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      Inhaled protein/peptide-based therapies for respiratory disease

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          Abstract

          Asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) are all chronic pulmonary diseases, albeit with different etiologies, that are characterized by airflow limitation, chronic inflammation, and abnormal mucus production/rheology. Small synthetic molecule-based therapies are commonly prescribed for all three diseases. However, there has been increased interest in “biologicals” to treat these diseases. Biologicals typically constitute protein- or peptide-based therapies and are often more potent than small molecule-based drugs. In this review, we shall describe the pros and cons of several different biological-based therapies for respiratory disease, including dornase alfa, a recombinant DNAase that reduces mucus viscosity and short palate lung and nasal epithelial clone 1 (SPLUNC1)-derived peptides that treat Na + hyperabsorption and rebalance CF airway surface liquid homeostasis.

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          Most cited references43

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          Airway mucus function and dysfunction.

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            Therapeutic antibodies for autoimmunity and inflammation.

            The development of therapeutic antibodies has evolved over the past decade into a mainstay of therapeutic options for patients with autoimmune and inflammatory diseases. Substantial advances in understanding the biology of human diseases have been made and tremendous benefit to patients has been gained with the first generation of therapeutic antibodies. The lessons learnt from these antibodies have provided the foundation for the discovery and development of future therapeutic antibodies. Here we review how key insights obtained from the development of therapeutic antibodies complemented by newer antibody engineering technologies are delivering a second generation of therapeutic antibodies with promise for greater clinical efficacy and safety.
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              The pathology of chronic obstructive pulmonary disease.

              The pathogenesis of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although tobacco smoking is the primary cause of this inhalation injury, many other environmental and occupational exposures contribute to the pathology of COPD. The immune inflammatory changes associated with COPD are linked to a tissue-repair and -remodeling process that increases mucus production and causes emphysematous destruction of the gas-exchanging surface of the lung. The common form of emphysema observed in smokers begins in the respiratory bronchioles near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD. The mechanism(s) that allow small airways to thicken in such close proximity to lung tissue undergoing emphysematous destruction remains a puzzle that needs to be solved.
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                Author and article information

                Contributors
                (919)966-7052 , robert_tarran@med.unc.edu
                Journal
                Mol Cell Pediatr
                Mol Cell Pediatr
                Molecular and Cellular Pediatrics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                2194-7791
                20 April 2016
                20 April 2016
                December 2016
                : 3
                : 16
                Affiliations
                [ ]Cystic Fibrosis and Pulmonary Diseases Research and Treatment Center, University of North Carolina, 7102 Marsico Hall, 125 Mason Farm Road, Chapel Hill, NC 27599-7248 USA
                [ ]Spyryx Biosciences, 801-9 Capitola Drive, Durham, NC 27713 USA
                [ ]Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599 USA
                Article
                44
                10.1186/s40348-016-0044-8
                4839019
                27098663
                fd75988b-12dc-4e7c-9c4f-89d13da81d0d
                © Fellner et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 15 January 2016
                : 13 April 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: HL108927
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/100000897, Cystic Fibrosis Foundation;
                Funded by: CF Trust INOVCF
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                cftr,biotherapies,neutrophil elastase (ne),inflammation,goblet cell metaplasia,nebulization,aerosolization,omalizumab,alpha-1-antitrypsin (aat),pulmozyme,mucociliary clearance,plunc,enac,bpifa1

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