Nonseptic Obstructive Airway Diseases
As a classification of pulmonary disease, COPD is the fourth leading cause of death in the United States, afflicting 16 million Americans with 20% of the population affected with some type of COPD. By 2010, it is estimated that COPD will be the third biggest cause of mortality within the world. Acute exacerbations of COPD account for $16 million spent annually in doctor visits. Forty thousand people die from COPD annually.3 This group of diseases is characterized by an increase in lung compliance with larger lung volumes and air trapping due to premature closure of the airways. The destruction of the lung architecture leads to hypoxia and hypercapnia (see Fig. 7-1).
This diagram summarizes the general immune response that leads to various pulmonary diseases through destruction of lung tissue. This may lead to hypoxia and hypercapnia.
These diseases are classified under COPD because the patients' presentations have similar characteristics (see Table 7-1). These patients present with hyperinflation, a barrel chest, and excessive use of accessory respiratory muscles. The pulmonary function test (PFT) demonstrates an increase in total lung capacity (TLC), inspiratory reserve capacity (IRC), and residual volume (RV) and a decrease in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), diffusion capacity of carbon monoxide (DLCO), and an FEV1/FVC ratio (see Fig. 7-2 and Table 7-2).4 Blood gases typically show hypoxia with or without hypercapnia. In the case of septic obstructive disease, like CF or bronchiectasis, the patient will have a chronic productive cough with excessive sputum production. Finally, from the adverse effects of treatment and a decrease in activity, many of these patients will also have muscle weakness, both type 1 and type 2 muscle fiber atrophy, osteopenia, or osteoporosis and may develop right-sided heart failure.
Table 7-1 Clinical Summary ||Download (.pdf)
Table 7-1 Clinical Summary
Dry, ↑ exertion
If present, nonproductive and weak
↑ Vascular markings
+ If HTN is severe
+ At end stage
↓ Breath sounds
Rapid rate, shallow
=, Increase rate
Pulmonary function tests. (Reprinted with permission from Ali J, Summer W, Levitzky M. Pulmonary Pathophysiology. New York: McGraw-Hill; 1999.)
Table 7-2 Classification of Lung Disease by Pulmonary Function Test ||Download (.pdf)
Table 7-2 Classification of Lung Disease by Pulmonary Function Test
Asthma (ICD-9-CM Code: 493)
Asthma is a chronic disease characterized by reversible obstruction to airflow within the lungs. Between asthmatic episodes lung function is relatively normal, and only exposure to a stimulant results in airway hyperreactivity and airway obstruction.5–7 It is estimated that there are 15 million people who suffer from asthma within the United States,8 and the World Health Organization reports an estimated 300 million with asthma worldwide.9 Asthma is the most common chronic disease in children with an incidence rate of 5.9% annually. There has been a 160% increase in asthma cases in children younger than 4 years since the 1980s.8 The increased incidence of asthma has been associated with increased exposure to nitric oxide, ozone, secondhand smoke, and indoor pollutants.10 It has been theorized that most cases of atopic or allergy-associated asthma is related to indoor exposure to irritants such as tobacco smoke, carbon monoxide, and nitric oxide from poorly vented heating systems, pesticides, dust mites, mold, rodents, cockroaches, and animal dander.8 There is a higher rate of asthma in females.6 Occupational exposure, which is related to the duration and intensity of exposure, is a factor for discussing adult-onset asthma. Asthma accounts for more than 10.4 million doctor appointments annually and more than $23 million is spent on medical management and on the loss of work time related to exacerbation of occupational asthma.8Table 7-3 lists the most common risk factors associated with asthma.
Table 7-3 Risk Factors of Asthma ||Download (.pdf)
Table 7-3 Risk Factors of Asthma
Thirty-four percent of children who develop asthma present with wheezing before the age of 3 years. The incidence rate in children younger than 3 years is 11.3%, whereas 15% present for medical evaluation between 3 and 6 years of age.11 Eighty percent of all asthmatic cases have an onset before the age of 5 years with 50% to 70% of these children reporting diminishing or absent symptoms in late adolescence or adulthood.7 Approximately 10% will continue to have symptoms, but these symptoms will be controllable, whereas 30% of children will remain symptomatic, with 17% of these children being classified as having severe asthma.12 Therefore, approximately 35% to 40% of children will be limited by lung disease in their activities and play. The most widely recognized phenotype of childhood asthma is atopic asthma. Atopic asthma is an allergy-associated form of asthma that accounts for 85% of all school-age asthma cases. It is associated with wheezing, cough, and shortness of breath, and the child may present with other atopic diseases such as eczema and hay fever.13 It has been suggested that children are most susceptible to atopic asthma due to the maturation process of lymphocytes as the immune system is developing along with the maturation and development of the lung and airway tissue.14
Asthma Affects People Across the Lifespan
The majority of asthmatic children have a family history of asthma, particularly on their mother's side. Maternal smoking compounds the risk of childhood asthma.11 There is a twofold increase in the risk of asthma development in the first year of life and a fourfold increase if the mother smokes and has allergies in the prenatal period.7 There is a 40% to 50% risk of a child developing asthma if one of the parents or the child's primary caregiver smokes.10 There is an increase in obesity-related asthma with 6.6% of all childhood asthma cases related to obesity. Obesity-related asthma is characterized by low-grade inflammation with an increase in cytokines and tumor necrosis factor α (TNF-α), which may upregulate airway inflammation.15 The persistence of childhood asthma is associated with a low FEV1 and a FEV1/vital capacity (VC) ratio less than 0.8 L, frequent asthmatic episodes, the need for anti-inflammatory medications, and atopy.11 Atopy is characterized by an immediate skin hypersensitivity reaction with wheal and flare.7 Approximately 3% of the elderly have a past medical history that includes asthma. It is estimated that 25% of the elderly are undiagnosed with asthma, even though the classic symptoms are present, and it takes an average of .5 years before a diagnosis is made. Only approximately one-third of the elderly are under appropriate medical care.16Table 7-4 includes the guidelines for classifying asthma as mild, moderate, or severe.
