Clinical Manifestations and Assessment of Respiratory Disease, 8th Edition-240-264.pdf

CHAPTER 14 Asthma Chapter Objectives Instrinsic asthma (nonallergic or nontopic asthma) After reading this chapter, you will be able to: Leukotriene Receptor Antagonists (LTRA) Describe the role of the national and interna...

CHAPTER 14 Asthma Chapter Objectives Instrinsic asthma (nonallergic or nontopic asthma) After reading this chapter, you will be able to: Leukotriene Receptor Antagonists (LTRA) Describe the role of the national and international National Asthma Education and Prevention Program (NAEPP) guidelines in the management of asthma. Nonsteroidal Antiinflammatory Drugs (NSAIDs) Describe the anatomic alterations of the lungs associated Occupational Asthma with asthma. Occupational Sensitizers Describe the etiology and epidemiology of asthma. Pulsus Paradoxus List risk factors associated with asthma. Radioallergosorbent Test (RAST) Describe the cardiopulmonary clinical manifestations Refractory Asthma associated with asthma. Reliever (Rescue) Medications Describe the general management of asthma. Remodeling Describe the clinical strategies and rationales of the Respiratory Infectious Disease Panel (RIDP) SOAPs presented in the case study. Respiratory Syncytial Virus (RSV) Define key terms and complete self-assessment questions Short-Acting Beta2-Agonists (SABAs) at the end of the chapter and on Evolve. Sick Building Syndrome (SBS) Specific Immunoglobulin E (sIgE) Key Terms Status Asthmaticus Allergic Bronchopulmonary Aspergillosis (ABPA) Sublingual Allergen Immunotherapy (SLIT) Allergic or Atopic Asthma Treatment-Resistant Asthma Anaphylactic Hypersensitivity Reaction Valved Holding Chamber (VHC) Anaphylaxis Anticholinergic Agents Chapter Outline Aspirin-Induced Asthma (AIA) National Asthma Education and Prevention Program Asthma and Chronic Obstructive Pulmonary Disease (COPD) Global Initiative for Asthma Overlap Syndrome (ACOS) Anatomic Alterations of the Lungs Asthma Control Action Plan Etiology and Epidemiology Asthma Phenotype Risk Factors in Asthma Beta2-Agonist Diagnosis of Asthma Bronchial Thermoplasty Other Diagnostic Tests for Asthma Charcot-Leyden Crystals Overview of the Cardiopulmonary Clinical Manifestations Controller Medications Associated With Asthma Cough Variant Asthma General Management of Asthma Curschmann Spirals Control-Based Asthma Management Program Difficult-to-Treat Asthma The Stepwise Management Approach to Control Asthma Dust Mites Symptoms and Reduce Risk Environmental Factors Nonpharmacologic Interventions in the Treatment of Eosinophils Asthma Exercise-Induced Bronchoconstriction (EIB) Indications for Referral for Expert Evaluation Extrinsic Asthma (allergic atropic asthma) Protocol When Asthma Is Controlled Fractional Concentration of Exhaled Nitric Oxide (FENO) Management of Asthma Exacerbation Gastroesophageal Reflux Disease (GERD) Management of Asthma With Comorbidities and Special GINA Populations Host Factors Respiratory Care Treatment Protocols Immunologic Mechanism Case Study: Asthma Immunoglobulin E–Mediated Allergic Reaction Self-Assessment Questions Inhaled Corticosteroids (ICSs) 218 Hippocrates first recognized asthma more than 2000 years than 30 kg/m2). In addition, asthma is more difficult to ago. Today, asthma remains one of the most common diseases control in obese patients. encountered in clinical medicine. The burdens associated with A relatively new role of the respiratory therapist is that of asthma in the United States—and worldwide—are enormous. asthma educator.1 In this function, the therapist’s goal is to be Although the precise annual numbers are not known, it is sure the patient and the family are cognizant of their role and estimated that asthma is linked to a multitude of lost school functions in the care of this usually chronic and often serious days, countless missed work days, numerous doctor visits, condition. The asthma educator must serve as a “change agent,” frequent hospital outpatient visits, and recurrent emergency and his/her effect as a convincing, empathetic communicator department visits and hospitalizations. will be tested. Toward this end, we have greatly expanded this Asthma is characterized by chronic airway inflammation chapter from previous editions. and is defined by the history of respiratory symptoms such Fortunately, since 1993 the understanding and treatment as wheeze, shortness of breath, chest tightness, and cough of asthma has been updated and continuously refined by the: that vary over time and in intensity and includes variable 1. National Asthma Education and Prevention Program expiratory airflow limitation. Both the symptoms and airflow (NAEPP): Expert Panel Report 3 (EPR-3), Guidelines for limitation typically vary over time and in intensity. The varia- the Diagnosis and Management of Asthma—Full Report, tions in symptoms and airflow limitation are commonly and triggered by factors such as exercise, allergen or irritant 2. Global Initiative for Asthma (GINA): The information exposure, change in weather, or viral respiratory infection. presented in this chapter is consistent with current NAEPP The patient’s symptoms and airflow limitation may resolve and GINA guidelines. spontaneously or in response to medications and may be absent for weeks or months at a time. In addition, the patient may experience episodic flare-ups (exacerbation) that may be life- National Asthma Education and threatening. Asthma episodes are usually associated with airway Prevention Program2 hyperresponsiveness to direct and indirect stimuli and chronic The first evidence-based asthma guidelines were published airway inflammation. in 1991 by NAEPP, which was under the direction of the Asthma is also described as a heterogeneous disease that National Heart, Lung, and Blood Institute (NHLBI) of the commonly has a set of observable characteristics that result National Institutes of Health (NIH). Today, these guidelines from the interaction of the patient’s genotype with the are structured around the following