The role of nebulized ICS in Acute Asthma in children 5 yrs and younger 2018 (1).pptx

The role of nebulized ICS in Acute Asthma in children 5 yrs and younger 2018

1. Role of Nebulized ICS in Acute Asthma In Children 5 years & younger

2. Outline Terminology Definition Epidemiology Pathophysiology Factors that Exacerbate Objectives of management

3. Terminology of Acute Asthma Acute Asthma exacerbation , also Known as: Acute severe asthma Asthma attack or episode Asthma flare-up Status asthmaticus ? Used less often, refers to an exacerbation that is severe & continuous ?

4. Definition Acute or sub-acute worsening in symptoms and lung functions from patient’s usual status , or in some cases the initial presentation of asthma. GINA 2014

5. Asthma exacerbations affect asthmatics of all ages, ethnicities, and asthma severities, and can occur frequently. In the US,~11 million people have an asthma exacerbation/year 11 million people/year Exacerbations result in significant: Costs to the health care system Impairments in quality of life for patients Lost time from work, school or activities Potential for serious sequelae: Hospitalizations and complications Rarely death (~180,000 deaths/year worldwide) Epidemiology

6. Hospitalizations and ED Visits in Children With Asthma Hospitalizations and ED visits are high among young children with asthma 1 or asthma-like symtoms 2 Higher in children aged 0–4 years vs older children (graph) 1 Recurrent ED visits occur in 10–13% of children 4,5 1 Akinbami LJ. No 381. National Center for Health Statistics. 2006; 2 Bisgaard H and Szefler S. Pediatr Pulmonol . 2007;42:723-8; 3 Shields AE, et al. Pediatrics. 2004;113:496-504; 4 Emerman CL et al. J Pediatr . 2001;138:318-24; 5 Stevens MW, Gorelick MW. Pediatrics . 2001;107;1357-62 . ED Visits and Hospital Discharges per 10,000 Population (2003–2004) 1 5–10 0–4 11–17 Age, years

7. Accessory respiratory muscle use Impaired diaphragm function Increased FRC Ventilation/perfusion mismatch Airway edema Mucous plugging Bronchospasm Asthma attacks are due to widespread narrowing of the airways which is a complex mechanism involving: Normal airway Narrowed airway during asthma attack  FRC: Functional Residual Capacity Pathophysiology

8. 8 Factors that exacerbate asthma:

9. Identify high risk patients Assess disease severity Institute appropriate therapy Assess response to therapy regularly Prevent further attacks Overall Objectives of Management

10. Risk factors for poor asthma outcomes in children ≤5 years GINA 2015, Box 6-4B (3/3) Risk factors for exacerbations in the next few months Uncontrolled asthma symptoms One or more severe exacerbation in previous year The start of the child ’ s usual ‘ flare-up ’ season (especially if autumn/fall) Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g. house dust mite, cockroach, pets, mold), especially in combination with viral infection Major psychological or socio-economic problems for child or family Poor adherence with controller medication, or incorrect inhaler technique

11. Assessments Medical History Physical Examination Objective Assessments Initial assessment and classification of severity:

12. Factors that increase the risk of asthma-related death includes any previous asthma and social history: Asthma history Near-fatal asthma requiring intubation and ventilation Hospitalization or emergency care for asthma in last 12 months Not currently using ICS , or poor adherence with ICS Currently using or recently stopped using OCS (indicating the severity of recent events) Over-use of SABAs (>1 canister/month) Previous sudden severe attack/s with few or no warning features despite regular treatment (brittle asthma) Lack of a written asthma action plan Food allergy Social history History of psychiatric disease or psychosocial problems Non-compliance with treatment or monitoring Failure to attend appointments Self-discharge from hospital Low socioeconomic status Obesity Initial assessment and classification of severity:

