CONSEQUENCES OF LONG-TERM INFLAMMATION
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Although asthma is classically defined as reversible airflow obstruction, and often remits in younger subjects with milder disease, the natural history of asthma is that various degrees of airflow obstruction may persist and, in the long-term, asthma may become moderately to fully irreversible. Severe, irreversible airflow obstruction may develop despite apparently appropriate therapy and in the absence of other risk factors, such as smoking and environmental insults. All studies of subjects with persisting asthma show increased decline in lung function compared with normal subjects. Persistent abnormal physiology is reflected both in reduced airflow rates and in increased airway responsiveness. The cellular and molecular mechanisms of airway remodeling are described elsewhere in this issue. Questions not yet clearly answered are the reasons for these persistent abnormalities in some asthmatics, and which subjects are most at risk. Factors that adversely impact the outcome as adults identified relatively consistently among many longitudinal studies of the natural history of asthma include: Female gender. Environmental tobacco smoke exposure in childhood. Personal tobacco smoking in adolescence and adulthood. Age of onset of symptoms. Severity of childhood asthma. Duration of asthma. Severity of lung function abnormality in childhood. Bronchodilator reversibility. Degree of airway hyperresponsiveness. Delay in initiating anti-inflammatory therapy. Remission among adult asthmatics is uncommon, but is associated with better initial lung function, young age, male gender, and lesser degrees of airway responsiveness. The role of atopy remains controversial. Conversely, risk factors for death from asthma include older age, smoking, atopy, impaired lung function, and moderate to high reversibility. Treatment can improve lung function, reduce airway responsiveness, and improve quality of life. The overall effect of treatment on the natural history of the disease is not yet clear, despite significant short-term improvements from effective anti-inflammatory therapy.