Book Review

Difficult Asthma

N Engl J Med 2000; 342:363-364February 3, 2000

Article

Difficult Asthma
Edited by Stephen T. Holgate, Homer A. Boushey, and Leonardo M. Fabbri. 567 pp., illustrated. London, Martin Dunitz, 1999. £65. ISBN: 1-85317-556-0

The clinical syndrome of asthma has been known for more than 2000 years, but much about the complex two-way interactions between the immune system and airway epithelium, the effect of the environment, and the underlying pathophysiology of the disorder remains obscure. For reasons that are not entirely clear, the prevalence of asthma has increased in the past decade; not only is the burden of the disease increasing, but morbidity and mortality from asthma have also increased in many parts of the world. Most patients with asthma have mild disease, but some patients have severe asthma that profoundly affects the quality of life, both for them and for their families.

Although we have learned much about the mechanisms and environmental factors that underlie asthma, little progress has been made in understanding how a condition that is easily managed in most cases becomes transformed into one that cannot be adequately controlled in some cases. Difficult Asthma focuses on this issue.

There is now a substantial body of experimental and clinical data pointing to an immunopathological basis of asthma, a concept that was in its early stages only a decade ago. Although it is difficult to include in a textbook every piece of new information in a rapidly developing field such as immunopathology, the two chapters devoted to the inflammatory process that causes difficult asthma are sufficiently detailed to provide the reader with a thorough understanding of the mechanisms underlying the clinical patterns of asthma.

The authors provide actual studies that help readers master four difficult forms of asthma: acute severe asthma with recurrent attacks, chronic difficult asthma, brittle asthma, and fatal asthma. Dramatic attacks of severe and progressively worsening airflow obstruction that fail to respond to appropriate therapy meet all the criteria for difficult asthma. This illness, often called status asthmaticus, is hard to manage and requires special experience and skills, including intubation and management of mechanical ventilation. The factors that trigger severe attacks and the mechanisms of prolonged and exaggerated bronchoconstriction remain elusive. Specific chapters deal with causes of severe attacks of asthma, including viral infections, exposure to allergens, occupational agents, and medications. The role of the pulmonary circulation, the value of respiratory-function testing, and the principles of intensive care during severe attacks are also reviewed.

Even though severe exacerbations are rare, asthma is also difficult when it steadily interferes with everyday life and requires close supervision and careful treatment with maximal doses of the best agents currently available. The reasons for this kind of difficult asthma are often hard to determine. Sometimes it arises from an incorrect diagnosis; viral bronchiolitis in a child or chronic obstructive bronchitis and emphysema in an elderly person may be confused with asthma. Monitoring of the patient's compliance with treatment and the search for complicating conditions are important issues addressed in this book. If the patient cannot adhere to treatment with conventional agents, or if the asthma is judged to be refractory to such therapy, other agents (antileukotrienes, immunosuppressants, xanthines, and anticholinergic drugs) have to be considered. Chapters in this book also deal with the routes of corticosteroid administration and the possibility of resistance to corticosteroids.

In some patients, asthma is not a problem on most days, but it occasionally causes sudden, severe attacks that necessitate unscheduled hospital visits and repeated courses of systemic corticosteroids. This unstable condition is called brittle asthma. The attacks often occur without an obvious trigger and may be life-threatening. Despite considerable treatment, the variability of peak air flow is chaotic, with sudden falls occurring in a patient with otherwise well-controlled asthma. Patients with brittle asthma tend to underestimate the seriousness of their condition, and even those who have survived nearly fatal attacks may not realize that they have a difficult disease. For physicians, this type of asthma is doubly difficult because the attacks can be hard to treat and because efforts to ensure the patient's compliance with preventive therapy often fail. Even more difficult and frustrating is the kind of asthma that carries an increased risk of death.

Difficult Asthma reviews retrospective studies of the causes of fatal asthma. The risk factors for death from asthma include previous attacks requiring intubation, respiratory acidosis, hypercapnia, severe attacks despite long-term use of oral corticosteroids, and attacks complicated by pneumothorax. The book also discusses the question of whether depression, other psychiatric disorders, or the excessive use of inhaled β-agonists increases the risk of death. The pathological findings in patients with fatal asthma have several cardinal features: occlusion of the bronchial lumen with tenacious secretions, hyperplasia of goblet cells and submucosal glands, thickening of the basement membrane, and tissue eosinophilia and, perhaps more important, infiltration by neutrophils. The recruitment of neutrophils into the bronchi probably depends on additional, as yet unexplored mechanisms that are activated in patients at risk for fatal asthma.

With this useful book as a guide, specialists and general readers will be well informed about the current clinical state of affairs and the advances that can be expected from further studies of asthma and particularly of its difficult aspects.

Gianfranco Del Prete, M.D.
Florence University, 50134 Florence, Italy