Jurnal pediatri

(1)

Nebulized 5% or 3% Hypertonic or 0.9% Saline for Treating Acute

Bronchiolitis in Infants

Khalid Al-Ansari, MD, FRCPC, FAAP(PEM), Mahmoud Sakran, MD, Bruce L. Davidson, MD, MPH, Rafah El Sayyed, MD, Khalid Al-Ansari, MD, FRCPC, FAAP(PEM), Mahmoud Sakran, MD, Bruce L. Davidson, MD, MPH, Rafah El Sayyed, MD,

Hella Mahjou

Hella Mahjoub, MD, b, MD, and Khalid Ibrahimand Khalid Ibrahim, , MDMD Objective

ObjectiveToTo cocompmpararee ththee efefﬁcaﬁcacycy anandd sasafefetyty ofof 5%5%,, 3%3%,, anandd 0.0.9%9% sasalilinene sosolulutitionon foforr trtreaeatitingng acacututee brbrononchchioiolilititiss in the prehospital setting.

in the prehospital setting. Study design

Study design This was a double-blind trial including consecutive infants aged <18 months treated in an urbanThis was a double-blind trial including consecutive infants aged <18 months treated in an urban urgent care setting. A total of 165 patients were randomized to receive nebulized 5%, 3%, or 0.9% (normal) saline urgent care setting. A total of 165 patients were randomized to receive nebulized 5%, 3%, or 0.9% (normal) saline with epinephrine every 4 hours. The primary efﬁcacy outcome was bronchiolitis severity score improvement at 48 with epinephrine every 4 hours. The primary efﬁcacy outcome was bronchiolitis severity score improvement at 48 hours (

hours ( cc22analysis). Scores and oxygen saturation immediately before and after each treatment were recorded toanalysis). Scores and oxygen saturation immediately before and after each treatment were recorded to assess safety.

assess safety. Results

Results A total of 187 previously healthy infants (median age, 3.1 months) diagnosed with bronchiolitis wereA total of 187 previously healthy infants (median age, 3.1 months) diagnosed with bronchiolitis were enrolled. Positivity for respiratory syncytial virus was similar in the 3 treatment groups (mean, 56%). At 48 hours, enrolled. Positivity for respiratory syncytial virus was similar in the 3 treatment groups (mean, 56%). At 48 hours, the mean severity score for the 5% saline group was 3.69

the mean severity score for the 5% saline group was 3.69 ÆÆ_{1.09, and that for the 0.9% saline group was 4.12}_{1.09, and that for the 0.9% saline group was 4.12} ÆÆ 1.11 (

1.11 ( PP = .04; difference, 0.43, 95% conﬁdence interval for the difference, 0.02-0.88). The mean severity score= .04; difference, 0.43, 95% conﬁdence interval for the difference, 0.02-0.88). The mean severity score fo

forr ththee 3%3% sasalilinene grgrououpp wawass inintetermrmedediaiatete atat 4.4.0000ÆÆ_1._1.22_{22.. Re}_Revi_visi_{sitt ra}_rate_{tess af}_afte_{terr di}_disc_scha_harge_{rge we}_were_{re si}_simi_mila_{larr in}_{in th}_the_{e 3}_{3 tr}_trea_eatm_tmen_entt groups. No adverse reactions or other safety concerns were identiﬁed.

groups. No adverse reactions or other safety concerns were identiﬁed. Conclusions

ConclusionsNebNebuliulizatzation wion withith 5%5% hyphypertertonionicc salsalineine isis safsafe, cae, cann bebe widwidelyely gengeneraeralizlizablable,e, andand may bmay bee supsuperierior toor to current treatment for early outpatient treatment of bronchiolitis.

current treatment for early outpatient treatment of bronchiolitis. (J Pediatr 2010;157:630-4)(J Pediatr 2010;157:630-4)..

