CME (February 2018)
Monthly Self-Study Series

Management of Preschool Wheeze in the Primary Care Setting


Dr. Sum Yi KONG,
MBChB (CUHK), MRCPCH,
FHKAM(Paediatrics), FHKCPaed
Specialist in Paediatrics


Dr. Daniel K. NG,
MB BS (HK), MD (HKU), M Med Sc (HKU)
FRCPCH (UK), FRCP (Edin), FHKAM (Paed)
Specialist in Paediatric Respiratory Medicine

Introduction

Wheeze is a common presenting complaint in preschool children. In Hong Kong, an increasing trend of hospital admission was reported for preschool wheeze and the annual hospitalization rate rose from 9.9 per 1,000 in 2004 to 19.1 per 1,000 population in 2013.1 Preschool refers to the group of children below the age of 6.0 years. Early preschool refers to those equal or younger than 24 months of age and late preschool refers to those older than 24 months.

This article refers wheeze to doctor-diagnosed wheeze only because parents-reported wheeze was show to be unreliable with around 60% accuracy and there was only 50% agreement between parents and doctors. Parents tend to misinterpret any noisy breathing from the airway or chest as wheeze. 2,3,4 It is also noted that children with doctor-confirmed wheeze demonstrated greater airway resistance than parentsreported wheeze. 5 Wheeze is produced in the presence of airway narrowing. Shortness of breath (such as tachypnea, insucking) may be due to airway narrowing, usually coexisting with troubling cough, are suggestive of wheeze. An episode of wheeze could last for a few hours to a few days. Recurrent wheeze is defined as more than 2 episode of doctordiagnosed wheeze.

Pre-school wheeze is classified as typical or atypical. Typical wheeze is defined as expiratory wheeze detected by trained medical staff without features listed in Table 1. Atypical pre-school wheeze, i.e. those with features listed in Table 1, should be referred to paediatric respiratory medicine (PRM) specialist for evaluation and management. Early preschool typical wheeze is due to acute bronchiolitis or asthma. For late preschool typical wheeze, the differential diagnoses include asthma and wheezy bronchitis

Clinical Features Probable Diagnoses
Ex-prematurity Bronchopulmonary dysplasia
Wheeze during both inspiration and expiration (Biphasic wheeze) Obstruction at the proximal lower airway like trachea and lobar bronchi
Persistent symptoms from birth Structural airway lesions like trachea/bronchomalacia , extramural compression by vessels, tracheoesophageal fistula
Productive wet cough Persistent bacterial bronchitis/ Cystic fibrosis /
Bronchiectasis / Primary ciliary dyskinesia /
Immunodeficiency / Tuberculosis
Failure to thrive Cystic fibrosis / Immunodeficiency / Tuberculosis
Recurrent pneumonia Recurrent aspiration secondary to gastroesophaheal reflux /Cystic fibrosis / Immunodeficiency
Neurological disorders Recurrent aspiration due to dysfunctional swallowing
Swallow problem e.g.
choking, gagging / vomiting
Dysfunctional swallowing, primary or secondary to structural lesions, like laryngeal cleft
Finger clubbing Bronchiectasis / Tuberculosis
Table 1. Features suggestive of atypical preschool wheeze

Acute bronchiolitis

Acute bronchiolitis is diagnosed based on history and physical finding. The definitions of bronchiolitis are different in different countries. In Hong Kong, it is defined as expiratory wheeze in the presence of viral infection. Respiratory syncytial virus (RSV) is a common etiology of acute bronchiolitis with potentially life-threatening courses in young infants. 6,7 Acute bronchiolitis is NOT responsive to inhaled bronchodilator but responsive to inhaled hypertonic saline for Asian children8. It is important to note that inhaled hypertonic saline is not effective for European children8

Preschool asthma

In contrast to bronchiolitis, asthma is characterized by the presence of airway hyper-responsiveness demonstrated by a clinical improvement after a trial of inhaled bronchodilator as suggested by the Global Initiative for Asthma.9 In the primary care setting, the diagnosis of preschool asthma comprises of auscultation for breath sound and wheeze before and 30 minutes after inhaling 8 puffs of salbutamol through an appropriate spacer device like aerochamber (Table 2). Positive bronchodilator responsiveness means airway hyperresponsiveness (AHR), a defining feature for asthma.

