Steroid Therapy in Acute Bronchiolitis A New Old Line of Therapy.

Bronchiolitis; Respiratory Syncytial Virus Clinical Trial

Official title:

Steroid Therapy in Acute Bronchiolitis A New Old Line of Therapy.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03436225
• Other study ID #: Steroid in bronchiolitis.
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: February 2019
• Est. completion date: March 2019

Study information

• Verified date: January 2019
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the present study is to evaluate the efficacy of steroid therapy and hospital stay in patients with acute bronchiolitis at assiut university children hospital.

Description:

Bronchiolitis is an acute lower respiratory tract infection in early childhood.A subcommittee of the American Academy of Pediatrics (AAP) together with the European Respiratory Society (ERS) underlined that is a clinical diagnosis, recognized as "a constellation of clinical symptoms and signs including a viral upper respiratory prodrome followed by increased respiratory effort and wheezing in children less than 2 years of age".

Bronchiolitis is the common reason for hospitalization of children in many countries, challenging both economy, area and staffing in pediatric departments. A substantial proportion of children will experience at least one episode with bronchiolitis, and as much as 2-3% of all children will be hospitalized with bronchiolitis during their first year of life. Bronchiolitis is the most common medical reason for admission of children to intensive care units (ICU) particularly those with risk Factors will have a severe course of bronchiolitis, providing challenges regarding ventilation, fluid balance and general support This may be a particular challenge for ICUs without a specialized pediatric section.

Many respiratory viruses have been associated with acute viral bronchiolitis although Respiratory Syncytial Virus (RSV) remains the most common identified virus causing bronchiolitis, occurring in epidemics during winter months.The infection starts in the upper respiratory tract, spreading to the lower airways within few days.The inflammation in the bronchioles is characterized by a peri-bronchial infiltration of white blood cell types, mostly mono nuclear cells, and oedema of the submucosa and adventitia. Damage may occur by a direct viral injury to the respiratory airway epithelium, or indirectly by activating immune responses. Oedema, mucus secretion, and damage of airway epithelium with necrosis may cause partial or total airflow obstruction, distal air trapping, atelectasis and a ventilation perfusion mismatch leading to hypoxemia and increased work of breathing. Smooth-muscle constriction seems to play a minor role in the pathologic process of bronchiolitis.

Risk factors for bronchiolitis are male gender, a history of prematurity, young age, being born in relation to the RSV season, pre-existing disease such as broncho pulmonary- dysplasia , underlying chronic lung disease , neuromuscular disease, congenital heart- disease , exposure to environmental tobacco smoke , high parity, young maternal age, short duration/no breast feeding , maternal asthma and poor socioeconomic factors.

Bronchiolitis often starts with rhinorrhoea and fever, thereafter gradually increasing with signs of a lower respiratory tract infection including tachypnoea, wheezing and cough. Very young children, particularly those with a history of prematurity, may appear with apnea as their major symptom.Feeding problems are common.

On clinical examination, the major finding in the youngest children may be fine inspiratory crackles on auscultation, whereas high-pitched expiratory wheeze may be prominent in older children. By observation, the infants may have increased respiratory rate, chest movements, prolonged expiration, recessions, use of accessory muscles, cyanosis and decreased general condition.

No routine laboratory or radio graphic diagnostic tests for bronchiolitis except for pulse oxymetry , have been shown to have a substantial impact on the clinical course of bron- chiolitis , and recent guidelines and evidence-based reviews recommend that no diagnostic tests are used routinely.

The present study describes the efficacy of steroid therapy in patients with acute bronchiolitis. Theoretically, corticosteroid, an anti-inflammatory agent, should be helpful in the treatment of bronchiolitis because airway inflammation and edema are the main pathophysiologies. Recent evidence has shown elevation of interleukins and other inflammatory mediators in the respiratory tracts of children with acute bronchiolitis. Eosinophil cationic protein, implicated in the pathogenesis of asthma, was found to have a significant role in RSV bronchiolitis. Most of these mediators could be found during the period of virus replication.The clinical effect of dexamethasone, with a long half -life of 36-72 hr, may peak after 3-4 hr of treatment. Corticosteroids widely used in different routes in the treatment of acute bronchiolitis:

Dexamethasone injection used in hospitalized children with acute bronchiolitis showed significantly reduction in the mean respiratory distress duration, mean duration of oxygen therapy and the mean length of hospital stay.

