Near-Fatal Asthma: Recognition and Management

Ruben D Restrepo; Jay Peters


Curr Opin Pulm Med. 2008;14(1):13-23. 

In This Article

Abstract and Introduction

Purpose of review: Near-fatal asthma continues to be a significant problem despite the decline in overall asthma mortality. The purpose of this review is to discuss recent advances in our understanding of the pathophysiology, diagnosis and treatment of near-fatal asthma.
Recent findings: Two distinctive phenotypes of near-fatal asthma have been identified: one with eosinophilic inflammation associated with a gradual onset and a slow response to therapy and a second phenotype with neutrophilic inflammation that has a rapid onset and rapid response to therapy. Patients who develop sudden-onset near-fatal asthma seem to have massive allergen exposure and emotional distress. In stable condition, near-fatal asthma frequently cannot be distinguished from mild asthma. Diminished perception of dyspnea plays a relevant role in treatment delay, near-fatal events, and death in patients with severe asthma. Reduced compliance with anti-inflammatory therapy and ingestion of medications or drugs (heroin, cocaine) have been associated with fatal or near-fatal asthma.
Summary: Near-fatal asthma is a subtype of asthma with unique risk factors and variable presentation that requires early recognition and aggressive intervention.

Near-fatal asthma (NFA) and fatal asthma represent the most severe clinical presentations ofasthma.[1,2,3] Although there are no universally agreed diagnostic criteria for NFA, it is typically associated with the presence of hypercapnia, acidemia, altered state of consciousness and the development of cardiorespiratory arrest requiring endotracheal intubation and mechanicalventilation.[4,5] NFA subjects typically have at least one asthma exacerbation in the year prior to admission, despite treatment for at least a year with ≥1200 μg/day beclomethasone or equivalent, long-acting β-agonists or theophylline, and with or without oral corticosteroids (≥5 mg/day prednisone orequivalent).[6] Patients with NFA may have one of two distinct patterns of progression ( Table 1 ).

The most common NFA phenotype is characterized by gradual deterioration over days or weeks and often occurs in patients with severe and poorly controlled asthma. It could also occur as a sub-acute exacerbation of asthma symptoms over hours todays.[7,8,9,10] Although this type of NFA is responsible for 80-85% of all fatal events associated with asthma, this pattern is generally considered preventable. Postmortem examination reveals extensive airway plugging with gelatinous, dense and tenacious mucus mixed with inflammatory and epithelial cells, epithelial denudation, mucosal edema, and an intense eosinophilic infiltration of thesubmucosa.[11,12,13,14,15,16,17,18,19,20] A second pattern of NFA is characterized by a history of unstable disease that is partially responsive to treatment. In this type of NFA, patients have hyper-acute or acute asphyxic asthma, in which respiratory failure develops within 2 h of the onset of symptoms. Patients in this group typically have massive allergen exposure as well as emotionaldistress.[21] Death can be sudden and unexpected.[18,22,23,24] Patients in this group have been also called brittle asthmatics. They have a faster rate of improvement to therapy and have shorter hospitalizations when compared with the slow-onsetNFA.[23,24]

Monitoring of peak expiratory flow rates (PEFRs) has led to the recognition of two distinct groups of patients at risk for NFA. The first group comprises patients presenting with hyperacute or asphyxic asthma who have abnormal physiological responses to their airwayconstriction.[23,24] Within this group, some patients may have blunted hypoxic ventilatory drive and not respond to bronchoconstriction and hypoxemia with hyperventilation, and some fail to perceive worsening bronchoconstriction of the airway (known as underpercievers). This group of patients present with hypercapnia, even duringmoderate exacerbations.[23] Although episodes of hypercapnia occur more frequently than the need for orotracheal intubation and mechanical ventilation in all NFA episodes, they do not necessarily imply a poor prognosis.[3] The sudden change in airflow in these patients probably results from acute bronchoconstriction rather than airway inflammation and edema.[3]

Pathologic examination in such cases shows absence of mucus plugs in the large majority of patients, and in almost all patients a greater proportion of neutrophils than eosinophils infiltrating the submucosa is observed.[3,18,19,21,22]

The second group of patients identified by routine PEFR monitoring consists of patients with marked diurnal variations in PEFR. These patients may have normal PEFRs on intermittent testing but have large fluctuations in flow and may develop sudden NFA attacks. These patients may have severe drops in their PEFR early in the morning (morning dippers) even during hospitalization and require continual monitoring of their PEFR.[24]

A recent report by Romagnoli et al.[6] found a low prevalence of atopy in NFA, suggesting that mechanisms different from atopy might be more relevant to the pathogenesis of severe asthma. Due to the many differences between NFA and severe asthma in terms of lung function and airway inflammation, NFA may represent a different disease that frequently cannot be distinguished from mild asthma when in stable conditions.

Since virtually all patients requiring hospitalization for asthma can be considered at risk for respiratory failure or death, and the long-term prognosis is poor,[3] recognition of risk factors and the understanding of the pathophysiology of NFA are of paramount importance to optimize the evaluation and therapy during their exacerbations and to decrease the rate of fatal events. In both phenotypes, the most important pathophysiological events that lead to death are cardiac arrhythmias and asphyxia followed by complications of invasive mechanical ventilation such as barotrauma and ventilator-associated pneumonia.[25•]


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