Diagnosis

Symptoms of asthma include recurrent episodes of wheezing, breathlessness, chest tightness, and cough — particularly at night and in the early morning — and are usually associated with airflow limitation that is at least partly reversible, either spontaneously or with treatment. As with other diseases, the patient history, physical examination, and laboratory testing are important components of a clinical evaluation for asthma.

The diagnosis of asthma is based primarily on history and physical examination. The clinical features a patient exhibits, particularly the symptoms he complains of and the signs noted on physical examination, are usually sufficient to make the diagnosis of asthma. Laboratory tests are mainly used to confirm the diagnosis of asthma and to grade its severity. However, peak flow testing can be used to monitor a patient's respiratory function in an effort to optimize his clinical management.

Clinical Features

The patient's history should identify symptoms, assess severity (pattern of symptoms, frequency, exercise tolerance, medication use, and hospitalizations), provide all family history of asthma and allergies, and identify possible precipitant factors (e.g., infections, exercise, and exposure to allergens and irritants).

Symptoms

Characteristic symptoms of asthma are cough, wheezing, and dyspnea. Dyspnea is the most common symptom of asthma. Asthma symptoms may be circadian — worse at night and early morning — because the small decrease in airway diameter that occurs normally during these times is exaggerated in patients with asthma. Breathlessness will also increase when asthma is exacerbated, such as in the presence of allergens, cold air, and exercise.

Cough is another common symptom of asthma (especially in children) and may even be the sole presenting symptom. Wheezing is also a characteristic feature of asthma. Although wheezing usually occurs on expiration, it may also be heard on inspiration. During a severe asthma attack, wheezing may become inaudible due to extreme reductions in airflow.

Symptoms that provide indications of or clues to asthma severity are the number of exacerbations per week, the number of nights with asthma symptoms per month, the frequency of bronchodilator use, or limitation of physical activities. For those whose asthma is more severe, it is important to ascertain the number of hospitalizations due to the disease and previous life-threatening asthma exacerbations. Two important indications to worsening asthma are increased nocturnal or early morning awakenings due to asthma symptoms and increased use of inhaled bronchodilators.

Signs

Physical examination of the respiratory system may reveal no apparent abnormality if a patient is not experiencing an asthma attack. During an asthma attack, contraction of the bronchial smooth muscle, edema, and increased mucus secretion narrow or close small airways, resulting in the inability to exhale completely and increased work of breathing in these patients.

Wheezing predominantly occurs on exhalation. However, it may be absent in severe asthma attacks (the so called quiet chest of asthma) due to marked limitation of airflow.

Laboratory Evaluation

Pulmonary Function Tests

Pulmonary function tests (PFTs) provide a direct assessment of the degree of airflow limitation. Also, by measuring the variability of this measurement, PFTs provide an indirect assessment of bronchial hyperresponsiveness (BHR). Abnormalities of lung function may exist even if a patient is asymptomatic.

Spirometry

Spirometry remains the best test in patients suspected of having asthma. Because asthma is an obstructive airways disease, a decrease in the absolute value and percent predicted of the forced expiratory volume in 1 second (FEV₁) to less than 80% of predicted normal may be present. However, in mild disease, FEV₁ can be normal. The airflow limitation is considered significantly "reversible" or "responsive" when the FEV₁ improves by at least 12% and by 200 mL (in adults) following an inhaled bronchodilator.

In addition to FEV₁, the ratio of FEV₁ to FVC (forced expiratory volume in 1 second to forced vital capacity) ratio is often below 70% in patients with asthma, and the forced expiratory flow that occurs from 25-75% of FVC (FEF_25-75) is considered to measure airway obstruction. It is possible that in chronic severe asthma, the airway obstruction may become "fixed" or "irreversible" due to airway remodeling and fibrosis, in which case there is little or no response to bronchodilators.

If a patient has normal air flow when assessed between attacks, provocative testing with a substance that causes airway narrowing (e.g., a methacholine challenge test) may be conducted. In patients with BHR, the provocative concentration of methacholine needed to lower FEV₁ by 20% (PC₂₀) is lower than in normal individuals.