13. Initial assessment of acute asthma exacerbations in children ≤5 years

14. Time of onset and cause (if known) of current exacerbation. Severity of asthma symptoms, including any limiting exercise or disturbed sleep. Any symptoms of anaphylaxis. Presence of high-risk factors for asthma-related death. Treatments used, response to any treatment given before admission to the emergency department and the time of the last dose. Any other complicating illness or any disease that might be aggravated by systemic corticosteroid therapy (diabetes or hypertension). Medical History

15. Early symptoms of an exacerbation may include any of the following: An acute or subacute increase in wheeze and shortness of breath. An increase in coughing especially while asleep. Lethargy or reduced exercise tolerance. Impairment of daily activities. Poor response to reliever medication.

16. Physical Examination Signs of exacerbation severity: Vital data ( pulse, respiratory rate and blood pressure). Signs ( level of consciousness, cyanosis and use of accessory muscles). Ability to complete sentences. Wheeze is not a good marker of severity. Complicating factors (e.g. anaphylaxis, pneumonia, atelectasis or pneumothorax). Signs of alternative condition that could explain acute dyspnea (cardiac failure, upper airway obstruction by foreign body aspiration, tumor, anaphylaxis/ angioedema or vocal cord dysfunction and pulmonary embolism).

17. Differential Diagnosis of Acute Asthma Airway obstruction Foreign body aspiration Tumor Anaphylaxis/ angioedema Vocal cord dysfunction Cardiogenic Pulmonary edema Hyperventilation syndrome Pneumonia Pulmonary embolism

18. Objective Assessments Physical examination alone may not indicate the severity of exacerbation, thus objective assessments are also needed. 1. Peak Expiratory Flow (PEF) Measures lung function. Baseline PEF should be recorded before starting treatment then at one hour and at intervals until clear response or a plateau is reached by treatment. PEF measurement may not be possible in patients with severe respiratory distress. 2. Pulse Oximetry Measures oxygen saturation. Should be measured before oxygen is commenced and monitored until a clear response is reached. Patients with SpO 2 <92% need hospitalization. Patients with SpO 2 <90% need aggressive therapy (serious distress).

19. 3. Arterial Blood Gas (ABG) For patients with SpO 2 <92% or with life threatening asthma or having poor response. Supplemental controlled oxygen should be continued while ABG are obtained. Fatigue and somnolence suggest that PaCO 2 may be increasing and airway intervention may be needed. PaO 2 <60 mmHg and normal PaCO 2 or >45 mmHg indicates respiratory failure. 4. Chest X-ray Not routine Recommended only in the below cases: Suspected pneumomediastinum or pneumothorax Suspected consolidation Life threatening asthma Failure to respond to treatment Requirement for ventilation Objective Assessments

20. Indications for immediate transfer to hospital for children ≤5 years GINA 2015, Box 6-10 *Normal respiratory rates (breaths/minute): 0-2 months: <60; 2-12 months: <50; 1-5 yrs : <40 Transfer immediately to hospital if ANY of the following are present: Features of severe exacerbation a t initial or subsequent assessment Child is unable to speak or drink Cyanosis Subcostal retraction Oxygen saturation <92% when breathing room air Silent chest on auscultation Lack of response to initial bronchodilator treatment Lack of response to 6 puffs of inhaled SABA (2 separate puffs, repeated 3 times) over 1-2 hours Persisting tachypnea * despite 3 administrations of inhaled SABA, even if the child shows other clinical signs of improvement Unable to be managed at home Social environment that impairs delivery of acute treatment Parent/ carer unable to manage child at home

21. Aims of treatment of ASA To relieve airflow obstruction . To relive hypoxemia . Restore lung function . Prevent future relapse . Develop written action plan As quickly as possible

