ACUTE RESPIRATORY DISTRESS SYNDROME
Acute respiratory distress syndrome (ARDS) is characterized by pulmonary edema and refractory hypoxemia. ARDS can lead to multiple organ failure and has a high rate of mortality. Increased capillary permeability is the hallmark of ARDS. Diagnosis is often difficult, and death can occur within 48 hours of onset if ARDS is not promptly diagnosed and appropriately treated.
The most common cause of ARDS is sepsis. Infection, including severe sepsis and pneumonia, is the leading predisposing factor for ARDS.
Injury to the lung from trauma
Trauma-related factors, such as fat emboli, sepsis, shock, pulmonary contusions, and multiple transfusions
Aspiration of gastric contents, viral pneumonia
Idiosyncratic drug reaction to ampicillin or hydrochlorothiazide
Inhalation of noxious gases (nitrous oxide, ammonia, chlorine)
Coronary artery bypass grafting
Acute miliary tuberculosis
Thrombotic thrombocytopenic purpura
Venous air embolism
ARDS is a heterogeneous syndrome that involves lung injury, which may develop as a result of endothelial and epithelial cell injury. Symptoms present from direct injury, including aspiration of gastric contents or inhalation of noxious gases, or indirect sources, such as chemical mediators released in response to systemic disease. Injury in ARDS involves both the alveolar and the pulmonary capillary epithelium. The causative agent triggers a cascade of cellular and biochemical changes.
Acute Phase: Sloughing of the Bronchial and Alveolar Epithelial Cells
In the acute phase of ARDS, protein-rich hyaline membranes form on the denuded basement membrane. Neutrophils adhere to the injured capillary endothelium and marginate through the interstitium into the air space filled with proteinrich edema fluid.
After it is initiated, the causative agent triggers neutrophils, macrophages, monocytes, and lymphocytes to produce various cytokines — which promote cellular activation, chemotaxis, and adhesion — and inflammatory mediators, including oxidants, proteases, kinins, growth factors, and neuropeptides, which initiate the complement cascade, intravascular coagulation, and fibrinolysis.
These cellular events increase vascular permeability to proteins, increasing the hydrostatic pressure gradient of the capillary. Elevated capillary pressure, such as results from fluid overload or cardiac dysfunction, greatly increases interstitial and alveolar edema, which is evident on chest X-rays as whitened areas in the lower lung. Alveolar closing pressure then exceeds pulmonary pressures, and the alveoli begin to collapse.
The exudative phase, or phase 1, usually occurs the first 2 to 4 days after onset of injury and involves inflammatory cells that have entered the air spaces from the alveolar capillaries.
During the exudative phase, fluid accumulates in the lung interstitium, alveolar spaces, and small airways. This causes the lungs to stiffen, impairing ventilation and reducing oxygenation of the pulmonary capillary blood, which results in reduced blood flow to the lungs. Platelets begin to aggregate and release substances (serotonin, bradykinin, and histamine), which attract and activate neutrophils.
The proliferative phase, or phase 2, begins 1 to 2 weeks after the initial lung injury. There is an influx of neutrophils, monocytes, lymphocytes, and fibroblast proliferation. This is a part of the inflammatory response.
During the proliferative phase, the released substances inflame and damage the alveolar membrane and later increase capillary permeability. Additional chemotactic factors released include endotoxins, tumor necrosis factor, and interleukin-1. The activated neutrophils release several inflammatory mediators and platelet aggravating factors that damage the alveolar capillary membrane and increase capillary permeability, allowing fluids to move into the interstitial space.
Next, as capillary permeability increases, proteins, blood cells, and more fluid leak out, increasing interstitial osmotic pressure and causing pulmonary edema.
The resulting pulmonary edema and hemorrhage significantly reduce lung compliance and impair alveolar ventilation.
Then, mediators released by neutrophils and macrophages also cause varying degrees of pulmonary vasoconstriction, resulting in pulmonary hypertension. The result of these changes is a mismatch in the ventilation-perfusion ratio. Although the patient responds with an increased respiratory rate, sufficient oxygen cannot cross the alveolar capillary membrane. Carbon dioxide continues to cross easily and is lost with every exhalation.