four components of care: environment—called asthma phenotype. The more common (1) assessment and monitoring of asthma, (2) patient education, asthma phenotypes include the following: (3) control of factors contributing to asthma severity, and Allergic or atopic asthma: This asthma phenotype is the (4) treatment medications. The NAEPP’s “stepwise asthma most easily identified. It typically appears in childhood management charts” are used to identify optimal treatment and is associated with a family history of allergic disorders plans for specific age groups—that is, 0 to 4 years, 5 to 11 such as eczema, allergic rhinitis, or food or drug allergies. years, and 12 years and older.3 Before treatment, the sputum of these patients often reveals eosinophilic airway inflammation. Patients with allergic asthma usually respond well to therapy with inhaled Global Initiative for Asthma4 corticosteroids (ICSs). In 1993 the GINA was launched in response to the collabora- Nonallergic asthma: This asthma phenotype is seen in some tive work between the NHLBI (see earlier) and the World adults who do not have allergies. The cellular characteristics Health Organization (WHO). Annually, the role of GINA of the sputum in these patients may be neutrophilic, is to collect the most current scientific evidence associated eosinophilic, or only a few inflammatory cells. Patients with asthma care and transfer this information into a practical with nonallergic asthma usually do not respond well to and user-friendly format. When completed, GINA then ICS therapy disseminates the most current standards of asthma care to a Late-onset asthma: Some adults, especially women, develop large network of health professionals, organizations, and public asthma for the first time in adult life. These patients are health officials. Since the inception of GINA, a number of usually nonallergic and typically require higher doses of important evidence-based clinical guidelines directed at the ICS therapy and are relatively resistant to corticosteroid education, prevention, diagnosis, and management of asthma treatment. Asthma with fixed airflow limitation: Some patients with a long history of asthma develop a fixed airflow 1 The specialty credentialing examination to earn the certified asthma educator limitation that is believed to be caused by airway wall (AE-C) credential is available for respiratory therapists and other health care remodeling—that is, airway structural changes that include professionals through the National Asthma Educator Certification Board subepithelial fibrosis, increased smooth muscle mass, (http://www.naecb.com). 2 enlargement of glands, neovascularization, and epithelial Expert Panel Response 3 (EPR-3): Guidelines for the diagnosis and manage- ment of asthma, 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln alterations..htm. (Last updated April 2012.) Asthma with obesity: Asthma with prominent respiratory 3 A free download of the EPR-3 summary and the complete guidelines are symptoms and little eosinophilic airway inflammation is available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. commonly seen in obese patients (body mass index greater 4 See http://www.ginasthma.org. Chapter 14 Asthma 219  DMC MA SMC MP HALV FIGURE 14.1 Asthma. DMC, Degranulated mast cell; HALV, hyperinflation of alveoli; MA, mucous accumulation; MP, mucous plug; SMC, smooth muscle constriction (bronchospasm). have been developed, refined, and updated annually. For Charcot-Leyden crystals, are formed from the breakdown example, each year GINA provides the following state-of- of eosinophils in patients with allergic asthma (Fig. 14.2). the-art documents5: The crystals are slender and pointed at both ends and have Global Strategy for Asthma Management and Prevention a pair of hexagonal pyramids joined at their bases. They At-A-Glance Asthma Management Reference vary in size and may be as large as 50 µm in length. The Pocket Guide for Asthma Management and Prevention goblet cells proliferate, and the bronchial mucous glands GINA teaching slide set enlarge. The airways become filled with thick, whitish, tenacious mucus. Extensive mucous plugging and atelectasis may develop. Anatomic Alterations of the Lungs As a result of smooth muscle constriction, bronchial mucosal Asthma is described as a lung disorder characterized by (1) edema, and excessive bronchial secretions, air trapping and reversible bronchial smooth muscle constriction, (2) airway alveolar hyperinflation develop (see Fig. 14.1). If chronic inflammation, and (3) increased airway responsiveness to an inflammation develops over time, these anatomic alterations assortment of stimuli. During an asthma attack, the smooth become irreversible, resulting in loss of airway caliber. In addi- muscles surrounding the small airways constrict. Over time tion, the cilia are often damaged, and the basement membrane the smooth muscle layers hypertrophy and can increase to of the mucosa may become thicker than normal (fibrosis). three times their normal thickness (Fig. 14.1). This whole process is referred to as “remodeling.” The airway mucosa becomes infiltrated with eosinophils A remarkable feature of bronchial asthma, however, is that and other inflammatory cells, which in turn cause airway many of the pathologic anatomic alterations of the lungs that inflammation and mucosal edema. Microscopic crystals, called occur during an asthma attack are completely absent between asthma episodes and that (at least in mild to moderate cases) remodeling does not occur to any great extent. 5 The GINA global strategy for asthma management and prevention documents In summary, the major pathologic or structural changes are freely available on the GINA website (http://www.ginasthma.org). observed during an asthma episode are as follows: 220 Chapter 14 Asthma  A B FIGURE 14.2 (A) At high magnification, numerous eosinophils are recognized by their bright red cytoplasmic granules, in this case of bronchial asthma. (B) In another patient with an acute asthma episode, Charcot-Leyden crystals (▲), which are derived from the breakdown of eosinophil granules, are seen microscopically (stained purplish-red). (From Klatt, E. C.. Robbins and Cotran atlas of pathology [3rd ed.]