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The diagnosis and management of asthma in young children can be challenging since there are many different types of wheezing associated with numerous underlying disorders. In order to assist clinicians, the Vietnamese clinical practice guideline for asthma was revised in 2018 by the members of Vietnam Respiratory Society and Medical Services Administration, under the Ministry of Health.
JOURNAL OF MEDICAL RESEARCH VIETNAM NATIONAL GUIDELINE FOR THE DIAGNOSIS AND TREATMENT OF ASTHMA IN CHILDREN UNDER YEARS: A SUMMARY Chau Quy Ngo2,3,6, Khue Ngoc Luong1, Quy Tran9, Dung Tien Nguyen9, Diem Huu Nguyet Phan7, Hong Thi Minh Pham8, Huong Thi Minh Le4, Son Binh Bao Bui5, Thuy Thi Dieu Nguyen4, Tuan Minh Dao4, Tuan Anh Tran7, Ngoc Van Le Truong1, Tru Van Nguyen1, Nguyen Thuy Nguyen1, Doi Quang Nguyen6, Giap Van Vu2,3,6 Medical Sevices Administration, Ministry of Health, Vietnam Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam Respiratory Center, Bach Mai Hospital, Hanoi, Vietnam Respiratory Department, National Pediatric Hospital, Hanoi, Vietnam Department of Pediatrics, Hue University of Medicine and Pharmacy, Hue, Vietnam Vietnam Respiratory Society, Vietnam Respiratory Department, Children’s Hospital number 1, HCM City, Vietnam Department of Pediatrics, Ho Chi Minh City Medicine And Pharmacy University, HCM City, Vietnam Department of Pediatrics, Bach Mai Hospital, Hanoi, Vietnam The diagnosis and management of asthma in young children can be challenging since there are many different types of wheezing associated with numerous underlying disorders In order to assist clinicians, the Vietnamese clinical practice guideline for asthma was revised in 2018 by the members of Vietnam Respiratory Society and Medical Services Administration, under the Ministry of Health This guideline focused on diagnosis and management of asthma in children under years old, with subjects including the definition, diagnosis, assessment and treatment of asthma We expect this guideline will be a useful tool for physicians as well as other health care professionals in clinical practice to diagnose and manage the asthma patients in children under years old Keywords: Asthma, children, guideline, GINA, Global initiative for asthma I INTRODUCTION Asthma is a common respiratory disease in children, and the rate of asthma in children is rising rapidly in both developed and developing countries Statistics from the World Health Organization showed that the prevalence of childhood asthma was about 7-10% [1; 2] In Corresponding author: Ngo Quy Chau, Bach Mai Hospital, Hanoi, Vietnam Email: ngoquychaubmh@gmail.com Received: 27/11/2018 Accepted: 12/3/2019 JMR 118 E4 (2) - 2019 Vietnam, there are no systematic, national statistics on the incidence and deaths resulting from childhood asthma Some regional studies have shown that the prevalence of childhood asthma is about - 8% [15] The diagnosis of asthma in children under years is often difficult, especially in children under years old because it is easily confused with bronchiolitis Diagnosing asthma clinically in young patients is standard as it is laborious to spirometry for children and immunological allergy tests are also non-specific for asthma 129 JOURNAL OF MEDICAL RESEARCH since they can yield a positive result in many other diseases, such as allergic rhinitis, eczema, etc Early diagnosis and treatment will improve the outcome of the disease In 2009, the Vietnamese Ministry of Health published a guideline for diagnosis and management of asthma in children but it has not been updated until now [16] Therefore, in 2018, experts of Vietnam Respiratory society worked together to revise this guideline based on new evidence from the latest studies around the world This revision has been approved by Vietnam Ministry of Health to apply throughout the country Definition Asthma is pathologically characterized by chronic airway inflammation, airway hyperresponsiveness (bronchospasm, edema, congestion, mucus hypersecretion), and airway obstruction Expiratory airflow limitation leads to signs such as wheeze, shortness of breath, chest tightness, and recurrent coughing fits Symptoms often occur at night and early morning that may resolve spontaneously