Finally, pulmonary edema worsens and hyaline membranes form. Inflammation leads to fibrosis, which further impedes gas exchange. Fibrosis progressively obliterates alveoli, respiratory bronchioles, and the interstitium. Functional residual capacity decreases, and shunting becomes more serious. Hypoxemia leads to metabolic acidosis. At this final stage, the patient develops increasing partial pressure of arterial carbon dioxide (PaCO2), decreasing pH and partial pressure of arterial oxygen (PaO2), decreasing bicarbonate levels, and mental confusion. The end result is respiratory failure.
Signs and Symptoms
Rapid, shallow breathing and dyspnea
Increased rate of ventilation
Intercostal and suprasternal retractions
Crackles and rhonchi
Restlessness, apprehension, and mental sluggishness
Diagnostic Test Results
Arterial blood gas (ABG) analysis with the patient breathing room air initially reveals a reduced PaO2 (less than 60 mm Hg) and a decreased PaCO2 (less than 35 mm Hg). Hypoxemia, despite increased supplemental oxygen, is the hallmark of ARDS. The resulting blood pH reflects respiratory alkalosis.
As ARDS progresses and the work of breathing increases, the partial pressure of carbon dioxide (PCO2) begins to rise and PaO2 decreases, despite oxygen therapy.
It is important to understand how ARDS differs from acute lung injury. Both have an acute onset, and patients have bilateral infiltrates on frontal chest radiograph and pulmonary artery wedge pressure (PAWP) less than or equal to 18 mm Hg or no clinical evidence of left atrial hypertension. The difference with ARDS is that the PaO2 is less than or equal to 200 mm Hg regardless of positive end-expiratory pressure (PEEP) level; with ALI, the PaO2 is less than or equal to 300 mm Hg regardless of PEEP level.
Pulmonary artery catheterization may show a PAWP of 12 to 18 mm Hg, and pulmonary artery pressure may show decreased cardiac output.
Serial chest X-rays in early stages show bilateral infiltrates and in later stages, long fields with a ground-glass appearance and “white outs” of both lung fields. Note: ARDS is defined by the presence of bilateral pulmonary infiltrates.
Chest computed tomography reveals bilateral opacities, pleural effusions, and decreased lung volume.
Sputum analysis, including Gram stain and culture and sensitivity, identifies causative organisms.
Blood cultures identify infectious organisms.
Toxicology testing reveals possible drug ingestion.
Therapy is focused on correcting the causes of ARDS and preventing progression of hypoxemia and respiratory acidosis.
Treatment may include:
intubation and mechanical ventilation
pressure-controlled inverse ratio ventilation
airway pressure release ventilation
inhaled nitric oxide
sedatives, opioids, and neuromuscular blockers
I.V. fluid administration or fluid restrictions
correction of electrolyte and acid-base imbalances
extracorporeal membrane oxygenation
Asthma is a complex disorder of the airways that is characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. Airflow limitation is caused by changes in the airway, causing bronchoconstriction, airway edema, and mucus hypersecretion. The National Heart Lung and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3) recommends monitoring of clinically relevant aspects of care and the importance of planned primary care and providing patients practical tools for self-management.
The development of asthma involves interaction between genetics and environmental exposures (EPR-3, 2007; GINA, 2017). Patients who are at high risk for asthma-related death require special attention.
Viral infections (one of the most important causes of asthma)
Pollen, air pollution
House dust or mold
Kapok or feather pillows
Food additives, including sulfites and some dyes
Noxious fumes, tobacco smoke
Patients with intrinsic, or nonatopic, asthma react to internal, nonallergenic factors.
Emotional stress and anxiety
Temperature or humidity variations
Coughing or laughing
Airway inflammation contributes to airway hyperresponsiveness, airflow limitation, respiratory symptoms, and disease chronicity (see the EPR-3 guidelines for pathophysiology).
In asthma, bronchial linings overreact to various stimuli, causing inflammation and smooth muscle spasms — contraction that severely constrict the airways. When the hypersensitive patient inhales a triggering substance, abnormal antibodies stimulate mast cells in the lung interstitium to release histamine and leukotriene. Histamine attaches to receptor sites in the larger bronchi, where it causes swelling in smooth muscles. Leukotriene attaches to receptor sites in the smaller bronchi and causes swelling of smooth muscle there. It also causes fatty acids called prostaglandins to travel by way of the bloodstream to the lungs, where they enhance histamine’s effects.
Histamine stimulates the mucous membranes to secrete excessive mucus, further narrowing the bronchial lumen. On inhalation, the narrowed bronchial lumen can still expand slightly, allowing air to reach the alveoli. On exhalation, increased intrathoracic pressure closes the bronchial lumen completely. Mucus fills the lung bases, inhibiting alveolar ventilation. Blood, shunted to alveoli in other lung parts, still cannot compensate for diminished ventilation.
