A 7-year-old boy with a history of atopic dermatitis as an infant, presents with an episode of continued cough and wheezing 2 weeks following a recent cold. The cough is keeping the family up at night. This is his third episode this winter and has gone on longer than the others. He has otherwise been quite healthy. He appears comfortable but is coughing intermittently. His examination is significant for mild inspiratory and expiratory wheezing but no crackles. His mother mentions that she had asthma as a child and is worried that this might be asthma. The pediatrician prescribes an inhaled bronchodilator and refers the child for spirometry before and after an inhaled bronchodilator.

The spirometry results in Table 49-1 show a mild to moderate baseline defect with marked improvement post bronchodilator. The flow volume loops provide graphical demonstration of the same data (Figure 49-1). This confirms the diagnosis of asthma and an asthma treatment plan is developed.

Interpretation: mild to moderate baseline defect with marked improvement post bronchodilator.

Asthma is a chronic inflammatory airway disorder with variable airflow obstruction and bronchial hyperresponsiveness that is at least partially reversible, spontaneously or with treatment (e.g., beta-2 agonist treatment). Patients with asthma have recurrent episodes of wheezing, breathlessness, chest tightness, and cough (particularly at night or in the early morning).

• About one in 12 people (25 million or 8% of the population) had asthma in 2009, including about one in 10 children.¹ Rates of asthma are increasing; the greatest rise in rates is among black children, an almost 50 percent increase between 2001 and 2009.¹

• The number of deaths linked to asthma in 2007 was 3,447.¹ Using the 2006 to 2008 Nationwide Emergency Department (ED) Sample database, the estimated overall annual number of in-hospital asthma-related deaths was 1,144 (0.06%).² Most patients died as inpatients (N = 1043) but 101 died in the ED. There were 37 asthma-related deaths per year among children.

• Asthma was the first-listed diagnosis for 479,000 hospital discharges in 2009 with an average length of stay of 4.3 days.¹

• Asthma-associated medical expenses increased from $48.6 billion in 2002 to $50.1 billion in 2007.¹ Many uninsured people with asthma (about 40%) and about 1 in 9 insured people could not afford their prescription drugs.¹ In one retrospective study based on insurance claims for children with asthma who initiated asthma control therapy between 1997 and 2007 (N = 8834), the mean annual out-of-pocket asthma medication cost was $154 (95% CI, $152-$156) among children aged 5 to 18 years and slightly lower (mean $151) among younger children.³ In this study, asthma-related hospitalization was higher for children aged 5 to 18 years who were in the top quartile of out-of-pocket costs (2.4 [95% CI, 1.9 to 2.8] hospitalizations per 100 children versus 1.7 [95% CI, 1.3 to 2.1] per 100 in the bottom quartile).

• More than half (59%) of children and 1/3 (33%) of adults who had an asthma attack missed school or work because of asthma in 2008; on average, children missed 4 days of school.¹

• Although the precise cause is unknown, early exposure to airborne allergens (e.g., house dust-mite, cockroach antigens) and childhood respiratory infections (e.g., respiratory syncytial virus, parainfluenza) are associated with asthma development. In one prospective cohort study, 50 percent of children who experienced severe RSV bronchiolitis at age 12 months or less had a subsequent asthma diagnosis.⁴

• In addition to environmental factors, asthma has an inherited component, although the genetics involved remain complex.⁵ The gene ADAM 33 (A Disintegrin And Metalloproteinase) may increase risk of asthma as metalloproteinases appear to effect airway remodeling.⁶ A recent nested case-control study found that genetic variation in the ATPAF1 gene predisposed children of different racial backgrounds to asthma.⁷

• In the Copenhagen Prospective Studies on Asthma in Childhood (N = 411 at-risk children followed prospectively from birth using spirometry), children with asthma by age 7 years (14%) had a significant airflow deficit as neonates.⁸ It was estimated that approximately 40 percent of the airflow deficit associated with asthma was present at birth and the remainder developed with clinical disease.

• The pulmonary obstruction characterizing asthma results from combinations of mucosal swelling, mucous production, constriction of bronchiolar smooth muscles and neutrophils (the latter, particularly important in smokers or those with occupational asthma).⁴ The smaller airways of children make them particularly susceptible.

• Over time, airway smooth muscle hypertrophy and hyperplasia, remodeling (thickening of the sub-basement membrane, subepithelial fibrosis and vascular proliferation and dilation), along with mucous plugging complicate the disease.⁴

• Allergen-induced acute bronchospasm involves immunoglobulin-E (IgE)-dependent release of mast cell mediators.⁴

Based on a cohort study, early life (first 5 years) risk factors for diagnosed asthma at age 10 years includes:⁹

• Family history of asthma (maternal [odds ratio (OR) 2.26; 95% confidence interval (CI) 1.24 to 3.73); paternal [OR 2.30; 95% CI 1.17 to 4.52]; sibling [OR 2.00; 95% CI 1.16 to 3.43]).

• Recurrent chest infections at 1 year of age (OR 2.67; 95% CI 1.12 to 6.40) and 2 years of age (OR 4.11; 95% CI 2.06 to 8.18).

• Atopy at 4 years of age (OR 7.22; 95% CI 4.13 to 12.62).

• Parental smoking at 1 year of age (OR 1.99; 95% CI 1.15 to 3.45).

• Male gender (OR 1.72; 95% CI 1.01 to 2.95).

