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Inhaled transmembrane ion transport modulators and non-steroidal anti-inflammatory drugs in asthma
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  1. S Biancoa,
  2. M Robuschia,
  3. A Vaghib,
  4. A Fumagallia,
  5. P Sestinic
  1. aRespiratory Diseases Clinic, University of Milan Bicocca, Ospedale S Gerardo, Monza, Italy, bOspedale di Garbagnate, Milan, Italy, cInstitute of Respiratory Diseases, University of Siena, Italy
  1. Dr P Sestini, Institute of Respiratory Diseases, Viale Bracci 3, 53100 Siena, Italysestini{at}unisi.it

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Several stimuli which affect the osmolarity of airway surface liquid may induce bronchoconstriction in asthmatic subjects, indicating that in these patients the control of the bronchial calibre is affected by the physicochemical characteristics of the airways lining fluid.1 In the last few years this hypothesis has been confirmed using a number of drugs which are known to affect cellular ion transport.2 Loop diuretics inhibit the bronchial obstructive response to ultrasonically nebulised distilled water (UNW) in a dose dependent fashion.3 It is still unclear, however, whether this protective activity is attributable to the main pharmacological activity of frusemide—the inhibition of the Cl/Na+/K+ co-transport—since loop diuretics far more potent than frusemide on this mechanism, such as piretanide, torasemide or bumetanide, are markedly less effective than frusemide in preventing UNW induced bronchoconstriction when given by inhalation in equipotent diuretic doses (fig 1).4 In addition to UNW, frusemide was also found to be effective in reducing the bronchoconstriction induced by a variety of “indirect” stimuli including exercise, allergens, hyperosmotic aerosols, metabisulphite, and aspirin.4 5

Figure 1

Protective effect against UNW induced bronchoconstriction of increasing doses of inhaled frusemide, administered from a pressurised metered canister (5 mg/puff) and piretanide administered through a jet nebuliser. Data are expressed as the percentage protection attained in the same patient using an optimal dose of 40 mg frusemide through a jet nebuliser. Values are mean (SE) of 8–12 asthmatic patients.

The natriuretic activity of frusemide is known to be partially inhibited by cyclo-oxygenase (COX) inhibitors, and a single study found a complete abrogation of the protective effect …

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