Status asthmaticus is an acute exacerbation of asthma that remains unresponsive to treatment, despite appropriate medical treatment regimens. When status asthmaticus occurs, hypoxia worsens, expiratory flow slows, and expiratory volumes decrease. If treatment is not initiated promptly, the patient begins to tire. Acidosis develops as arterial carbon dioxide increases. The situation becomes life threatening when no air movement is audible on auscultation (a silent chest) and partial pressure of arterial carbon dioxide (PaCO2) rises to over 70 mm Hg.
Usual prodromal signs or symptoms
Rapidity of onset
Associated illnesses and/or comorbid conditions
Emergency department visits, hospitalizations, ICU admissions, intubations
Usual prodromal signs or symptoms
Limitations with exercise
Missed days from work or school.
Signs and Symptoms
Sudden dyspnea, wheezing, and tightness in the chest
Coughing that produces thick, clear, or yellow sputum
Tachypnea, along with use of accessory respiratory muscles
Hyperresonant lung fields
Diminished breath sounds
Diagnostic Test Results
Be careful not to confuse diagnostic criteria with contributing information. Diagnostic criteria include the following:
Episodic symptoms of airflow obstruction are present.
Airflow obstruction or symptoms are at least partially reversible.
Exclusion of alternative diagnoses.
Pulmonary function tests reveal low-normal or decreased vital capacity, increased total lung and residual capacities, and decreased FEV1.
Serum immunoglobulin E levels may increase from an allergic reaction. This is not diagnostic of asthma.
Complete blood count with differential reveals an increased eosinophil count.
Chest X-rays may show hyperinflation with areas of atelectasis.
With ABG analysis, partial pressure of arterial oxygen and PaCO2 are usually decreased, except in severe asthma, when PaCO2 may be normal or increased, indicating severe bronchial obstruction.
Skin testing identifies specific allergens but is not diagnostic of asthma. Skin testing to aeroallergens identifies contributing factors.
Pulmonary function testing includes pre- and postbronchodilator. A bronchial challenge could be considered a methacholine challenge, which would absolutely be contraindicated in a patient with diagnosed asthma.
Electrocardiography shows sinus tachycardia exacerbation or right axis deviation and peaked P waves (indicating cor pulmonale during a severe attack that resolves after the attack).
Exercise-induced bronchospasm (EIB) is a phenomenon of airway narrowing that occurs during or after exercise or physical exertion. EIB controlled by a short-acting β-adrenergic agonist 15 minutes before exercise or physical exertion.
The National Asthma Education and Prevention Program Expert Panel Report 3, (EPR-3) define asthma control as “the degree to which the manifestations of asthma symptoms, functional impairments, and risks of untoward events are minimized and the goals of therapy are met.” Every patient with asthma should be able to recognize symptoms that suggest inadequate asthma control. Written action plans detailing medications and environmental control strategies tailored for each patient are recommended for all patients with asthma.
Monitoring asthma control is the goal for asthma therapy and distinguishing between classifying asthma severity and monitoring asthma control.
Distinguishing between classifying asthma severity and monitoring asthma control.
Severity: the intrinsic intensity of the disease process. Assess asthma severity to initiate therapy.
Control: the degree to which the manifestations of asthma are minimized by therapeutic interventions and the goals of therapy are met. Assess and monitor asthma control to adjust therapy.
Impairment and Risk of Asthma:
The two key domains of severity and control are impairment and risk. The domains represent different manifestations of asthma, they may not correlate with each other, and they may respond differentially to treatment.
Impairment: frequency and intensity of symptoms and functional limitations the patient is experiencing currently or has recently experienced.
Risk: the likelihood of either asthma exacerbations, progressive decline in lung function (or, for children, lung growth), or risk of adverse effects from medication.
Quick-relief medicines are taken at the first sign of symptoms for immediate relief:
Short-acting inhaled beta2 agonists
Long-term control medicines are taken every day to prevent symptoms and attacks:
Inhaled corticosteroids: the most effective long-term maintenance medications for chronic asthma
Inhaled corticosteroids and long-acting inhaled beta2-agonists
Long-acting beta2agonist are ALWAYS administered and inhaled corticosteroid
Antileukotrienes or leukotriene modifiers — montelukast sodium
Identification and avoidance of precipitating factors
Desensitization to specific antigens
Low-flow humidified oxygen (supplemental oxygen is rarely prescribed at home for patients with asthma)
Relaxation exercises controlled breathing exercises.
