Deborah A. Bohan
Wheezing is a common presenting symptom of respiratory illness in children. Although the most frequent cause of wheezing in children is asthma, conditions in the respiratory, gastrointestinal, cardiovascular, and other systems can cause children to have problems exchanging air. Problems can range from minimal to life-threatening in severity. The primary care provider needs to sort it all out efficiently, effectively, and inexpensively with the least stress possible to the child and family. Obtaining a detailed history (including family history) and focused physical exam will help in making an accurate diagnosis.
1. Describe the prevalence and epidemiology of asthma.
2. Understand the definition of asthma and describe its pathophysiology.
3. Recognize the symptoms of asthma.
4. Establish an appropriate asthma management plan based on new National Heart, Lung and Blood Institute (NHLBI) guidelines.
Case Presentation and Discussion
James Washington is a 4-year-old black male who recently moved to the area with his family. James comes to your office with his mother, Mary Washington, with a chief complaint of difficulty breathing and cough. His symptoms started this morning shortly after waking up, although his mom says he has had some congestion and a runny nose for the past 2–3 days.
The important parts of the history in a child with wheezing depend, in part, upon whether a diagnosis such as asthma has been made previously and the reason for the current evaluation. Is this an initial diagnosis, a disease monitoring visit, or an acute exacerbation? In the case of a wheezing child, the history should focus on the presenting symptoms, precipitating factors, and typical symptom patterns.
What other historical data do you need to collect from James?
Important additional information to obtain includes:
• Previous history of dyspnea, wheezing, or persistent cough
• Previous office, clinic, or emergency department visits for this same complaint
• Previous hospitalizations or intubations
• Whether steroids were ever prescribed and, if so, last course and for how long
• Precipitating factors
• General medical history, including medications and immunizations
James has had four or five similar episodes over the past 2 years that resulted in unscheduled visits to his former pediatrician’s office. Each time, James was sent home with a prescription for an albuterol inhaler to be used as needed. According to Mom, he has a lot of “colds” year round, and they seem to last for a long time. During these episodes, James often wakes up at night coughing. His daycare providers have noticed that he will often start to cough while playing and has to stop his activity to “catch his breath.”
James was born at 39 weeks gestational age via a normal spontaneous vaginal delivery. He has no significant medical illnesses other than the wheezing. He has never been prescribed steroids nor hospitalized overnight. He takes no medications other than the albuterol as described, has no known drug allergies, and his immunizations are up to date by record review. He has no complaints of vomiting, heartburn, or hoarseness, and actively engages in vigorous running games with his playmates when “his asthma” is not acting up.
James lives with his parents and an older sister. There is a history of secondhand smoke exposure—Mom smokes in the house. They have one dog, two cats, and a hamster (all house pets).
Dad was diagnosed with asthma as a child but “grew out of it.” He still has environmental allergies to dust and pollens and takes an over-the-counter antihistamine as needed.
Wheezing and Asthma in the Child
Many aspects of current and past history as well as physical examination can help the clinician distinguish between transient wheezing and asthma in the young child and confirm asthma in the older child. Although many parents confuse wheezing with upper airway congestion or noisy breathing, a history of previous healthcare provider–diagnosed wheezing is helpful to confirm true wheeze. Most wheezing and coughing in children occurs in association with viral illnesses, but wheezing or coughing apart from obvious infection, such as with exercise, activity, exposure to allergens, or exposure to environmental tobacco smoke, suggests more persistent disease. Additionally, coughing that has responded to bronchodilator therapy is consistent with an asthma cough. Frequent nocturnal coughing may be associated with more severe asthma.
Past medical history, including birth history, prematurity, and history of oxygen requirement or mechanical ventilation, documents important factors that can help differentiate other conditions seen in pediatric patients with recurrent respiratory symptoms. This is especially relevant because often non-atopic infants can have bronchopulmonary dysplasia and airway hyperresponsiveness similar to asthma with a different underlying pathophysiology. Determining the severity of previous respiratory episodes, including urgent or emergent care, hospitalization, and hypoxia, helps the clinician quantify symptom control and potentially predict subsequent episodes. Previous response to therapy, including bronchodilators and steroids (both inhaled and systemic), can also help confirm a diagnosis of asthma. Finally, a prior history of other allergic conditions increases the risk for developing asthma.
The evaluation of a child with recurrent respiratory symptoms should include a thorough review of the family medical history and environmental exposures. A history of healthcare provider–diagnosed asthma in a parent is an important risk factor for persistent wheezing in children. Reviewing the family history for the presence of other atopic disease, such as allergic rhinitis, food allergy, and eczema, can help to establish an atopic genetic background for the patient.