Breath sound Wheeze Bronchodilator
responsiveness
+
+
+
-
+
-
-
-
-
Table2. Definition of clinical responsiveness to bronchodilator

Asthma might be atopic with a positive personal history of atopy (eczema or allergic rhinitis or urticaria or allergic conjunctivitis) or family history of asthma or positive skin prick test/elevated IgE or eosinophil count or non-atopic. The latter is more commonly found in those born premature.

Wheezy bronchitis

This is not a well -described entity and should be distinguished from persistent bacterial bronchitis which is associated with inspiratory crackles and responsive to a long course of antibiotics (2-4 weeks). This entity is rarely seen in the authors' department and is most secondary to other causes like gastroesophageal reflux or sequelae of prematurity complicated by environmental risk factors like tobacco exposure. This entity should be referred to specialist in PRM.

Investigations

Although routine chest radiography and laboratory testing may not be necessary in making the diagnosis in acute wheeze, they should be considered in recurrent wheezer or if there are clinical suspicion of alternative diagnoses. Chest radiographs and skin prick test are the basic investigations for recurrent pre-school wheeze.

Atopy can be diagnosed by a positive skin prick test (SPT) to aeroallergen. Together with female gender and late-onset preschool wheeze index, i.e. number of emergency admission for wheeze per year between 2-6 years old, they are predictors for future asthmatic hospitalization after the age of 6 years10. (Table 3) While allergic rhinitis and family history of asthma are associated with a higher chance for asthma preventer prescription after the age of 6 years . 10 Investigations for atypical recurrent preschool wheeze are listed in Table 4. :

Late preschool wheeze admission index 0 0.5 1 1.5 2 2.5 3
Risk Factors              
Female
@SPT+ve Probability* 0.16 0.28 0.44 0.61 0.76 0.86 0.93
@SPT-ve Probability* 0.07 0.13 0.22 0.37 0.54 0.70 0.83
Male
@SPT +ve Probability* 0.11 0.19 0.32 0.49 0.66 0.8 0.89
@SPT -ve Probability* 0.04 0.08 0.15 0.26 0.42 0.59 0.74
Table 3: Probabilities of emergency asthma admission after the age of 6 years comparing children with various risk factors

* Probability of having asthma admission after the age of 6 years, † Number of admissions for preschool wheeze at age between 2 to 5.9 years divided by number of years, SPT: Skin prick test.

  1. Pneumatic aurioscope with tympanogram for otitis media with effusion, which suggest ciliary dyskinesia
  2. Imaging with chest radiograph or computer tomography of thorax to look for features such as congenital lung condition, cystic fibrosis, recurrent aspiration, bronchiectasis, foreign body ingestion, post-infective condition or tuberculosis.
  3. Flexible bronchoscopy to look for possibly laryngeal or tracheal anomalies
  4. Nasal brushing for cilia study for ciliary dyskinesia
  5. 24-hours oesophgeal pH monitoring and pH-impedance monitoring (MII-pH) for gastro-esophageal reflux disease (GERD)
Table 4 Investigations for atypical wheeze

Management (Table 5)

Management Acute Bronchiolitis Asthma
nebulized hypertonic (3%) saline yes contraindicated
ipratropium bromide No evidence yes
short-acting beta-2-agnoist No evidence yes (except in severe cases)
nebulized adrenaline yes no
high flow nasal cannula (HFNC), i.e. minute ventilation x9, for wheeze with moderate severity. HHHF creates a PEEP of 2-4 cm water and wash out CO2 yes yes
Continuous positive airway pressure (CPAP) for moderate /severe expiratory wheeze Yes Yes
Systemic steroid No Yes (in moderate to severe cases)
Table 5: Relief of acute typical wheeze

The management of typical preschool wheeze would be based on the diagnosis, i.e. asthma or bronchiolitis/ bronchitis. General measures include maintenance of hydration and nutrition and provision of respiratory support in terms of oxygen or heated humidified high flow or positive airway pressure like CPAP.

