the MDI and the mouth of the patient allows the aerosol to lose speed, reducing impaction against the oropharynx. In this manner, local adverse effects are reduced and the lung deposition of the drug is increased.
They administer individual doses of drugs in a powder form contained in capsules that should be broken open before their administration unidose systems , or in blisters that move around in a device or have powder reservoirs multidose systems.. Other advantages of DPI are that they do not require propellants for their administration, which makes them more respectful of the environment, and many of them have an indicator of the doses remaining. The main drawbacks are that patients perceive to a lesser degree the drug entering the airway, which may complicate treatment compliance, and its price is generally higher than that of MDI.
DPI should be stored in a dry setting, as humidity favors the agglomeration of the powder that can obstruct the inhalation system. It has been demonstrated that if the inhalation technique is correct, there is no difference between the administration of a drug by means of DPI or MDI.
The dispersion of the powder into particles that enter into the inhaled fraction is produced by the formation of turbulent airflows inside the powder container, which break the powder agglomerations up into smaller-sized particles and separate the transport particles from the drug. The greater the resistance of the device, the more difficult it is to generate the inspiratory effort, but at the same time the deposition of the drug in the lungs is greater.
The first models of aerosol deposition in the lungs were based on very simple pulmonary morphologies. They used a small number of breathing conditions and a limited range of particle sizes, and were usually models confined to an area of the respiratory tract instead of models of the entire respiratory tract. In addition, they were limited to aerosols generated in industrial settings, like mining..
The first mathematic model of particle deposition was done in by Findeisen. This author, basing his study on the anatomical understanding of the age, divided the respiratory tract into only 9 generations, reaching the alveolar sacs and ducts.
oboitata.com/wp-includes/2020-04-08/buscador-de-personas-por-nombre-trackidsp-006.php This model assumed a series of dimensions, flow speeds, transit times, and types of ramification for each generation, and formulas were established in order to calculate the particle deposition in each generation according to the 3 basic mechanisms of deposition: impaction, sedimentation, and diffusion.
The main limitations of this model are that the airways above the trachea were not contemplated, and the anatomic simplicity of the lower airway model used.