or due to medication [2] Diagnosis A diagnosis of asthma in children under years old should be based on clinical history and clinical symptoms associated with subclinical features while also considering other differential diagnoses [1], [2] 3.1 Clinical Table Clinical Features that Increase the Probability of Asthma Factors that increase the probability of asthma Factors that lower the probability of asthma Wheezing with one of the symptoms: Cough Dyspnea AND Any signs of the following: Symptoms recurring frequently Symptoms are worse at night or in the early morning Occurs on exertion, laughing, crying, or exposure to tobacco smoke, cold air, pets Occurs when no evidence of respiratory infections. A history of allergy (allergic rhinitis, eczema) A family history of atopy and allergic diseases (parents, siblings) Has widespread wheezing/ rhonchi heard on auscultation Any signs of the following: Symptoms happen only in cold air Isolated cough in absence of wheeze or difficulty breathing Normal lung auscultation despite symptoms Signs / symptoms suggestive of other diagnoses No response to a trial of asthma therapy (bronchodilators and asthma preventive medications) Response to adequate asthma treatment Note: Wheezing must be correctly confirmed by doctor, because parents may mistake wheezing with other abnormal sounds 130 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH 3.2 Subclinical No any laboratory test to make correctly diagnosis asthma in children under years old Table Subclinical tests Test Value Chest x ray is not recommended for routine assess- Chest X ray ment Indicated in cases of severe asthma or clinical signs that suggest another diagnosis The tests can be performed if available The test is used to evaluate susceptibility status to Prick tests or Specific IgE testing allergens. Positive allergy tests to help to increase the probability of asthma diagnosis. However, a negative test does not exclude asthma diagnosis The airway obstructive syndrome that responds to pos- Spirometry or peak flow meter itive bronchodilator test (Increase in at least 12% and (if the child is capable of cooperating) 200 mL in FEV1, PEF after bronchodilator test) (children under years are often not possible) Impulse Oscillometry (IOS) FeNO measurement Measurements of specific airway resistance, which contributes to the assessment of airflow limitation Assessing airways inflammation, is not recommended routinely Note: Normal spirometry results not necessarily exclude a diagnosis of asthma, particularly in the case of intermittent or mild asthma Bronchodilator test is negative neither exclude asthma 3.3 Diagnostic criteria Satisfying the following criteria: (see Table Factors that suggests the possibility of asthma): (1) Wheezing ± persistent recurrent cough (2) Airway obstruction syndrome: widespread wheeze/rhonchus heard on auscultation (± Impulse Oscillometry) (3) Response to bronchodilator drugs or response to a trial of asthma therapy (4-8 weeks) and clinical status is worse when the drug is discontinued (4) Past or family history of allergic diseases or has trigger factors (5) The other wheezing etiologies were excluded JMR 118 E4 (2) - 2019 131 JOURNAL OF MEDICAL RESEARCH Table Asthma Predictive Index Major criteria Minor criteria Parents of children with asthma Wheezing not related to a cold Eczema (to be diagnosed by doctor) Peripheral blood Eosinophils ≥ 4% Allergic reaction to inhaled allergens (determined by medical history or allergic tests) Food allergy 3.4 Differential Diagnosis Not all that wheezes are asthma The bronchodilator test should be performed in children with wheezing (inhaled salbutamol spray 2.5mg/time, continuously 2-3 times in 20 minutes) If the child does not respond or responds poorly after hour, should consider the differential diagnosis of the following: Table Differential diagnosis Diseases Manifestations Bronchiolitis Children under 24 months, wheezing occurs for the first time, with symptoms of upper respiratory viral infections, poor response to bronchodilators [2], [6] Rhinosinusitis Abnormal breathing sounds coming from the nose and throat, nose and throat examination find antrochoanal polyp accompanied by odor, lung examination is completely normal [9], [7] Foreign