Respiratory care
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Airway mucus hypersecretion and secretion retention can result from inflammation, irritation, stimulation, or mucus-producing tumors. Secretion clearance can be furthered hampered by ciliary dysfunction and by weakness or restrictive lung disease, leading to an ineffective cough. There are a number of different mucoactive medications that have been used to reduce hypersecretion, make secretions easier to transport, or increase the efficiency of cough or mucus clearance. In this paper, I review the pathophysiology of secretory hyper-responsiveness and mucus hypersecretion and discuss the different aerosol medications that can be used to augment secretion clearance.
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Aerosol delivery equipment used to administer inhaled medications includes the nebulizer, positive expiratory pressure devices added to the nebulizer, and valved holding chambers (spacers). These devices are semi-critical medical devices, and as such, infection prevention and control (IPC) guidelines recommend that they be cleaned, disinfected, rinsed with sterile water, and air-dried. There is confusion surrounding the care of aerosol devices because of inconsistencies in the various published IPC guidelines, lack of a standard of practice among institutions and respiratory therapists (RTs), and manufacturer's instructions for use of these devices are not always compatible with guidelines or practice. ⋯ The mouthpiece/mask of disposable nebulizers should be wiped with an alcohol pad, the residual volume should be rinsed out with sterile water after use, and the nebulizer should be replaced every 24 h. The RT plays a significant and responsible role in providing and teaching aerosol therapy to patients. The RT and all stakeholders need to work together to provide a standard of care for the safe use of aerosol delivery devices.
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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.