Table 7-4 Classification of Asthma ||Download (.pdf)
Table 7-4 Classification of Asthma
Peak Expiratory Flow
Twice a week, nocturnal twice per month, exacerbation with exertion
Once a day
Wide variations >30%
Significant intolerance to exertion
The etiology is unknown, but several factors have been associated with the development of asthma. It has been theorized that children are most susceptible to the development of asthma because there is less epithelial cell differentiation leading to more fragile airways. The exposure to allergens and, particularly, respiratory viral infections lead to an increase in the proliferation and migration of endothelial cells, recruitment of perivascular supporting cells, an increase in fibroblastic cells, and less normal epithelial cells. The consequence is the development of a hyperactive respiratory immune response.9,14,17 Maternal smoking has been linked to the increased exacerbation of existing asthma in children. These children also have a higher incidence of infections that may contribute to the development of asthma. Early infections, particularly infections due to the respiratory syncytial virus (RSV) and ureaplasma urealyticum, are associated with asthma.7,14,18 There also appears to be a genetic link. Chromosomes 5, 11, and 14 appear to contribute to the inflammatory process of asthma.12,19
The stimulants that cause asthmatic episodes are similar whether the patient is a child or an adult. Stimulants may include air pollutants, pollen associated with allergies, respiratory infections, exertion, and medications. Children are more at risk because of allergies, whereas the elderly are more susceptible to pollutants and medications. Medications that have been linked to asthma include nonsteroidal anti-inflammatory drugs (NSAIDS), aspirin, nonselective β-blockers, and angiotensin-converting enzyme (ACE) inhibitors.16
Airways are characterized by the infiltration of inflammatory cells. There is evidence of remodeling in composition and organization of the walls of the airways. Smooth muscle hyperplasia and hypertrophy are present as well as increased proliferation of epithelial cells. There is hyperplasia of the goblet cells and hypertrophy of vascular tissue and finally, an increased accumulation of myofibroblast cells.9 The inflammation is associated with the increase in mast cells and eosinophils.20
Asthma May Also Be Exacerbated by Exercise
It is theorized that exercise-induced asthma (EIA) is due to loss of water and heat from the lower respiratory system. Breathing through the mouth during exercise bypasses the nasal passages that warm and humidify the inspired air. By bypassing the nasal passages, there is a resultant loss of heat and water from the mucosa and the lower airways, and the lower airways have to compensate. It is postulated that the loss of heat causes hyperemia, vascular engorgement, and bronchial edema, which reduce the lumen size of the bronchioles.21 The severity of EIA is determined by minute ventilation during exercise, temperature, humidity of air, and baseline airway reactivity.21
Whether antigens, allergies, or exercises stimulate the asthmatic episode, the result is the onset of an inflammatory process (see Fig. 7-1). There is a release of T cells that causes a cell-mediated immune response of particularly CD4 helper/inducer cells. The activation of T cells stimulates the release of antibodies from the humoral-mediated immune system. The elevation of immunoglobin E (IgE) antibodies is associated with asthma-activated mast cells and eosinophils, which in turn help to further promote this inflammatory process by releasing other proinflammatory mediators.7,12,19 This inflammatory process is associated with bronchoconstriction and airway obstruction.16
Asthma is associated with an increase in airway resistance. It is theorized that the drying of the airways, in the presence of EIA, stimulates the inflammatory process and leads to bronchoconstriction and an increase in airway resistance.22 The resistance is related to contraction of the smooth muscle of the bronchioles. There is edema and cellular infiltration of the airways that also contribute to airway obstruction.23
The classic symptoms of asthma are wheezing, dyspnea, chest pain, facial distress, and usually a nonproductive cough18 (see Fig. 7-3). Airways may become obstructed with viscous, tenacious mucus during acute exacerbation that leads to further hyperinflation. These symptoms are more severe in children than in adults. There is an increased risk of an asthmatic attack in children because of the natural lower lung compliance and less compliance with medication.18 Symptoms in adults may also include paroxysmal nocturnal dyspnea, morning chest pain, and increased symptoms with exposure to cold.16 In the case of a severe asthma attack that is refractory to bronchodilators, called status asthmaticus, the patient may present with decreased breath sounds, cyanosis, exhaustion, hypercapnia, and pending respiratory failure.24It is important to note that EIA symptoms related to bronchoconstriction may present 6 to 8 hours after cessation of submaximal aerobic exercise or immediately after short intense bouts of exercise.22,21
Patient in an acute asthmatic attack. Note the shortness of breath, anxiety, and general increase in sympathetic discharge. (Image from www.netterimages.com. Reused with permission of Elsevier, Inc. All rights reserved.)
The guidelines for diagnosis vary and are based on the age of the patient. In infants, the diagnosis of asthma is made based on at least three episodes of wheezing observed by a physician.18 In children, asthma is diagnosed by a history of intermittent episodes of wheezing, coughing, shortness of breath, and chest tightness. These symptoms are worse at night or in the early morning hours. An allergen, pollutant, or exercise may be identified as stimulant.18 In older children and adults, an improvement in FEV1 by 15% or more after use of a bronchodilator and sustained improvement in symptoms and lung function with corticosteroids are also consistent with the diagnosis of asthma.16,18 Finally, the diagnosis of EIA requires the documentation of a 15% decrease in the peak expiratory flow recording following exercise.21
The first intervention for asthma is prevention. Smoking cessation, as well as minimizing the exposure to secondhand smoke, is important for any woman who is pregnant. It is also important to receive an annual flu shot and avoid stimulants that precipitate an asthmatic episode.21 The use of high-efficiency particulate air vacuums, mattress covers, and methods to improve heating and home ventilation systems may be effective in reducing the incidence of asthmatic episodes or atopic asthma.8
EIA exacerbation can be minimized through medication and by performing a warm-up approximately 45 to 60 minutes before the exercise program. This warm-up exercise period should consist of 30-second exercise bouts with 2-minute rest periods. This reduces the severity of signs and symptoms of EIA.21
The Goal of Treatment Is to Minimize Exacerbation25
The use of short- and long-acting bronchodilators is the main defense in controlling asthma.21 There are several types of bronchodilators that can be prescribed, and it is important that the patient and the therapist understand the proper use of the medication (refer to Table 7-5). β-Adrenergic agonists can be used to increase smooth muscle relaxation that results in bronchodilation and inhibits the release of mediators. Cromolyn, a corticosteroid, is also effective as a prophylactic but not as a rescue drug.21 More recently, there are other medications being trialled for management of asthma when more traditional methods are not sufficient. These include the use of leukotriene modifiers that block the proinflammatory mediators that promote smooth muscle contraction, vascular leakage, mucus secretion, and airway hyperactivity. IgE inhibitors such as malizurals and other medications like etanercept that block TNF-α are also under investigation. Finally, immunosuppressive medications, methotrexate, and cyclosporine are also being used for the chronic severe cases of asthma.20
Table 7-5 Common Medications Used for Asthma and Other COPD ||Download (.pdf)
Table 7-5 Common Medications Used for Asthma and Other COPD
Albuterol (Ventolin, Proventil)
Atrovent (w/albuterol, Combivent)
Prevents bronchoconstriction (anticholinergic)
Establishment of a routine exercise program is also important in the treatment of asthma. Fifty percent of children with asthma are severely deconditioned, but the level of deconditioning cannot be predicted by the history of asthma.5 People with asthma have a positive response to exercise with improved minute ventilation and oxygen consumption and decrease in blood lactate.21
Wheezing and breathlessness are poor predictors for asthma.16 Asthma that persists into adulthood can be associated with irreversible obstructive disease that may increase the incidence of deaths related to end-stage obstructive disease and increases the risk of pneumonia. Severe asthma is defined as asthmatic symptoms that persist despite maximized medical therapy with one or more exacerbation annually. There is a predominance of neutrophil cells associated with airway inflammation and there is a 30% to 50% loss in expiratory airflow, which appears to be associated with a fixed loss of the elastic recoil of the lung that is not associated with emphysema.26,27
Emphysema (ICD-9-CM Code: 492)
Emphysema is the second most prevalent disease within the category of COPD, with only asthma having a higher incidence. Emphysema is characterized by abnormal, irreversible enlargement of the airways distal to the terminal bronchioles, leading to decrease in driving pressure and intraluminal pressure, which leads to the impairment in expiratory airflow and maintenance of airway patency during inspiration28,29 (see Figs. 7-4 and 7-5). This may result in destruction of the acini, which are the functional units of the lungs for gas exchange. Each acinus is composed of one to three respiratory bronchioles and the alveolar ducts and sacs.
