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.
Highlights
For hundreds of years, the pulmonary system has been used to deliver pharmacologically active compounds to the body [47]
Inhaled nicotine is readily absorbed across the pulmonary epithelia into the bloodstream where it can exert its psychotropic effects on the brain [5]
cystic fibrosis (CF) lung disease is characterized by the accumulation of dehydrated/viscous mucus, leading to chronic infection/inflammation goblet cell metaplasia, neutrophilia, and bronchiectasis [26, 38]
Summary
The pulmonary system has been used to deliver pharmacologically active compounds to the body [47]. For many peptides/proteins, an inability to cross the respiratory epithelium after inhaled delivery may be advantageous as it would result in a high ratio of lung to systemic bioavailability and would reduce off-target effects [25]. Biological therapeutics, including proteins (e.g., antibodies, enzymes) and peptides, show considerable promise and are emerging as alternatives to small molecule-based drugs [19].
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