Porth's Essentials of Pathophysiology, 4e

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Disorders of Ventilation and Gas Exchange

C h a p t e r 2 3

to collect the sweat followed by chemical analysis of its chloride content, remains the standard approach to diagnosis. Newborns with CF have elevated blood levels of immunoreactive trypsinogen, presumably because of secretory obstruction in the pancreas. A variety of new- born screening tests are in place to identify infants with cystic fibrosis, most of which consist of a combination of immunoreactive trypsinogen and limited DNA analy- sis. These tests can be done on blood spots collected for routine newborn screening tests. Treatment measures are directed toward early and aggressive measures to slow progression of secondary organ dysfunction and sequelae such as chronic lung infection and pancreatic insufficiency. 51 They include the use of antibiotics to prevent and manage infections, the use of chest physical therapy (chest percussion and pos- tural drainage) and mucolytic agents to prevent airway obstruction, and nutritional therapy including pancre- atic enzyme replacement. Routine laboratory evaluations are key to assessing pulmonary function and response to therapeutic interventions. These studies include radio- logic examinations, pulmonary function testing, and microbiologic cultures of respiratory secretions. Appropriate antibiotic therapy directed against bacte- rial pathogens isolated from the respiratory tract is an essential component in the management of CF lung dis- ease. Antibiotics are initially used to prevent colonization with P. aeruginosa; they are used as maintenance therapy once the airways are colonized with P. aeruginosa and other organisms such as S. aureus; and they are adminis- tered as aggressive treatment during acute exacerbations of pulmonary symptoms caused by infections. 51 To avoid adverse effects and to obtain high airway concentrations, the inhalation route is often used as an option for home delivery of these agents, with other routes of delivery being used during periods of progressive symptoms. The abnormal viscosity of airway secretions is attrib- uted largely to the presence of polymorphonuclear white blood cells and their degradation products. A purified recombinant human deoxyribonuclease (rhDNase), an enzyme that breaks down these products, has been developed. 54 Clinical trials have shown that the drug, which is administered by inhalation, can decrease pul- monary symptoms and reduce the frequency of respi- ratory exacerbations. Although many persons benefit from the therapy, the drug is costly, and recommenda- tions for its use are evolving. Up to 90% of patients with CF have complete loss of exocrine pancreatic function and inadequate diges- tion of fats and proteins. They require supplemental vitamins and minerals and enteric-coated, pH-sensitive pancreatic enzyme supplements. At one time, a low-fat, high-protein, high-calorie diet was recommended. With the advent of improved pancreatic enzyme products, however, normal amounts of fat in the diet are usually tolerated and preferred. Progress of the disease is variable. Improved medi- cal management has led to longer survival. 49,51,52 Today, many people with the disease can expect to live into their 40s and beyond. Lung transplantation is being used as a treatment for persons with end-stage lung disease.

The last 10 years have seen promising results from research into the management of cystic fibrosis using small molecules called cystic fibrosis transmembrane regulator protein (CFTR) modulators designed to increase the time the CFTR channels in the cell surface remain open. 53

SUMMARY CONCEPTS

■■ Obstructive airway disorders due to bronchial smooth muscle hyperreactivity or changes in bronchial wall structure, injury to the mucosal lining of the airways, or excess respiratory tract secretions are characterized by limitation in movement of atmospheric air into and out of the gas exchange portion of the lung. ■■ Bronchial asthma is a chronic disorder of the airways that causes reversible episodes of airway obstruction due to bronchial smooth muscle hyperreactivity and airway inflammation. Extrinsic (or atopic) asthma is a type I hypersensitivity reaction triggered by an allergen; whereas intrinsic asthma is triggered by respiratory tract infections, exercise, drugs and chemicals, air- borne pollutants, and gastroesophageal reflux. ■■ An asthmatic episode is characterized by two types of responses—acute and late phase.The acute-phase response results in immediate bronchoconstriction on exposure to an inhaled antigen and usually subsides within 90 minutes. The late-phase response develops 4 to 8 hours after exposure to an asthmatic trigger; and involves inflammation and increased airway responsiveness that prolong the attack and cause a vicious cycle of exacerbations. ■■ Chronic obstructive pulmonary disease (COPD) encompasses two types of obstructive airway disease: emphysema, with enlargement of air spaces and destruction of lung tissue, and chronic obstructive bronchitis, with increased mucus production, obstruction of small airways, and a chronic productive cough. Persons with COPD often have overlapping features of both emphysema and chronic bronchitis, and both are manifested by eventual mismatching of ventilation and perfusion. As the conditions advance, signs of respiratory distress and impaired gas exchange become evident, with development of hypercapnia and hypoxemia. ■■ Bronchiectasis is an uncommon form of COPD that is characterized by an abnormal dilation of the large bronchi associated with infection and destruction of the bronchial walls.

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