For asthma, as-needed or regular bronchodilator and systemic corticosteroid for moderate/severe asthma are treatment of choice for asthma. Bronchodilator is effective in asthma except in very severe case. For bronchiolitis, the use of nebulized hypertonic (3%) saline or nebulized adrenaline are helpful8 Nebulized hypertonic (3%) saline (HS) was shown to be beneficial in reducing clinical symptoms in acute bronchiolitis by improving mucociliary clearance, reducing airway edema and mucus viscosity. 11,12,13 Nebulized adrenaline was shown to have short term improvement in acute bronchiolitis. 14,15

The use of nebulized HS should be followed by vigorous chest physiotherapy, especially in early preschool child who has ineffective coughing, to assist removal of secretion from the pharynx after it is coughed out from the chest. Salbutamol is not effective in the management of bronchiolitis. 6,16 Glucocorticoids (either inhaled or systemic) is not advised in the management of acute bronchiolitis. 17 Antibiotic was not shown to be beneficial in the acute management of bronchiolitis and should not be prescribed in the absence of evidence of bacterial infection or clinical evidence of sepsis.18

Pressure support is useful during acute attack of wheeze. It can be given by heated-humidified- high flow nasal cannula (HHHFNC) or continuous positive airway pressure (CPAP).

Preventive Management

Avoidance of indoor pollutants like tobacco exposure and outdoor pollutants like NO2 is the most important preventive measure. Smoking cessation treatment should be offered to those smokers at home.

For those with persistent asthma, i.e. SOB >= 1 per month for at least 2 months, >1 hospitalization in 1 year or severe attack leading to use of systemic steroids, daily inhaled corticosteroids (ICS) should be prescribed for 3 months and stopped afterward. Daily ICS is usually given at daily dose of equal or less than 160 microgram fluticasone 19 he adult height impact from ICS is none for boy and no more than 2 centimeters shorter for girl. 20 If the patient deteriorates with stoppage of ICS, it should be resumed for another 6 months before trial of stoppage.

Other option for pre-school asthma includes the use of intermittent inhaled corticosteroid (ICS) 21 or montelukast for 1-2 weeks at the first sign of a viral cold and continue for 7 days or till symptoms had disappeared for 48 hours. 22, 23,24 Pre-emptive high dose ICS (budesonide 400 mcg QID for 3 days, then BD for 7 days 25; budesonide 1mg BD for 7 days 26 ; fluticasone propionate 750mcg daily at first sign of illness until symptoms resolved for 48 hours 27 reduced the risk of exacerbations needing rescue oral corticosteroids by more than 30% as compared to placebo (RR 0.68; 95% CI 0.53-0.86)28. However pre-emptive high dose ICS has no effect on reducing asthma-free day.

Administration of RSV passive immunization (Palivizumab) to babies born before 35 weeks gestation were effective to prevent RSV bronchiolitis and early preschool wheeze.29,30 For acute bronchiolitis, it was noted that post-RSV bronchiolitis airway hyperresponsiveness exists for few weeks to months.31 Montelukast can be given regularly for 3 months to treat the post-RSV transient airway hyperresponsiveness32,33

It is important to stop the montelukast at the end of 3 months to assess the need for montelukast.

Use of spacer

It is important to use a spacer to assist the administration of inhaled medication from metered dose inhalers (MDIs) especially upon acute exacerbation. It is applied to face via face mask or mouth piece and each administration should involve at least 5 tidal breath for each puff given. Spacers can be washed with detergent and allowed drip dry to decrease the static charge which may decrease the availability of aerosols.34 An alternative would be use of spacer free of static charge, e.g. aerochamber.