An environmental history should document the presence of potential allergens in the home, including pets and cockroaches; the use of allergen covers for mattresses and pillows; the frequency of cleaning bed linens; and the presence of carpets, upholstered furniture, and stuffed animals. Other potential sources of irritation in the home include tobacco smoke, fireplaces, home heating systems, and home cooling systems. As mentioned earlier, children sensitized to certain allergens are more likely to have asthma.
Overview of Asthma
Asthma is the leading serious chronic illness of children in the United States and the most common chronic disease of childhood. Asthma can be difficult to identify in many cases because of its complexity and heterogeneity; therefore, clinicians need to understand the pathophysiology and natural history of the disease along with the diversity of patient response in order to make an early diagnosis and develop an appropriate management strategy (Centers for Disease Control and Prevention [CDC], 2006a, 2006b).
Epidemiology of Asthma
The following are some pediatric asthma statistics:
• In 2006, an estimated 6.8 million children under age 18 (almost 1.2 million under age 5) were diagnosed with asthma (CDC, 2006b).
• The highest current prevalence rate was seen in those 5–17 years of age (106.3 per 1,000 population), with rates decreasing with age. Overall, the rate in those under 18 years (92.8 per 1,000) was much greater than those over 18 years (72.4 per 1,000) (CDC, 2006b).
• Approximately 12.8 million school days are missed annually due to asthma (CDC, 2006a)
• Asthma has the following impact annually on the medical community (CDC, 2006a):
12.7 million physician visits
1.9 million asthma-related emergency room visits
• Asthma has the following annual financial impact:
Direct healthcare costs of more than $11.5 billion
Indirect healthcare costs of $4.6 billion
Prescription drug costs of $5 billion
The statistics on pediatric asthma are quite alarming. More than 9 million U.S. children have been diagnosed with asthma. The prevalence of asthma has increased 75% over the past two decades, and in children under the age of 5 years, asthma rates have increased more than 160%. This has resulted in more than 12 million missed school days annually and a tremendous financial burden in healthcare-related costs (more than $20 billion annually) (CDC, 2006a, 2006b).
The morbidity related to asthma is staggering. People with asthma miss more days at work or school than the average American. Asthma patients and their families spend on average $1,000 per year on medications. The annual cost of asthma in 1998 was estimated to be $11.3 billion, with hospitalizations accounting for most of these costs. The costs associated with asthma continue to increase (Asthma and Allergy Foundation, 2000).
Racial differences in the prevalence of asthma have been demonstrated in the data collected by the National Center for Health Statistics (2002). There continue to be racial and ethnic differences in asthma prevalence and healthcare use and mortality. In 2004, the lifetime prevalence of asthma in persons younger than 14 years of age was highest in the black population with a prevalence of 12.5% in comparison with 7.1% in Hispanics and 7.5% in whites.
An analysis of data from the National Health and Nutrition Examination Survey III (NHANES; CDC, 2002) showed low education status, female sex, current or past smoking history, pet ownership, atopy, and obesity all to be associated with an increased prevalence of asthma. The effect of socioeconomic status on asthma prevalence was further illustrated by this study. There was a statistically significant difference in the prevalence of asthma noted in non-Hispanic black children from families with income less than half the federal poverty level. This difference remained significant even in comparison with non-Hispanic white children from very poor families. The difference in prevalence rates can be postulated to be caused by environmental exposures that are unique to children from poor families that increase the risk of developing bronchial hyperreactivity and asthma. This difference in environmental exposures can be related to the percentage of disadvantaged black children who live in urban areas rather than rural areas. The population at highest risk for asthma is African American children from poor urban neighborhoods (Simon et al., 2003; Smith et al., 2005).
Studies have shown a relationship between parental smoking and childhood asthma. There seems to be an increased risk of early onset asthma in children exposed to tobacco smoke with an increased incidence of wheezing until age 6 years (Strachan & Cook, 1998; Weitzman, Gortmaker, Walker, & Sobol, 1990). The National Health Interview Survey (NHIS) data collected in 1981 show an increased risk of asthma in children under the age of 5 whose mothers smoked at least one half pack of cigarettes per day (odds ratio 2.1, P = 0.001) (Weitzman et al., 1990). In addition, the American Academy of Pediatrics (1997) policy statement on the hazards of environmental tobacco smoke to children’s health clearly documents the particularly deleterious effect of tobacco smoke on children’s lungs. This policy statement notes the negative effect that parental smoking has on both the frequency of exacerbations and the severity of asthma symptoms in their children. Furthermore, when parents reduce the secondhand smoke exposure to their children, the child’s asthmatic symptoms are not as severe.