Emphysema. Notice the hyperinflation of the lungs on this P-A (posterior-anterior) X-ray with flattening of the diaphragm and elongation of the cardiac silhouette. (Courtesy of Dana Gryzbicki, MD, University of Pittsburgh, PA.)
Emphysema. This disease results in the destruction of bronchioles and parenchymal tissue, which leads to the loss of elastic recoil properties of the lung. This results in the dilatation of airways, which leads to air trapping and hyperinflation. (Courtesy of Dana Gryzbicki, MD, University of Pittsburgh, PA.)
Emphysema can be classified as centriacinar, panacinar, or paraseptal, based on the location of the anatomical disruption. See Fig. 7-6 for the illustrations of different types of emphysema. The key structure in the classification of emphysema is the respiratory bronchiole. Centriacinar or centrilobular emphysema involves the enlargement and destruction of the first- and second-order respiratory bronchioles, and the alveoli remain intact. Centriacinar emphysema is most commonly associated with smoking. In contrast, the enlargement and destruction of the entire acinus are the defining characteristics of panacinar emphysema, where there is a more even distribution of destruction and dilatation of the entire acinus.30 Paraseptal emphysema involves the periphery of the secondary lobule along the septum. Paraseptal emphysema is not typically associated with the progression of end-stage COPD but can be associated with an increased risk of pneumothorax (PTX).28
Types of emphysema. (Modified with permission from Gurney JW. Pathophysiology of obstructive airways disease. Radiol Clin North Am. 1998; 36(1):15-27.)
Cigarette smoking has been linked to the development of centriacinar emphysema; however, a small proportion of smokers will develop panacinar emphysema. Approximately 10% to 15% of patients with a significant history of smoking will develop clinically significant obstructive disease. A large proportion of the small particles in cigarette smoke are distributed to the first- and second-order bronchioles. Many of the particles are removed through a well-developed lymphatic system of the lower lobes; however, the particles that are also deposited in the upper lobes are revoked at a slower removal rate due to the smaller size of its lymphatic system.28 The loss of FEV1 function occurs more than twice as fast as the aging process and declines by 25% for each pack year of smoking.28,31 It is associated with a very insidious onset, which occurs over 30 to 40 years.
Cigarette smoking is associated with an increase in cellular apoptosis, early and excessive cell death. There is an increased accumulation of apoptotic cells and slow cell removal with macrophage dysfunction. There is also an increase in TNF-α and a decrease in surfactant protein. These changes lead to alteration of alveolar and small airway function, inflammatory and proteolytic activity, and changes in the endothelium and epithelium cells. The consequences of destruction of the alveolar wall, decrease in surface area, loss of functioning pulmonary capillary bed, and loss of the parenchyma lead to air trapping and ventilation–perfusion (V̇/Q̇) mismatch.3,32
The etiology of emphysema is based on the protease–antiprotease hypothesis in which there is an imbalance between protease, which causes tissue breakdown, and antiprotease enzymes. This imbalance leads to the loss of lung parenchyma and elastic recoil, which the small airways depend on return to their resting states during exhalation. The elastic property of the parenchyma also provides a normal level of airway resistance during inspiration. This loss of parenchyma tissue results in the loss of radial traction on the airways. The end result is dilation of airways, premature airway closure and air trapping, and an increase in RV.28,29,33
The nicotine in cigarette smoke attracts neutrophils, activates alveolar macrophages, and inactivates the protective nature of antiprotease.34 The alveolar macrophages and neutrophils contain protease enzymes, which are capable of destroying the elastic property of the lung tissue, thus producing emphysema.28 The cigarette smoke also causes a proliferation of endothelial cells, smooth muscle cells, platelet aggregation, and destruction of pulmonary capillaries. The impairment to the small blood vessels within the pulmonary system may lead to the decrease in DLCO and the development of secondary hypertension.3,31,32
As a consequence of intrinsic pulmonary damage, hyperinflation of the lungs occurs, which eventually leads to the compensatory changes of the chest wall. This disruption of normal chest wall mechanics leads to dysfunction of the inspiratory muscles, particularly of the diaphragm. The dysfunction of the diaphragm is an important cause of respiratory failure in patients with emphysema. Hyperinflation causes shortening of inspiratory muscles and flattening of the diaphragm with the loss of sarcomeres. The end result is a loss of diaphragmatic excursion and subsequent decline in the mechanical effectiveness of the diaphragm, and other respiratory muscles needed to support the increased demand of ventilation.35
The most common complaint of patients with emphysema is dyspnea on exertion (DOE). The result of a physical examination reveals the following findings: diminished breath sounds and wheezing, which are typically associated with exertion, and a prolonged expiratory phase.36 The patient will present with an enlarged anterior–posterior dimension of the chest wall, called a barrel chest, with an increase in rib angle. The accessory muscles are commonly hypertrophied from overuse. There is hyperresonance sound upon mediate percussion, which is consistent with the hyperinflation of the lungs. The presence of a chronic cough and sputum production will vary and depend on the infectious history of the patient. As the disease advances, many patients become cachectic, or emaciated, and begin to show signs of right-sided heart failure due to secondary pulmonary hypertension. The classic signs and symptoms of right-sided heart failure include peripheral pitted edema, weight gain, jugular vein distension, diminished appetite, right upper quadrant discomfort, and ventricular gallop, S3 heart sound (see Fig. 7-7). Emphysema is considered as a systemic disease with the increase of the inflammatory process. Patients with emphysema commonly suffer from osteoporosis, skeletal muscle disease, depression, and an increase in incidence of cardiovascular disease.29,37 Beyond the physical examination, PFT results are consistent with other obstructive airway diseases, which include a decline in FVC, FEV1, and FEV1/FVC ratio that indicates small airway disease. There is an increase in TLC and RV.38 The chest X-ray reveals hyperinflation with a flattened diaphragm, decreased vascular markings, and possible enlargement of the right side of the heart. Because of the destruction of the gas-exchange areas of the lungs, there is also a mismatch between ventilation and perfusion (V̇/Q̇) that is demonstrated on a V̇/Q̇ scan.36
Patient with a diagnosis of emphysema. Note the generalized muscle wasting, shortness of breath with pursed-lip breathing, and use of accessory muscles with a forward-leaning posture. (Image from www.netterimages.com. Reused with permission of Elsevier, Inc. All rights reserved.)
Patients who present with the classic presentation of emphysema will have arterial blood gas analysis that typically reveals hypoxia and normal-to-slight hypocapnia. These patients present with tachypnea, labored breathing, and a normal-to-low body mass index (BMI). Some patients with emphysema will present with signs more associated with chronic bronchitis including hypoxemia, hypercapnia, signs of right-sided heart failure, copious secretions, and an above-normal BMI.3Caution must be taken in this basic medical description because many patients with emphysema will present with a mixture of clinical features.