body aspiration Occurs suddenly, the child coughs, wheezing, difficulty breathing, has a history of infiltration syndrome, localized air trapping on chest x-ray, bronchoscopy removal of foreign bodies [2] Anatomical malformations (vascular Wheezing occurs early before months of age, ring, congenital tracheal stenosis ), should be combine clinical and subclinical features, Abnormal function bronchoscopy, CT scan [11], [12] (dyskinesia tracheobronchial, dysfunction of vocal cords, vascular rings or laryngeal webs, vocal cord dysfunction) Bronchial compression by: mediastinal tumors, enlarged lymph nodes, bronchial cysts 132 Coughing, wheezing, persistent shortness of breath, no response to bronchodilator drugs Diagnosis based on posterior-anterior and lateral chest X-ray film, chest CT scan found the airway is compressed by tumor [1] JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH Diseases Manifestations Pulmonary infiltrates with increased eosinophils Clinical symptoms like asthma, caused by parasites, roundworms or other causes such as drugs or other allergens, progressing well and can heal itself [2] Gastroesophageal reflux syndrome or recurrent aspiration syndrome, bronchoesophageal fissure With a history of vomiting or recurrent respiratory infections, esophageal pH test, bronchoscopy, contrast enhanced esophagography to confirm the diagnosis [7] Congenital immunodeficiency Recurrent respiratory infection, not respond to conventional antibiotic therapy, IgG levels less than SDs below the mean for age, Family history of sibling have congenital immunodeficiency [5] 3.5 Assessment of the level of severe asthma Table Assessment the Intensity of asthma exacerbation Mild - Alert - Shortness of breath on exertion, can be lying-flat positioning - Talks in whole sentences - Tachypnea, no dyspnea - SpO2 ≥ 95% Moderate Severe - Alert - Shortness of breath, prefer to sit more than supine position - Talks in short phrases - Tachypnea, chest wall indrawing - SpO2: 92 - 95% Life threatening - Agitated - Continuously shortness of breath, must in head elevation position - Talks in single/few words, - Tachypnea, chest wall indrawing clearly - SpO2 < 92% - Drowsy, confused, coma - Slow breathing, apnea episodes - Unable to talk - Reduced vesicular breathing sounds or silent chest - Cyanosis, SpO2 < 92% Table Classifying asthma severity Components of severity Intermittent Daytime Symptoms Persistent Mild Moderate Severe ≤ times/ week ≤ times/week but not daily Daily Throughout the day Nighttime awakenings to times/month to times/month > time/week Short-acting beta2 agonist use for symptom control ≤ times/ week > times/week but not daily Daily Several times per day Interference with normal activity None Minor limitation Some limitation Extremely limited JMR 118 E4 (2) - 2019 133 JOURNAL OF MEDICAL RESEARCH Table Assessment of Asthma Control Clinical symptoms In the past weeks, has the child had: Well controlled Partially controlled Uncontrolled Daytime asthma symptoms for more than a few minutes, more than once a week? □ Yes □ No Activity limitation due to asthma □ Yes □ No Reliever medication needed more than once None of these a week □ Yes □ No – of these – of these Night waking or night coughing due to asthma □ Yes □ No Treatment 4.1 Treatment of acute attack 4.1.1 Management of asthma at home Initial treatment at home - Two puffs Salbutamol 200 mcg inhalation spray by pMDI + spacer, may be repeated every 20 minutes, if needed - Then take the child to the medical facility as soon as possible Need to take the child to the health facility immediately if your child has any of the following signs: - Children too breathless - Symptoms of children dose not reduce immediately after puffs bronchodilator inhalation spray for hours - The parents and care-givers cannot treat asthma attack at home 4.1.2 Management of asthma attack in the hospital 134 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH Moderate Asthma Mild Asthma OUTPATIENT TREATMENT OUTPATIENT TREATMENT - Nebulized salbutamol 2,5 mg/time - Salbutamol inhalation spray with MDI plus Spacer (2 - puffs/times every 20 minutes x times if needed (re-assess after every inhalation spray) [10] - Nebulized salbutamol 2,5 mg/time -Salbutamol inhalation spray with