Conclusion

Wheeze is a common sign in preschool children and recurrent preschool typical wheeze is due to either infection or asthma. Responsiveness to bronchodilator given via a spacer would confirm airway hyperresponsiveness (AHR). Recurrent AHR would confirm asthma even in children too young to undertake spirometry. For those with atypical wheeze, a referral to a specialist in paediatric respiratory medicine is advised.

References

  1. W Chiu, LP Lee, DK Ng, TK Lau, P Lam, JY Chan. Consensus Report on Management of Wheezing in Preschool Children. Hong Kong Society of Paediatric Respirology. Journal of Paediatric Respirology and Critical Care 2011:7(4):4-13.

  2. Cane RS , Ranganathan SC, McKenzie SA. What do parents of wheezy children understand by "wheeze"? Arch Dis Child. 2000; 82(4):327-32.

  3. Cane RS, McKenzie SA. Parents' interpretations of children's respiratory symptoms on video. Arch Dis Child. 2001 Jan;84(1):31-34.

  4. Levy ML, Godfrey S, Irving CS, Sheikh A, Hanekom W, Bush A, et al. Wheeze detection: recordings vs. assessment of physician and parent. J Asthma 2004;41(8):845-53.

  5. Lowe L, Murray CS, Martin L, Deas J, Cashin E, Poletti G, et al. Reported versus confirmed wheeze and lung function in early life. Arch Dis Child 2004;89(6):540-3

  6. Meissner HC. Viral Bronchiolitis in Children. N Engl J Med. 2016;374(1):62-72

  7. Rodriguez R, Ramilo O: Respiratory syncytial virus: How, why and what to do. J Infect 2014; 68(Suppl 1):S115-S118

  8. Siu KK, Leung SY, Kong SY, Ng DK. Management of recurrent preschool doctor-diagnosed wheeze. Indian J Pediatr (in press)

  9. 2017 Pocket Guide for Asthma Management and Prevention. Global Initiative for Asthma (GINA).

  10. Yu PT, Chan JY, Poon F, Lee RS, Leung SY, Ng JP, et al. The predictive factors in preschool wheezers for subsequent asthma hospitalization after the age of 6 years. Pediatr Respirol Crit Care Med. 2017;1:11-6.

  11. Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulised hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev 2013; 7:CD006458

  12. Zhang L, Mendoza-Sassi RA, Klassen TP, et al. Nebulized hypertonic saline for acute bronchiolitis: a systematic review. Pediatrics 2015;136:687-701.

  13. Maguire C, Cantrill H, Hind D, Bradburn M, Everard ML. Hypertonic saline (HS) for acute bronchiolitis: Systematic review and meta-analysis. BMC Pulmonary Medicine. 2015;15:148

  14. Hartling L, Bialy LM, Vandermeer B, TjosvoldL, Johnson DW, Plint AC et al: Epinephrine for bronchiolitis. Cochrane Database Syst Rev 2011; 6:CD003123

  15. Hartling L, Fernandes RM, Bialy L, Milne A, Johnson D, Plint A, et al. Steroids and bronchodilators for acute bronchiolitis in the first two years of life: Systematic review and meta-analysis. BMJ 2011; 342:d1714

  16. Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database of Systematic Reviews 2014;6:CD001266.

  17. Fernandes, RM, Bialy LM, Vandermeer B, Tjosvold L, Plint AC , Johnson DW , et al. Glucocorticoids for acute viral bronchiolitis in infants and young children. Cochrane Database Syst Rev 2013;6: CD004878.

  18. Farley B, Spurling, G, Eriksson L, Del Mar, Chris B. Antibiotics for bronchiolitis in children under two years of age. Cochrane Database Syst Rev 2014;10: CD005189.

  19. Bleecker ER, Bateman ED, Busse WW, Woodcock A, Frith L, House KW, Jacques L, Davis AM, Haumann B, Lotvall J. Once-daily fluticasone furoate is efficacious in patients with symptomatic asthma on low-dose inhaled corticosteroids. Ann Allergy Asthma Immunol. 2012;109(5):353-358.