Smoking cessation is instrumental in the care of patients with emphysema because it leads to a slower decline in FEV1 when compared to the patients who continue to smoke.39 Smoking cessation has been the only treatment that has shown to slow the alterations in the natural progression of emphysema with patients with mild disease.29 In addition, there are several other treatment options. Pharmacology interventions include short-acting and long-acting β2-agonists that cause bronchodilation of the airways. Anticholinergic drugs can be used, but are not usually the first line of medications. These medications, such as Atrovent, block bronchoconstriction. Refer to Table 7-5 for a summary of medications used in treating emphysema. Xanthine derivatives (eg, theophylline) also produce bronchodilation, accelerate mucociliary transport, and limit the inflammatory response. Corticosteroids are common agents used for their anti-inflammatory effects. It is also important that the patients receive the preventive vaccinations against influenza and pneumococcus.20
Long-term oxygen therapy helps correct hypoxemia and minimizes secondary pulmonary hypertension. The threshold for oxygen prescription include a Pao2 less than 55 mm Hg, an oxygen saturation less than 88%, evidence of cor pulmonale, or a hemocrit greater than 56% (Table 7-6).39 Oxygen therapy has been shown to reduce the level of dyspnea, decrease maximal voluntary ventilation and polycythemia by correcting hypoxemia, decrease pulmonary hypertension, improve quality and quantity of sleep, and decrease nocturnal arrhythmias. Supplemental oxygen can also improve cognitive function and exercise tolerance. The use of BiPAP ventilation, which is a form of mechanical ventilation, provides airway pressure on both inspiration and expiration to decrease the work of breathing and prevent early airway closure. This minimizes air trapping and has also been found to reduce the retention of carbon dioxide.
Table 7-6 Indications for Supplemental Oxygen ||Download (.pdf)
Table 7-6 Indications for Supplemental Oxygen
Pao2 ≤ 55 mm Hg or Sao2 ≤ 89% at rest
Pao2 ≤ 55 mm Hg or Sao2 ≤ 89% with exercise
Pao2 ≤ 55 mm Hg or Sao2 ≤ 89% during sleep
Evidence of pulmonary hypertension or cor pulmonale, mental or psychological impairment, polycythemia, and a Pao2 of 56–59 mm Hg or an Sao2 ≤ 90% at any time
Medicare Criteria for Reimbursable Oxygen Supplementationa
Pao2 ≤ 55 mm Hg or Sao2 ≤ 88%
Pao2 of 56 to 59 mm Hg or Sao2 ≤ 89% if there is evidence of cor pulmonale, polycythemia, or congestive heart failure, hematocrit > 56%)
Drop in Pao2 > 10 mm Hg or Sao2 > 5% with signs and symptoms of hypoxia
Pulmonary rehabilitation has become a widely accepted intervention in the care of patients with emphysema but is still not covered by many insurance plans, although research supports its positive effects of increasing maximal exercise tolerance, oxygen uptake, and exercise endurance. There is also an improvement of the perceived level of dyspnea and a decrease in muscle fatigue. There is an improvement in quality of life, including the improvement in self-worth, well-being, and an increased sense of self-control.39 Pulmonary rehabilitation should include general muscle strengthening with emphasis on the upper body; aerobic conditioning; and education about smoking cessation, nutrition, vaccinations, proper use of medications and supplemental oxygen, and the disease process.
Bullectomy is a common surgical intervention for a patient with emphysema with significant bullae disease. A bulla is a large air space greater than 1 cm in diameter, which is the result of destruction of the parenchyma. A bulla no longer participates in gas exchange or diffusion. A bulla may also cause compression of adjacent functional lung tissue, which further impairs diffusion. Bullae are associated with a 15% to 20% incidence of PTX. A bullectomy is indicated when there is a significant level of dyspnea, clear presence of bullae that compress viable tissue, and when there is a high incidence of PTX. A bullectomy results in the reduction of pulmonary vascular and airway resistance, a reduction of functional residual capacity (FRC), and less air trapping. If enough diseased tissue is removed, the diaphragm may return to a more normal position that will improve muscle contraction.39,40
Volume reduction is the surgical resection of approximately 20% of dysfunctional lung tissue, thus reducing the hyperinflated state (see Figs. 7-8 and 7-9). The most common complication is air leaking in which there is a disruption of subatmospheric pressure within the thorax.39 From the outcomes of the NIH National Emphysema Treatment Trial (NETT) study, it has been determined that the patients with the best outcome have primarily upper lobe disease and have a decrease in exercise capacity, less than 25 W for women and less than 40 W for men.40
Surgical entrance into the chest wall via thoracotomy as a precursor to volume reduction surgery. The ribs and intercostal muscles are identified. The ribs are counted to ascertain the proper level for entering the chest cavity. (Courtesy of Peter Fergen, MD, University of Pittsburgh, PA.)
Volume reduction surgery. Rib-spreading retractors increase the exposure of the chest cavity. (Courtesy of Peter Fergen, MD, University of Pittsburgh, PA.)
Lung transplantation is a viable option for patients with end-stage disease who have maximized medical intervention. Patients with emphysema are potential candidates for either single- or double-lung procedures. Transplantation has the potential to significantly improve quality of life, but there are still questions as to whether transplantation extends the life of the recipient.39,40
In general, the prognosis of emphysema varies depending on the degree of obstruction, the presence of hypercapnia, the recurrence of infections, and the development of right-sided heart failure. It is generally accepted that an FEV1 of less than 25% is associated with a 50% mortality rate in 2 years.39
α1-Antitrypsin Deficiency (Genetically Acquired Emphysema) (ICD-9-CM Code: 493.8)
α1-Antitrypsin is an enzyme that is predominantly synthesized by the liver parenchymal cells and counterbalances the degradation of tissue caused by protease, a proteolytic enzyme. α1-Antitrypsin primarily inhibits neutrophil elastase, which works to break down and remove bacteria from the airways.41 The normal level of α1-AT is 104 to 276 mg/dL. At an α1-AT level below 50 mg/dL, the genetic disorder α1-ATD should be suspected.42 Genetic emphysema or α1-ATD commonly presents as panacinar disease.42,43 The degree of deficiency is associated with the severity of the disease.
