Bronchial Asthma: Diagnosis and Long-Term Treatment in Adults

3 Lehrbereich Allgemeinmedizin der Albert-Ludwigs-Universität Freiburg i. Br.

*Klinik für Pneumologie und Beatmungsmedizin, Interdisziplinäres Lungenzentrum, Klinikum Bremen-Ost, Züricher Str. 40, 28325 Bremen, Germany, ed.tso-nemerb-mukinilk@aneku.reteid

Abstract

Introduction

Bronchial asthma is a serious global health problem. 5% to 10% of persons of all ages suffer from this chronic airway disorder. This review article presents important considerations of diagnosis and treatment in view of the current national and international asthma guidelines.

Methods

Selective literature review, with attention to the current national and international guidelines.

Results/Discussion

Bronchial asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperreactivity and a variable degree of airway obstruction. It is diagnosed on the basis of the clinical history, physical examination, and pulmonary function tests, including reversibility testing and measurement of bronchial reactivity. The goal of treatment is to control the symptoms of the disease effectively and in lasting fashion. Long-term treatment with inhaled corticosteroids is the basis of asthma treatment, alongside preventive measures and patient education. Bronchodilators such as beta2 sympathomimetics are used for rapid symptomatic relief of acute attacks.

Keywords: bronchial asthma, bronchial hyperreactivity, lung function, pharmacotherapy, inhaled corticosteroids

Recurrent episodes of acute shortness of breath, typically occurring at night or in the early morning hours, are the cardinal manifestation of bronchial asthma. Further symptoms include cough, wheezing, and a feeling of tightness in the chest. Asthmatic symptoms can often arise after physical exercise.

The following discussion of bronchial asthma is largely based on the German national care guidelines for asthma, on the international recommendations for asthma management of the Global Initiative for Asthma (GINA, www.ginasthma.com), and on the recommendations of the German Airway League (Deutsche Atemwegsliga) (1–3).

The learning objectives of this article are:

to become acquainted with the various conditions that enter into the differential diagnosis of bronchial asthma, and

to be able to apply the new types of treatment recommended for adult patients by the current national and international guidelines.

Depending on the severity of bronchial asthma in the individual patient, there may be phases of partial or total freedom from symptoms, alternating with periods of variably severe illness. This fact has been integrated into the definition of bronchial asthma, which is now defined as a chronic inflammatory disease of the airways characterized by bronchial hyperreactivity and a variable degree of airway obstruction (1–3).

Airway obstruction in bronchial asthma is mainly caused by the following four mechanisms (2):

Manifestations of asthma

The cardinal manifestation of asthma consists of recurrent episodes of shortness of breath of acute onset, typically at night or in the early morning hours.

Bronchial asthma afflicts about 10% of children and 5% of adults. An atopic diathesis, i.e., a genetic predisposition toward the production of IgE antibodies in response to (for example) pollen, house dust mites, fungi, or animal-derived proteins, is the most important risk factor for bronchial asthma. In childhood, bronchial asthma is usually due to allergies; on the other hand, in 30% to 50% of adults with asthma, no allergy can be identified, at least not with the standard techniques. Non-allergic asthma in adults can arise, for example, after a viral infection of the lower respiratory tract. Viral infections can, in turn, promote the development of an allergic sensitization. Intrinsic asthma may reflect the simultaneous presence of sinusitis, nasal polyposis, and an intolerance to acetylsalicylic acid (ASA) or related non-steroidal anti-inflammatory drugs (NSAIDs); this is the so-called Samter’s syndrome.

Allergy and asthma

About 10% of children suffer from asthma. Childhood asthma is usually due to allergy.

In 30% to 50% of asthmatic adults, no allergy is found as the cause of asthma.

Acute worsening of asthma (an asthma attack or exacerbation) can arise at any time without any prodromal symptoms and independently of the previous severity of the disease. Bronchial obstruction during an acute attack can progress, either slowly or rapidly, to life-threatening severity. The mortality due to asthma in Germany has declined by about one-third in the last decade, yet it nonetheless remains relatively high compared to that in other countries (2141 deaths due to asthma in 2004 according to the German Federal Statistical Office [Statistisches Bundesamt], 2005). The reduction in asthma-related mortality is generally attributed to the introduction of maintenance therapy with inhaled corticosteroids (ICS) (4). Around the world, however, there is little correlation between the lethality of asthma and its prevalence. The World Health Organization (WHO) estimates the number of DALYs ("disability-adjusted life years") lost to asthma at 15 million per year, which corresponds to 1% of the global loss of DALYs due to illness.

Diagnostic assessment

Airway obstruction is measured objectively with pulmonary function tests. The most important such test is spirometry, which measures the forced expiratory volume in one second (FEV₁), the forced vital capacity (FVC), and the Tiffeneau parameters (FEV₁/VC). Normal pulmonary function values do not rule out disease if they have been obtained during a symptom-free interval. Further aspects of the basic diagnostic assessment of bronchial asthma, including history-taking, symptoms, and physical findings, are summarized in box 1 (1–3).

Box 1

Basic diagnostic evaluation of bronchial asthma *1

History

Sudden onset of symptoms, often at night or in the early morning hours, typically shortness of breath and cough (productive or unproductive), particularly

Precipitants of asthmatic symptoms in the patient’s environment at home, at work, and during leisure activities

Symptoms

Intermittent and variable (may also be absent, e.g., during symptom-free intervals or in mild disease)

Findings on physical examination

*1 modified from (1), (3).

The practical value of peak expiratory flow (PEF) measurement lies in the determination of circadian variability, which is a suitable parameter for self-monitoring of asthma in outpatient follow-up. "Min % Max" is the minimal value of PEF expressed as a percentage of the maximal value, i.e., the lowest value in the morning prior to the administration of a bronchodilator drug as a percentage of the current best value. A circadian variability greater than 20% is typical of inadequately treated asthma (2, 5).