Pathophysiology of Asthma
Asthma is a chronic inflammatory disease characterized by episodic and reversible symptoms. The impact of respiratory infections on asthma incidence is an area of debate. The hygiene hypothesis, proposed by Strachan (1989), is based on the concept that immune responses are mediated by two types of lymphocyte populations: T-helper 1 and T-helper 2 cells. T-helper 1 lymphocytes produce interferon-γ and interleukin-2, and T-helper 2 lymphocytes produce interleukins that can lead to the development of IgE-mediated atopy and allergy. The exposure to airway infections and allergens early in life promotes the maturation of T-helper 1 lymphocytes over T-helper 2 lymphocytes, thereby decreasing the risk of developing allergic conditions (Gore & Custovic, 2005). Persons living in more rural environments may be exposed to allergens early in life with the development of increased T-helper 1 lymphocyte population and less atopy and asthma. There have been several studies supporting this theory as well as studies contradicting these findings (McDonnell et al., 1999; Strachan, Butland, & Anderson, 1996). The varied conclusions may be a result of the intensity, the timing, and the duration of the exposure. The underlying genetic susceptibility of the individual may also contribute to whether a particular exposure in childhood leads to the development of asthma later in life (King, Mannino, & Holguin, 2004). The most frequently cultured infectious pathogens in asthmatics undergoing bronchoscopy with bronchoalveolar lavage are viruses (adenovirus, parainfluenza, influenza, and respiratory syncytial virus), Mycoplasma pneumoniae, and Chlamydia pneumoniae (Kraft, 2000; Martin et al., 2001; McDonald, Schoeb, & Lindsey, 1991).
Asthma has been suspected to have a strong genetic component, with studies demonstrating increased prevalence of asthma among first-degree relatives of asthmatic subjects (20–25%) versus a general population prevalence (of 4%) (Sandford, Weir, & Pare, 1996; Scirica & Celedon, 2007; Sibbald & Turner-Warwick, 1979). Asthma is regarded as a “complex” disease (i.e., one shaped by many genes and environmental factors that interact to determine susceptibility). The components of the asthma phenotype are passed down through families in complex patterns, but the genes responsible for these inherited components have not yet been identified. The disease appears to result from gene–environment and/or gene–gene interactions; however, it is unknown how many genes may be involved in asthma susceptibility and the strength of their effects. Another possibility is that a large number of genes can contribute to the development of asthma in a population, but that a small subset of genes may shape the disease in affected individuals.
The pathophysiology of asthma involves the following components:
• Airway inflammation
• Intermittent airflow obstruction
• Bronchial hyperresponsiveness
Some of the principal cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play an important role in the regulation of airway inflammation through the release of numerous cytokines (see Figure 17-1). Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the consequence of immunoglobulin E–dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response. Airway edema occurs 6–24 hours following an allergen challenge and is referred to as the late asthmatic response. Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve. Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction (Busse, O’Bryne, & Holgate, 2006).
Figure 17-1 Key elements of the pathophysiology of asthma.
From Busse, W. W., O’Bryne, P. M., Holgate, S. T. (2006). Asthma pathogenesis. In: N. F. Adkinson, Jr., J. W. Yunginger, W. W. Busse, B. S. Bochner, S. T. Holgate, F. E. R. Simons, (Eds.), Middleton’s allergy: Principles and practice, (6th ed., Chapter 66). St. Louis, MO: Mosby. Used with permission.
Other Common Causes of Wheezing in Children
Classically, with an acute asthma exacerbation, the child presents with wheezing and respiratory distress. Bronchospasm can also present as cough, chest pain, shortness of breath, and fatigue with exertion.
Asthma is the most likely cause of recurrent wheezing in children younger than 5 years. The most common causes of wheezing in young children are asthma, allergies, gastroesophageal reflux disease, infections, and obstructive sleep apnea. Response to bronchodilators may help differentiate asthma from other causes of wheezing. Chest radiography should be performed in children with recurrent wheezing or a single episode of unexplained wheezing that does not respond to bronchodilators. (See Table 17-1.)