22. Written asthma action plans GINA 2014, Box 4-2 (1/2) NEW!

23. Initial management of asthma exacerbations in children ≤5 years Therapy Dose and administration Supplemental oxygen 24% delivered by face mask (usually 1L/min) to maintain oxygen saturation 94-98% Inhaled SABA 2–6 puffs of salbutamol by spacer, or 2.5mg by nebulizer, every 20 min for first hour, then reassess severity. If symptoms persist or recur, give an additional 2-3 puffs per hour. Admit to hospital if >10 puffs required in 3-4 hours. Systemic corticosteroids Give initial dose of oral prednisolone (1-2mg/kg up to maximum of 20mg for children <2 years; 30 mg for 2-5 years) GINA 2014, Box 6-10 Therapy Dose and administration Supplemental oxygen 24% delivered by face mask (usually 1L/min) to maintain oxygen saturation 94-98% Inhaled SABA 2–6 puffs of salbutamol by spacer, or 2.5mg by nebulizer, every 20 min for first hour , then reassess severity. If symptoms persist or recur, give an additional 2-3 puffs per hour . Admit to hospital if >10 puffs required in 3-4 hours. Systemic corticosteroids Give initial dose of oral prednisolone (1-2mg/kg up to maximum of 20mg for children <2 years; 30 mg for 2-5 years) Additional options in the first hour of treatment Ipratropium bromide For moderate/severe exacerbations, give 2 puffs of ipratropium bromide 80mcg (or 250mcg by nebulizer) every 20 minutes for one hour only Magnesium sulfate Consider nebulized isotonic MgSO 4 (150mg) 3 doses in first hour for children ≥2 years with severe exacerbation

24. Medications used in acute asthma Oxygen in Acute asthma exacerbation Nasal canula or mask . Controlled low flow oxygen therapy using oximetry to maintain saturation at 94 – 98 % . Gradual weaning ( oximetry ) SABA in Acute asthma exacerbation Sometimes given by continuous nebulization followed by intermittent on demand therapy . Epinephrine in Acute asthma exacerbation IM + standard therapy only if associated with anaphylaxis & angio-oedema .

25. Medications used in acute asthma Ipratropium promide : Moderate to severe exacerbation . Together with SABA. For 1 hour only. Better improvement in PEF & FEV1 . Shorten hospitalization stay.

26. Medications used in acute asthma Magnesium sulphate: Nebulized : In severe exacerbations. 150 mg, 3 doses only in first hour. Most often given with salbutamol . IV: Not recommended routinely. Single 2 g infusion over 20 mins if : FEV1 ˂ 25- 30 % & fail to reach 60 %. Persistent hypoxemia.

27. Medications used in acute asthma Antibiotics in Acute asthma exacerbation NOT RECOMMENDED except in: Strong evidence of lung infection. Infected sinuses.

28. Medications used in acute asthma Systemic steroids in Acute asthma exacerbation In emergency room within 1 hour if : Initial SABA fails to achieve lasting improvement of symptoms. Exacerbation while taking OCS. History of previous exacerbation requiring OCS. Route: Oral = IV. Oral liquid formula needs 4 hrs to produce clinical improvement.

29. Medications used in acute asthma Direct delivery to airways Earlier onset due to their non-genomic effect vs SCS which involves genomic transcription. Potential benefits of reduced SCS side-effects & greater efficacy in reducing airway reactivity and edema. Evidence for greater bronchodilation when beta agonists used along with ICS . ICS in Acute asthma exacerbation Histone deacetylase Mitogenic activated protein kinase phosphatase-1 Nuclear factor KB

30. ICS in Acute asthma exacerbation The combination of high-dose ICS and salbutamol in acute asthma provided greater bronchodilation than salbutamol alone (Evidence B), A high dose ICS can be as effective as oral CS at preventing relapses. (Evidence B). ß 2 -Agonist

31. 31 Challenges of Inhaled Therapies for Young Children Small tidal volume Small airways Rapid respiration Inability to hold breath with inhaled medication Nose breathing Aversion to masks Cognitive ability Fussiness and crying Everard ML. Adv Drug Deliv Rev. 2003;55:869-878; Murakami G. Ann Allergy. 1990;64:383-387; Newman SP. J Aerosol Med. 1995(suppl 3);S18-22; Geller DE. Curr Opin Pulm Med. 1997;3:414-419; Newhouse MT. Chest. 1982;82(suppl 1):39S-41S.

