Respiratory care
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Aerosolized medications are routinely used for the treatment of critically ill patients. This paper reviews aerosol delivery devices with a focus on issues related to their performance in pulmonary critical care. Factors affecting aerosol drug delivery to mechanically ventilated adults and spontaneously breathing patients with artificial airways are reviewed. Device selection, optimum device technique, and unmet medical needs of aerosol medicine in pulmonary critical care are also discussed.
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Imaging techniques have been used extensively to study the delivery of inhaled medications. Deposition scintigraphy involves the quantification of deposited aerosol dose and is performed using 2-dimensional planar or 3-dimensional positron emission tomography (PET) or single-photon-emission computed tomography (SPECT) imaging techniques. Planar techniques have an extensive history of use, and quantification methods are well established. ⋯ These studies include measurements of ventilation, mucus and cough clearance, and, more recently, liquid absorption in the airways. Clearance measurements have been used to assess therapeutic response in conditions such as cystic fibrosis. Future directions in aerosol-based imaging are likely to include use of novel probes to measure new physiological processes in the lung, more thorough integration of anatomical imaging, and use of multiple probes to simultaneously image drug and disease or interacting physiological processes.
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Inhalation therapy has matured to include drugs that: (1) deliver nucleic acids that either lead to the restoration of a gene construct or protein coding sequence in a population of cells or suppress or disrupt production of an abnormal gene product (gene therapy); (2) deliver peptides that target lung diseases such as asthma, sarcoidosis, pulmonary hypertension, and cystic fibrosis; and (3) deliver peptides to treat diseases outside the lung whose target is the systemic circulation (systemic drug delivery). These newer applications for aerosol therapy are the focus of this paper, and I discuss the status of each and the challenges that remain to their successful development. Drugs that are highlighted include: small interfering ribonucleic acid to treat lung cancer and Mycobacterium tuberculosis; vectors carrying the normal alpha-1 antitrypsin gene to treat alpha-1 antitrypsin deficiency; vectors carrying the normal cystic fibrosis transmembrane conductance regulator gene to treat cystic fibrosis; vasoactive intestinal peptide to treat asthma, pulmonary hypertension, and sarcoidosis; glutathione to treat cystic fibrosis; granulocyte-macrophage colony-stimulating factor to treat pulmonary alveolar proteinosis; calcitonin for postmenopausal osteoporosis; and insulin to treat diabetes. The success of these new aerosol applications will depend on many factors, such as: (1) developing gene therapy formulations that are safe for acute and chronic administrations to the lung, (2) improving the delivery of the genetic material beyond the airway mucus barrier and cell membrane and transferring the material to the cell cytoplasm or the cell nucleus, (3) developing aerosol devices that efficiently deliver genetic material and peptides to their lung targets over a short period of time, (4) developing devices that increase aerosol delivery to the lungs of infants, (5) optimizing the bioavailability of systemically delivered peptides, and (6) developing peptide formulations for systemic delivery that do not cause persistent cough or changes in lung function.
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Aerosolized medications are frequently used in the pulmonary function laboratory. The 2 most common implementations are bronchodilators and bronchial challenge agents. Bronchodilator administration is not well standardized, largely because of the various methods of delivery available for clinical practice. ⋯ Interpretation of pre- and post-bronchodilator studies is confounded by the definitions of airway obstruction and bronchodilator responsiveness. Protocols for administering bronchial challenge aerosols (methacholine, mannitol, hypertonic saline) are well defined but are susceptible to some of the same problems that limit comparison of bronchodilator techniques. Bronchial challenges with inhaled aerosols are influenced not only by the delivery device but by the patient's breathing pattern, particularly in protocols that include deep inspiratory efforts.
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Nonadherence to prescribed medications results in disease instability and poor clinical control, with increases in hospital admissions, emergency room visits, school/work absenteeism, morbidity, and mortality. Poor patient adherence to therapy can be due to lack of cognition, competence, or contrivance. Patients who have not been trained or fail to understand use of drug and device combinations (cognition) often do not have the ability to use an aerosol device correctly (competence). ⋯ Ensuring effective aerosol therapy and optimizing its role in disease management involve not only delivery of aerosolized medications to the lungs, but also understanding why, when, and how to use the medications, competence to use the device, motivation to adhere to therapy, and not contriving to use the device in a way that will prevent effective drug delivery. This paper explains some of the problems with patient education and adherence to aerosol therapy and suggests strategies to evaluate, monitor, and improve patient adherence effectively in primary care. Factors affecting patient adherence to prescribed medications, effective educational interventions, and strategies to promote patient adherence to aerosol therapy are also discussed.