Assessing Asthma Control
Asthma questionnaire tools assess asthma control and identify patients at risk for an asthma exacerbation. The Asthma Control Test (ACT) is an example of one of the asthma assessment tools. The ACT is a short, simple, patient-based tool for assessing asthma control, including identifying patients with poorly controlled asthma. The ACT is reliable, valid, and responsive to changes in asthma control over time. A cutoff score of 19 or less identifies patients with poorly controlled asthma.
The 2007 National Asthma Education and Prevention Expert Panel Report 3 guidelines classify asthma severity:
Intermittent asthma is characterized as follows:
Symptoms of cough, wheezing, chest tightness, or difficulty breathing less than twice a week.
Flare-ups are brief, but intensity may vary.
Nighttime symptoms less than twice a month.
No symptoms between flare-ups.
Lung function test FEV1 is 80% or more above normal values.
Peak flow has less than 20% variability am to am or am to pm, day to day.
Mild persistent asthma is characterized as follows:
Symptoms of cough, wheezing, chest tightness, or difficulty breathing 3 to 6 times a week.
Flare-ups may affect activity level.
Nighttime symptoms 3 to 4 times a month.
Lung function test FEV1 is 80% or more above normal values.
Peak flow has less than 20% to 30% variability.
Moderate persistent asthma is characterized as follows:
Symptoms of cough, wheezing, chest tightness, or difficulty breathing daily.
Flare-ups may affect activity level.
Nighttime symptoms 5 or more times a month.
Lung function test FEV1 is above 60% but below 80% of normal values.
Peak flow has more than 30% variability.
Severe persistent asthma is characterized as follows:
Symptoms of cough, wheezing, chest tightness, or difficulty breathing that are continual.
Frequent nighttime symptoms.
Lung function test FEV1 is 60% or less of normal values.
Peak flow has more than 30% variability.
Acute bronchitis is a common, self-limiting, respiratory tract infection characterized primarily by a cough generally lasting 1 to 3 weeks. The distinguishing characteristic of bronchitis is obstruction of airflow and an inflammatory response within the epithelium of the bronchi causing airway hyperresponsiveness and increased mucus production. The inflammation occurs as a result of an airway infection or environmental triggers. The causative pathogen for bronchitis is rarely identified, although viral infections accounting for an estimated 89% to 95% cases (Tackett & Atkins, 2012). The most common viral pathogens include adenovirus, coronavirus, influenza A and B, metapneumovirus, parainfluenza virus, respiratory syncytial virus, and rhinovirus (Albert, 2010). Bacteria may cause bronchitis in people with underlying respiratory disease. Mycoplasma pneumoniae and Chlamydia pneumoniae are bacterial pathogens that primarily affect young adults. Bordetella pertussis can also lead to acute bronchitis especially in unvaccinated patients (Albert, 2010). Testing for pertussis may be warranted. Chest radiographs are indicated when acute bronchitis cannot be clinically distinguished from pneumonia. Inflammation in acute bronchitis is usually transient and resolves after the infection has subsided.
The management of acute bronchitis is primarily supportive and is focused on controlling cough. Antibiotic therapy has a minor role in acute bronchitis (Hart, 2014). Inappropriate use of antibiotics for viral respiratory infections contribute to antibiotic resistance and possible adverse events. Inhaled beta agonists should be reserved for patients with underlying pulmonary disease. Over-the-counter medications, such as dextromethorphan or guaifenesin, administered as directed in the appropriate age group may be efficacious, despite lack of substantial evidence. Antitussive therapy may be helpful for sleep distribution contributed to nocturnal cough.
Expectorants have been shown to be ineffective in the treatment of acute bronchitis (Albert, 2010). Patient education must address etiology and symptomatology, rationale for duration of cough, and appropriate medical interventions.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Chronic obstructive pulmonary disease (COPD) is a common yet preventable disease characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities (GOLD, 2017). This disorder leads to airway obstruction, hyperinflation, and abnormal gas exchange causing dyspnea and functional limitation. Overlap is present between COPD and the other disorders that cause airflow limitation, such as asthma emphysema, chronic bronchitis, bronchiectasis, and bronchiolitis. Spirometry is required to make the diagnosis of COPD. The primary risk factor for COPD is cigarette smoking.