. Philadelphia, PA: Elsevier.) Smooth muscle constriction of bronchial airways (bron­ Regardless of this debate, the experts are—for the most chospasm) part—in full agreement that the risk factors for asthma can Excessive production of thick, whitish bronchial secretions be divided into host factors, which are primarily genetic, that Mucous plugging result in the development of (intrinsic) asthma, or environ- Hyperinflation of alveoli (air trapping) mental factors that trigger the clinical manifestations of In severe cases, atelectasis caused by mucous plugging (extrinsic) asthma, or a combination of both (Box 14.2). Bronchial wall inflammation leading to fibrosis (in severe cases, caused by remodeling) Host Factors Genetics. There are several persistent and intermittent genetic phenotypes of asthma. Although the genetic factors Etiology and Epidemiology associated with asthma are varied and not fully understood, According to the latest information from the Centers for the search for genetic links to asthma has primarily focused Disease Control and Prevention (CDC) and the National on the following four areas: (1) the production of allergen- Center for Health Statistics (NCHS), in the United States specific immunoglobulin E (IgE) antibodies, (2) airway about 18.4 million adults (percent of adults: 7.6%), and 6.2 hyperresponsiveness, (3) inflammatory mediators, and (4) million children (percent of children: 8.4%), have asthma—a T-helper cells (Th1 and Th2), which are an important part total of about 25 million. According to the CDC, about 6.5% of the immune system. The T-helper cells are lymphocytes of the all physician office visits are asthma related and about that recognize foreign pathogens or, in the case of autoimmune 1.9 million visits to the emergency department per year disease, normal tissue. Th1 cells are involved in what is called have asthma as the primary diagnosis. Asthma is the cause cell-mediated immunity, which usually deals with infections of about 3651 deaths per year in the United States. Asthma caused by viruses and certain bacteria. They are the body’s is nearly twice as prevalent in young boys as young girls. In first line of defense against pathogens that invade the body the adult, however, asthma is more common in women than cells. They tend to be inflammatory. Th2 cells are involved in men. in humoral-mediated immunity, which deals with bacteria, The WHO6 estimates that about 235 million people toxins, and allergens. They are responsible for stimulating the worldwide suffer from asthma. Low-income and middle- production of antibodies in response to extracellular pathogens. income countries account for more than 80% of the mortality. They tend not to be inflammatory. Worldwide, asthma is the most common chronic disease among children. Clearly, the effect of asthma on health, quality of Sex. Before the age of 14 years, the prevalence of asthma is life, and the economy is substantial. nearly two times greater in boys than in girls. Asthma severity in boys generally peaks around age 5 to 7 years and lessens Risk Factors in Asthma dramatically during puberty. As children become older, the Asthma authorities are not in full agreement as to how the prevalence of asthma narrows between the sexes as many girls risk factors for certain kinds of asthma should be categorized— experience the onset of asthma during puberty. In adulthood, for example, should a certain type of asthma be placed under the prevalence of asthma is greater in women than in men. the heading of extrinsic versus intrinsic asthma, or allergic versus nonallergic asthma, or atopic versus nonatopic asthma Obesity. Asthma is more commonly seen in obese people (Box 14.1). (body mass index greater than 30 kg/m2). In addition, asthma is more difficult to control in obese patients. Obese patients also have more problems with lung function and more comorbidities 6 http://www.who.int/en/. compared with normal weight patients with asthma. Chapter 14 Asthma 221  BOX 14.1 Commonly Used Categories for Risk Factors in Asthma Extrinsic Asthma (Allergic or Atopic Asthma) degranulate and release chemical mediators such as When an asthma episode can clearly be linked to exposure histamine, eosinophil chemotactic factor of anaphylaxis to a specific allergen (antigen), the patient is said to have (ECF-A), neutrophil chemotactic factors (NCFs), leukotrienes extrinsic asthma (also called allergic or atopic asthma). (formerly known as slow-reacting substances of anaphylaxis Common indoor allergens include house dust mites, furred [SRS-A]), prostaglandins, and platelet activating factor (PAF) animal dander (e.g., dogs, cats, and mice), cockroach allergen, (see Fig. 14.3B). fungi, molds, and yeast. Outdoor allergens include pollens, 3. The release of these chemical mediators stimulates fungi, molds, and yeast. In addition, there are a number of parasympathetic nerve endings in the bronchial airways, occupational substances associated with asthma. leading to reflex bronchoconstriction and mucous hyper- Extrinsic asthma is an immediate (type I) anaphylactic secretion. Moreover, these chemical mediators increase hypersensitivity reaction. It occurs in individuals who have the permeability of capillaries, which results in the dilation atopy, a hypersensitivity condition associated with genetic of blood vessels and tissue edema (see Fig. 14.3C). predisposition, and an excessive amount of IgE antibody The patient with extrinsic asthma may demonstrate an production in response to a variety of antigens. From 10% early asthmatic (allergic) response, a late asthmatic response, to 20% of the general population are atopic and therefore or a biphasic asthmatic response. The early asthmatic have a tendency to develop an immunoglobulin E–mediated response begins within minutes of exposure to an inhaled allergic reaction such as