B

ronchiolitis is among the most cronchiolitis is among the most coommon and serious lower respiratory tract infectimmon and serious lower respiratory tract infectionons in young children, affectings in young children, affecting main

mainly ly infaninfants ts aged 2-5 aged 2-5 monthmonths.s.1,21,2 Incidence peaks between December and March.Incidence peaks between December and March.3,43,4 In the United States in 2002,In the United States in 2002, 149 000 patients with bronchiolitis required hospitalization, with a mean hospital stay of 3.3 days and admission costs 149 000 patients with bronchiolitis required hospitalization, with a mean hospital stay of 3.3 days and admission costs of $500 million.

of $500 million.55In Qatar in 2008, about 4600 patients made about 6100 visits to pediatric emergency centers for bronchiolitis;In Qatar in 2008, about 4600 patients made about 6100 visits to pediatric emergency centers for bronchiolitis; 20% of these patients were hospitalized.

20% of these patients were hospitalized.

The mainstay of treatment remains supportive care, with supplemental

The mainstay of treatment remains supportive care, with supplemental ox ox ygen and hydration if needed, and a trial of bron- ygen and hydration if needed, and a trial of bron-chodilator therapy (albuterol/salbutamol or epinephrine) as an option.

chodilator therapy (albuterol/salbutamol or epinephrine) as an option.6-86-8 Using the bronchiolitis severity score to assessUsing the bronchiolitis severity score to assess pat

patienientsts oveoverr timtime,e, inhinhalealedd 3%3% hyphypertertonionicc salsalineine wiwithth epiepinepnephrihrinene admadminiinistestered byred by nebnebuliulizazationtion eveeveryry 6-86-8 houhoursrs hashas beebeenn foufoundnd to improve the bronchiolitis s

to improve the bronchiolitis seveeverity score and reduce the length of hospital stay in hospitrity score and reduce the length of hospital stay in hospitaalized patients when compared withlized patients when compared with 0.9% saline with epinephrine;

0.9% saline with epinephrine;9-139-13this treatment is not routinely recommended, however.this treatment is not routinely recommended, however.88In patients with cystic ﬁbrosis, hy-In patients with cystic ﬁbrosis, hy-pertonic saline concentration of 3%, 7%, and 12% have shown prom

pertonic saline concentration of 3%, 7%, and 12% have shown promise iise in a dose-response pattern for improving mucociliary n a dose-response pattern for improving mucociliary clearance and maintaining lung function compared with 0.9% saline.

clearance and maintaining lung function compared with 0.9% saline.14,1514,15Cough and chest tightness at the time of hypertonicCough and chest tightness at the time of hypertonic saline administration were reported in those patients, however.

saline administration were reported in those patients, however.

Early, prehospital intervention for bronchiolitis with a safe, effective, and inexpensive agent might save lives, reduce Early, prehospital intervention for bronchiolitis with a safe, effective, and inexpensive agent might save lives, reduce com-plications and hospitalizations, and be applicable for use worldwide, including small communities where hospital care is plications and hospitalizations, and be applicable for use worldwide, including small communities where hospital care is not available. We reasoned that a hypertonic saline concentration >3% could be safe and more efﬁcacious, alleviating severe not available. We reasoned that a hypertonic saline concentration >3% could be safe and more efﬁcacious, alleviating severe symptoms and avoiding the need f

symptoms and avoiding the need f oror hospitalization in some instances. To build on the therapeutic beneﬁt of 3% saline forhospitalization in some instances. To build on the therapeutic beneﬁt of 3% saline for inpatients with acute bronchiolitis,

inpatients with acute bronchiolitis,9-139-13

we applied the dose-response and safety data from stable patients with cystic fibrosis, we applied the dose-response and safety data from stable patients with cystic fibrosis, cautiously focusing on 5% rather than higher concentrations for our infant patients. We compared 5% saline with 3% saline cautiously focusing on 5% rather than higher concentrations for our infant patients. We compared 5% saline with 3% saline and 0.9% (normal) saline in terms of efficacy and safety in treating acute bronchiolitis in the outpatient, early and 0.9% (normal) saline in terms of efficacy and safety in treating acute bronchiolitis in the outpatient, early treatment*infir-mary setting.

mary setting.