Oral dexamethasone used in pediatric out patients with acute bronchiolitis produced demonstrable clinical improvement in the initial 4 hr of treatment and reduced the hospitalization rate.

Corticosteroid inhalation therapy used in RSV- bronchiolitis showed evidence of prolonged positive effects in reduction of the incidence of subsequent respiratory symptoms in the near future. However, the best and sufficient length of the treatment period, as well as the dose of the inhaled steroid, need to be determined..

Fluticasone propionate, a potent corticosteroid, has been demonstrated in vitro to inhibit virus-induced chemokine production by airway cells in patients infected with Respiratory Syncytial Virus. However, the inhibition was found to take at least 48 hr to reach its full effect.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: March 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 2 Years

Eligibility

Inclusion Criteria:

1. Infants and young children aged from 3 months to 2 years with acute bronchiolitis.

2. Infants aged <12 months with respiratory rate over 60 breaths/min, childrens aged >12months with respiratory rate over 50 breaths/min.

3. Patients with an O2- saturation, breathing room air, under 95%.

4. Patients with apathy and/or refusal to eat.

5. Patients with normal white blood cell count for age.

6. Full term babies without chronic disease.

Exclusion Criteria:

1. Infants aged < 3 months, children aged >2 years

2. known or suspected asthma (by observing the good response to first dose of salbutamol nebulization especially among those with personal history of atopy).

3. Proven or suspected acute bacterial infection.

4. Presence of symptoms more than 7 days.

5. Previous treatment with corticosteroid by any route within 2 weeks.

6. Having a contra- indication to corticosteroid.

7. Severe cases requiring initial admission to intensive care unit with endotracheal intubation (in order to reduce confounding factors such as nosocomial infection or complication due to mechanical ventilation).

8. A previous history of intubation.

9. Premature babies (due to possible respiratory problems associated with prematurity).

10. Children with chronic cardiopulmonary diseases (Bronchopulmonary- dysplasia , Congenital Heart Disease and Cystic fibrosis)

11. Children with immunodeficiencies .

12. Children with neuromuscular disease.

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis; Respiratory Syncytial Virus

Intervention

Drug:
• Dexamethasone orally.
Administered orally (0.15mg /kg / dose) twice daily for 3 to 5 days.
• Dexamethasone parenteral.
Administered parenteral (0.15mg /kg / dose) twice daily for 3 to 5 days.
• Inhaled nebulized Budesonide.
Administered for inhalation (1 mg/ 2ml) twice daily for 3 to 5 days.
• Inhaled nebulized salbutamol.
Administered for inhalation (0.15mg /kg / dose) daily every 6-8hrs

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (25)

American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006 Oct;118(4):1774-93. — View Citation

Berger I, Argaman Z, Schwartz SB, Segal E, Kiderman A, Branski D, Kerem E. Efficacy of corticosteroids in acute bronchiolitis: short-term and long-term follow-up. Pediatr Pulmonol. 1998 Sep;26(3):162-6. — View Citation

Bordley WC, Viswanathan M, King VJ, Sutton SF, Jackman AM, Sterling L, Lohr KN. Diagnosis and testing in bronchiolitis: a systematic review. Arch Pediatr Adolesc Med. 2004 Feb;158(2):119-26. Review. — View Citation

Carlsen KH, Leegaard J, Larsen S, Orstavik I. Nebulised beclomethasone dipropionate in recurrent obstructive episodes after acute bronchiolitis. Arch Dis Child. 1988 Dec;63(12):1428-33. — View Citation

Carroll KN, Gebretsadik T, Griffin MR, Wu P, Dupont WD, Mitchel EF, Enriquez R, Hartert TV. Increasing burden and risk factors for bronchiolitis-related medical visits in infants enrolled in a state health care insurance plan. Pediatrics. 2008 Jul;122(1): — View Citation