Peak expiratory flow rate

A peak flow meter is simple to use and can be used by patients at home or work to monitor daily variability in peak expiratory flow rate (PEFR). Peak flow monitoring can also be used for short-term monitoring, to manage exacerbations, and for daily long-term monitoring. When used in these ways, the patient's own measured personal best is the most appropriate reference value.

Because peak flow may decrease before the patient experiences dyspnea, regular monitoring of PEFR can help detect early signs of deterioration. By the time wheezing is audible, the PEFR may already have decreased by as much as 25%. Patients who have PEFR measurements consistently less than 80% of their best effort may need additional medications to control their asthma. A PEFR of less than 50% of best effort indicates a severe exacerbation of asthma.

Skin tests

Many patients with asthma are atopic, and their reaction to a wide range of external allergens can be a common exacerbating factor of asthma. A drop of each allergen solution is distributed on the forearm and a needle introduced through the drop into the skin surface to a depth of about 1 mm. The patient's skin reaction at the site, if any, is assessed 15-20 minutes later. A positive, wheal-and-flare reaction indicates that specific immunoglobulin E (IgE) antibodies to that particular allergen are bound to mast cells in the skin.

Blood tests

The measurement of allergen-specific IgE in the serum is determined using radioallergosorbent test (RAST). RASTs are not more accurate than skin testing, and a positive test does not guarantee that the patient is allergic because an individual can have elevated allergen-specific IgE that circulates in the blood without having clinical symptoms associated with actual exposure to that allergen.

Peripheral blood eosinophils

An elevation in the peripheral blood eosinophil count can be an indicator of inflammation that is allergic in nature. However, the correlation with asthma disease activity is easier to identify in large epidemiologic studies than in individual patients. Thus, peripheral blood eosinophilia is not commonly used to follow the course of a patient's disease.

Radiology tests

The chest X-ray of a patient with asthma is often normal. However, hyperinflation of the lungs may be observed in acute exacerbations.

Differential Diagnosis

There are several conditions that should be considered in the differential diagnosis of asthma. These conditions vary significantly depending on the patient's age.

Children

In infants with a suspected diagnosis of asthma, congenital malformations (e.g., tracheosophageal fistula, vascular rings) should be considered and appropriate evaluations need to be performed to rule out such malformations. Young children commonly have viral upper respiratory tract infections that can cause symptoms similar to those of an asthma exacerbation. Foreign-body obstructions must be considered in children who have rapid onset of unilateral wheezing. Underlying disorders such as cystic fibrosis and immunodeficiency disease should be considered in children with chronic cough and sputum production [Beers and Berkow, 1999].

Adults

Chronic obstructive pulmonary disease (chronic bronchitis and emphysema) and heart failure are the primary diseases that need to be considered in the differential diagnosis of asthma in adults. Less commonly, patients with obstruction of the large airways — whether from tumors, vocal cord dysfunction, or sarcoidosis — present with wheezing [Beers and Berkow, 1999]. Asthma can coexist with chronic bronchitis or emphysema and this is more common in elderly patients.

Misdiagnosis

Epidemiologic studies suggest that asthma is often underdiagnosed or misdiagnosed.

Children

In children younger than age 5, the most common cause of asthmatic symptoms (i.e., wheezing and cough) is a viral upper respiratory tract infection. A landmark study by Martinez et al. [1995] established that there are two general patterns of wheezing in young children (i.e., wheezing that occurs before age 6). The first is an eventual resolution of wheezing during the preschool years, possibly as a result of airway growth. The second pattern is continued wheezing throughout childhood. The risk factors strongly associated with persistent wheezing include atopy (e.g., eczema, rhinitis, and food allergy), family history of allergy or asthma, and perinatal exposure to passive smoke or inhaled allergens.