Table 17–1 Causes of Wheezing in Children and Infants
Many infants wheeze early in life. Risk factors for persistent wheezing and a predisposition to asthma include:
• Frequent symptoms in the first 12 months of life
• Elevated IgE levels
• Maternal history of asthma
• Maternal smoking
More than 85% of wheezing episodes in children are triggered by viral infections. The prevalence of asthma in school-age children in the United States is now estimated to be 9%, having doubled in about 20 years. Wheezing is extremely common, occurring in at least 50% of children, but in the absence of dyspnea or effects on sleep or activities, wheezing is not likely to be caused by asthma. Wheezing in early childhood is associated with bronchial hyperreactivity and reduced lung function in later life, and may be a reason for early intervention and maintenance medication. Children who have severe intermittent wheezing usually develop atopy. There also are transient wheezers, who usually clear by age 3, and nonatopic wheezers who do not seem to develop later asthma, although they may continue to wheeze occasionally when older.
Suspicion of asthma is increased when any one or several historical factors are present (Bush, 2007; Graham, 2006):
• Three or more episodes of otitis media (1.5 times increased risk)
• Pneumonia (1.8 times increased risk)
• Atopic dermatitis (1.9 times increased risk)
• Family asthma history (2 times increased risk)
• Laryngotracheitis (2 times increased risk)
• Allergic rhinitis (2.2 times increased risk)
• Any wheezing in first 3 years (3.3 times increased risk)
• Sinusitis (3.5 times increased risk)
• Family sinusitis history (3.9 times increased risk)
• Recurrent wheezing in first 3 years (4.7 times increased risk)
• Recurrent wheezing in years 4 through 6 (15 times increased risk)
The disease process is variable both from person to person and in each person from episode to episode. At one extreme, sufferers are continuously ill and are frequently in and out of the hospital; at the other extreme symptoms are rare, intermittent, often mild, and sometimes unrecognized. Milder symptoms of asthma often blend into those of allergic bronchitis that often accompanies allergic rhinitis (Akinbami & Schoendorf, 2002; Hopp et al., 1988). This variation can make diagnosis of certain patients extremely challenging, and the history and physical exam should be tailored to exclude other causes of wheezing, as listed earlier. Despite the myriad causes of wheezing in children, presumptive clinical diagnosis usually is possible by obtaining a thorough clinical history and examination.
What physical examination data do you want to collect?
On physical examination, James has a nonproductive cough and some audible wheezing. His height is at the 45th percentile and his weight is at the 50th percentile with a body mass index of 17 placing him just below the 85th percentile. He is afebrile with a heart rate of 92 and a respiratory rate of 24 with mild accessory muscle use but no retractions. His oxygen saturation on room air is 92%. His head, eyes, ears, nose, and throat examination is normal except for boggy turbinates with some clear rhinorrhea and slight postnasal drainage. His tone of his voice is normal with no hoarseness noted; no visible caries nor dental erosion noted and his neck is supple with full range of motion and no lymphadenopathy. On ausculation of his lungs there are expiratory wheezes in all lung fields and an increased expiratory phase. Overall air movement is good. James’s cardiac exam reveals a regular rate and rhythm without murmurs or gallops. Radial and femoral pulses are 2+ bilaterally. The abdomen is scaphoid with good bowel sounds and there is no tenderness to palpation, masses, or hepatosplenomegaly. The remainder of the physical exam is normal.
Should you do diagnostic studies?
You pause for a moment to consider what, if any, diagnostic studies you should do. Based upon a negative history (no complaints of vomiting, heartburn, painful belching, or recurrent pneumonias) and the lack of physical findings (no hoarseness, tenderness, tooth erosion, or masses), you have no evidence that his wheezing is due to gastroesophageal reflux or a tumor. His cardiac examination is normal, making a cardiovascular condition also unlikely. You are comfortable with your diagnosis of asthma. However, James does have a history of multiple episodes of wheezing and no history of having had a chest X-ray which leaves you somewhat uncomfortable. Thus, the healthcare provider may consider obtaining an initial chest radiograph to rule out other pulmonary pathology. Given this child’s history, you decide to order a chest X-ray (PA and lateral), which reveals a normal cardiothymic silhouette, normal orientation of the great vessels, and mild hyperexpansion. Because of the father’s history of dust and pollen allergies, you also order a radioallergosorbent test (RAST) along with a total IgE level.
Making the Diagnosis
The 2007 guidelines from the National Asthma Education and Prevention Program (NAEPP); National Heart, Lung and Blood Institute; and National Asthma Education and Prevention Program Expert Panel Report 3 (EPR-3) are moving away from the initial severity classification to a classification based on disease control. Asthma “severity” refers to the underlying intensity of the disease before treatment is initiated, and it is important to remember that severity and control are related.