α1-ATD is the most common autosomal recessive genetic cause of liver disease in children43,44 and only second to CF in genetic pulmonary disease.44 Beyond the second decade of life, α1-ATD is primarily associated with lung disease.45 It is estimated that 1.29 million patients suffer from α1-ATD in the United States and another 1.1 million worldwide, which causes end-stage obstructive lung disease.44–46 There is an estimated 25 million carriers of α1-ATD worldwide. The prevalence is 1 in 1,500 people of European descent.41
α1-ATD can be divided into four categories based on variation in allele. An allele is one or more alternative forms of a gene on a chromosome. There have been more than 100 alleles identified with 34 associated with functional deficiency in the circulating α1-AT.41 Allele M involves a variation that carries little to no risk of disease, because the α1-AT level is sufficient enough not to cause cellular damage.42 The deficient variants that most commonly lead to liver or lung disease are allele S, allele Z, and allele null (0). Allele Z is the most common variant that is characterized by a normal level of α1-AT synthesis, but the secretion is only 15% of predicted levels. Allele Z accounts for 95% of severe α1-ATD. Allele S and allele 0 with the null variants are characterized by little α1-AT production, accounting for the most severe expression of the disease. The Z allele and null variants most predictably lead to premature lung disease.42,43
The onset of symptoms associated with pulmonary dysfunction typically begins in the 30s with the diagnosis of α1-ATD occurring between 40 and 50 years of age.42,45It is estimated that up to 13% of patients with emphysema actually have α1-ATD. Only approximately 10% of α1-ATD cases are actually diagnosed correctly. Most are initially diagnosed with asthma or nongenetic emphysema.43 A correct diagnosis takes 7.2 years on an average, and it is not uncommon that the patient is seen by 6 to 10 physicians before a correct diagnosis is made.45 Diagnosis prior to 20 years of age is typically related to liver dysfunction.44
Smoking has been associated with the acceleration of lung disease in the presence of α1-ATD. It has been estimated that cigarette smoking accelerates the progression of the lung disease by 19 years.45 Patients with α1-ATD or a family history of α1-ATD should not smoke! The tobacco smoke increases the level of oxidant exposure, alveolar macrophages, and neutrophils in the airways, along with other inflammatory cells. Cigarette smoke also inactivates α1-AT and leads to neutrophil protease being unopposed, thus causing the degradation of proteins within the lungs.43 An elastase–antielastase hypothesis has been proposed to explain the destructive changes that occur because of this deficiency. Neutrophil protease is capable of cleaving many of the proteins from connective tissue within the lung. Without the appropriate level of α1-AT, neutrophil protease is unopposed, which leads to an imbalance, with degradation occurring at a faster rate than repair and remodeling.43
The primary significance of α1-ATD is the premature development of emphysema, occurring in the third or fourth decade of life. Shortness of breath is typically the first symptom that causes the patient to present for medical intervention.43 Patients also report a chronic cough in 37% of all cases, sputum production (38%), wheezes (44%), and hyperreactive airways (20%).45 Many patients may present with weight loss, cor pulmonale, and polycythemia as the disease progresses to end stage.47 For up to 20% of patients, the clinical presentation of pulmonary impairment will also have liver disease, and up to 70% of patients will have abnormal liver enzymes.42
Upon examination of α1-ATD, the diagnostic testing shows similar findings to smoke-related emphysema. The results of PFTs demonstrate an obstructive pattern with a decline in FVC, FEV1, and FEV1/FVC ratio. DLCO is also diminished. There is an increase in TLC and RV. Radiological studies show the classic signs of hyperinflation and a decrease in vascular markings particularly of the lower lobes. Smoking-related emphysema shows more upper lobe or uniform disease throughout the lungs.42,44,47 High-resolution CT scan is the gold standard for diagnosis. When a patient younger than 50 years presents with signs and symptoms of emphysema or asthma with impairment more excessive than expected, blood testing should be conducted to test the serum α1-AT level.43
Most of the available treatment protocols are consistent with the treatments for emphysema such as bronchodilators, aerosolized or systemic corticosteroids, cessation of smoking, and preventive vaccinations. Pulmonary rehabilitation and supplemental oxygen therapy also are effective in the management of α1-ATD. It has been recommended that if the plasma level of α1-AT is less than 11 μmol/L, the patient should be given augmentation therapy (Prolastin, Aralast, and Zemaira), with the goal to increase α1-AT above 15 μmol/L (80 mg/dL), which appears to protect the lungs and slow down the decline of PFTs.41,42 Work is also being done to develop gene therapy for the treatment of α1-ATD. The most common surgical intervention for end-stage lung disease due to α1-ATD is lung transplantation. The clinical trials for lung volume reduction have shown that it is an ineffective procedure because of the primary presence of lower lobe disease. However, the effectiveness of this procedure is still in question.42
The prognosis of α1-ATD depends on the type of variant or allele, history of cigarette smoking, age of onset of symptoms, and the development of infectious bronchiectasis. Rapid decline in PFTs is associated with a worse prognosis.42 Sixty-two percent of patients with α1-ATD will die from respiratory failure, whereas 13% will die from end-stage liver disease.45,47
Chronic Bronchitis (ICD-9-CM Code: 491)
Chronic bronchitis is a clinical diagnosis that consists of a persistent cough that produces sputum for more than 3 months per year for at least two consecutive years in the absence of another definable medical cause. It is associated with obstruction of the airways and mucus plugging.1,23 It is estimated that 15 million people suffer from chronic bronchitis in the United States.48Cigarette smoking is the most important risk factor in the development of chronic bronchitis.49
Smoking causes inflammation throughout the lung tissue with an increase in macrophages and T lymphocytes found within the airways. This inflammation is associated with airway remodeling, hypertrophy of submucosal glands, enlargement of smooth muscle cells, fibrosis of airway walls, and goblet cell hyperplasia.50 Polymorphonuclear neutrophils are suspected to be the primary cause of the chronic airway inflammation.51 The increased activity of macrophages and neutrophils leads to the release of various enzymes such as interleukin 8, TNF-α, and elastase, which leads to further inflammation and airway destruction.52 The inflammation within the airways is correlated with alveolar wall destruction and rupture of the attachment between the outer airways and the alveoli. The end result is the loss of the elastic recoil within the lung tissue, which leads to airway obstruction and hyperinflation of the lungs.34
Approximately 15% of smokers will develop emphysema or chronic bronchitis. In the smokers who go on to develop chronic bronchitis, the exposure to nicotine causes an inflammatory response, as discussed previously, which stimulates mucus secretion, and disruption of the architecture of the airways and capillary system.34,53
There are other risk factors that have been identified in the development of chronic bronchitis. Age and the degree of airway obstruction along with the degree of hypoxia and hypercapnia are associated with chronic bronchitis. Aging is associated with a decline in B cells and T cells and a decrease in responsiveness to protect the airway. There is also a decrease in ciliary function and in the presence of chronic bronchitis, there is a further decline in CD4 and CD8 cells. This imbalance increases airway destruction and mucus production and retention.52 There is a greater risk of chronic bronchitis if the patient requires systemic steroids for medical management. At times of exacerbation, the patient may develop acute respiratory failure with secretion retention and severe abnormal blood gases requiring mechanical ventilation.54
Chronic bronchitis can be divided into subsets based on the degree of pulmonary dysfunction and sputum production. Acute tracheobronchitis is not associated with any pulmonary dysfunction but is typically associated with an acute viral infection. With simple chronic bronchitis, there is a mild-to-moderate decline in FEV1 and an increase in sputum production. Complicated chronic bronchitis pertains to a patient who is of advanced age, has an FEV1 of less than 50% of predicted, and has repeated exacerbations, poor nutrition, and comorbidities. Exacerbations that are associated with an increase in purulent secretions are likely from a bacteria infection such as streptococcus or Haemophilus influenzae. Finally, with chronic bronchitis, infection is distinct from the other subsets in that the patient has constant sputum production throughout the year.54
Upon inspection of the lung tissue in the presence of chronic bronchitis, there is hypertrophy and increased density of the secretory cells down the tracheobronchial tree. Along with airway obstruction from the loss of elastic recoil, there is inflammation of the respiratory bronchioles, hypertrophy of the smooth muscle at the level of the small noncartilaginous airways, and mucus plugging that further narrows or occludes the small airways.24,49 The end result is a retention of mucus in the airways that lead to further airway obstruction and creates a vicious cycle of further pulmonary infections and destruction.54
These patients commonly present with an increase in shortness of breath and a productive cough during the acute exacerbation. There is an increase in sputum production and purulence along with a positive culture that confirms an infection. H. influenzae is the most common source of infection. A wheeze may be present upon auscultation. The physical examination and testing will reveal a barrel chest; decline in the FVC, FEV1, and FEV1/FVC ratio; decrease in DLCO; and commonly, hypercapnia and hypoxemia. The patients may also report anorexia associated with dyspnea while eating24,49 (see Fig. 7-10).