asthma, hay fever, allergic rhinitis, antigen and resolves in about 1 hour. A late asthmatic and eczema. Such individuals develop a wheal-and-flare response begins several hours after exposure to an inhaled reaction to a variety of skin test allergens, called a positive antigen but lasts much longer. The late asthmatic response skin test result. Extrinsic asthma is family-related and usually may or may not follow an early asthmatic response. An early appears in children and in adults younger than 30 years old. asthmatic response followed by a late asthmatic response It often disappears after puberty. is called a biphasic response. Because extrinsic asthma is associated with an antigen antibody–induced bronchospasm, an immunologic mechanism Intrinsic Asthma (Nonallergic or Nonatopic Asthma) plays an important role. As with other organs, the lungs are When an asthma episode cannot be directly linked to a protected against injury by certain immunologic mechanisms. specific antigen or extrinsic inciting factor, it is referred to Under normal circumstances these mechanisms function as intrinsic asthma (also called nonallergic or nonatopic without any apparent clinical evidence of their activity. In asthma) (Fig. 14.4). The etiologic factors responsible for patients susceptible to extrinsic or allergic asthma, however, intrinsic asthma are elusive. Individuals with intrinsic asthma the hypersensitive immune response actually creates the are not hypersensitive or atopic to environmental antigens disease by causing acute and chronic inflammation. and have a normal serum IgE level. The onset of intrinsic asthma usually occurs after the age of 40 years, and typically Immunologic Mechanisms there is no strong family history of allergy. 1. When a susceptible individual is exposed to a certain In spite of the general distinctions between extrinsic and antigen, lymphoid tissue cells form specific IgE (reaginic) intrinsic asthma, a significant overlap exists. Distinguishing antibodies. The IgE antibodies attach themselves to the between the two is often impossible in a clinical setting. surface of mast cells in the bronchial walls (Fig. 14.3A). Precipitating factors known to cause intrinsic asthma are 2. Reexposure or continued exposure to the same antigen referred to as nonspecific stimuli. Some of the more common creates an antigen-antibody reaction on the surface of nonspecific stimuli associated with intrinsic asthma are the mast cell, which in turn causes the mast cell to discussed in the main text. BOX 14.2 Risk Factors for Asthma Host Factors Tobacco smoke (passive smoking and active smoking) Genetics (e.g., genes predisposing to atopy, airway hyper- Outdoor/indoor air pollution responsiveness airway inflammation) Diet: Especially in the case of food allergies Obesity Sex Other Risk Factors Certain drugs (e.g., aspirin) and food additives and Environmental Factors preservatives Allergens Exercise Indoor: Domestic mites, furred animals (e.g., dogs, Gastroesophageal reflux cats, mice), cockroach allergen, fungi, molds, yeast Sleep Outdoor sensitizers and allergens (e.g., flour laboratory Emotional stress rodents, paints) Perimenstrual asthma Infections (primarily viral) Allergic bronchopulmonary aspergillosis 222 Chapter 14 Asthma  BOX 14.3 Agents Associated With Occupational Asthma A Antigen Peripheral lymphoid tissue IgE Sensitized mast Animal and Plant Proteins cell Flour, amylase NCF Bacillus subtilis enzymes (detergent manufacturing) ECF-A SRS-A Prostaglandins Colophony, such as pine resin (electrical soldering, Histamine Leukotrienes PAP cosmetics, adhesives) Soybean dust B Antigen IgE-antigen interaction Midges, parasites (fish food manufacturing) NCF Coffee bean dust, meat tenderizer, tea, shellfish, ECF-A amylase, egg proteins, pancreatic enzymes, papain Histamine Storage mites, Aspergillus, indoor ragweed, grass Smooth muscle constriction, (granary workers) IgE-antigen interaction Leukotrienes mucus hypersecretion, dilation of blood vessels, and Psyllium, latex (hospital workers) C tissue edema Ispaghula, psyllium (laxative manufacturing) FIGURE 14.3 The immunologic mechanisms in extrinsic asthma Poultry droppings, mites, feathers (see Box 14.2). Locusts, dander, urine proteins Wood dust, such as western red cedar, oak, mahogany, zebrawood, redwood, Lebanon cedar, African maple, eastern white cedar Chemical irritants or fumes Dust and air Grain dust, molds, insects, grain pollutants Silkworm moths and larvae Industrial or Tobacco occupational exposure smoke Inorganic Chemicals Irritant Persulfate (beauticians) Drugs vapors Nickel salts Smooth muscle constriction Emotional Platinum salts, vanadium Cold air stress Organic Chemicals Infections Exercise Ethanolamine diisocyanate (automobile painting) Disinfectants, such as sulfathiazole, chloramines, Alveolus formaldehyde, and glutaraldehyde Latex (hospital workers) Antibiotics, piperazine, methyldopa, salbutamol, cimeti- dine (manufacturing) FIGURE 14.4 Some factors known to trigger intrinsic asthma (see Ethylene diamine, phthalic anhydride Box 14.2). Toluene diisocyanate, diphenylene, tetramines, trimellitic anhydride, hexamethyl tetramine, acrylates (plastics industry) Environmental Factors Allergens Outdoor and Indoor Air Pollution. Outbreaks of asthma exacerbations have been reported in areas of increased levels about 15% of cases of asthma among adults of working of air pollution, especially when the environmental air is laden age. High-risk work environments for occupational asthma with pollutant particulates less than 5 µm in diameter. The include farming and agricultural work, painting (including role of outdoor air pollution in causing asthma remains con- spray painting), cleaning work, and plastic manufacturing. troversial. Similar associations have been reported in relation Most occupational asthma is immunologically mediated and to indoor pollutants such as smoke and fumes from gas and has a latency period of months to years after the onset of biomass fuels used for heating and cooling, molds, and cockroach