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Hypertonic Saline Treatment and Airway Inflammatory Phenotypes in Preschool Children With Acute Asthmatic Attack

Information source: Wolfson Medical Center
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Asthma

Intervention: hypertonic saline-salbutamol combination (Drug); Normal saline-salbutamol combibation (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Wolfson Medical Center

Official(s) and/or principal investigator(s):
Avigdor Mandelberg, MD, Principal Investigator, Affiliation: The Sackler School of Medicine, Tel Aviv University, Israel

Summary

To investigate the efficacy of adding Inhaled Hypertonic Saline treatment (HS) for 1-6 year old children with asthmatic attack presenting to Emergency Room (ER) and the relation to airways inflammatory phenotype and to post attack bronchial hyperreactivity.

Background: In 1-6 year old children, the most common causes of acute exacerbations of asthma requiring urgent medical care are viral respiratory infections. Most of these children are not atopic.

The inflammatory response to these wheezy attacks and whether the different kind of inflammatory responses correlate to clinical outcomes are not known.

HS is considered an effective and safe treatment for infants with acute viral bronchiolitis (Cochrane 2008). HS acts in the airways in several mechanisms: HS re-hydrates secretions and improving mucus rheology, reduce edema of the airway wall by absorbing water from the mucosa and submucosa, causes sputum induction and cough, which can help to clear the sputum out of the bronchi, stimulates cilial beat via the release of prostaglandin E2 (Assouline 1977), breaks the ionic bonds within the mucus gel, thereby lowering the viscosity and elasticity of the mucus secretion.

It is estimated that all the above HS responding elements may play a role in this viral induce wheezing. The above mentioned theoretical benefits provide the rationale for the possible treatment of viral induced acute wheezing ("asthma") attack with nebulized HS in young pre-school children presenting to the Pediatric Emergency Unit with acute (mostly viral induced) wheezing.

Therefore, the purpose of the present study is to 1. Investigate the addition of frequently nebulized 5% HS/albuterol combination to standard therapy of acute asthmatic episodes presenting to the emergency room (ER) in preschool children in a prospective, randomized, double-blind, controlled fashion. 2. Investigate the characterization of induced sputum cytology in preschool children with acute asthmatic attack and whether there is a correlation between specific sputum cytology and response to therapy. 3. Investigate airways hyper-responsiveness to adenosine 5'-monophospate and to methacholine in preschool children 2-6 years old at 2 weeks and at 3 months following acute asthmatic exacerbation and look for correlation with the response to treatment and sputum cytology.

Clinical Details

Official title: Interventional Study: Hypertonic Saline-salbutamol Combination Treatment for Preschool Children With Acute Asthmatic Attack Presenting to the ER and the Relation to Airway Inflammatory Phenotypes: A Double Blind Control Study

Study design: Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Primary outcome: Improvement in Clinical scores

Secondary outcome:

Composition of inflammatory cells in induced sputum

Adenosine and Metacholine bronchial challenge tests

Detailed description: A randomized double blind, controlled, (DBCR) trial. To investigate the efficacy of adding inhaled Hypertonic Saline (HS) treatment for 1-6 year old children with asthmatic attack presenting to Emergency Room and the relation to airways inflammatory phenotype and to post attack bronchial hyperreactivity to adenosine 5'-monophosphate and to methacholine.

Background:

Children under the age of 5 years have the highest hospitalization rate of asthma. The most common causes of acute exacerbations of asthma requiring urgent medical care are viral respiratory infections. Most of these children < 6 years old are not atopic.

The inflammatory response to these mostly viral-induced asthmatic attacks is not well characterized in the literature. Moreover, it is not known whether the different kind of inflammatory responses exist in this population and how this correlate to clinical outcomes.

These investigators have previously demonstrated in wheezy infants with acute viral bronchiolitis that nebulized hypertonic saline produces a clinical significant reduction in length of hospital stay and improves the clinical score and is considered an effective and safe treatment for infants with acute viral bronchiolitis (Cochrane 2008).

Hypertonic saline solution acts in the airways in several mechanisms:

It Stimulates cilial beat via the release of prostaglandin E2 (Assouline 1977) and increases mucociliary clearance.

It Breaks the ionic bonds within the mucus gel, thereby reducing the degree of cross linking and entanglements and lowering the viscosity and elasticity of the mucus secretion.

HS induces an osmotic flow of water into the mucus layer, re-hydrating secretions and improving mucus rheology.

HS reduces edema of the airway wall by absorbing water from the mucosa and submucosa.

HS can cause sputum induction and cough, which can help to clear the sputum outside of the bronchi and thus improve airway obstruction.

It is estimated that many of the above hypertonic saline responding elements may play a role in this viral induce wheezing such as: mucosal and submucosal edema, peribronchial infiltrate of inflammatory cells, necrosis and desquamation of ciliated epithelial cells, and excess mucus secretion. The combination of an airway wall swelling, sloughing of necrotic debris, increased mucus production and impaired secretion clearance, eventually contribute in addition to bronchospasm to airway obstruction, gas trapping, atelectasis and impaired gas exchange. Moreover, as postulated in "status asthmaticus", the relative contribution of these "non-spasmodic" pathological and pathophysiological consequences of viral and asthmatic inflammation to airway obstruction, gas trapping, atelectasis and impaired gas exchange become even more important in these children already treated with maximum dilatation dose of bronchodilating drugs in the emergency department.

The above mentioned theoretical benefits provide the rationale for the possible treatment of viral induced acute wheezing ("asthma") attack with nebulized hypertonic saline solution in young pre-school children presenting to the Pediatric Emergency Unit with acute (mostly viral induced) wheezing.

Therefore, the purpose of the present study is to investigate the addition of frequently nebulized 5% HS/albuterol combination to standard therapy of acute asthmatic episodes presenting to the emergency room (ER) in preschool children in a prospective, randomized, double-blind, controlled fashion.

Investigate the characterization of induced sputum cytology in preschool children with acute asthmatic attack and whether there is a correlation between specific sputum cytology and response to therapy.

Investigate airways hyper-responsiveness to adenosine 5'-monophospate and to methacholine in preschool children 2-6 years old at 2 weeks and at 3 months following acute asthmatic exacerbation and look for correlation with the response to treatment and sputum cytology.

Eligibility

Minimum age: 1 Year. Maximum age: 6 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Children, age: 1-6 years old

- Presenting to the ER with acute wheezing episode

Exclusion Criteria:

- Any chronic (lung, cardiac, immunologic, neurologic) disease

Locations and Contacts

The Edith Wolfson MC, Holon, Israel; Recruiting
Avigdor Mandelberg, MD, Phone: 972-3-5028790, Email: avigdrom@netvision.net.il
Dorit Ater, MD, Sub-Investigator
Additional Information

Starting date: January 2009
Last updated: August 2, 2010

Page last updated: October 04, 2010

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