Patient with a diagnosis of chronic bronchitis. Note the cyanosis, use of accessory muscles, and sputum production. (Image from www.netterimages.com. Reused with permission of Elsevier, Inc. All rights reserved.)
The standard of care includes antibiotic treatment in the presence of an acute infection and short-acting β-agonists, long-acting bronchodilators, and inhaled corticosteroids. Frequently, these patients may be on chronic inhaled or intravenous antibiotics on a monthly basis to control infections. Smoking cessation is the most effective way to decrease mortality. The patients may also be taking expectorants and mucolytics to assist in management of sputum. Patients are encouraged to be well-hydrated. Bronchodilators may be used to manage bronchospasms. As this disease progresses, supplemental oxygen may be required to correct hypoxemia, and some form of pulmonary hygiene may need to be incorporated into the patient's daily routine. Pulmonary rehabilitation is becoming recognized as a key component in the medical treatment plan. Finally, some pulmonologists are administrating an antiprotease, such as prolastin, to counteract the destruction of elastase caused by the chronic inflammatory process.49,55
The prognosis of chronic bronchitis is dependent on age, smoking, and the degree of airway obstruction. The 10-year mortality rate is 60% in smokers, whereas it is only 15% in nonsmokers. If the FEV1 is less than 1 L, the median survival rate is 4 years. Patients who spend at least 50% of the day in bed are four times more likely to die than patients who are mobilized early and frequently.49,54
Bronchiolitis Obliterans (ICD-9-CM Code: 496)
Bronchiolitis obliterans (OB) is an acute inflammatory injury usually characterized by a diffuse destruction of the bronchioles. There are multiple causes of OB in the adult population including an infectious process, toxic fume exposure, collagen vascular disease, chronic bronchitis, and lung transplantation. Most recently it has been recognized as the exposure to diacetyl, an additive used in artificial butter flavoring for popcorn, has been linked to OB.56 In pediatric patients, OB is primarily a complication of severe lower airway infection.57,58
The characteristics of OB may vary based on the underlying disease. In the presence of OB with organizing pneumonia (BOOP), an infection, there is fibroblastic proliferation in the small airways and mild chronic inflammatory infiltrates consistent with increased composition of alveolar macrophages in the alveoli.59 Polyp formation within the bronchioles consisting of granulation tissue can extend into the terminal bronchioles, which can partially or completely obstruct the airway. These polyps form at the site of epithelial injury. The proliferative form of OB is characterized by inflammation and infiltration of mesenchymal cells, which are composed of fibroblasts, myofibroblasts, and other extracellular substances, that leads to fibrosis and airway destruction.60 The proliferative form of OB has three principal processes that include an acute inflammatory phase with reversible fibrosis. In the first form, the basement membrane is intact, which allows for recovery. The second is described as an acute to subacute inflammatory presence with irreversible bronchiole fibrosis, and the most severe pattern is the chronic inflammatory picture with irreversible fibrosis. This third pattern is mostly associated with complications from transplantation and graft-versus-host disease.60 With obstructive pulmonary disease like emphysema and asthma, injury of the bronchioles is associated with mucus plugging, inflammatory infiltration, smooth muscle hypertrophy, goblet cell hyperplasia, and bronchial gland hypertrophy. This leads to narrowing of the airways that compounds the loss of elastic recoil and results in further airway obstruction.59
Constrictive OB is an uncommon idiopathic form of OB. The usual site of injury with constrictive OB is isolated to the bronchioles with preservation of distal airways. It is characterized by mural fibrosis, resulting in reduction in the lumen size of the bronchioles. Compared to nonconstrictive idiopathic OB, there is luminal narrowing due to scarring rather than smooth muscle hypertrophy.59,60
Recently, the most common cause of OB is associated with lung transplantation and is associated with the loss of graft function. It is speculated that OB is the result of chronic rejection. The hallmark sign is submucosal bronchiolar fibrosis preceded by bronchiolar inflammation resulting in epithelial necrosis through a process of lymphohistiocytic-mediated cytotoxicity that targets the respiratory bronchioles. The end process is the deposition of collagen and airway obliteration also referred to as vanishing airway disease. Transplanted OB is associated with frequency and severity of acute cellular rejection, ischemic and reperfusion injury, cytomegalovirus (CMV), and other bacterial or fungal respiratory infections. The incidence of OB associated with transplantation has been reported as high as 80% in recipients after 5 years with an onset of 16 to 20 months.58,61 More than 50% of recipients who survive beyond 3 months will develop OB.62 OB in transplant recipients can be classified as active or inactive, based on the presence or absence of lymphocytic infiltration, respectively.63 There are three typical patterns that OB can follow: a rapid and relentless decrease in FEV1 with death within 1 year of diagnosis, an insidious onset with a slow decline in FEV1, and finally, a rapid decrease in FEV1 onset followed by a stabilization over a prolonged period of time.61
In children and infants, OB is the primary cause of obstructive pulmonary disease. The primary site of injury involves the inflammation of the peripheral, small airways. The onset is typically the result of a viral infection, adenovirus, RSV, parainfluenza, influenza, and rhinovirus. Thirty-four percent of children who require mechanical ventilatory support as part of the medical therapy for severe respiratory infection will go on to develop OB as opposed to only 3% in cases where children did not require mechanical ventilation.57 Hyperactivity of the airways may develop as a result of this chronic inflammatory process.24,59
In general, there is a pronounced degree of fibroproliferative activity in the bronchioles that leads to or adds to further airway obstruction. There is the presence of derangement of epithelial function, local necrosis, fibropurulent exudate, and deposition of collagen.57,60 The damage is typically confined to the cartilaginous airways, with sparing of the respiratory bronchioles, alveolar ducts, pulmonary alveoli, and interstitium. In larger airways, there may be signs of bronchiectasis, mucus plugs, and chronic inflammatory infiltrates by lymphocytes, macrophages, and plasma cells.59,63
Frequently, there is an insidious onset with progressive dyspnea with exertion, often associated with a cough in the development of OB. Upon auscultation, wheezing and crackles are present when OB presents with an obstructive pattern. In the stage where there is an increase in sputum production, there may be the presence of low-pitched wheezing or rhonchi. Patients commonly complain of dyspnea, a low-grade fever, and a persistent cough.63 In children, the signs and symptoms will include hypoventilation and hypercapnia, intercostal retractions, tachypnea, grunting, expiratory wheezes, crackles, hyperinflation, and atelectasis.57,59 On examination of lung function, there is a decrease in FVC and FEV1 as well as an increase in RV57,61; in the presence of small airway involvement, there will also be a reduction of the FEV1/FVC ratio. A chest X-ray will illustrate hyperinflation and patchy atelectasis, and a high-resolution CT scan will reveal mosaic perfusion, vascular attenuation, and central bronchiectasis.57,58
Medical management begins with prevention, primarily to decrease the incidence of exposure to toxic gases, minerals, and organic particulates.60 Therapy also includes the use of supplemental oxygen, antiviral medications, and corticosteroids to suppress the inflammatory process. Bronchodilators may be used for the management of bronchospasm. For transplant recipients, prevention and early treatments of acute rejection and viral infection are the best medical approaches to preserve the function of the donor lung.63
Mortality is generally low for OB and is predominantly associated with the underlying pathology that is responsible for the inflammatory process. Death due to OB in children is approximately 1%.59 In the transplant population, the mortality rate has been reported as high as 56% with more than 60% of the deaths related to a respiratory infection.
