Acute severe asthma: pathophysiology and pathobiology of gas exchange abnormalities

Acute severe asthma, or "status asthmaticus", is a devastating clinical condition ultimately resulting in life-threatening hypoxaemia. The pivotal intrapulmonary mechanism of this condition is profound ventilation/perfusion (V'A/Q') mismatch, characterized by a predominant bimodal blood flow pattern reflecting a marked deterioration (increase) of the dispersion of pulmonary blood flow. This V'A/Q' profile is consistent with the presence of numerous alveolar units with low V'A/Q' ratios, in which ventilation is markedly reduced, although never abolished, but perfusion is maintained. Further V'A/Q' worsening whilst breathing 100% O2 suggests the presence of an underlying vigorous hypoxic vascular response. Of equal importance, gas exchange disturbances are poorly related to the severity of reduced maximal airflow rates. Inhaled platelet-activating factor (PAF), both in normal individuals and asthmatic patients, results in moderate-to-severe disturbance of V'A/Q' status, a finding that is probably related to altered microvascular permeability within the airway wall. Salbutamol, but not ipratropium bromide, prevented all PAF-induced systemic and lung function abnormalities, possibly because venoconstriction in the bronchial circulation was antagonized. Taken together, these findings support the hypothesis that platelet-activating factor may play a critical role in the pathobiology of severe acute exacerbations of asthma.

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