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Life-threatening asthma, part 1: Identifying the risk factors

Life-threatening asthma, part 1: Identifying the risk factors

Despite our increased understanding of the pathogenesis of asthma and improved therapies, asthma mortality and morbidity remain disturbingly high. Recognition of acute life-threatening asthma exacerbations by physicians is essential, since initiation of early aggressive therapy is critical in averting fatal outcomes.

Near-fatal asthma can be defined as the development of respiratory arrest resulting from asthma, with a PaCO2 greater than 50 mm Hg and/or an altered state of consciousness.1 Yet virtually all patients requiring hospitalization for asthma can be considered at risk for respiratory failure or death. By understanding the risk factors and pathophysiology of life-threatening asthma, clinicians can optimize their approach to all patients with asthma exacerbations.

In this article, we will review the risk factors for near-fatal asthma and the clinical presentation. In an upcoming issue of The Journal of Respiratory Diseases, we will summarize the key elements of pharmacologic management.

IDENTIFYING PATIENTS AT RISKPatterns of progression

Patients with life-threatening asthma may have 1 of 2 distinct patterns of progression. Most patients have a gradual worsening of symptoms. This may occur over days or weeks or as a subacute exacerbation over hours to days. A minority of patients (up to 8% to 13% in some studies) have hyperacute or acute asphyxic asthma, in which respiratory failure develops within 2 hours of symptom onset.2-5 In a large prospective study, Plaza and associates4 found that patients with hyperacute asthma had significantly higher rates of impaired consciousness and absence of breath sounds on admission, fewer hours of mechanical ventilation, and fewer days of hospitalization.

Some patients with hyperacute asthma have a high variability in peak expiratory flow rate (PEFR).1 A sudden change in airflow in such patients probably results from acute bronchoconstriction rather than airway inflammation and edema, and it rapidly can lead to respiratory failure.1

A subset of these patients have abnormal physiologic responses to airway narrowing because of a blunted hypoxic ventilatory drive.6,7 They do not respond to bronchoconstriction and hypoxemia with hyperventilation,and they present with hypercapnia, even during moderate exacerbations.7,8

A second subgroup of patients do not perceive dyspnea even when they have severe obstruction and may be relatively symptom-free even with severe asthma.7,9 Although these subgroups may represent a small proportion of patients with asthma, they must be identified because they are at a much greater risk for death.

Studies show that the airway mucosa of patients who die of rapid-onset asthma exacerbations contains a higher percentage of neutrophils and a smaller percentage of eosinophils than that of patients with gradual worsening of symptoms.10,11 These data also suggest that patients with hyperacute asthma have a different pathophysiology than patients with a slower deterioration. Although patients with sudden deterioration have an increased mortality risk, they are more responsive to asthma therapy; in contrast, patients with gradual worsening take longer to respond to therapy and have longer hospitalizations.

Regularly monitoring PEFR allows us to identify another group of patients who are at risk for life-threatening asthma.7,12 Sudden life-threatening exacerbations may develop in patients who have a normal PEFR, but with intermittent large fluctuations. This is true even after patients have been initially stabilized during acute exacerbations of asthma. Hetzel and associates11 showed that PEFR measurements had greater than 50% variability in 9 of 10 cases of respiratory failure occurring in patients after hospitalization for asthma. Identification of these "morning dippers" can lead to modification of therapy to attenuate or prevent sudden exacerbations.

In most patients with gradual worsening, ventilation-perfusion (V./Q. ) mismatch develops as a result of smooth muscle bronchoconstriction, airway edema, inflammation, and formation of mucous plugs. Airway narrowing leads to hyperinflation, causing intrinsic positive end-expiratory pressure (auto-PEEP), which is compounded by "breath stacking." One prospective study of patients with sudden-onset, near-fatal exacerbations of asthma suggests that the loss of lung elastic recoil and hyperinflation at total lung capacity are risk factors for life-threatening asthma exacerbations.9

Increased dead space also develops as a result of decreased capillary blood flow to areas of hyperinflation.13 Because of increased intrathoracic pressure, venous return is decreased, and the large negative pleural pressures generated during inspiration lead to increased ventricular afterload.13 Thus, the pulmonary and hemodynamic changes in asthma exacerbations can cause significant instability.

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