Based on the EPR-3 guidelines, the provider must first determine the severity of the asthma. After the child’s asthma becomes well controlled on medication (plus the elimination of environmental triggers as much as possible), the provider then determines classification based on the lowest level of treatment needed to maintain control. This second classification is made after a period of time in which the provider follows the child. The National Heart Lung and Blood Institute (2007) provides assessment guidelines for the clinician about evaluating components of asthma severity and asthma control (See Tables 17-2 and 17-3).
Classification of the Severity of James’ Asthma
Based upon his history, physical examination, and environmental and family risk factors, James was diagnosed with an asthma exacerbation with underlying mild persistent asthma.
Having determined the asthma severity level that James is experiencing based on his history and physical examination findings, you are ready to identify an appropriate medication plan. You prescribe a short burst of oral steroids and an inhaled short acting beta2-agonists (SABA) to treat his acute asthma symptoms and this exacerbation. Oral systemic steroids are used to quickly treat the inflammatory response. A SABA provides quick relief of bronchospasm, relaxing airway smooth muscles, which results in a prompt increase in airflow. A spacer is used so that a higher proportion of small, respirable particles are inhaled rather than having particles from the MDI deposited in the oropharynx. This is particularly important for children who receive inhaled medication via MDI devices.
Inhaled corticosteroids are considered long term control medications and are effective agents to block late reactions to allergens and reduce airway hyperresponsiveness. They also act to inhibit the release of key inflammatory agents.
James was started on oral prednisolone (2 mg/kg divided BID for 5 days) and albuterol 5 mg via MDI (2 puffs) with spacer every 4 hours PRN. Based on the NAEPP guidelines, he will start a low-dose inhaled corticosteroid (0.25 mg budesonide BID) as his daily maintenance medication along with a short-acting bronchodilator (5 mg albuterol via MDI [2 puffs] with spacer) as needed.
Control of Environmental Factors and Other Conditions That Can Affect Asthma
EPR-3 describes new evidence for using multiple approaches to limit exposure to allergens and other substances that can worsen asthma; research shows that single steps are rarely sufficient. EPR-3 also expands the section on other common conditions that asthma patients can have and notes that treating chronic problems such as rhinitis and sinusitis, gastroesophageal reflux, overweight or obesity, obstructive sleep apnea, stress, and depression may help improve asthma control.
Table 17–2 Classifying Asthma Severity in Children 0-4 Years of Age Not Currently Taking Long-Term Control Medication
Table 17–3 Assessing Asthma Control and Adjusting Therapy in Children 0-4 Years of Age
What kind of follow-up plan is appropriate for a child with a new asthma management plan?
James returns for a follow-up visit in 4 weeks. According to Mom, he has been sleeping well with no nighttime awakenings and has not had any difficulty keeping up with the other children at daycare.
He continues to take his budesonide as prescribed and after the first week of treatment, James has not needed to use his albuterol. His RAST testing indicated high reactivity to dust mites and ragweed and moderate reactivity to dog epithelium. Total IgE level was 42. (Normal in reference laboratory is < 35.)
Asthma control can be very complicated and should be tailored to the individual’s lifestyle, the individual’s history and risk factors, and daytime and nighttime symptoms; the need for “rescue” medications should be used as the best determinant for adjusting therapy. The history obtained at follow-up visits for patients with asthma is helpful in determining if control is adequate. Some examples of pertinent historical questions include current medications and other therapies, how often a short-acting beta2-agonists (SABA) is used, school attendance and performance, and physical activity. You assess that James is well controlled (see Table 17-3 on p. 262).
Key Points from the Case
1. Asthma is a variable disease that commonly begins in early childhood; healthcare providers must learn to recognize the signs and symptoms of asthma in infants and young children.
2. Along with well-known environmental triggers, genetic factors may play a role in disease severity and individual response to treatment.
3. Establishing a diagnosis of asthma involves thorough history taking and physical examination, as well as the exclusion of other possible causes of wheezing. The history should focus on symptoms (i.e., cough or wheeze), precipitating factors or conditions, and the child’s typical symptom patterns. Additional history should include a history of atopy, family history of asthma, environmental history, and past medical history. The physical exam is generally normal in the absence of an acute exacerbation. Abnormal findings can suggest severe disease, suboptimal control, or associated atopic conditions.
4. When a diagnosis of asthma is established in a child who is not currently on controller medications, asthma severity should be assessed so that appropriate controller therapy can be started. Treatment should be based on the new EPR-3 treatment guidelines and tailored to the individual needs of the patient because responses to treatment often vary. Asthma control is zero or two or fewer times per week of daytime symptoms or need for SABA; zero limitations on daily activities including exercise; zero nocturnal symptoms or awakening due to asthma (think cough in younger patients); normal or near normal lung function results when available; and finally, no exacerbations.
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