History and physical examination

Acute attacks of shortness of breath and cough occurring early in the morning are typical of asthma. Auscultation of the chest reveals rales, rhonchi, and wheezes.

Standards and individualized norms exist for both PEF measurement and spirometry (2, 3).

Whole-body plethysmographic pulmonary function analysis provides further information, e.g., for the demonstration of obstruction (airway resistance, Raw) or overdistention (intrathoracic gas volume, ITGV). Objective criteria for the confirmation of the diagnosis of bronchial asthma are given in box 2. An algorithm for the diagnostic assessment of asthma is shown in figure 1 .

Box 2

Criteria for the diagnosis of asthma *1

Demonstration of obstruction (FEV₁/VC < 70%) and FEV₁ increase by >15% (at least 200 mL) with respect to the initial value, and possibly also decrease of the specific airway resistance by at least 1 kPa × sec, measured at least 15 min after the inhalation of four puffs of a short-acting beta2 sympathomimetic agent, e.g., 400 µg of salbutamol

Or: FEV₁ worsening by >15% during, or within 30 minutes after, physical exercise (exertional asthma), possibly with an increase of the specific airway resistance by at least 150%

Or: FEV₁ improvement by >15% (or by at least 200 mL, if the initial value is below 1300 mL), and possibly also decrease of the specific airway resistance by at least 1 kPa × sec, after daily high-dose administration of an inhaled corticosteroid (ICS) for a maximum of four weeks

Or: in patients with normal pulmonary function despite a typical history for asthma, demonstration of non-specific bronchial hyperreactivity by means of a standardized, multilevel inhalational provocative test and of a more than 20% circadian variation in PEF with measurements taken over 3 to 14 days

*1 modified from (1), (3).

Algorithm for the diagnosis of bronchial asthma. The numbers attached to each panel indicate the hierarchical level (modified from 1,3)

Further diagnostic studies include, for example, bronchial provocation testing for the determination of bronchial reactivity; this kind of test is highly sensitive, but not very specific (6). Stepwise allergological testing includes skin-prick testing, the measurement of specific IgE in serum, and an allergen-specific nasal or bronchial provocation test. The use of non-invasive markers of airway inflammation, such as the nitrous oxide (NO) concentration in exhaled air or sputum eosinophilia, has not been prospectively validated for the establishment of the diagnosis of bronchial asthma, but can be helpful in therapeutic follow-up (7, 8). The indications for arterial blood gas analysis, determination of diffusion capacity, and radiological examination of the thoracic organs are determined individually, particularly for the purposes of differential diagnosis.

Differential diagnosis

The following entities should be considered in the differential diagnosis of bronchial asthma because of their frequency and clinical significance (1, 3):

In as many as 10% to 20% of cases, a clear-cut distinction between asthma and COPD cannot be drawn.

The definition of controlled asthma

Diagnostic evaluation

Obstruction of the respiratory tract is objectively demonstrated with pulmonary function testing. Spirometry is the most important testing technique.

A four-part, multilevel treatment plan was previously recommended for the long-term treatment of bronchial asthma, based on a classification of disease severity by the clinical findings and the results of pulmonary function testing (1, 3). In the current "Global Strategy for Asthma Management and Prevention" issued by the Global Initiative for Asthma (GINA), however, the classification system is based on the degree of clinical control that has been achieved, ranging from "controlled" to "partly controlled" to "uncontrolled" (table 1) (2). This new classification is meant to emphasize the point that the severity of asthma depends not just on the severity of the underlying illness itself, but also on its response to treatment. Furthermore, the severity of asthma can fluctuate considerably over a period of months to years.

Table 1

*1 modified from (2); *2 any exacerbation in one week fulfills the definition of uncontrolled asthma

GINA’s Global Strategy defines clinically controlled asthma as follows (2):

Classification

The GINA classification takes account not only of the severity of the underlying illness, but also of its response to treatment.

No need for rapidly-acting bronchodilators for symptomatic treatment ("relievers"), or at most two times per week

The treatment of bronchial asthma

The definitive endpoint of asthma management is the achievement of the best possible quality of life. This includes, for example (1, 3) (evidence level D):

Non-pharmacological treatments are listed in Text box 3 (1, 3).

Box 3

Non-pharmacological treament *1

Structured patient education: improved self-management leading to better symptomatic control, reduction of the number of asthma attacks and emergency situations, improved quality of life, and improvement in various other parameters of disease course including days taken off from school or work and days spent in hospital (evidence level A)

Physical training (reduction of asthma symptoms, improved exercise tolerance, improved quality of life, reduced morbidity) (evidence level C)

Respiratory therapy and physiotherapy (e.g., breathing techniques, pursed-lip breathing) (evidence level C)

*1 modified from (1).

The goals of pharmacotherapy are the suppression of the inflammation of asthma and the reduction of bronchial hyperreactivity and airway obstruction. The medications used for these purposes belong to two groups:

Relievers (medications taken for symptomatic relief as necessary) include mainly the inhaled, rapidly-acting beta2 sympathomimetic agents, e.g., the short-acting drugs salbutamol, fenoterol, and terbutaline and the long-acting drug formoterol. Inhaled anticholinergic drugs and rapidly-acting theophylline (solution or drops) play a secondary role as relievers.

Controllers (medications used for preventive, maintenance therapy) include the inhaled corticosteroids (ICS), inhaled long-acting beta2 agonists (LABA) such as formoterol or salmeterol, montelukast, and delayed-release theophylline preparations.

Formoterol can be used as a reliever because of its rapid onset of action or as a controller in combination with corticosteroids.

The undesired adverse effects that these medications can produce are listed in the e-box.