Methods

We conducted a double-blinded, randomized, parallel-group clinical trial to We conducted a double-blinded, randomized, parallel-group clinical trial to compare the efﬁcacy and safety of 5% and 3% hypertonic saline versus 0.9% compare the efﬁcacy and safety of 5% and 3% hypertonic saline versus 0.9% (normal) saline for the treatment of acute bronchiolitis. The study was (normal) saline for the treatment of acute bronchiolitis. The study was

con-From the Division of Pediatric Emergency Medicine, From the Division of Pediatric Emergency Medicine, Department of Pediatrics, Hamad Medical Corporation, Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar (K.A., M.S., R.E., H.M., K.I.); Weill Cornell Doha, Qatar (K.A., M.S., R.E., H.M., K.I.); Weill Cornell Medi

Medicalcal ColleCollege,Doha,ge,Doha, Qatar(K.A.,B.D.);Qatar(K.A.,B.D.); andDivisionof andDivisionof Pulmonary and Critical Care Medicine, University of Pulmonary and Critical Care Medicine, University of Washington School of Medicine, Seattle, WA (B.D.) Washington School of Medicine, Seattle, WA (B.D.) Supported by Hamad Medical Corporation which Supported by Hamad Medical Corporation which em-ploys all of the physicians except B.D., who also worked ploys all of the physicians except B.D., who also worked at Hamad. The authors declare no conﬂicts of interest. at Hamad. The authors declare no conﬂicts of interest. Registered at

Registered at clinicaltrials.govclinicaltrials.gov:: ID# ID# NCT01016NCT01016249.249. 0022-3476/$ - see front matter. Copyright

RS

RSV V ReRespspiriratatorory y sysyncncytytiaial l viviruruss

630 630

(2)

ducted between September 2007 and December 2008 in the short-stay unit of the Pediatric Emergency Center of Hamad General Hospital, the only pediatric emergency facility in Qatar. The center serves an average of 200 000 patients annually and manages 42 beds in a short-stay unit. Patients admitted to the unit are assessed at least every 6 hours by a pe-diatrician to determine readiness for discharge. The length of stay in the unit for bronchiolitis ranges from 6 to 168 hours.

Infants aged #18 months presenting to the unit for the

treatment of moderate to severe viral bronchiolitis were eligi-ble for the study. Inclusion criteria were a prodromal history consistent with viral upper respiratory tract infection fol-lowed by wheezing and/or crackles on auscultation and a Wang bronchiolitis severity score16 of $4 (Table I;

available at www.jpeds.com) on presentation.

Patients were excluded from the study if they had one or more of the following characteristics: born at#34 weeks’

ges-tation, previous history of wheezing, steroid use within 48 hours of presentation, obtundation and progressive respira-tory failure requiring intensive care unit (ICU) admission, history of apnea within 24 hours before presentation, oxygen saturation#85% on room air at the time of recruitment,

his-tory of a diagnosis of chronic lung disease, congenital heart disease, or immunodeﬁciency. The 6 attending physicians covering the 18 beds in the respiratory section of the short-stay unit were trained on using the Wang bronchiolitis sever-ity score and its practical application on 4 patients with bron-chiolitis before the start of the study. Written informed consent, sought from a parent or legal guardian as soon as the patient was admitted to the unit, was obtained for every participant. The study was approved by the hospital’s Institu-tional Review Board.

Study Procedures

Patients were examined on presentation in the Pediatric Emergency Center’s examination area, and those needing further treatment or observation were admitted to the short-stay unit. Patients with bronchiolitis were assessed for study eligibility within 2 hours of the initial physician as-sessment. In patients for whom consent was obtained, plain chest radiography was performed, and nasopharyngeal swabs were taken for detection of respiratory syncytial virus (RSV) (RSV Respi-Strip; Coris Bioconcept, Gembloux, Bel-gium). Then a computer-generated list of random numbers was used by the enrolling physicians in consecutive order to identify a sealed envelope containing 1 of 3 codes identifying 1 of 3 different 500-mL bags of sterilely prepared blinded study solution containing 5%, 3%, or 0.9% saline, prepared fresh each morning by a pharmacist blinded to patient assignment.