COPD should be considered in any patient who has dyspnea, chronic cough or sputum, and/or a history of exposure to risk factors for the disease (GOLD, 2017). Management for stable COPD is based on the individualized assessment of symptoms and future risk of exacerbations (GOLD, 2017).
The formal diagnosis of COPD is made with spirometry; when the ratio of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) is less than 70% of that predicted for a matched control, it is diagnostic for a significant obstructive defect. Criteria for assessing the severity of airflow obstruction (based on the percent predicted post bronchodilator FEV1) are as follows:
Stage I (mild): FEV1 80% or greater of predicted
Stage II (moderate): FEV1 50% to 79% of predicted
Stage III (severe): FEV1 30% to 49% of predicted
Stage IV (very severe): FEV1 less than 30% of predicted or FEV1 less than 50% and chronic respiratory failure.
Exposure to irritants
Exposure to organic or inorganic dusts
Exposure to noxious gases
Respiratory tract infection
COPD is characterized by increased numbers of neutrophils, macrophages, and T lymphocytes (CD8 more than CD4) in the lungs.
The irritants inflame the tracheobronchial tree, leading to increased mucus production and a narrowed or blocked airway. As the inflammation continues, changes in the cells lining the respiratory tract increase resistance in the small airways, and severe imbalance in the ventilation-perfusion ([V with dot above]/[Q with dot above]) ratio decreases arterial oxygenation.
Additional effects include narrowing and widespread inflammation within the airways. Bronchial walls become inflamed and thickened from edema and accumulation of inflammatory cells, and smooth muscle bronchospasm further narrows the lumen. Initially, only large bronchi are involved, but eventually, all airways are affected. Airways become obstructed and close, especially on expiration, trapping the gas in the distal portion of the lung. Consequent hypoventilation leads to a [V with dot above]/[Q with dot above] mismatch and resultant hypoxemia and hypercapnia.
Chronic bronchitis is defined clinically as the presence of a chronic productive cough for 3 months during each of 2 consecutive years with other causes of cough being excluded (GOLD, 2017). Chronic bronchitis is caused by the overproduction and hypersecretion of mucus by goblet cells. Mechanisms responsible for excessive mucus in COPD are overproduction and hypersecretion by goblet cells and decreased elimination of mucus. Chronic bronchitis leads to decreased airflow obstruction by luminal obstruction of small airways, epithelial remodeling, and decreased airway surface tension.
Chronic bronchitis causes hypertrophy of airway smooth muscle and hyperplasia of the mucous glands, increased numbers of goblet cells, ciliary damage, squamous metaplasia of the columnar epithelium, and chronic leukocytic and lymphocytic infiltration of bronchial walls. Hypersecretion of the goblet cells blocks the free movement of the cilia, which normally sweep dust, irritants, and mucus away from the airways. Accumulating mucus and debris impair the defenses and increase the likelihood of respiratory tract infections.
Signs and Symptoms
Copious gray, white, or yellow sputum
Dyspnea and tachypnea
Use of accessory muscles
Jugular vein distention
Weight gain due to edema or weight loss due to difficulty eating and increased metabolic rate
Wheezing, prolonged expiratory time, and rhonchi
Diagnostic Test Results: Chronic Bronchitis
Chest X-rays show hyperinflation and increased bronchovascular markings.
Pulmonary function studies indicate increased residual volume, decreased vital capacity and forced expiratory flow, and normal static compliance and diffusing capacity.
ABG analysis reveals decreased partial pressure of arterial oxygen and normal or increased partial pressure of arterial carbon dioxide. ABGs provide the best evidence as to acuteness and severity of disease exacerbation.
Sputum analysis reveals many microorganisms and neutrophils.
Electrocardiography shows atrial arrhythmias; peaked P waves in leads II, III, and aVF and, occasionally, right ventricular hypertrophy.
Beta2 agonists (bronchodilators)
Short-acting beta agonist (SABA)
Long-acting beta agonist (LABA)
Long-acting muscarinic agonist (LAMA)
Vaccination according to the Center of Disease Control and Prevention (CDC) is a safe and effective modality to reduce infection. Infections lead to exacerbations of COPD (GOLD, 2017).
