The use of 4.5% hypertonic saline challenge test in diagnosing asthma in children with chronic recurrent cough

  • Bambang Supriyatno
  • Dina Medina
  • Alan R Tumbelaka
  • Nastiti N Rahajoe
Keywords: 4.5% hypertonic saline challenge test, bronchial provocation test, asthma, chronic recurrent cough


Background The 4.5% hypertonic saline (HS) challenge test has
several benefits compared to histamine challenge test as gold stan-
dard. Saline is an inexpensive non-pharmacological substance
which is relatively safe. Its mechanism in inducing bronchospasm
resembles that of asthma. Moreover, it can easily be made in a
modest medical laboratory.
Objective To determine the ability of 4.5% HS challenge test com-
pared to histamine challenge test in diagnosing asthma in children
with chronic recurrent cough (CRC).
Methods This study was a diagnostic test on children with CRC
aged 6 to 14 years, conducted in outpatient clinic of Department of
Child Health, Cipto Mangunkusumo Hospital, Jakarta. All subjects
underwent lung function tests. Subjects whose FEV 1 was <80% were
diagnosed as asthmatic and underwent the 4.5% HS challenge test
only. Those whose FEV 1 was 80% underwent the histamine chal-
lenge test followed by the 4.5% HS challenge test one or two weeks
later. Test results were expressed as positive or negative. Based on
the results, we calculated the sensitivity, specificity, predictive val-
ues, and likelihood ratios of the 4.5% HS challenge test.
Results Forty-five subjects, consisting of 22 boys and 23 girls,
were enrolled. The average age of subjects was 9 years old. Atopic
history in the family or in subjects themselves was found in 80% of
subjects. Eight subjects had FEV 1 of <80%. Forty-four subjects
were diagnosed with asthma based on a baseline FEV 1 of <80%
or a positive histamine provocation test. Thirty-seven subjects had
a positive 4.5% HS challenge test; all had asthma. Sensitivity and
specificity of the 4.5% HS challenge test were 84.1% and 100.0%,
respectively; the positive and negative predictive values were
100.0% and 12.5%, respectively. The positive likelihood ratio was
infinite and negative likelihood ratio was 0.16.
Conclusion The 4.5% hypertonic saline challenge test can be used
as an alternative bronchial provocation test in diagnosing asthma in
children with CRC. Further study with larger sample size is needed
for widespread usage.

Author Biographies

Bambang Supriyatno
Department of Child Health, Medical School, University of
Indonesia, Jakarta, Indonesia.
Dina Medina
Department of Child Health, Medical School, University of
Indonesia, Jakarta, Indonesia.
Alan R Tumbelaka
Department of Child Health, Medical School, University of
Indonesia, Jakarta, Indonesia.
Nastiti N Rahajoe
Department of Child Health, Medical School, University of
Indonesia, Jakarta, Indonesia.


