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The respiratory system is constantly filtering through the external environment as humans breathe air. The airways must maintain the ability to clear inhaled pathogens, allergens, and debris to maintain homeostasis and prevent inflammation. The respiratory system subdivides into a conducting portion and a respiratory portion.  The majority of the respiratory tree, from the nasal cavity to the bronchi, is lined by pseudostratified columnar ciliated epithelium. The bronchioles are lined by simple columnar to the cuboidal epithelium, and the alveoli possess a lining of thin squamous epithelium that allows for gas exchange.

A number of diseases affect the respiratory system, which may be due to some degree of defective barrier function, a genetic mutation or an inflammatory process.  The following discussion outlines a few major diseases that affect respiration. Though not comprehensive, the importance of the proper functioning of the respiratory system and what occurs when a component is malfunctioning may be appreciated based on the few selected diseases discussed below. Asthma Asthma is an inflammatory disease that results in remodeling of the airway walls and causes a hyperreactivity response from environmental triggers, with the overproduction of mucus.[9] Asthma is a common and chronic health condition that affects both adults and children. The incidence is increasing and poses a strong concern for the impacts on health, economic burden, and environmental quality.[10] The cause of asthma is inflammation and edema of the airway that results in bronchospasms that block air entry into the lungs. It may be triggered by environmental factors such as dust, pollen, debris, and pathogens. The response to such triggers is bronchoconstriction, a process in which smooth muscle tightens and narrows the caliber of the bronchi and bronchioles, resulting in wheezing and shortness of breath. Bronchoconstriction occurs through a series of complex interactions between the mucosal epithelium, mast cells, smooth muscles, and the parasympathetic nervous system.[11] Cystic Fibrosis

The cause of asthma is inflammation and edema of the airway that results in bronchospasms that block air entry into the lungs. It may be triggered by environmental factors such as dust, pollen, debris, and pathogens. The response to such triggers is bronchoconstriction, a process in which smooth muscle tightens and narrows the caliber of the bronchi and bronchioles, resulting in wheezing and shortness of breath. Bronchoconstriction occurs through a series of complex interactions between the mucosal epithelium, mast cells, smooth muscles, and the parasympathetic nervous system.[11] Cystic Fibrosis Cystic fibrosis is a disease that once had a life expectancy of a few months and now has a median lifespan of about 40 years.[12]  It requires early diagnosis and optimized, mutation-specific treatment to maintain a quality of life for patients. Cystic fibrosis is an autosomal recessive pathology caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene, CFTR, most commonly the phe508del gene.[13] CFTR protein functions as an ion channel that regulates the amount of liquid through the secretion of chloride and inhibition of sodium absorption from exocrine glands. Chloride and bicarbonate transport play a role in regulating the thickness of the epithelial lining fluid, maintaining pH and sensing the presence of incoming pathogens or irritants. When uncontrolled, the increased sodium reabsorption causes water to follow and results in thick mucus secretions in nearly every organ system.[13] Though thousands of mutations of the CFTR have been described, each mutation manifests with varying effects on the gene and can result in differing phenotypic manifestations in patients, some resulting in more mild disease, others in much more severe prognosis. Cystic fibrosis may affect multiple organ systems, from the lungs to the digestive tract, the pancreas, the liver or the reproductive organs.[14] In the majority of patients, Cystic fibrosis leads to chronic, progressive lung disease and eventually death. Recurrent and infectious exacerbations lead to structural changes and damage to the respiratory system. These complications, in turn, dictate the treatment goals for this condition; to improve mucociliary clearance and to reduce the frequency of bacterial infections while aiming to enhance the quality of life.[12] Ciliary Dyskinesia

In the majority of patients, Cystic fibrosis leads to chronic, progressive lung disease and eventually death. Recurrent and infectious exacerbations lead to structural changes and damage to the respiratory system. These complications, in turn, dictate the treatment goals for this condition; to improve mucociliary clearance and to reduce the frequency of bacterial infections while aiming to enhance the quality of life.[12] Ciliary Dyskinesia The respiratory system relies heavily on the ability of cilia to move mucus and inhaled materials up into the proximal airways and away from the lower respiratory tract.  Primary ciliary dyskinesia (PCD) often presents with situs abnormalities, chronic sinus or pulmonary diseases, and abnormal sperm motility. Ciliary movement plays a role in many organs of the body. When impaired, this manifests in several organ systems. In the respiratory system, impaired mucociliary clearance occurs and results in recurrent infections of the sinuses, ears, and lungs. In the reproductive tract, both sperm motility from flagellae and the fimbriae of fallopian tubes are affected and often lead to infertility. Situs invertus occurs as a result of defective cilia during embryogenesis, as normal functioning cilia are required in the visceral rotation of organs.[4] The diagnosis of PCD, though complex and often missed or misdiagnosed, frequently involves analysis of cilia at an ultrastructural level and molecular genetic testing with one of the 33 genes associated with PCD.[15] The triad of chronic sinusitis, bronchiectasis, and situs invertus, resulting from ciliary dyskinesia are known as Kartagener syndrome.[4]