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Asthma is a chronic disease associated with reversible inflammation of the bronchial walls leading to narrowing of the airways. It is among the most common chronic diseases, and its prevalence is rising particularly in children. Acute onset of bronchial inflammation can lead to an asthma attack, with severe forms being life-threatening. While the exact cause of bronchial inflammation is unknown, there are numerous triggers including: environmental allergens (pollen, dust, and others), chemical allergens (cleaning agents, smoke, and others), exercise, stress, cold air, and medications.
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Diagnosis and Management
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The diagnosis of asthma is challenging because the clinical signs and symptoms overlap with many other respiratory diseases. Laboratory testing to rule out diseases such as cystic fibrosis (see Chapter 7) and infections (see Chapter 5) is important for the evaluation. Diagnosis begins with assessment of airway obstruction with spirometry and chest x-ray. The diagnostic evaluation for asthma must involve identification of inflammatory triggers. Identification of elevated concentrations of IgE in the plasma indicates a generalized allergic response. Antigen-specific IgE testing identifies immune responses to specific allergens and is useful in young children and patients with a contraindication to skin testing.
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Initial diagnosis and monitoring of patients with an acute asthmatic reaction involves assessment of oxygenation for disease severity and pulmonary function. Evaluation of arterial blood gases also assesses oxygenation status. Evaluation of electrolytes, pH, and anion gap is helpful in evaluating acid–base status, pulmonary function, and tissue hypoxia (Table 14–2).
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Chronic Obstructive Pulmonary Disease
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Like asthma, COPD is a chronic inflammatory lung disease associated with airway obstruction. Inflammation leads to thickening of the airway wall and decreased air flow, as well as destruction of the alveoli and increased airspace. Patients with COPD have 2 main conditions, emphysema or chronic bronchitis. The biggest risk factor for both is cigarette smoking, followed by exposure to pollution. Currently, COPD is a major cause of morbidity and mortality worldwide, because it can lead to respiratory failure.
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Diagnosis and Monitoring
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A diagnosis of COPD is confirmed by the presence of clinical symptoms such as chronic cough, wheezing, and/or respiratory failure, combined with airflow obstruction determined by spirometry. Patients with COPD are followed by measuring arterial blood gases to assess oxygen status and monitor the benefit of long-term oxygen therapy. Exacerbations and increased disease severity are commonly monitored by measuring a complete blood count (CBC) to assess the level of inflammation, testing for respiratory infections (Chapter 5), and measurement of electrolytes, pH, and anion gap to assess acid–base status, pulmonary function, and tissue hypoxia (Table 14–2).
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Respiratory Distress Syndrome
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Acute Respiratory Distress Syndrome (ARDS)
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ARDS is the rapid onset of respiratory failure due to systemic inflammation, trauma, or severe pulmonary infection in anyone over 1 year of age. It is associated with significant morbidity and mortality primarily due to oxygen deprivation and multisystem organ failure that results from pulmonary failure. A consensus group published the Berlin definition of ARDS as hypoxemia with bilateral lung infiltrates and/or respiratory failure within 1 week of a clinical insult, with new or worsening respiratory symptoms in the absence of cardiovascular insult or left pulmonary hypertension.
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The diagnosis of ARDS requires a careful clinical history to identify a recent clinical insult and/or the timing of new-onset respiratory symptoms. Chest x-ray or CT scan should be performed to visualize bilateral opacities. Cardiovascular ischemia and fluid overload should be ruled out by echocardiogram and/or cardiac biomarker analysis. Hypoxemia is classified by measuring arterial blood gasses and calculating the ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen (PaO2/). The Berlin definition divides hypoxemia into mild (PaO2/ between 200 and 300 mm Hg), moderate (PaO2/ between 100 and 200 mm Hg), and severe (PaO2/ <100 mm Hg).
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Neonatal Respiratory Distress Syndrome
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RDS of the newborn is most commonly associated with incomplete development of the fetal lungs. The pulmonary system is one of the last to completely develop, and as a result, RDS is a common cause of morbidity and mortality in preterm infants. Symptoms of RDS begin within a few hours of birth due to a deficiency of pulmonary surfactant. Surfactant, a mixture of phospholipids and proteins, coats the alveolar surfaces and separates alveolar airspace from liquid-coated lung epithelial cells, preventing lung collapse during exhalation. RDS patients suffer both lung collapse and hyperextension of alveoli leading to fibrosis, or hyaline membrane disease. The alveoli in an RDS lung are perfused, but not ventilated, resulting in hypoxia, hypercapnia, and respiratory acidosis.