MDI plus Spacer (2 - puffs/times every 20 minutes x times if needed (re-assess after every inhalation spray) [10] Assess after one hour Good response - Not wheezing - Not dyspnea - SaO2 ≥ 95% Outpatient treatment - Continue to Salbutamol inhalation spray by MDI every hours for 24 - 48 hours - Re-examination appointment Partial response - Stlill have wheeze - Still have dyspnea - SaO2 92 - 95% Consider for admission Nebulized Salbutamol + Ipratropium 250 mcg/times) - Soon oral prednisone (when does not respond to 1st times of nebulization) No response - Still have wheeze, dyspnea, chest wall indrawing - SaO2 < 92 % Hospitalized -Nebulized salbutamol + Ipratropium x times if needed - Oral prednisolone (if after times of nebulization, management as severe asthma attacks Figure Approach for managing mild and moderate asthma JMR 118 E4 (2) - 2019 135 JOURNAL OF MEDICAL RESEARCH Incomplete response - Transfer to ICU - Nebulized salbutamol every hour - Nebulized ipratropium every - hours - Can use high dose ICS - Intravenous hydrocortison or Methylprednisolon - Infusion Magnesium sulfat (> year) - Infusion Aminophylin - Infusion salbutamol, intubation and mechanical ventilation Severe Asthma Admit to ICU - Oxygen via face mask - Nebulized salbutamol combination with ipratropium bromide every 20 minutes x times (re-assessment after each nebulization) - Intravenous hydrocortisone or methyl prednisone Re-assess after hour Life threatening asthma Admit to ICU -Oxygen via face mask -Subcutaneous adrenalin every 20 minutes x times -Nebulized salbutamol combination with ipratropium bromide every 20 minutes x times (re-assess after each nebulisation) -Intravenous Hydrocortisone or Methyl -prednisolon Good response Continue - Nebulized salbutamol ± Ipratropium every – 6h for 24h - Intravenous Hydrocortison or Methylprednisolon Good response - Not dyspnea - SaO2 ≥ 95% OUTPATIENT TREATMENT - Salbutamol inhalation spray by MDI every - hours for 24 - 48 hours - Oral Prednisolone for days - Re-examination appointment Figure Approach severe and life threatening asthma Dosing: - Intravenous Hydrocortisone mg/kg or methylprednisolone 1mg/kg every hours [10] - Magnesium sulfate (>1 year), average dose of 50mg/kg intravenous infusion for 20 minutes [10] - Theophylline (≤ year) - Intravenous infusion Aminophylline: attack dose of 5mg/kg for in 20 minutes, maintenance dose: mg/kg/hour If feasible, should monitor the blood theophylline levels in the 12th hour and then every 12 - 24 hours (keep 60 - 110mmol/l is equivalent to 10 - 15mg/ml) [10] - Subcutaneous Adrenalin (Adrenalin ‰ 0.01 ml / kg, maximum 0.3 ml/time every 20 minutes, maximum times [2] - Salbutamol: attack dose of 15 mg/kg by intravenous infusion for 20 minutes, then maintain mg/kg/minute Need to check blood gases and potassium every hours [10] Assess the risk factors for severe events 136 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH - History of severe and life threatening asthma attack - Emergency hospitalization or endotracheal intubation for acute asthma in the past year - Currently using or recently discontinued oral corticosteroids - Too dependent on short acting bronchodilator drugs (β2 agonist) - A history of psychiatric disorders or excessive panic - Not cooperate or uncontrol asthma Medications and interventions that should not be used in acute asthma - Antibiotics: use only when there is evidence of infection - Infusion: use only when there are signs of dehydration (be careful to avoid fluid overload) - Sedatives, expectorant drugs (group of acetylcysteine causes bronchospasm), group of antihistamine causes decreased secretion, cough syrup medications containing dextromethorphan, respiratory physiotherapy 4.2 Maintenance treatment 4.2.1 Objectives The goals of asthma management in young children are to: - Achieve good control of symptoms and maintain normal activity levels - Minimize future risk – that is, reduce the risk of flare - ups, maintain lung function and lung development as close to normal as possible and minimize side effects from medications 4.2.2 Indication - The child’s symptom pattern suggests a diagnosis of asthma and respiratory symptoms are uncontrolled and/or wheezing episodes are frequent (e.g three or more episodes in a