exposure. infestation—e.g., in the sick building syndrome (SBS). Although the cause is not fully understood, it is known that an IgE-mediated allergic reaction and cell-mediated Occupational Sensitizers (Occupational Asthma). Occu- allergic reactions are often involved. Box 14.3 shows additional pational asthma is defined as asthma caused by exposure to agents known to cause occupational asthma. It also should an agent encountered in the work environment. More than be noted that many leisure-time activities can cause asthma 300 different substances have been associated with occupa- by exposing individuals to harmful particles and fumes. For tional asthma. Occupational asthma is seen predominantly example, severe asthma episodes have been triggered by hobbies in adults. It is estimated that occupational sensitizers cause associated with sawdust and sealants (e.g., commonly found Chapter 14 Asthma 223 in a woodworker’s shop) and the various fumes that can be asthmatic population may be sensitive to aspirin and NSAIDs. inhaled by car enthusiasts (e.g., car exhaust, paints, polishes, Beta-blocking drugs administered orally (e.g., propranolol, cleaning products, scented air fresheners, etc.). metoprolol) and intraocular medications for glaucoma are also associated with asthma exacerbations. Infections (Predominantly Viral). Although bacte- rial infections may cause asthma, viral upper and lower Food Additives and Preservatives. Sulfites (common airway infections are more likely to contribute to asthma. For food and drug preservatives found in such foods as processed example, several viruses seen during infancy are associated with potatoes, shrimp, dried fruits, beer, wine, and sometimes lettuce the activation of the asthma phenotype. Such viruses include the in salad bars) have often been associated with causing severe respiratory syncytial virus (RSV), human rhinovirus (HRV), asthma exacerbations. About 5% of the asthmatic population is and parainfluenza virus. These conditions often produce a sensitive to foods and drinks that contain sulfites. The synthetic pattern of symptoms that parallel many features of childhood lemon yellow dye tartrazine may provoke an asthma episode. asthma. For example, it is estimated that about 40% of children with RSV infection will continue to wheeze or have asthma Exercise-Induced Bronchoconstriction. Asthma is into later childhood. sometimes associated with vigorous exercise. In children, exercise is a common trigger of asthma symptoms. Research Microbiome. The collection of microorganisms and their has shown that the drying and cooling of the airways during genetic material, both within the host and the host’s surrounding exercise is the primary trigger mechanism. Running in cold environment, is associated with the development of allergic air is the activity that causes the most bronchospasm, whereas disorders and asthma. For example, delivery by cesarean section swimming in a warm environment causes the fewest asthma has a higher risk factor for the development of asthma. symptoms (assuming the water is nonchlorinated and the pool area is well ventilated). Tobacco Smoke. Exposure to tobacco smoke, both prenatally and after birth, is associated with a greater risk for Gastroesophageal Reflux. Gastroesophageal reflux developing asthma-like clinical manifestations in early child- disease (GERD), or regurgitation, appears to significantly hood. Infants of smoking parents are four times more likely contribute to bronchoconstriction in some patients. The precise to develop wheezing illnesses in the first year of life. In fact, mechanism of this relationship is not known. The patient the concern of exposing children to tobacco smoke has resulted may complain of burning, substernal pain, belching, and a in several states enacting legislation that prohibits smoking bitter, acid taste, particularly when lying down. Incidentally, in motor vehicles when children are passengers. unrecognized GERD is one of the most common causes of a hard-to-diagnose cough; unrecognized sinusitis is the other Outdoor and Indoor Air Pollution. Air pollution causes most common cause. diminished lung function and increased asthma-related morbidity. Similarly, indoor pollutants (e.g., smoke and fumes Sleep (Nocturnal Asthma). Patients with asthma often from gas or biomass fuels that are used for heating and cooling, have more breathing difficulty late at night or in the early molds, and cockroach infestations) are also related to decreased morning as serum cortisol levels drop at night. Precipitating lung function and increased morbidity. factors associated with nocturnal asthma include gastro- esophageal reflux and retained airway secretions (caused by Diet. Research has suggested that infants given formulas a suppressed cough reflex during sleep). Additional precipitat- of intact cow’s milk or soy protein have a higher incidence of ing factors include exposure to irritants or allergens in the wheezing symptoms in early childhood compared with infants bedroom and prolonged time between medication doses. given breast milk. Studies have also indicated that certain Eradication of nocturnal asthma is one measure of good characteristics of Western diets, such as the following, have asthma control. been associated with asthma: Increased use of processed foods Emotional Stress. In some patients, the exacerbation of Decreased antioxidants (in the form of fruits and asthma appears to correlate with emotional stress and other vegetables) psychologic factors. This is most likely mediated by histamine Increased omega-6 polyunsaturated fatty acid (found in release from circulating mast cells. margarine, vegetable oil, and eggs) Decreased omega-3 polyunsaturated fatty acid (found in Perimenstrual Asthma (Catamenial Asthma). Clinical fish oil) manifestations associated with asthma often worsen in women Foods that clearly cause an allergy and/or asthma symptoms during the premenstrual and menstrual periods. The symptoms (usually demonstrated by oral challenges) of course should be