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Respiratory distress syndrome of the newborn is most commonly associated with incomplete development of the fetal lungs. The pulmonary system is one of the last to completely develop, and as a result, RDS is a common cause of morbidity and mortality in preterm infants.
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RDS can be addressed by preventing preterm births or by administration of corticosteroids at least 48 hours prior to a premature birth. Corticosteroids induce surfactant production, significantly reducing neonatal morbidity and mortality due to RDS. Assessment of FLM status is essential for clinical decisions for women with symptoms of preterm labor and for those whose labor is induced prior to 39 weeks gestation.
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Selected Laboratory Tests for Assessment of Fetal Lung Maturity
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FLM is most commonly assessed by testing the amount of surfactant in the amniotic fluid in women after 30 weeks gestation. The diagnostic test most commonly used to assess FLM is the lamellar body count (LBC) assay. Surfactant is packaged into storage granules called lamellar bodies that pass into amniotic fluid in the third trimester of pregnancy. LBCs >50,000/μL suggest maturity. Lamellar bodies are similar in size to platelets and can be counted on a standard whole blood counter.
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Fetal lung maturity can also be predicted by measuring the lecithin–sphingomyelin ratio. An L/S ratio >2.0 indicates lung maturity.
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Another method to assess fetal lung maturity is through calculation of the surfactant–albumin (S/A) ratio. The S/A ratio increases throughout gestation proportionally with lung maturity. Surfactant-based phospholipids, particularly lecithin (phosphatidylcholine) and phosphatidyl–glycerol (PG), also increase in the amniotic fluid during fetal lung maturation, while lipids not originating from the lung, such as sphingomyelin, remain fairly constant throughout gestation. Because of this, FLM can also be predicted by measuring the lecithin–sphingomyelin ratio. An L/S ratio >2.0 indicates lung maturity. Qualitative detection of PG in amniotic fluid is a rapid and sensitive alternative for predicting FLM in late pregnancy. PG measurements are particularly useful in blood and meconium-contaminated amniotic fluid specimens as all other tests described above are affected by these contaminants.
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Lung cancer, defined as any tumor of the respiratory epithelium or pneumocytes, is the leading cause of cancer-related mortality worldwide. The leading risk factor for lung cancer is cigarette smoking, accounting for up to 90% of cases. Exposure to environmental carcinogens, irradiation, and genetic disorders are also risk factors for developing lung cancer. There are 2 main types of lung cancers: small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Among NSCLCs the most common lung tumor type is adenocarcinoma. Most lung cancers are caused by acquired mutations, amplifications, or rearrangements in oncogenes including epidermal growth factor receptor (EGFR), fibroblast growth factor receptor type 1 (FGFR1), anaplastic lymphoma kinase (ALK), KRAS, NRAS, BRAF, HER2, PTEN, and MET, among others. Although some lung cancers are discovered in asymptomatic patients, the most common clinical signs include coughing up blood, wheezing, and shortness of breath.
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Diagnosis and Monitoring
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The diagnostic workup for lung cancer begins with discovery of a new pulmonary mass by chest x-ray, CT scan, or MRI. A definitive diagnosis of lung cancer and type is determined through histological and immunohistochemical analysis of tumor tissue. Molecular testing of advanced-stage adenocarcinoma type (NSCLC) is required to direct therapy. In particular, patients with EGFR mutations are more likely to respond to tyrosine kinase inhibitor (TKI) therapy and have longer progression-free survival. Patients with a KRAS gene mutation with or without an EGFR mutation do not respond to TKI therapy and should be treated alternatively. Advanced-stage non-small cell lung adenocarcinomas should also be tested for rearrangements in the ALK gene. About 5% to 10% of all NSCLC patients carry this rearrangement, which can be treated with an ALK inhibitor.
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Prior to initiating therapy, baseline CBC and liver function panel should be measured to screen for metastases. Response to therapy and tumor recurrence can be monitored by performing regular chest x-rays and/or CT scans, as well as a CBC and liver function tests. Measurement of cytokeratin 19 fragments (CYFRA 21-1) in serum is useful for assessing prognosis in early and late stages, and in monitoring therapy in advanced stages of NSCLC. Serum neuron-specific enolase (NSE) may be useful in monitoring therapy and tumor recurrence in both NSCLC and SCLC.