season) - Children have severe wheezing episodes which triggered by virus although less frequently (1 - episodes in a season) - The child has been having asthma symptoms and needs to use regular inhaled SABA ( > - times/week) - The children have been to hospitalized with severe and life threatening asthma attack 4.2.3 Drug selection When drug selection should note two phenotypes - Intermittent wheezing is onset due to virus: Montelukast (LTRA) - Wheezing is onset due to many factors: inhaled corticosteroid (ICS) 4.2.4 Treatment of asthma severity Choose the initial treatment method according to the severity at the first time of assessment Table Choose the initial treatment method according to the severity Components of severity Preferred option Other option Intermittent As needed inhaled SABA, LTRA Mild Persistent Low dose ICS LTRA Moderate Persistent Moderate dose ICS Low dose ICS + LTRA Severe Persistent High dose ICS Moderate dose ICS + LTRA JMR 118 E4 (2) - 2019 137 JOURNAL OF MEDICAL RESEARCH SABA: short - acting beta2 agonists ; ICS: inhaled corticosteroid; LTRA: leukotriene receptor antagonist For intermittent asthma use LTRA during first episode when symptoms of upper respiratory viral infection and maintain - 21 days 4.2.5 Treatment base on the level of symptom control After the initial assessment, the therapy is chosen depending on the level of asthma control Access to treatment maintenance under “step up” or “step down” to control symptoms and minimize the risk of acute attacks as well as side effects of the drug in the future Steps to maintain a specific treatment are presented in Table [2] Table Stepwise approach to asthma treatment base on the level of symptom control Step Step Step Step Consider this step for children with Preferred controller choice Symptom pattern consistent with asthma and asthma symptoms not well - controlled, or ≥ exacerbations per year; Intermittent wheezing onset Symptom pattern not by virus and no consistent with asthma but wheezing episodes or few interval occur frequently (e.g symptoms every - weeks) Give diagnosis trial for three months LTRA (2 - week) Daily low - dose ICS Asthma diagnosis, and but not well - controlled on low - dose ICS Moderate dose ICS Continue moderate dose ICS + refer for expert assessment low - dose ICS + LTRA - Addition of LTRA - Increasing the dose of ICS Other controller choice No Reliever As needed short - acting beta2 agonists (all children) LTRA Asthma not well - controlled on moderate dose ICS Caution for all children Assess symptom control, future risk, comorbidities Self - management: education, inhaler skills, written asthma action plan, adherence Regular review: assess response, adverse events, establish minimal effective treatment (Where relevant): environmental control for smoke, allergens, indoor/outdoor air pollution For children - years old: maintenance treatment decision according to Table 10 138 JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH Table 10 Decide on asthma treatment in children from to years Preferred controller choice Viruses induced trigger asthma Many factors induced Asthma symptom onset or there is evidence of allergy Persistent asthma LTRA Low dose ICS Assess after weeks Good response: Discontinuing drug treatment and follow up Not response: - Switch to ICS, - Refer for expert assessmen Good response: Continue for months, then Discontinuing drug treatment Not response: - Refer for expert assessment - Moderate dose ICS - OR combination with LTRA 4.2.6 Assess response and treatment adjusting Table 11 Assess response and treatment adjusting Level of asthma symptom control Management Well controlled Consider stepping down when asthma symptoms are well controlled for months or more. Choose an appropriate time when stepping down (not during respiratory infections, not traveling, not during weather changes). For children treated with ICS, reduce the maintenance dose ICS 25 - 50% every months Partly controlled Before stepping up treatment, check the following: technical adjustment, ensure compliance with the prescribed dose, look for risk factors i.e exposure to allergens, cigarette smoke Uncontrolled Need to step up treatment after checking the above issues 4.2.7 Re - examination - After each acute asthma