32. Choose the Most Appropriate Delivery Device to Administer ICS Educate patient and caregiver on proper use of device Incorrect use of pMDI is of particular concern for the very young Improper inhaler technique may contribute to treatment failure ICSs administered via MDI remain off label (not FDA approved) for children aged <4 years (fluticasone HFA) or <5 years (beclomethasone HFA) Pulmicort Respules® (budesonide inhalation suspension) is FDA approved for use in children as young as 1 year Lenney et al. Respir Med. 2000;94:496-500; McFadden. J Allergy Clin Immunol. 1995;96:278-283.

33. Technique for Optimal Nebulizer Use Slow tidal breathing Occasional deep breaths Use of a mouthpiece or tightly fitting face mask 33 NAEPP. Publication no. 97-4051.

34. Pulmicort nebulizing suspension: Indications: In acute asthma attack together with bronchodilators : - Improve asthma symptoms. - Oral prednisolone reduction. - Rapid discharge from hospital.

35. -0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 *** ** ** ** * * Placebo 0.25 mg o.d. 0.5 mg o.d. 1 mg o.d. Nighttime Daytime Mean change from baseline in asthma symptoms Pulmicort Respules dosages * p 0.050; ** p 0.010; *** p 0.001 vs placebo ICS-naïve patients Pulmicort ® Respules ® improve asthma symptoms Kemp et al. Ann Allergy Asthma Immunol 1999;83:231–239

36. Oral prednisolone reduction Ilangovan et al , 1993 1.5 1.0 0.5 Prednisolone (mg/kg/alternate day) Treatment (weeks) -4 4 8 8 12 16 Run-in Budesonide nebulising suspension Open follow-up p < 0.001 p < 0.05 Budesonide Placebo Budesonide after placebo

37. Effect of treatment on hospital stay Sung et al, 1998 1.0 Probability of remaining in hospital 0.2 0.4 0.6 0.8 20 40 60 80 100 120 140 Time (hours) Pulmicort ® Respules ® Placebo

38. “ Mean hospital stay was significantly shorter in the Budesonide-treated patients ” * Mean hospital stay Hours n=80 2.9 5.5 Oxygen 6-10 Lpm Nebulized 0.5% salbutamol 0.15mg/kg Placebo nebulization Single dose of prednisolone 2 mg/kg PO Oxygen 6-10 Lpm Nebulized 0.5% salbutamol 0.15mg/kg Placebo tablets Nebulized budesonide 800 mc (at admission and at half-hour intervals for 3 doses) * Devidayal, Singhi S, Kumar L, Jayshree M: Efficacy of nrbulized budesonide compared to oral prednisolone in acute bronchial asthma. Acta Paediatrica (Oslo) 1999;88(8):835-40. In acute asthma …Rapid Patient Discharge

39. Conclusion Hospital Admission Rate : The addition of budesonide nebulization decreased the admission rate of severe acute asthma by 33.5 %

40. Pulmicort Respules  Studies: Post-discharge (  30 days) use of Pulmicort Respules ® reduces the risk of a recurrent exacerbations compared with use of other controllers, including non-nebulized ICSs Camargo CA Jr, et al. Am J Health-Syst Pharm . 2007;64:1054-106. McLaughlin T, et al. Curr Med Res Opin . 2007;23:1319-28.

41. Why Nebulized Budesonide? Lack of coordination between inhalation and the device Even the spacer with the lowest inspiratory flow rate may be not suitable especially for young children The only steroid FDA approved for children from 12 months of age The safety profile is high , compared with any other inhaled steroid