often peak 2 to 3 days before menstruation begins. Premenstrual avoided. asthma correlates with the late luteal phase of ovarian activity, the phase during which circulating progesterone and estrogen Other Risk Factors levels are low. Drugs. Asthma exacerbations are associated with the ingestion of aspirin and other nonsteroidal antiinflammatory Allergic Bronchopulmonary Aspergillosis. Allergic drugs (NSAIDs). It is estimated that as much as 20% of the bronchopulmonary aspergillosis (ABPA) is characterized by 224 Chapter 14 Asthma an exaggerated response of the immune system—a hypersen- FEV1/FVC ratio is reduced sitivity response—to the Aspergillus fungus (see Chapter 18, Normal is more than 0.75 to 0.80 in adults Pneumonia, Lung Abscess Formation, and Important Fungal Normal is >90% in children Diseases) in patients with asthma and cystic fibrosis. ABPA FEV1 increases by >12% and (or ≥200 mL) after 4 weeks can cause airway inflammation and bronchospasm. Patients of antiinflammatory therapy with ABPA often have symptoms of poorly controlled asthma, Or peak expiratory flow rate (PEFR) by >20% on such as wheezing, cough, shortness of breath, and reduced the same peak expiratory flowmeter exercise tolerance. In addition, the asthma patient needs to be assessed for: Control of asthma symptoms over the previous 4 weeks—for example: Diagnosis of Asthma Daytime or night symptoms The diagnosis of asthma often can be challenging. For example, Unable to sleep because of asthma symptoms in early childhood, the diagnosis of asthma frequently is based Relievers needed more than twice a week on the assessment of the child’s symptoms and physical Risk factors for more asthma outcomes—for example: findings—and good clinical judgment. For instance, the child Exacerbations for uncontrolled symptoms or poor has a 5- to 10-fold greater chance of being diagnosed with adherence asthma if the child has what is referred to as either one major Fixed airflow limitation for lack of ICS therapy, low criterion, such as a parent with asthma or the presence of initial FEV1, smoking, or occupational exposures atopic dermatitis, or two minor criteria, such as allergic rhinitis, Medication side effects such as frequent use of ICS wheezing apart from colds, or a peripheral eosinophil count therapy or long-term high-dose ICS greater than 4%. Every asthma patient should be assessed for inhaler In the older child and the adult, a complete history and technique, adherence, treatment issues, medication side effects, physical examination, along with the demonstration of reversible and any comorbidities (e.g., rhinitis, rhinosinusitis, GERD, and variable airflow obstruction, will in most cases confirm the obesity, obstructive sleep apnea, depression, and anxiety) and diagnosis of asthma. However, in the elderly patient, asthma is a written action plan.7 often undiagnosed because of the presence of comorbid diseases that complicate the diagnosis. In addition, the diagnosis of Other Diagnostic Tests for Asthma asthma is often missed in the patient who acquires asthma Because patients often have normal lung function between in the workplace. This form of asthma is called occupational asthma episodes, measurements of airway responsiveness to asthma (see Box 14.3). Because occupational asthma usually a bronchial provocation test, allergy tests, and an exhaled nitric has a slow and insidious onset, the patient’s asthma is often oxide test may be helpful in the diagnosis of asthma. misdiagnosed as chronic bronchitis or chronic obstructive pulmonary disease (COPD). As a result, the asthma is either Bronchial Provocation Test not treated at all or treated inappropriately. Because airflow limitation may be absent during the initial Finally, even though asthma usually can be distinguished assessment in some patients, a bronchial provocation test may from COPD, in some patients—those who have chronic be helpful in assessing airway hyperresponsiveness. This is respiratory clinical manifestations and fixed airflow most often done with inhaled methacholine. However, his- limitations—it is often very difficult to differentiate between tamine exercise, eucapnic voluntary hyperventilation, or inhaled the two disorders—that is, asthma or COPD (this problem mannitol may also be used. is discussed further later in this chapter under Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome, Allergy Tests page 225). The presence of allergic asthma can be assessed by skin prick GINA provides an excellent guideline to help in the clinical testing or by measuring the level of specific immunoglobulin diagnosis of asthma. GINA’s guideline is based on the following E (sIgE), (via radioallergosorbent test [RAST]) in serum. two key defining features of asthma: The skin prick test uses common environmental allergens, is A history of variable respiratory symptoms—for example: inexpensive, has a high sensitivity, and is simple and fast to Wheezing, shortness of breath, chest tightness, and perform. The measurement of sIgE is more expensive but cough that are often worse at night, varying over time may be preferred by patients who do not wish to undergo a and intensity, or triggered by colds, exercise, and allergen series of needle pricks, have a widespread skin disease, or have exposure.) a history of anaphylaxis. The patient’s physical examination often appears normal, but may demonstrate wheezing on auscultation, especially Exhaled Nitric Oxide during a forced expiration. Clinicians are now able to judge the control of eosinophilic The evidence of variable expiratory airflow limitation such airway inflammation caused by asthma by measuring fractional as (one or more of the following): concentration of exhaled nitric oxide (FENO). In adults, the FEV1: >12% (or ≥200 mL) after inhaling a bronchodilator In children: >12% of their predicted PEFR: Daily variability >10% In children: >13% 7 For an example of an asthma action plan, see Fig. 14.9, page 235. Chapter 14 Asthma 225 normal FENO is less than 25 ppb. The normal FENO in bronchial provocation test. Conditions associated with asthma, children is less than 20 ppb. The FENO levels rise with such as rhinitis, laryngeal disorders, dysfunctional breathing, eosinophilic airway inflammation; a high FENO (greater than cardiac conditions, and overtraining, need to be excluded. 