Patients received 5mL of the study nebulization mixed with 1.5 mL of epinephrine in a double-blinded fashion on enrollment and every 4 hours thereafter until they were ready for discharge. Inhaled medications were delivered through a tight-ﬁtting face mask by pressurized oxygen with the ﬂow meter set at 10 L/min. Additional nebulized epinephrine (5 mL) delivered in the same way could be administered with

blinded study solution at a maximum frequency of every hour, and additional treatment (eg, supplementary oxygen, hydration) could be given at the discretion of the treating physician. Patients were withdrawn from the study if oxygen saturation within 30 min after nebulization fell below 85% on room air or if clinical deterioration was deemed to warrant hospital admission.

A patients could be discharged when the treating physician determined she or he did not need supplementary oxygen, was feeding adequately without intravenous ﬂuids, and had minimal or absent wheezing, crackles, and chest retractions, provided that oxygen saturation was$94% and the severity

score was <4. However, quite frequently, the actual time of discharge was determined based on social factors, such as availability and consensus of family members. At discharge, patients were sent home with an albuterol metered-dose in-haler with an appropriately sized Aerochamber and mask at-tachment (Forest Laboratories, Dublin, Ireland). Daily telephone follow-up by a study nurse was mandatory for 1 week after discharge. A patient could return to the Pediatric Emergency Center earlier if desired or necessary.

Study Measurements and Outcomes

Immediately before each scheduled nebulization (initial and every 4 hours), immediately after, and 2 hours after, the fol-lowing measurements were collected for each patient: bron-chiolitis severity score, oxygen saturation on room air, and heart rate. The primary efﬁcacy outcome in this double-blinded study was mean prenebulization bronchiolitis sever-ity score for each treatment group at 48 hours. Secondary outcomes were the severity scores at 24 hours and trend over time to 72 hours, 2-hour postnebulization severity scores trending over time, and safety measures. The latter in-cluded severity scores and oxygen saturation levels immedi-ately before versus after nebulization, number of patients requiring ICU admission, number requiring readmission to the short-stay unit, and the number revisiting the Pediatric Emergency Center in the week after discharge.

Statistical Analysis

We predicted a dose response with a superior (lower) severity score at 48 hours for patients not already discharged in the 5% saline group compared with the 0.9% saline group, with an intermediate value for the 3% saline group. We also predicted that mean scores starting at about 16 hours af-ter the start of treatment would conﬁrm this relationship. We predicted that by 72 hours, the group mean differences would disappear, due to relatively refractory illness among remain-ing patients regardless of saline group assignment. Given that pervious studies of hospitalized patients with bronchiolitis had severity scores of ~7, we estimated that our less ill outpa-tients’ mean severity scores would be ~6. We felt that a 10% improvement in severity score at 48 hours for not-yet-discharged patients randomized to the 5% saline group compared with the 0.9% saline group would be clinically sig-niﬁcant. Assuming that the 0.9% saline group remained at a score of 6, a reduction to 5.4 for the 5% saline group and

(3)

to an intermediate value for the 3% saline group would con-ﬁrm our hypothesis. We calculated descriptive statistics (mean, standard deviation and frequency) with percentages for relevant variables, using c2tests for categorical variables

and one-way analysis of variance with post hoc Bonferroni correction for continuous variables. We used SPSS 14.0 sta-tistical packages (SPSS Inc., Chicago, Illinois) for all data en-try and analysis.

