Induced sputum: comparison between isotonic and hypertonic saline solution inhalation in patients with asthma

Chest. 2001 Dec;120(6):1815-21. doi: 10.1378/chest.120.6.1815.


Background: Sputum induction by hypertonic saline solution inhalation is widely used to study airways secretions in patients with asthma. However, hypertonic saline solution is a potent indirect bronchoconstrictor.

Study objectives: We studied the validity of isotonic saline solution (0.9%) inhalation as a means to induce sputum by comparing it to hypertonic saline solution (4.5%) inhalation.

Patients: Sixteen patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion.

Methods: Subjects underwent sputum induction twice at 1-week intervals. Saline solution (hypertonic or isotonic) was inhaled for three periods of 5 min. The parameters assessed in sputum samples were cell counts, sodium, eosinophil cationic protein (ECP), and albumin concentrations, osmolality, and pro-matrix metalloproteinase (MMP)-9 activity by zymography.

Results: The maximal fall in peak expiratory flow during sputum induction was greater after inhalation of hypertonic saline solution than after inhalation of isotonic saline solution (p < 0.01). Each subject produced analyzable sputum on both visits. There were no statistically significant differences in total and differential sputum cell counts, and the reproducibility coefficients were high for eosinophils and neutrophils when comparing the two methods. Likewise, sputum levels of ECP and albumin as well as sputum pro-MMP-9 activity were not different between the two methods, and were highly reproducible as shown by high intraclass coefficients (Ri) of correlation (0.72, 0.74, and 0.77 for ECP, albumin, and pro-MMP-9, respectively). Sputum sodium concentrations and osmolality were higher after inhalation of hypertonic saline solution (p < 0.05).

Conclusion: In patients with moderate-to-severe asthma reporting a clinical history of mucus hypersecretion, inducing sputum by isotonic or hypertonic saline solution inhalation leads to comparable results in eosinophil and neutrophil cell counts and fluid phase mediators/proteins.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Asthma / diagnosis*
  • Asthma / immunology
  • Blood Proteins / metabolism
  • Double-Blind Method
  • Eosinophil Granule Proteins
  • Eosinophils / immunology
  • Female
  • Humans
  • Leukocyte Count
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Neutrophils / immunology
  • Osmolar Concentration
  • Peak Expiratory Flow Rate
  • Predictive Value of Tests
  • Ribonucleases*
  • Saline Solution, Hypertonic*
  • Sodium Chloride*
  • Sputum* / cytology
  • Sputum* / immunology


  • Blood Proteins
  • Eosinophil Granule Proteins
  • Saline Solution, Hypertonic
  • Sodium Chloride
  • Ribonucleases
  • Matrix Metalloproteinase 9