Lymphangioleiomyomatosis (ICD-9-CM Code: 496)
Lymphangioleiomyomatosis (LAM) is a rare disease that affects women in their reproductive years. It is a multisystem disease that is characterized by nonneoplastic proliferation of atypical smooth muscle cells in the parenchyma and lymphatic system. It is also associated with the development of renal angiomyolipomas in approximately 50% of the cases.64,65
The etiology of LAM is unknown, but there may be a genetic link because LAM is present in the autosomal genetic disorder tuberous sclerosis complex on chromosome 16. Typically, the onset of LAM is in the early to mid-30s and has an incidence of 1 per 1 million.66 The pulmonary system is the primary site of dysfunction.64 There are two patterns of LAM: tumor sclerosis gene LAM, which is also associated with central nervous system involvement including seizures and cognitive impairments, and sporadic LAM, which does not have any neurological involvement.67
Upon examination of the lung tissue, there is diffuse formation of cysts that leads to degradation of supportive elastic fibers by an imbalance between α1-AT and elastase. There is a proliferation of immature smooth muscle cells (LAM cells) within the walls of the airways, which leads to the destruction of alveoli and obstruction of the small airways.64–66
This disease is frequently misdiagnosed as asthma, COPD, pulmonary fibrosis, tuberculosis (TB) infection, or sarcoidosis. On an average, there is a 4-year delay between the onset of symptoms and the diagnosis, unless the patient experiences a spontaneous PTX; then the average time to obtain a correct diagnosis is slightly more than 2 years.67 The chest X-ray demonstrates nonspecific changes with preserved or increased lung volumes, hyperinflation, diffuse reticular opacities, pleural effusions, and a PTX. High-resonance CT scan is the best tool for diagnosis because it is very sensitive in detecting cystic formation and honeycombing without fibrosis and dilatation of the thoracic duct. There may also be the dilatation of the thoracic duct. The results of PFTs may show an obstructive, restrictive, or mixed pattern.65 The majority of cases demonstrate an obstructive volume pattern. Approximately 35% of patients will have normal a PFT until late into the disease67; however, a reduction of DLCO is seen in most cases regardless of the pattern.65,66
The most common presenting signs and symptoms are DOE and PTX. The patient may also present with a nonproductive cough, hemoptysis, chylous pleural effusion, wheezing, chest pain, abdominal pain, and ascites, if associated with dilatation and cysts involving the lymphatic system of pelvis and abdomen. Symptoms may worsen with the use of oral contraceptives.64,66 Signs and symptoms of right-sided heart failure may be documented in association with pulmonary hypertension.65,67
Treatment includes counseling the patient to avoid pregnancy because the hormonal changes worsen the disease. The patient should also be encouraged to avoid labor-intensive jobs because of the risk of PTX. Corticosteroids and cytotoxin are typically not effective in alleviating signs and symptoms. It has been suggested that the use of progesterone and tamoxifen may stabilize the disease progression.66 More recently, antiestrogen and luteinizing hormone are being used to manipulate the endocrine system as well as oophorectomy, which appears to slow the progression of the disease.68
Death is usually due to respiratory failure. Mortality rates are variable and are greatly influenced by the degree of small airway obstruction and impairments in DLCO. On an average, there is a 50% to 80% survival rate at 8 to 10 years after the onset of symptoms.64,66 Patients whose primary complaint is dyspnea have a significantly higher mortality rate as opposed to those suffering from PTX; 10-year survival rates are 47% and 89%, respectively.67
Septic Obstructive Airway Diseases
This group of diseases is also under the umbrella term of COPD, but these diseases are classified as septic diseases because of the presence of purulent sputum production and a high incidence of pulmonary infections. The hallmark clinical feature is a productive cough with excessive secretion production. The PFT findings are similar with a decrease in expiratory effort despite an increase in TLC. Many of these patients develop hypercapnia, which leads to pulmonary hypertension and cor pulmonale.
Cystic Fibrosis (ICD-9-CM Code: 277)
CF is the most common autosomal recessively inherited disorder in Caucasians.69 Within the lungs, this genetic defect leads to excessive production of thick, dehydrated, hyperviscous mucus and impairment of the mucociliary blanket.70,71 The incidence is 1 in 3,000 births in the United States and Europe. Chronic bouts of inflammation and infection lead to the breakdown of protein in the lungs. Obstructions of small airways develop from mucus plugs and destruction of the cartilaginous support of the airways. The end result is bronchiectasis, which is a permanent dilatation of the bronchi that is characterized by inflamed airways, which are full of purulent sputum23 (see Figs. 7-11 and 7-12).
Cystic fibrosis. Notice the hyperinflation of the lung, the fibrotic changes throughout the lung fields, particularly the upper lobes, and decreased aeration. (Courtesy of Joseph Pilewshi, MD, University of Pittsburgh, PA.)
Cystic fibrosis. This gross pathology slide clearly illustrates destruction of the parenchymal tissue and the large cyst formation. (Courtesy of Dana Gryzbicki, MD, University of Pittsburgh, PA.).