Elderly

In elderly patients, a life of exposure to smoking or inhaled environmental irritants makes diseases such as bronchitis or emphysema relatively common. Proper diagnosis in these patients can be further complicated by the difficulty some older people have performing pulmonary function tests, including PEFR. However, it is important to determine the extent of reversibility of the airflow obstruction. If reversibility can be demonstrated, these patients should then receive appropriate management for asthma.

Forms of Asthma

Seasonal Asthma

Seasonal asthma is often linked with seasonal allergic rhinitis and some patients are asymptomatic between seasons. Children may be particularly likely to present with seasonal asthma.

Cough-variant Asthma

These patients seldom, if ever, present with wheezing. Cough is their principal, and perhaps only, symptom; it frequently occurs at night so that daytime examinations result in normal findings. Cough-variant asthma is seen more often in children than adults. Documentation of morning and evening variability in PEFR and documentation of BHR by methacholine challenge testing may be helpful.

Occupational Asthma

Certain chemicals and antigens, chronically inhaled in the workplace, can act as sensitizers over time to cause BHR in previously normal individuals. Once sensitized, these individuals develop bronchoconstriction, not only after exposure to the same workplace chemical or antigen but also to any of the various triggers typical of asthma. Removal from the workplace and from the offending sensitizer leads to a return to normal in many (but not all) patients with occupational asthma.

Nocturnal Asthma

The term nocturnal asthma is sometimes applied to patients who have symptoms predominantly at night. It is characteristic of uncontrolled asthma in any patient and may dominate the clinical picture of some patients. There is a circadian variation in lung function in normal individuals that can result in as much as an 8-10% decrease in PEFR during the night and early morning hours (e.g., at 4 a.m.), compared with afternoon and early evening hours (e.g., at 4 p.m.).

In asthmatics, the diurnal variation in airflow obstruction becomes exaggerated, with afternoon to morning decrements of up to 50% of PEFR associated with symptoms. Research studies have demonstrated that patients with nocturnal asthma have more airway inflammatory cells and higher BHR at 4 a.m. compared with 4 p.m. In addition, night-time exposure to allergens present in the bedroom may exacerbate asthma symptoms.

Exercise-induced Bronchoconstriction

Although exercise provokes bronchoconstriction in many patients with poorly controlled asthma, it is the predominant trigger of their asthma in some patients; this entity is referred to as exercise-induced bronchoconstriction (EIB). EIB usually occurs during or within minutes after vigorous activity.

The fall in lung function reaches its maximum about 5-20 minutes after stopping the activity. Symptoms often will resolve spontaneously over the next 20-30 minutes (see figure below).

The Effect of Exercise Testing on Airway Caliber*

From Global Strategy for Asthma Management and Prevention NHLBI/WHO Workshop Report [1995].
Click on image for larger version.

The diagnosis of EIB is usually made based on the patient's history. If the history is unclear, however, an exercise challenge test can be used to establish the diagnosis of EIB. A 15% decrease in PEFR or FEV1 or greater (measured just before and then at 5-minute intervals after exercise for 30-60 minutes) is good documentation of EIB.

Aspirin-sensitive Asthma

Aspirin and other nonsteroidal anti-inflammatory drugs can trigger symptoms in a subset of adult asthmatics. Although the incidence of aspirin sensitivity varies based on the methodology used, it usually does not exceed 5-10% of patients with asthma. Patients with aspirin-sensitive asthma often experience symptoms of asthma only as an adult, in the third to fourth decades of life.

Corticosteroid-resistant Asthma

The small minority of patients who do not respond well to treatment with corticosteroids are considered to have corticosteroid-resistant asthma. If control of asthma can be achieved only with high-dose corticosteroids despite removing all other trigger factors, the patient is considered to have "relative resistance" to corticosteroid therapy. In complete corticosteroid resistance, a patient has no response to corticosteroids. The prevalence of complete corticosteroid-resistant asthma may be less than 1 in 1000 patients with asthma.

References

Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999.

Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995;19:133-128.

Global Strategy for Asthma Management and Prevention NHLBI/WHO Workshop Report; January 1995.

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