Predicting Asthma Control and Exacerbations: Chronic Asthma as a Complex Dynamic Model.

Urs Frey


Curr Opin Allergy Clin Immunol. 2007;7(3):223-230. 

In This Article

Abstract and Introduction

Purpose of review: Predicting asthma episodes is notoriously difficult but has potentially significant consequences for the individual, as well as for healthcare services. The purpose of this review is to describe recent insights into the prediction of acute asthma episodes in relation to classical clinical, functional or inflammatory variables, as well as present a new concept for evaluating asthma as a dynamically regulated homeokinetic system.
Recent findings: Risk prediction for asthma episodes or relapse has been attempted using clinical scoring systems, considerations of environmental factors and lung function, as well as inflammatory and immunological markers in induced sputum or exhaled air, and these are summarized here. We have recently proposed that newer mathematical methods derived from statistical physics may be used to understand the complexity of asthma as a homeokinetic, dynamic system consisting of a network comprising multiple components, and also to assess the risk for future asthma episodes based on fluctuation analysis of long time series of lung function.
Summary: Apart from the classical analysis of risk factor and functional parameters, this new approach may be used to assess asthma control and treatment effects in the individual as well as in future research trials.

Asthma exacerbations are seen in unstable asthma and are often a feature of difficult asthma in adults[1,2,3] or children.[4,5] Different phenotypes of difficult asthma have been described (Fig. 1): phenotype (a) is those patients with persistent airway obstruction with or without episodic deterioration and with poor response to oral steroids; phenotype (b) is those patients with recurrent episodes of severe airway narrowing over minutes to hours with no obvious triggers (brittle asthma type I), and phenotype (c) is those patients who experience a fatal or near-fatal episode of asthma (brittle asthma type II).

Different phenotypes of difficult asthma

The long-term control of asthma is influenced by both long-term and short-term factors, which are not independent of each other. Long-term effects on asthma control include, for example, developmental differences related to prenatal tobacco exposure in children, and the adverse effects of obesity or airway remodeling. Short-term factors include, for example, seasonal pollen exposure or acute lower respiratory tract infections. The integrated effect of both short-term and long-term factors will determine the asthma phenotype, as well as the overall risk for asthma exacerbations.

The identification of the different asthma phenotypes and the assessment of their associated risk factors are a first step towards better evaluation of future risks. For example phenotype (a), characterized by fixed airway obstruction, is mainly determined by long-term factors, leading to chronically poor asthma control. In children, adverse influences on airway development may include chronic lung disease of prematurity, inborn airway stenosis or malacia, tobacco exposure during pregnancy, postnatally acquired bronchiolitis obliterans, recurrent gastro-esophageal reflux or airway remodelling as a consequence of, or in parallel with, chronic inflammation of the airways.[4] Similar factors are relevant in adults, although the distinction between the type (a) phenotype and chronic obstructive pulmonary disease is often unclear. Interestingly, recent evidence places emphasis on the role of smooth muscle function associated with both fixed airway obstruction as well as excessive bronchial hyperreactivity.[6] Smooth-muscle length is determined by the dynamic equilibrium of two counteracting mechanisms: smooth muscle constriction and stretching with tidal respiration. Increased disposition to the constricting action of smooth muscle is found in prematurity, allergic sensitization and asthma, whereas the tidal stretching of the smooth muscle is impeded in restrictive lung disorders such as occur with chest wall deformity, obesity, pregnancy, or spinal cord injury.[6] The history of additional factors such as these may help to identify the risk for persistent airway obstruction as a complication of asthma. Other asthma phenotypes such as brittle asthma (b) and fatal asthma (c) are thought to be related to either an increased exogenous stimulus and/or to excessive airway inflammation and bronchial reactivity. However, the relationship between stimulus, airway inflammation, bronchial reactivity, symptoms and perception of symptoms is poor. In a recent study, a trigger was identified in fewer than 50% of all fatal asthma episodes.[7]

Many studies have tried to identify clinical risk factors that predict severe airway obstruction or rehospitalization rates on a short-term basis.[1,3,8,9,10,11,12,13,14,15,16,17*,18,19,20,21,22,23,24,25] There is consistent evidence that frequent asthma symptoms, repeated hospitalizations or emergency visits in the past, frequent use of inhaled short-acting β2-agonists, current use of systemic corticosteroids or recent withdrawal from systemic corticosteroids are risk factors for future asthma exacerbations, hospitalizations or even death. Additional risk factors and comorbidities include allergic rhinitis, severe nasal sinus disease, gastro-esophageal reflux, cardiovascular disease or chronic obstructive pulmonary disease, psychiatric illness or psychosocial problems, low socioeconomic status and urban residence, illicit drug use and sensitivity to alternaria. Alexithymia, a psychological trait characterized by difficulty in perceiving body sensations and expressing emotions,[26] and menstruation[27] are more frequently related to severe asthma and near-fatal asthma.


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