  20. Strunk RC, Sternberg AL, Szefler SJ, Zeiger RS, Bender B, Tonascia J; Childhood Asthma Management Program (CAMP) Research Group. Long-term budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents. J Pediatr. 2009;154(5):682-7.

  21. Chong J, Haran C, Chauhan BF, Asher I. Intermittent inhaled corticosteroid therapy versus placebo for persistent asthma in children and adults. Cochrane Database Syst Rev. 2015;7:CD011032.

  22. Robertson CF, Price D, Henry R, Mellis C, Glasgow N, Fitzgerald D, Lee AJ, Turner J, Sant M. Short-Course Montelukast for Intermittent Asthmain ChildrenA Randomized Controlled Trial. Am J Respir Crit Care Med. 2007; 175: 323-329.

  23. Nwokoro C, Pandya H, Turner S, Eldridge S, Griffiths CJ, Vulliamy T, Price D, Sanak M, Holloway JW, Brugha R, Koh L, Dickson I, Rutterford C, Grigg J. Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial. Lancet Respir Med. 2014;2:796-803.

  24. Robertson CF, Price D, Henry R, et al. Short-course montelukast for intermittent asthma in children: a randomized controlled trial. Am J Respir Crit Care Med 2007;175(4):323-329.

  25. Svedmyr J, Nyberg E, Thunqvist P, Asbrink-Nilsson E, Hedlin G. Prophylactic intermittent treatment with inhaled corticosteroids of asthma exacerbations due to airway infections in toddlers. Acta Paediatr 1999;88(1):42-47.

  26. Bacharier LB, Phillips BR, Zeiger RS, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonists in preschool children with moderate-to-severe intermittent wheezing. J Allergy Clin Immunol 2008;122(6):1127-1135.e8.

  27. Ducharme FM, Lemire C, Noya FJ, et al. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. N Engl J Med. 2009;360(4):339-353.

  28. Ducharme FM, Tse SM, Chauhan B. Diagnosis, management, and prognosis of preschool wheeze. Lancet. 2014;383(9928):1593-1604.

  29. American Academy of Pediatrics Policy Statement. Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection. Pediatrics. 2014;134:415-420, e620-e638.

  30. Mochizuki H, Kusuda S, Okada K, Yoshihara S, et al. Palivizumab prophylaxis in preterm infants and subsequent recurrent wheezing: 6 year follow up study. Am J Respir Crit Care Med 2017. Feb 2: p.2-42

  31. Eriksson M, Bennet R, Nilsson A. Wheezing following lower respiratory tract infections with respiratory syncytial virus and influenza A in infancy. Pediatr Allergy Immunol 2000;11:193-197.

  32. Bisgaard H. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383.

  33. Bisgaard H, Flores-Nunez A, Goh A, Azimi P, Halkas A, Malice MP, Marchal JL, Dass SB, Reiss TF, Knorr BA.. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children. Am J Respir Crit Care Med. 2008;178(8):854-60.

  34. Ng DKK, Chow PY, Lam YY. Administration of Aerosolized Medications. Hong Kong Medical Diary 2003; 10 (1).

Self-Assessment Questions

Please indicate whether the following statements are true or false.

1. Typical preschool wheeze is due to either asthma or bronchiolitis / bronchitis.

2. Typical preschool wheeze might have biphasic wheeze.

3. Significant improvement with salbutamol indicates airway hyperresponsiveness.

4. Asthma might not have airway hyperresponsiveness.

5. Hypertonic saline is effective for treatment for acute bronchiolitis in Asian children.

6. Inhaled corticosteroid is not effective for preschool asthma.

7. Montelukast is effective for acute bronchiolitis.

8. Environmental tobacco exposure is an important risk factor for poor control of preschool asthma.

9. Palivizumab is effective to prevent RSV bronchiolitis in infants.

10. Atypical preschool wheeze might have finger clubbing.