We calculated that having 45 patients per group would provide 80% power to show a mean severity score improve-ment of 10% for the 5% saline group versus the 0.9% saline group, assuming a standard deviation of about 1 for each mean severity score. We did not intend to deﬁnitively com-pare the 5% and 3% saline groups. To account for patients discharged before the 48-hour time point, we added 10 pa-tients to each group, for a sample size of 55 papa-tients per group. Patients properly enrolled with outcome data at 48 hours were included in the analysis.

Results

A total of 187 previously healthy infants diagnosed with viral bronchiolitis, median age 3.1 months (range, 9 days to 14.7 months), were enrolled in the study. Sixteen infants were ex-cluded from the analysis; 9 should have been exex-cluded from enrollment (4 born at #34 weeks’ gestational age, 2 with

a history of apnea with cyanosis before enrollment, 1 with previously known severe laryngomalacia, and 2 who had received steroids within 24 hours before enrollment), 1 infant was enrolled twice in the study (the second enrollment was excluded from the analysis), and 6 infants were electively re-moved by their parents. Of the 171 infants remaining, 57 were randomized to receive 5% hypertonic saline, 58 to re-ceive 3% hypertonic saline, and 56 to rere-ceive 0.9% saline. Subjects’ baseline characteristics before enrollment were sim-ilar in the 3 treatment arms (Table II).

Efﬁcacy

Figure 1 shows bronchiolitis severity scores from baseline to 72 hours. At the primary outcome time point of 48 hours, the mean severity score for the 5% saline group was 3.69 Æ_1.09,

and that for the 0.9% saline group was 4.12 Æ_{1.11 (}_P_{= .04;}

difference, 0.43; 95% conﬁdence interval for the difference, 0.02-0.88). The mean severity score for the 3% saline group was intermediate, at 4.00 Æ _{1.22. At 24 hours after}

randomization, the mean severity score for the 5% saline group was 3.75 Æ _{1.27, and that for the 0.9% saline group}

was 3.97 Æ _{1.40 (}_P_{= .38). The mean severity score for the}

3% saline group at 24 hours was 4.00 Æ _{0.98. Figure 1}

shows a consistent trend favoring 5% saline starting about 8 hours after randomization and continuing to 72 hours.

Additional epinephrine doses were prescribed for 3 infants (5.3%) in the 5% saline group, 1 infant (1.7%) in the 3% saline group, and 3 infants (5.4%) in the 0.9% saline group (P = .53).

Follow-Up

The mean length of stay was 1.56 Æ_{1.38 days for the 5%}

sa-line group, 1.4Æ_{1.41 days for the 3% saline group, and 1.88} Æ_{1.76 days for the 0.9% saline group (}_P_{= .36). Time to}

dis-charge for the 3 groups is displayed in Figure 2. Three infants (1.6%) were lost to follow-up after discharge, 2 in the 5% saline group and 1 in the 0.9% saline group.

The rate of revisits to the Pediatric Emergency Center in the 7 days after discharge was high and similar in the 3 treat-ment groups: 35 (61%) in the 5% saline group, 35 (59%) in the 3% saline group, and 35 (63%) in the 0.9% saline group (P = .91). Short-stay readmission was required for 10 infants (18%) in the 5% saline group, 8 infants (14%) in the 3% saline group, and 7 infants (13%) in the 0.9% saline group (P = .73). One infant in the 0.9% saline group required a 2-day stay in the ICU during a hospital admission in the week after the study visit. Antibiotic usage was similar in the 3 groups: 19% in the 5% saline group, 22% in the 3% saline group, and 18% in the 0.9% saline group. No study subjects received corticosteroid therapy.