Avoidance of air pollutants
Emphysema is pathologically defined as an abnormal permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by the destruction of alveolar walls (GOLD, 2017). Airflow limitation in emphysema is due to loss of elastic recoil and decrease in airway tethering. A permanent enlargement of air spaces distal to the terminal bronchioles, emphysema leads to a significant decline in the alveolar surface area available for gas exchange. Loss of individual alveoli with septal wall destruction leads to airflow limitation. The various subtypes of emphysema include proximal acinar, panacinar, or distal acinar.
Physical examination thoracic examination reveals diminished breath sounds, diffuse or focal wheezing, diffusely, hyperresonance upon percussion, prolonged expiration, and classically a 2:1 increase in anterior to posterior diameter.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD, 2017) guidelines recommend various instruments to assess severity of symptoms, risk of exacerbations, and the presence of comorbidities, which are important to the patient’s experience of the disease and prognosis. The most widely used research tool, the St. George’s Respiratory Questionnaire (SGRQ), is a 76-item questionnaire that includes three component scores (i.e., symptoms, activity, and impact on daily life) and a total score. The GOLD guidelines suggest using the COPD Assessment Tool (CAT) or the modified Medical Research Council (mMRC) dyspnea scale.
Signs and Symptoms
Prolonged expiration and grunting
Crackles and wheezing on inspiration
Decreased breath sounds
Clubbed fingers and toes
Decreased tactile fremitus
Decreased chest expansion
Chronic cough with or without sputum production
Accessory muscle use
Mental status changes, if carbon dioxide retention worsens
Anorexia and cachexia
Diagnostic Test Results
Chest X-rays in advanced disease show a flattened diaphragm, reduced vascular markings at the lung periphery, overaeration of the lungs, a vertical heart, enlarged anteroposterior chest diameter, and a large retrosternal air space.
Pulmonary function studies indicate increased residual volume and total lung capacity, reduced diffusing capacity, increased inspiratory flow, and decreased FEV1/FVC.
ABG analysis usually reveals reduced partial pressure of arterial oxygen and a normal partial pressure of arterial carbon dioxide until late in the disease process. ABGs provide the best evidence as to acuteness and severity of disease exacerbation.
Electrocardiography shows tall, symmetrical P waves in leads II, III, and aVF; a vertical QRS axis and signs of right ventricular hypertrophy are seen late in the disease.
Complete blood count usually reveals an increased hemoglobin level late in the disease when the patient has persistent, severe hypoxia.
Pneumococcal conjugate vaccine is recommended for all babies and children younger than 2 years of age, all adults 65 years or older, and people 2 through 64 years old with certain medical conditions. Pneumococcal polysaccharide vaccine is recommended for all adults 65 years or older, people 2 through 64 years old who are at increased risk for disease due to certain medical conditions, and adults 19 through 64 years old who smoke cigarettes (CDC, 2016, pneumococcal vaccination).
Aerosolized or systemic corticosteroids
Lung volume reduction surgery
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Cystic fibrosis is a hereditary disorder affecting the exocrine gland and causing severe damage to multiple organ systems. Chronic progressive lung disease is the most prominent cause of morbidity and death in patients with cystic fibrosis.
Cystic fibrosis is accompanied by many complications and has a median survival rate of 31 years. The disease affects males and females and is the most common fatal genetic disease in children of European ancestry. There are more than 30,000 patients with cystic fibrosis in the United States (Cystic Fibrosis Foundation, 2017).
Inherited as an autosomal recessive trait, the responsible gene, on chromosome 7q, encodes a membrane-associated protein called the cystic fibrosis transmembrane regulator (CFTR). The exact function of CFTR remains unknown, but it appears to help regulate chloride and sodium transport across epithelial membranes.
Most cases of cystic fibrosis arise from the mutation that affects the genetic coding for a single amino acid, resulting in a protein (CFTR) that doesn’t function properly. CFTR resembles other transmembrane transport proteins, but it lacks the phenylalanine in the protein produced by normal genes. This regulator interferes with chloride channels regulated by cyclic adenosine monophosphate, and with other ions, by preventing adenosine triphosphate from binding to the protein or by interfering with activation by protein kinase.
The mutation affects volume-absorbing epithelia (in the airways and intestines), salt-absorbing epithelia (in sweat ducts), and volume-secretory epithelia (in the pancreas). Lack of phenylalanine leads to dehydration, which increases the viscosity of mucous gland secretions and leads to obstruction of glandular ducts. Cystic fibrosis has a variable effect on electrolyte and water transport.
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