exacerbation, the child should be re - examined within week Frequency of re - examination depends on levels of initial asthma control, response to treatment and self - management capabilities of the child's parents Ideally, the child should be re - examined within - months of starting treatment, then every - months/time - Assess asthma control level, risk factors, side effects of medication, adherence, and ask parents not to worry child at each visit Follow up child's height at least time/year - If the child can use spirometry or Impulse Oscillometry (IOS), they should be measured every months to help decide whether or not to step up or step down treatment 4.2.8 Discontinuation of treatment - Consider discontinuing maintenance therapy if the patient sustained resolution of symptoms JMR 118 E4 (2) - 2019 139 JOURNAL OF MEDICAL RESEARCH within - 12 months, is at the lowest step of treatment and has no exposure to risk factors However, the physician should not stop treatment during seasons when respiratory infections and airborne pollen are common and while children are traveling - Once maintenance therapy has been discontinued, re - examination should be considered after - weeks to check for symptom recurrence 4.2.9 Maintenance therapy medication dosages Table 12 Maintenance therapy medication dosages for children under years Dose (mcg/day) Medications Low Moderate High Fluticasone propionate MDI (HFA) + spacer 100 200 400 Beclomethasone dipropionate MDI (HFA) + spacer 100 200 400 Budesonide MDI + spacer 200 400 800 Child from months to years: oral mg/ day at night Montelukast HFA: hydrofluoroalkane; MDI: metered dose inhaler Conflicts of Interest No potential conflict of interest relevant to this article was reported Acknowledgments The authors would like to express the great appreciation to Dr Ai Lan Kobayashi (Omaha- USA), Dr Josh Solomon (ColoradoUSA), Dr Laurie Manka (National Jewish Health, Colorado - USA), Dr Vu Thi Thu Trang (Respiratory Center- Bach Mai Hospital), Dr Dao Ngoc Phu (Respiratory Center- Bach Mai Hospital) for their valuable work during the translation this guideline into English version Their willingness to give their time so generously has been very much appreciated REFERENCES Global Initiative for Asthma (2016) Global Strategy for Asthma Management and Prevention Global Initiative for Asthma (2016) Diagnosis and Management of Asthma in 140 Children Years and younger - Pocket Guide for Health Professionals Global Initiative for Asthma (2009) Global Strategy for Asthma Management and Prevention in Children Years and Younger Global Initiative for Asthma (2005) Pocket Guide for Asthma Management and Prevention in Children Hamasaki Y, Kohno Y, Ebisawa M, Kondo N, Nishima S, Nishimuta T, Morikawa A; Japanese Society of Allergology; Japanese Society of Pediatric Allergy and Clinical Immunology (2014) Japanese Guideline for Childhood Asthma 2014; Allergol Int.; 63(3): 335 - 356 British Thoracic Society and Scottish Intercollegiate Guidelines Network (SIGN 141) (2014) British guideline on the management of asthma - A national clinical JMR 118 E4 (2) - 2019 JOURNAL OF MEDICAL RESEARCH guideline National Asthma Council Australia (2015) Australian Asthma Handbook - Quick Reference Guide - Version 1.1 (2015) Papadopoulos NG et al (2012) International consensus on (ICON) pediatric asthma; Allergy; 67(8): 976 - 997 Bacharier LB, Boner A, Carlsen KH, Eigenmann PA, Frischer T, Götz M, Helms PJ, Hunt J, Liu A, Papadopoulos N, PlattsMills T, Pohunek P, Simons FE, Valovirta E, Wahn U, Wildhaber J; European Pediatric Asthma Group (2008) Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report; Allergy; 63(1): - 34 10 Taketomo CK, Hodding JH, Kraus DM (2010) Pediatric Dosage Handbook, 17th Edition, Lexi-Comp, Inc 11 Brand PL, Caudri D, Eber E, Gaillard EA, Garcia-Marcos L, Hedlin G, Henderson J, Kuehni CE, Merkus PJ, Pedersen S, Valiulis A, Wennergren G, Bush A (2014) JMR 118 E4 (2) - 2019 Classification and pharmacological treatment of preschool wheezing: changes since 2008 Eur Respir J.; 43(4): 1172 - 1177 12 Schultz A, Brand PL (2011) Episodic viral wheeze and multiple trigger wheeze in preschool children: a useful distinction for clinicians? 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