Choi J, Lee GL. Common pediatric respiratory emergencies. Emerg Med Clin North Am. 2012 May;30(2):529-63, x. doi: 10.1016/j.emc.2011.10.009. Epub 2011 Dec 17. Review. — View Citation

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Klassen TP, Sutcliffe T, Watters LK, Wells GA, Allen UD, Li MM. Dexamethasone in salbutamol-treated inpatients with acute bronchiolitis: a randomized, controlled trial. J Pediatr. 1997 Feb;130(2):191-6. — View Citation

Maayan C, Itzhaki T, Bar-Yishay E, Gross S, Tal A, Godfrey S. The functional response of infants with persistent wheezing to nebulized beclomethasone dipropionate. Pediatr Pulmonol. 1986 Jan-Feb;2(1):9-14. — View Citation

Murray J, Bottle A, Sharland M, Modi N, Aylin P, Majeed A, Saxena S; Medicines for Neonates Investigator Group. Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study. PLoS One. 2014 Feb 26;9(2):e89186 — View Citation

Nagakumar P, Doull I. Current therapy for bronchiolitis. Arch Dis Child. 2012 Sep;97(9):827-30. doi: 10.1136/archdischild-2011-301579. Epub 2012 Jun 25. Review. — View Citation

Noah TL, Becker S. Respiratory syncytial virus-induced cytokine production by a human bronchial epithelial cell line. Am J Physiol. 1993 Nov;265(5 Pt 1):L472-8. — View Citation

Noah TL, Wortman IA, Becker S. The effect of fluticasone propionate on respiratory syncytial virus-induced chemokine release by a human bronchial epithelial cell line. Immunopharmacology. 1998 Jun;39(3):193-9. — View Citation

Reijonen T, Korppi M, Kuikka L, Remes K. Anti-inflammatory therapy reduces wheezing after bronchiolitis. Arch Pediatr Adolesc Med. 1996 May;150(5):512-7. — View Citation

Roosevelt G, Sheehan K, Grupp-Phelan J, Tanz RR, Listernick R. Dexamethasone in bronchiolitis: a randomised controlled trial. Lancet. 1996 Aug 3;348(9023):292-5. — View Citation

Schimmer BP, Parker KL. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitor of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG,editors. Goodman & Gilman's the pharmacological basis of therapeutics, 9th edition. New York: McGraw-Hill; 1996.pp 1459-1485.

Schuh S, Coates AL, Binnie R, Allin T, Goia C, Corey M, Dick PT. Efficacy of oral dexamethasone in outpatients with acute bronchiolitis. J Pediatr. 2002 Jan;140(1):27-32. — View Citation

Sheeran P, Jafri H, Carubelli C, Saavedra J, Johnson C, Krisher K, Sánchez PJ, Ramilo O. Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. Pediatr Infect Dis J. 1999 Feb;18 — View Citation

Stockman LJ, Curns AT, Anderson LJ, Fischer-Langley G. Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006. Pediatr Infect Dis J. 2012 Jan;31(1):5-9. doi: 10.1097/INF.0b013e31822e68e6. — View Citation

Tal A, Bavilski C, Yohai D, Bearman JE, Gorodischer R, Moses SW. Dexamethasone and salbutamol in the treatment of acute wheezing in infants. Pediatrics. 1983 Jan;71(1):13-8. — View Citation

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resolution of respiratory distress.	A total clinical score = 3 and oxygen saturation = 95 % at room air together with respiratory score of 0 or 1, a wheezing score of 0 or 1, and a retraction muscle score of 0 or 1	<7 days
Secondary	Reduction of mean duration of symptoms.	Improvement of respiratory symptoms within fewer days .	<7 days
Secondary	Reduction of duration of oxygen therapy.	Reduction the need for more oxygen therapy .	<7 days
Secondary	Reduction of average Length of hospital stay.	Decrease Length of hospital stay.	<7 days