• Recent use of acetaminophen has also been associated with asthma symptoms in adolescents (OR 1.43; 95% CI 1.33 to 1.53 and OR 2.51; 95% CI 2.33 to 2.70 for at least once a year and at least once a month use versus no use, respectively).¹⁰ One possible mechanism is through acetaminophen reducing the immune response and prolonging rhinovirus infection.¹¹

• Environmental mold is also a risk factor; in one study the OR was 1.8 (95% CI 1.5 to 2.2) for asthma diagnosed at age 7 years for a 10-unit increase in the Environmental Relative Moldiness Index value in the child’s home in infancy.¹²

• In one study, consumption of salty snacks (OR 4.8; 95% CI 1.50 to 15.8) was strongly associated with the presence of asthma symptoms, especially in children with television/video-game viewing of >2 hours/day.¹³

• In a prospective study of children following an episode of severe bronchiolitis, risk factors for physician-diagnosed asthma by age 7 years included maternal asthma (OR 5.2; 95% CI 1.7 to 15.9), exposure to high levels of dog allergen (OR 3.2; 95% CI 1.3 to 7.7), aeroallergen sensitivity at age 3 years (OR 10.7; 95% CI 2.1 to 49.0), recurrent wheezing during the first 3 years of life (OR 7.3; 95% CI 1.2 to 43.3), and CCL5 mRNA expression in nasal epithelia during acute RSV infection (OR 3.8; 95% CI 1.2 to 2.4).⁴

• Obesity has also been associated with risk of wheezing in children (OR 1.62, 95% CI 1.13 to 2.32).¹⁴

• Not surprisingly, in patients with severe or difficult-to-treat asthma, recent exacerbation history was the strongest predictor of future asthma exacerbations.¹⁵ High concentrations of pollen also increase the risk of asthma- and wheeze-related ED visits by up to 15 percent.¹⁶

The diagnosis of asthma is made on clinical suspicion (presence of symptoms of recurrent and partially reversible airflow obstruction and airway hyperresponsiveness) and confirmed with spirometry.⁵ Alternative diagnoses should be excluded.

Clinical Features

Asthma’s most common symptoms are recurrent wheezing, difficulty breathing, chest tightness, and cough. An absence of wheezing or normal physical exam does not exclude asthma.³ In fact, up to 25 percent of patients with asthma have normal physical examinations even though abnormalities are seen on pulmonary function testing.⁴ As part of the diagnosis of asthma, ask about the following:³

• Pattern of symptoms and precipitating factors. Symptoms often occur or worsen at night and during exercise, viral infection, exposure to inhalant allergens or irritants (e.g., tobacco smoke, wood smoke, or airborne chemicals), changes in weather, strong emotional expression (laughing hard or crying), menstrual cycle, and stress.³

• Family history of asthma, allergy or atopy in close relatives.

• Social history (e.g., daycare, workplace, or social support).

• History of exacerbations (e.g., frequency, duration, or treatment), and impact on patient and family. The preschool-aged asthmatic population tends to be characterized as exacerbation prone with relatively limited impairment while older children and adolescents have more impairment-dominant disease.¹³

Findings on physical exam may include:³

• Upper respiratory tract—Increased nasal secretion, mucosal swelling, and/or nasal polyp.

• Lungs—Decreased intensity of breath sounds is the most common (33% to 65% of patients).⁴ Additional findings may include wheezing, prolonged phase of forced exhalation, use of accessory respiratory muscles, appearance of hunched shoulders, and chest deformity. During a severe exacerbation of asthma, minimal airflow may result in no audible wheezing.

• Skin—Atopic dermatitis and/or eczema (see Chapters 130, 132, and 133). There is a strong association between asthma, allergic rhinitis and atopic dermatitis (Figure 49-3). The “atopic triad” with the coexistence of all three conditions at one time (Figure 49-3) is less common. Children with asthma are also more likely to develop pityriasis alba, a chronic skin disorder characterized by patches of lighter skin mainly on the face (Figure 49-4). In a US study of children with physician-confirmed atopic dermatitis (N = 2270), 38.0 percent reported symptoms of asthma and allergic rhinitis on a survey;¹⁷ similarly in a population study in Taiwan using the National Insurance register, of the 66,446 individuals diagnosed with atopic dermatitis, about half had a concomitant diagnosis of allergic rhinitis and/or asthma.¹⁸ Data support a sequence of atopic manifestations beginning typically with atopic dermatitis in infancy followed by allergic rhinitis and/or asthma in later stages.¹⁹

Findings in patients with status asthmaticus (prolonged/severe asthma attack that is not responsive to standard treatment) may include:⁴

• Tachycardia (heart rate >120 beats/minute) and tachypnea (respiratory rate >30 breaths/minute).

• Use of accessory respiratory muscles.

• Pulsus paradoxus (inspiratory decrease in systolic blood pressure >10 mm Hg).

• Mental status changes (due to hypoxia and hypercapnia).

• Paradoxical abdominal and diaphragmatic movement on inspiration.

Laboratory Testing

Spirometry is recommended by NAEP for all patients over 4 years of age to determine airway obstruction that is at least partially reversible (Figures 49-1, 49-2, 49-5, and 49-6).³ SOR B The British Thoracic Society also recommends an assessment of the reversibility of airway obstruction in response to an inhaled bronchodilator.