Safety

No patient was withdrawn from the study because of apnea, cyanosis, or decreased oxygen saturation. No patient re-quired hospital or ICU admission during their study visit for bronchiolitis. Severity scores immediately after and im-mediately before nebulization and oxygen saturations imme-diately after and immeimme-diately before nebulization were

Table II. Baseline characteristics of enrolled infants

Characteristics 0.9% saline (n = 56) 3% saline (n = 58) 5% saline (n = 57) P value Age, months, mean Æ3.302.43 3.84Æ2.84 4.02Æ2.56 .32 Duration of symptoms before enrollment, (days) 3.6Æ1.87 4.7Æ4.34 4.6Æ3.22 .14

Male/female, n 31/26 39/19 31/26 .35

Baseline severity score 5.77Æ1.37 6.16Æ1.53 5.65Æ1.14 .11 Baseline O₂saturation, % 97.36Æ1.16 97Æ1.39 97.42Æ1.15 .15 RSV-positivity, n (%) 31 (55.4%) 34 (58.6%) 31 (54.4%) .89 Chest X-ray, n (%) Normal 42 (75%) 44 (75.9%) 44 (77.2%) Viral pneumonia 11 (19.6%) 13 (22.4%) 10 (17.5%) .81 Collapse/consolidation 3 (5.4%) 1 (1.7%) 3 (5.3%)

T

HE

J

OURNAL OF

P

EDIATRICS 

www.jpeds.com

Vol. 157, No. 4

(4)

obtained for each patient at baseline and 24, 48, and 72 hours after study entry, and the difference between the each set of prenebulization and postnebulization values was calculated to explore whether nebulization negatively affected either measurement in any of the treatment groups. The results were similar among the 3 groups and demonstrated no evidence of toxicity.

Discussion

In our study group, nebulization with 5% hypertonic saline proved superior to 0.9% saline for improving the bronchio-litis severity score in patients with viral bronchiobronchio-litis in the early treatment setting, and possibly superior to 3% saline

as well. If our results are confirmed, we believe this simple, inexpensive, easily applied, safe, and apparently effective treatment could be generalized for use worldwide in clinics, infirmaries, and hospitals caring for pediatric patients. Bron-chiolitis morbidity 1,17might be minimized by systematic in-troduction of this helpful early intervention. However, a multicenter trial with a larger sample size and relevant clin-ical outcome is needed to confirm and extend our results.

Grewal et al18 reported no difference in efficacy between nebulized 3% and 0.9% saline in the emergency department at 2 hours after randomization. Our study found no differ-ences that early. Grewal et al did find a difference in hospital-ization rate that was clinically significant, but not statistically significant due to their limited sample size.18

Our study has some limitations. The relatively small num-ber of patients enrolled does not allow us to distinguish the efficacy of 3% saline and 5% saline in a definitive way. In addition, although our primary measure was the calculated bronchiolitis severity score, objectively determined by phys-ical examination and blinded with respect to treatment as-signment, this is not the only measure that determines clinical (as opposed to social) readiness for discharge from the infirmary. This instrument has been previously validated for its relationship to disease improvement, interobserver, in-traobserver, and intrasubject variation, however.16,19Finally, it is possible that some of our patients had early presentation of asthma rather than acute bronchiolitis. We tried to limit the likelihood of enrolling subjects with asthma by following strict inclusion criteria. The proportion of our patients with a positive RSV assay was similar to that reported for other bronchiolitis populations1 and is higher than what would be expected for asthma. Moreover, if asthma were prevalent among our patients, then we would have expected to see worsening of clinical symptoms on exposure to hypertonic saline.

We conclude that nebulization with 5% hypertonic saline is safe and may be superior to current treatment for early in-ﬁrmary outpatient treatment of bronchiolitis. Planning for a multicenter trial to explore the clinical beneﬁt of this ther-apy with a larger sample size is underway. n

Submitted for publication Dec 3, 2009; last revision received Feb 22, 2010; accepted Apr 29, 2010.

References

1. Coffen SE. Bronchiolitis: inpatient focus. Pediatr Clin North Am 2005; 52:1047-57.

2. Hall CB. Respiratory syncytial virus. In: Feigin RD, Cherry JD, eds. Text-book of Pediatric Infectious Diseases. 3rd ed. Philadelphia: Saunders; 1991. p. 1633-56.

3. Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 1986;140: 543-6.