CF is the result of mutation of the gene, CF transmembrane regulator (CFTR), which is associated with the failure of chloride secretion that results in dehydration of endobronchial secretions and cripples the mucociliary function as well as disrupts the function of the pancreas and reproductive system. This leads to an increased attraction to bacteria because of the decreased ability to contain and remove bacteria. CFTR is also associated with the transportation of bicarbonate and sodium and has been linked to the differentiation of osteoblastic cells.72,73
Ninety percent of people who are diagnosed with CF will also have pancreatic insufficiency.69 Recently, it has been recognized that early diagnosis and treatment is important to the aggressive nutritional support that aids in the management of musculoskeletal and pulmonary health.74 Through infancy and childhood, patients with CF will suffer from nasal polyps; failure to thrive syndrome; chronic or recurrent pneumonia; and a chronic cough, pancreatitis, and gastroesophageal reflux disease (GERD).69
The diagnostic findings are similar in patients with other obstructive lung diseases. A chest X-ray typically demonstrates hyperinflation and flattening of the diaphragm. High-resolution CT scans are more sensitive than conventional radiographic studies to detect airway changes and progression of bronchiectasis; there is a strong correlation between CT scan findings and PFTs.72 PFTs reveal an obstructive pattern and a decline in DLCO as the disease progresses. Abnormal arterial blood gases will be consistent with hypoxia and hypercapnia with advancement of the disease.
Most patients will present with a chronic productive cough, dyspnea with accessory muscle use, inspiratory crackles and wheezing, and clubbing of the nail beds.69,75 Patients also present with weight loss, decreased activity tolerance, pancreatic insufficiency, hemoptysis, and sputum production. This clinical picture may be complicated with osteoporosis, muscle wasting, diabetes mellitus, chronic back pain, and developmental delays.24,76 CF is associated with the following complications: massive hemoptysis and spontaneous PTX, which are associated with chronic infection and inflammation.77
Treatment primarily addresses pulmonary care and management of pancreatic insufficiency. Antibiotic and antifungal medications have become the mainstay in managing active infection and minimizing chronic colonization.78 Research has shown that high dosages of ibuprofen have resulted in a reduction in inflammation and slowed the decline in FEV1. Clinically, the risk to renal and gastrointestinal system is too high, and most physicians will not prescribe the use of ibuprofen. Also, low-dose levels have also been linked to the increase of neutrophil migration into the lungs. Other pharmaceutical interventions are being directed at the primary CFTR defect or the direct consequences of its mutation.79 Sputum retention is managed by a variety of airway and pulmonary hygiene techniques.76,80 Additionally, the primary surgical intervention for CF is a double-lung transplantation. Therapy should also include management of osteoporosis and proper nutritional support. Finally, a well-rounded exercise program should be prescribed that addresses aerobic and endurance training, muscle strengthening, spine and osteoporosis care, and energy conservation as the disease progresses. See Chapter 17 for more information on the disease and treatment of CF.
The prognosis is dependent on the aggressiveness of the genetic expression of the disease as well as on the quality of the medical care. Certainly the lifespan of patients with CF has improved with advances in antibiotics, management of pancreatic insufficiency, hypoxia, and hypercapnia. The median life expectancy has increased over the years to 38 years of age.72 Eighty percent of people with CF will succumb to respiratory failure; others will die from complications of right-sided heart failure, severe hemoptysis, and spontaneous PTX.81,82
Bronchiectasis (ICD-9-CM Code: 494)
Bronchiectasis is the permanent dilatation of the bronchi from the destruction of the muscular and elastic properties of the lung. It is characterized by thickening of the bronchial walls, impairment of the mucociliary blanket, hypersecretion of purulent sputum, and bacterial colonization.23,83,84 Indeed, purulent overproduction of secretions is the hallmark of this pulmonary disease.85 There is a classification system for bronchiectasis that describes the distortion of the bronchi. Cylindrical bronchiectasis is associated with relatively uniform dilatation, whereas varicose bronchiectasis is characterized by local constrictions superimposed on cylindrical bronchiectasis. Finally, saccular or cystic bronchiectasis is associated with more severe disease and leads to the formation of bullae.84
Bronchiectasis is usually associated with other underlying pulmonary diseases, but there are rare cases of idiopathetic bronchiectasis that accounts for approximately 30% of the cases.86 Bronchiectasis is typically associated with CF, primary ciliary dyskinesia, and connective tissue disorders, such as rheumatoid arthritis (RA), lupus, α1-ATD, emphysema, and recurrent pulmonary infections.84
There is a higher prevalence of bronchiectasis in underdeveloped countries because of the lack of antibiotics. There is an increased number of patients being treated for bronchiectasis because people are living longer due to medical advances with various pulmonary diseases.87 It has been suggested that there may be a genetic predisposition, as well as environmental factors, that contributes to the development of bronchiectasis.84 The onset of bronchiectasis is commonly seen in the middle aged or in the elderly, but in the cases of congenital lung disease, the diagnosis may be made in childhood or early adulthood.85
There are two key factors that account for the development of bronchiectasis: the presence of intense and chronic inflammation and an inadequate defense mechanism to minimize the effects of infection resulting in tissue damage. These are the foundations for bronchial dilatation, inflammation, and weakening of the bronchial walls, which account for the impairment of the mucociliary escalator. Pooling of secretions creates an environment for bacterial colonization and infection. The increased levels of macrophages contribute to the influx of neutrophils. This increase in neutrophils stimulates phagocytosis; the production of reactive oxygen mediators; the release of proinflammatory mediators such as interleukin-1, interleukin-8, tumor necrosis factor; and the release of protease that causes irreversible loss of the elastin layer and causes the destruction of the smooth muscle and cartilaginous support of airways.85 There is a dysfunction of natural killer cells and the consequences of this cellular response leads to the increase in oxidative stress that causes further tissue damage. A vicious circle hypothesis has been proposed to describe the cycle of infection and chronic immune response, both of which cause lung tissue damage.88
The clinical presentation of bronchiectasis is associated with persistent production of large volumes of secretions, frequent hemoptysis, and recurrent infections. Secretions collect within the bronchioles in dependent positions.85 Crackles, high- and low-pitched rhonchi, and pleural rubs may be heard on auscultation. The patient may also present with fever, fatigue, dyspnea, finger clubbing, and a chronic productive cough with foul-smelling sputum, which may have a bloody tinge to it.84,85 The remaining part of the physical examination is consistent with the underlying disease process. When the underlying disease is an obstructive process such as emphysema or CF, there will be a barrel chest and an obstructive pattern on the PFT. Bronchiectic changes can be seen on X-ray in the presence of a restrictive disease process but, typically, are not associated with overproduction of sputum.84
The diagnosis is primarily made upon clinical history and physical examination. The chest X-ray is relatively nonspecific, but usually illustrates hyperinflation with focal areas of atelectasis. A high-resolution CT scan is the gold standard for diagnosis, which documents dilatation of bronchi with or without bronchial wall thickening.84
The principal treatment for bronchiectasis involves the management of the underlying disease, which commonly includes the use of antibiotics, corticosteroids, and bronchodilators. Nutritional support, supplemental oxygen, airway clearance, and rehabilitation are also key components in the management of a patient with bronchiectasis. Surgical resection of the lung tissue that is the source of repeated infections or hemoptysis and lung transplantation may be an effective treatment plan to minimize recurrent exacerbations and further loss of lung function.85,87
The prognosis is dependent on the underlying disease and its severity, the quality and responsiveness to medical treatment, and the age of the patient. The majority of patients will succumb to respiratory failure or right-sided heart failure related to pulmonary hypertension.87,88