50 ppb) suggests a need to increase the patient’s controller medication. A common cause of increased FENO is patients’ Pregnant Women. Women planning a pregnancy should be lack of compliance with their prescribed ICS therapy. asked if they have a history of asthma so the appropriate advice can be provided regarding asthma management and Diagnosis of Asthma in Special Populations medications. GINA describes the challenges associated with diagnosing asthma among special populations, including patients with The Elderly. Asthma is often underdiagnosed in the elderly cough-variant asthma, occupational and work-aggravated because of their acceptance of dyspnea as being “normal” in asthma, athletes, pregnant women, the elderly, smokers and old age, lack of fitness, and reduced activity. A careful history ex-smokers, patients already taking controller medications, and physical examination, combined with an electrocardiogram and obese patients. and chest x-ray, will help in the diagnosis. In addition, a history of smoking or biomass fuel exposure, COPD, and Cough-Variant Asthma. Some patients have a chronic cough overlapping asthma and COPD (called asthma-COPD overlap as their primary—if not their only—symptom. It is especially [ACO], Table 14.1) should be considered. common in children and is most often seen at night. Evalu- ations during the day are often normal. In these cases, tests Smokers and Ex-Smokers. Asthma and COPD may be difficult directed at the patient’s airway hyperresponsiveness, and the to distinguish, especially in older patients, smokers and ex- search for possible sputum and blood eosinophils, may be smokers, and patients with ACO. The history and pattern of helpful in confirming the diagnosis of asthma. symptoms and past records can be helpful in distinguishing these patients from patients with asthma. Occupational and Work-Aggravated Asthma. Asthma acquired in the workplace is a frequently missed diagnosis. Because of Confirming the Diagnosis of Asthma in Patients Taking Controller the insidious onset of occupational asthma, it is often misdi- Medications. Between 25% and 35% of the patients with a agnosed as chronic bronchitis or COPD and therefore treated diagnosis of asthma cannot be confirmed as having asthma. inappropriately or not at all. The development of a constant In these patients, a trial of either a lower or higher dose of cough, wheezes, and rhinitis should raise suspicion, especially controller treatment is recommended. If the diagnosis cannot in the nonsmoker. The diagnosis of occupational asthma requires be confirmed, the patient should undergo an expert evaluation a defined history of occupational exposure to sensitizing agents, and diagnosis. the absence of asthma symptoms before beginning employment, and a documented relationship between the asthma symptoms Obese Patients. Because the respiratory symptoms associated and the workplace—an improvement in the asthma symptoms with obesity can mimic asthma, it is important to confirm when away from the workplace and a worsening of the asthma the diagnosis of asthma with objective measurements of variable symptoms on return to the workplace. airflow limitation. Athletes. Exercise-induced bronchoconstriction (EIB) should be confirmed by lung function tests, including a 226 Chapter 14 Asthma  OVERVIEW of the Cardiopulmonary Clinical Manifestations Associated With Asthma The following clinical manifestations result from the pathophysi- enhances intrapulmonary airflow. The increased negative ologic mechanisms caused (or activated) by bronchospasm intrapleural pressure, however, also causes blood vessels in (see Fig. 10.10) and excessive bronchial secretions (see Fig. the lungs to dilate and blood to pool. Consequently, the volume 10.11)—the major anatomic alterations of the lungs associated of blood returning to the left ventricle decreases. This causes with an asthma episode (see Fig. 14.1). a reduction in cardiac output and arterial blood pressure during inspiration. CLINICAL DATA OBTAINED AT THE Increased blood pressure during expiration PATIENT’S BEDSIDE During expiration, the patient often activates the accessory The Physical Examination muscles of expiration in an effort to overcome the increased Vital Signs airway resistance. The increased power produced by these Increased respiratory rate (tachypnea) muscles generates a greater positive intrapleural pressure. Several pathophysiologic mechanisms operating simultane- Although increased positive intrapleural pressure may help ously may lead to an increased ventilatory rate: offset the airway resistance, it also works to narrow or squeeze Stimulation of peripheral chemoreceptors (hypoxemia) the blood vessels of the lung. This increased pressure on the Decreased lung compliance and increased ventilatory rate pulmonary blood vessels enhances left ventricular filling and relationship results in an increased cardiac output and arterial blood pres- When lungs are hyperinflated, the patient must work harder sure during expiration. to breathe at the flat portion of the volume-pressure curve Chest Assessment Findings (see Fig. 3.2) Expiratory prolongation (I/E ratio >1 : 3) Anxiety Decreased tactile and vocal fremitus Increased Heart Rate (Pulse) and Blood Pressure Hyperresonant percussion note Use of Accessory Muscles During Inspiration Diminished breath sounds Use of Accessory Muscles During Expiration Diminished heart sounds Pursed-Lip Breathing Wheezing Substernal Intercostal Retractions Crackles Substernal, supraclavicular, and intercostal retractions during inspiration may be seen, particularly in children. CLINICAL DATA OBTAINED FROM LABORATORY Increased Anteroposterior Chest Diameter (Barrel Chest) AND SPECIAL PROCEDURES Cyanosis Cough and Sputum Production During