4. Mullins JA, Lamonte AC, Bresee JS, Anderson LJ. Substantial variability in community respiratory syncytial virus season timing. Pediatr Infect Dis J 2003;22:857-62.

5. PelletierAJ, MansbachJM, Camargo CA.Direct medicalcostsof bronchio-litis hospitalizations in the United States. Pediatrics 2006;118:2418-23.

Figure 1. Mean bronchiolitis severity score assessments over time. At 48 hours, the time of primary outcome assess-ment, a signiﬁcant difference between 5% saline and 0.9% saline was seen (standard deviations not shown).

Figure 2. Actual times of discharge from the pediatric emergency center for the 3 treatment groups. Discharge time was affected by medical and social factors.

(5)

6. Hall CB. Respiratory syncytial virus and parainﬂuenza virus. N Engl J Med 2001;344:1917-28.

7. Darville T, Yamauchi T. Respiratory syncytial virus. Pediatr Rev 1998;19: 55-61.

8. American Academy of Pediatrics Subcommittee on Diagnosis and Man-agement of Bronchiolitis. Diagnosis and manMan-agement of bronchiolitis. Pediatrics 2006;118:1774-93.

9. Mandelberg A, Tal G, Witzling M, Someck E, Houri S, Balin A, et al. Nebulized 3% hypertonic saline treatment in hospitalized infants with viral bronchiolitis. Chest 2003;123:481-7.

10. Sarrell EM, Tal G, Witzling M, Someck E, Houri S, Cohen HA, et al. Nebulized 3% hypertonic saline solution treatment in ambulatory children with viral bronchiolitis decreases symptoms. Chest 2002; 122:2015-20.

11. Tal G, Cesar K, Oron A, Houri S, Ballin A, Mandelberg A. Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchio-litis reduces hospitalization stay: 2 years experience. Isr Med Assoc J 2006;8:169-73.

12. Kuzik BA, Al-Qadhi SA, Kent S, Flavin MP, Hopman W, Hotte S, et al. Nebulized hypertonic saline in the treatment of viral bronchiolitis in in-fants. J Pediatr 2007;151:266-70.

13. Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in children. Cochr Da-tabase Syst Rev 2008;CD006458.

14. Robinson M, Hemming AL, Regnis JA, Wong AG, Bailey DL, Bautovich GJ,et al.Effect of increasing dosesof hypertonic saline on mu-cociliary clearance in patients with cystic ﬁbrosis. Thorax 1997;52:900-3. 15. Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic ﬁbrosis. N Engl J Med 2006;354:229-40.

16. Wang EE, Milner RA, Navas L, Maj H. Observer agreement for respira-tory signs and oximetry in infants hospitalized with lower respirarespira-tory infections. Am Rev Respir Dis 1992;145:106-7.

17. Willson DF, Landrigan CP, Horn SD, Smout RJ. Complications in in-fants hospitalized for bronchiolitis or respiratory syncytial virus pneu-monia. J Pediatr 2003;143:S142-9.

18. Grewal S, Ali S, McConnell DW, Vandemeer B, Klassen TP. A random-ized trial of nebulrandom-ized 3% hypertonic saline with epinephrine in the treatment of acute bronchiolitis in the emergency department. Arch Pediatr Adolesc Med 2009;163:1007-12.

19. Chin HJ, Ban Q. Reliability and validity of the respiratory score assess-ment of acute bronchiolitis. Malay J Med Sci 2004;11:34-40.

T

HE

J

OURNAL OF

P

EDIATRICS 

www.jpeds.com

Vol. 157, No. 4

(6)

Table I. Determination of bronchiolitis severity scores

Score 0 1 2 3

Respiratory rate, breaths/minute <30 31-45 46-60 >60 Wheezing None Terminal expiratory or only

with stethoscope

Entire expiration or audible on expiration without stethoscope

Inspiration and expiration without stethoscope Retraction None Intercostals only Tracheosternal Severe with nasal ﬂaring

General condition Normal - - Irritabity, lethargy, poor feeding