1. Hoop RS, Townly R, Brennan BA, Dave NK. Bron-
chial challenge techniques in children: Metacholine,
histamine, hiperventilation, and osmolar. In: Hellman
BC, editor. Pediatric respiratory disease: diagnosis and
treatment. 3rd ed. Philadelphia: WB Saunders; 1993.
p. 131-42.
2. Anderson SD, Smith CM, Rodwell LT, Riedler J,
Robertson CF. The use of nonisotonic aerosols or evalu-
ating bronchial hyperresponsiveness. In: Spector SL,
editor. Provocation testing in clinical practice. New
York: Marcel Dekker; 1995. p. 249-76
3. Riedler J, Dalton M, Holst D, Robertson C. Hyper-
tonic saline challenge in an epidemiologic survey of
asthma in children. Am J Respir Crit Care Med
4. Araki H, Sly PD. Inhalation of hypertonic saline as bron-
chial challenge in children with mild asthma and nor-
mal children. J Allergy Clin Immunol 1989;84:99-107.
5. Riedler J, Gamper A, Eder W, Oberfeld G. Prevalence
of bronchial hyperresponsiveness to 4,5% hypertonic
saline and its relations to asthma and allergy symptoms
in Austrian children. Eur Respir J 1998;11:355-60.
6. Liz G, Pietrzyk JJ. Response dose ratio as an index of
bronchial responsiveness to hypertonic saline challenge
in an epidemiological survey of asthma in polish chil-
dren. Pediatr Pulmonol 1998;25:375-82.
7. Supriyatno B, Rahajoe NN. Uji provokasi bronkus
dengan salin hipertonik. Presented at the Asian
Asthma Academy; 2002 August; Jakarta, Indonesia.
8. Niggeman B, Illi S, Madloch C, Volkel K, Lau S,
Bergman R, et al. Histamine challenges discriminated
between symptomatic and asymptomatic children. Eur
Respir J 2001;17:246-53.
9. Murray AB, Ferguson AC, Morrison B. Airway respon-
siveness to histamine as a test for overall severity of asthma
in children. J Allergy Clin Immunol 1981;68:19-24.
10. Cockroft DW, Murdock Ky, Berscheid BA, Gore BP.
Sensitivity and specificity of histamine PC 20 determi-
nation in a random selection of young college students.
J Allergy Clin Immunol 1992;89:23-30.
11. Enarson DA, Vedal S, Schulzer M, Dybuncio A, Chan-
yeung M. Asthma, asthma- like symptoms, chronic bron-
chitis, and the degree of bronchial hyperresponsiveness
in epidemiologic surveys. Am Rev Respir Dis 1987; 136:
12. Anderson S, Rodwell LT, Davidkas E, Spring AF, Toit
JD. The protective effect of nedocromil sodium and
other drugs on airway narrowing provoke by hyperosmolar
stimuli: A role for the airway epithelium? J Allergy Clin
Immunol 1996;98:S124-34.
13. Boucher RC. Human airway ion transport. Am J Respir
Crit Care Med 1994;150:581-93.
14. Akdis CA, Blaser K. Histamine in the immune regula-
tion of allergic inflammation. J Allergy Clin Immunol
15. Gelfad EW. Role of histamine in the pathophysiology
of asthma: Immunomodulatory and antiinflammatory
activities of H1-receptor antagonist. Am J Med
16. Emmanuel MB. Histamine and the antiallergic anti-
histamines: A history of their discoveries. Clin Exp
Allergy 1999;29:S.1-11.
17. Wright AL, Holberg CJ, Morgan WJ, Taussig LM,
Halonen M, Martinez FD. Reccurent cough in child-
hood and its relation to asthma. Am J Respir Crit Care
Med 1996;153;1259-65.
18. Faniran AO, Peat JK, Woolcock AJ. Persistent cough:
Is it asthma? Arch Dis Child 1998;79:411-14.
19. Gunadi S. Pendekatan klinik batuk kronik dan atau
berulang pada anak [dissertation]. Surabaya: Fakultas
Kedokteran Universitas Airlangga; 1991.
20. Rahajoe N, Natalina S, I Boediman, Darmawan BS. Batuk
kronik berulang pada bayi dan anak. In: Firmansyah A,
Trihono PP, Oswari H, Nurhamzah W, editors. Proceed-
ings of the 11th National Congress of the Indonesian
Society of Pediatricians. Jakarta: IDAI Pusat; 1999. p. 18.
21. Nishimura H, Mochizuki H, Tokuyama K, Morikawa
A. Relationship between bronchial hyperresponsiveness
and development of asthma in children with chronic
cough. Pediatr Pulmonol 2001;31:412-18.
22. Weiss ST. Dose asthma progress to chornic obstruc-
tive pulmonary disease? In: Johnstron SL, Holgate ST,
editors. Asthma critical debates. Iowa: Blackwell Sci-
ence; 2002. p. 99-114.
23. Clough JB, Williams JD, Holgate ST. Effect of atopy
on the natural history of symptoms, peak expiratory
flow and bronchial responsiveness in 7- and 8-year
old children with cough and wheezing: A 12-month
longitudinal study. Am J Rspir Crit Care Med
24. Irwi RS, Patter MR, Holland PS, Corwin WR, Hugher JP.
Postnasal drip cause cough and is associations with revers-
ible upper airway obstructions. Chest 1984;85: 346-51.
25. Smith CM, Anderson SD. Inhalations challenge using
hypertonic saline in asthmatic subject: a comparisons
with responses to hyperpnea, metacholine and water.
Eur Respir J 1990;3:144-55.
How to Cite
Supriyatno B, Medina D, Tumbelaka A, Rahajoe N. The use of 4.5% hypertonic saline challenge test in diagnosing asthma in children with chronic recurrent cough. PI [Internet]. 10Oct.2016 [cited 12Aug.2022];45(3):93-. Available from:
Received 2016-10-05
Accepted 2016-10-05
Published 2016-10-10