mannitol inhalation test for asthma diagnosis
- related: Asthma reactive airway disease
- tags: #literature #pulmonary
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This patient demonstrates a >15% fall in FEV1 from baseline, and thus has a positive mannitol inhalational challenge test. Bronchoprovocation testing is indicated in patients who have symptoms suggestive of asthma but do not respond to a bronchodilator and have normal spirometry. Bronchoprovocation can be performed with direct or indirect stimuli. Direct stimuli, such as methacholine and histamine, induce bronchoconstriction mainly by directly stimulating airway smooth muscle to contract. A test utilizing a direct agent is considered positive when the provocative dose results in a 20% fall in FEV1 from baseline.
Mannitol is an indirect stimulus, causing bronchoconstriction by increasing airway surface osmolarity, which results in mast cell activation and the release of inflammatory mediators that act on the airway's smooth muscle, causing constriction. It is felt that indirect agents correlate better with airway inflammation than direct spasmogens. Bronchoprovocation with mannitol correlates well with other indirect stimuli, such as hypertonic saline, exercise, and eucapnic voluntary hyperpnea of dry air. Indirect stimuli are more specific than the direct stimuli and thus are more helpful in confirming the diagnosis of asthma. The sensitivity of indirect stimuli, however, is relatively low compared with direct agents, except in studies of elite athletes, where the sensitivity for mannitol to identify exercise-induced bronchoconstriction was shown to be high, leading some to utilize mannitol as a surrogate for testing exercise-induced bronchoconstriction. Direct agents have a high sensitivity and high negative predictive value, making these stimuli the agents of choice for excluding asthma. Direct stimuli have a low specificity as tests can be positive in normal subjects, as well as those with allergic rhinitis, congestive heart failure, and smoking-related COPD.
Mannitol is delivered in dry powder form following a standard protocol whereby patients are asked to inhale increasing doses: 0, 5, 10, 20, 40, 80, 160, 160, and 160 mg again, with FEV1 measured 1 min after each dose. The dose is increased unless a 10% fall is noted, whereby the previous dose is repeated, as was the case with the patient presented here. Testing continues until the FEV1 falls 15% from baseline or the maximum cumulative dose of 635 mg is reached. Many patients report cough yet are able to complete testing.1