Mannitol versus hypertonic saline: Safety and efficacy of mannitol and hypertonic saline in sputum induction and bronchial hyperreactivity assessment

Chron Respir Dis. 2015 Aug;12(3):197-203. doi: 10.1177/1479972315576144. Epub 2015 Mar 11.


Eosinophilic asthma phenotype predicts good response to corticosteroids and associates to asthmatic exacerbations. Sputum induction by hypertonic saline (HS) inhalation is technically demanding. Bronchial hyperresponsiveness (BHR) to osmotic agents indirectly mirrors active airway inflammation. We compared the safety and ability of HS and mannitol to induce sputum and measure BHR. We evaluated the stability of inflammatory phenotypes. We studied 35 non-smoking asthmatics randomized to undergo HS and mannitol challenges on 2 days 1 week apart. Sputum was sampled for cell analysis and phenotyped as eosinophilic (≥3% eosinophils) and non-eosinophilic (<3%) asthma. Nineteen subjects had BHR to mannitol and nine of them also had BHR to HS. Drops in forced expiratory volume in 1 s were higher from HS challenge than from mannitol challenge. Adequate sputum samples were obtained from 80% subjects (68% mannitol and 71% HS). Eosinophils and macrophages from both challenges correlated. Neutrophils were higher in sputum from HS. Ninety percent samples were equally phenotyped with HS and mannitol. Fractional exhaled nitric oxide, sputum eosinophils and BHR correlated in both challenges. HS and mannitol showed similar capacity to produce valuable sputum samples. BHR to both osmotic stimuli partially resembled airway eosinophilic inflammation but mannitol was more sensitive than HS to assess BHR. Eosinophilic phenotype remained stable in most patients with both stimuli.

Keywords: Asthma; eosinophils; hypertonic saline; mannitol; phenotype; sputum.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Asthma / complications
  • Asthma / immunology
  • Asthma / physiopathology*
  • Breath Tests
  • Bronchial Hyperreactivity / complications
  • Bronchial Hyperreactivity / diagnosis*
  • Diuretics, Osmotic / adverse effects
  • Diuretics, Osmotic / pharmacology*
  • Eosinophils
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Macrophages
  • Male
  • Mannitol / adverse effects
  • Mannitol / pharmacology*
  • Middle Aged
  • Neutrophils
  • Nitric Oxide / analysis
  • Saline Solution, Hypertonic / adverse effects
  • Saline Solution, Hypertonic / pharmacology*
  • Sputum / cytology*
  • Sputum / drug effects*
  • Sputum / metabolism
  • Young Adult


  • Diuretics, Osmotic
  • Saline Solution, Hypertonic
  • Nitric Oxide
  • Mannitol