an asthma episode the patient may produce an Pulmonary Function Test Findings excessive amount of thick, whitish, tenacious mucus. At other Moderate to Severe Asthma Episode (Obstructive Lung Pathology) times, because of large numbers of eosinophils and other FORCED EXPIRATORY VOLUME AND FLOW RATE FINDINGS white blood cells, the sputum may be purulent. FVC FEVT FEV1/FVC ratio FEF25%–75% Pulsus Paradoxus ↓ ↓ ↓ ↓ When an asthma episode produces severe alveolar air trapping and hyperinflation, pulsus paradoxus is a classic clinical FEF50% FEF200–12001 PEFR MVV manifestation. Pulsus paradoxus is defined as systolic blood ↓ ↓ ↓ ↓ pressure that is more than 10 mm Hg lower on inspiration than on expiration. This exaggerated waxing and waning of LUNG VOLUME AND CAPACITY FINDINGS arterial blood pressure can be detected by using a manual VT IRV ERV RV blood pressure cuff or, in severe cases, by palpating the strength N or ↑ N or ↓ N or ↓ ↑ of the pulse. Pulsus paradoxus during an asthma attack is believed to be caused by the major intrapleural pressure swings VC IC FRC TLC RV/TLC ratio that occur during inspiration and expiration and is associated ↓ N or ↓ ↑ N or ↑ N or ↑ with a severe life-threatening condition. Decreased blood pressure during inspiration During inspiration the patient frequently recruits accessory muscles of inspiration. The accessory muscles help produce an extremely negative intrapleural pressure, which in turn 1 NOTE: The FEF200–1200 is rarely used in pediatrics. Chapter 14 Asthma 227  OVERVIEW of the Cardiopulmonary Clinical Manifestations Associated With Asthma—cont’d Arterial Blood Gases ASTHMA-COPD OVERLAP (ACO) GINA provides an approach to distinguishing among asthma, MILD TO MODERATE ASTHMA EPISODE COPD, and the overlap of asthma and COPD (termed asthma Acute Alveolar Hyperventilation With Hypoxemia2 and COPD overlap [ACO]). Rather than attempting to provide (Acute Respiratory Alkalosis) a formal definition of ACO, GINA presents the clinical manifesta- pH PaCO2 HCO3− PaO2 SaO2 or SpO2 tions that identify and characterize ACO, assigning equal weight ↑ ↓ ↓ ↓ ↓ to features of asthma and COPD. Table 14.1 provides the (but normal) highlights provided by GINA that distinguish the features of asthma, COPD, and ACO. SEVERE ASTHMA EPISODE (STATUS ASTHMATICUS) Acute Ventilatory Failure With Hypoxemia3 (Acute RADIOLOGIC FINDINGS Respiratory Acidosis) Chest Radiograph (During an Asthma Episode) pH4 PaCO2 HCO3− 4 PaO2 SaO2 or SpO2 Increased anteroposterior diameter (“barrel chest”) ↓ ↑ ↑ ↓ ↓ Translucent (dark) lung fields (but normal) Depressed or flattened diaphragm As the alveoli become enlarged during an asthma attack, Oxygenation Indices5 the residual volume and functional residual capacity increase. Moderate to Severe Stages This condition decreases the radiographic density of the lungs. Q̇ S/Q̇ T DO26 V̇ O2 C(a-v)O2 O2ER SvO2 Consequently, the chest radiograph shows lung shadows ↑ ↓ N N ↑ ↓ that are translucent or darker than normal in appearance. Because of the increased residual volume, functional residual capacity, and total lung capacity, the diaphragms are depressed ABNORMAL LABORATORY TESTS and flattened (Fig. 14.5). AND PROCEDURES Sputum Examination Eosinophils Charcot-Leyden crystals Casts of mucus from small airways (Curschmann spirals) IgE level (elevated in extrinsic asthma) 2 See Fig. 5.2 and Table 5.4 and related discussion for the acute pH, PaCO2, and HCO3− changes associated with acute alveolar hyperventilation. 3 See Fig. 5.2 and Table 5.5 and related discussion for the acute pH, PaCO2, and HCO3− changes associated with acute ventilatory failure. 4 When tissue hypoxia is severe enough to produce lactic acid, the pH and HCO3− values will be lower than expected for a particular PaCO2 level. 5 C ( a-v )O2 , Arterial-venous oxygen difference; DO2, total oxygen delivery; O2ER, oxygen extraction ratio; Q̇ S /Q̇ T, pulmonary shunt fraction; SvO2, mixed venous oxygen saturation; V̇ O2, oxygen consumption. 6 The DO2 may be normal in patients who have compensated to the decreased oxygenation status with (1) an increased cardiac output, (2) an increased hemoglobin FIGURE 14.5 Chest x-ray film of a 2-year-old patient during an level, or (3) a combination of both. When the DO2 is normal, the O2ER is usually normal. acute asthma attack. 228 Chapter 14 Asthma  OVERVIEW of the Cardiopulmonary Clinical Manifestations Associated With Asthma—cont’d TABLE 14.1 Common Features of Asthma, Chronic Obstructive Pulmonary Disease (COPD), and Asthma and COPD Overlap, Including Features That Favor Asthma or COPD Common Features of Asthma, COPD, and Asthma and COPD Overlap Features That Favor Asthma or COPD Asthma and Feature Asthma COPD COPD Overlap Favors Asthma* Favors COPD* Age of onset Usually Usually >40 years Usually age >40 Onset before age Onset after 40 childhood of age years, but may 20 years years onset but can have had commence at symptoms in any age childhood or early adulthood Pattern of Symptoms may Chronic usually Respiratory Variation in Persistence of respiratory vary over time continuous symptoms symptoms over symptoms symptoms (day to day, or symptoms, including minutes, hours, despite treatment over longer particularly exertional or days Good and bad days periods), often during exercise, dyspnea are Symptoms worse but always daily limiting activity with better or persistent but during the night symptoms and Often triggered worse days variability may be or early morning exertional by exercise, prominent Symptoms triggered dyspnea emotions by exercise, Chronic cough and including emotions, sputum preceded laughter, dust, including laughter, onset of dyspnea, or exposure to dust, or exposure unrelated to allergens to allergens triggers Lung function Current and/or FEVl may be Airflow limitation Record of variable Record of persistent historical improved by not fully airflow limitation airflow limitation variable airflow therapy, but reversible, but (spirometry, peak (postbronchodilator limitation postbronchodilator often with current flow) FEV1/FVC