Bronchodilators For Infants And Children

  • Shiyi Liang Medical Biosciences, Imperial College London

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Introduction

Bronchodilators are a type of drug that dilates the bronchi when the airway narrows or airway muscles contract pathologically.1 Respiratory conditions can happen in infants and children, for example, asthma, respiratory distress syndrome, chronic lung disease, pneumonitis, and pneumonia. Many of these conditions have symptoms of bronchoconstriction and inflammation as part of the physiologic response.2 Bronchodilators can treat and even prevent some conditions in certain age groups.3 However, infants and children are not as fully developed as adults, so some types of bronchodilators may be less effective in infants and children in comparison to adults. 

Common respiratory conditions in infants and children

According to the European Lung Foundation, asthma, and cystic fibrosis are the two main respiratory diseases in children. Bronchiolitis often affects babies under 2 years old, and it is one of the most common causes of hospitalisation for infants under 1 year old.4 This article will explain several common respiratory conditions that can require bronchodilator therapy. 

According to the Centre for Disease Control and Prevention, the National

Current Asthma Prevalence data (2021) showed more than 6.5% of US children (aged under 18) have current asthma.5 Asthma is a chronic disease with airway inflammation, characterised by airway obstruction hence breathing difficulties. Children who experience asthma may have symptoms like wheezing, cough, shortness of breath, and chest tightness.6 The symptoms can be triggered by allergens, air pollutants, physical exercise, and even strong emotions, leading to an asthma attack.7 

The pathophysiology of asthma includes the inflammatory response to the external trigger, and the immune cells like neutrophils, lymphocytes, and mast cells will accumulate around the airway. Their action often causes damage to the airway epithelial cells, causing airway swelling, increased music production, and bronchial muscle contraction, hence leading to asthma symptoms.6 Wheezing can be regarded as a sign of asthma in infants but infants often develop wheezing due to viral infection.8 It is still controversial whether viral-induced wheezing can progress into asthma as infants enter their childhood. 

Bronchiolitis is a common respiratory disease in children and babies under 2. It is often a virus infection of the lower respiratory tract. Although bronchiolitis is mild to moderate and is self-limited in most cases, it can develop into serious conditions like respiratory failure in babies if not taken seriously.9 According to the Office for Health Improvement & Disparities of the UK, there were approximately 518 admissions to hospital per 100,000 population for emergency bronchiolitis in children under the age of 2 in England.10 

Most bronchiolitis patients are infected by Respiratory Syncytial Virus (RSV), but more and more viruses have shown their potential to induce a similar infection. Examples include Human rhinovirus, Coronavirus, Human metapneumovirus, and Adenovirus.9 The virus triggers an inflammatory response in the small airways and obstructs the airway because of excess mucus production and epithelial cell death. The initial symptoms are similar to a common cold, including runny nose, cough, nasal congestion, and sometimes fever. As time passes, the small airway muscles contract, narrowing the airway and leading to wheezing and short rapid breaths.11

Other respiratory diseases require bronchodilators, but they may not be diagnosed in infants and children, in particular, chronic obstructive pulmonary disease (COPD), which mostly happens in smokers and people older than 40. However, the risk of developing COPD increases if infants and children are exposed to second-hand smoke constantly.12 

Types of bronchodilators

Drug administration through inhalation allows direct delivery of drugs to the airway and lungs, which is more advantageous over other systemic routes. Bronchodilators can be long-acting or short-acting and they have different acting mechanisms. Some bronchodilators can be used in adults and children, but there can be more suitable choices for infants and children as they are not fully grown and their organ functions are not fully developed. Some studies showed that infants 0 to 12 months of age with wheezing and bronchiolitis are not responsive to bronchodilators, and bronchodilators did not reduce hospitalisation.13 

Short-acting bronchodilators (e.g., albuterol)

Albuterol, also known as Salbutamol, is a short-acting bronchodilator. It can be administered to newborn babies and children. Albuterol acts on a receptor in the airway called the β2-adrenergic receptor and it induces bronchial muscle relaxation, and quicker mucus removal from mucus-producing cells, resulting in a wider and clearer airway for breathing. Albuterol is often administered through a nebulizer for infants and children, even if it has an oral syrup form and can also be administered intravenously.14 The recorded recommended dose for children aged 4 and older is 90 to 180 mcg administered every 4 to 6 hours, which would be 1 to 2 puffs from a nebulizer, and should not exceed 12 puffs within 24 hours. It is suggested that a dose of albuterol of 1 mg/kg is potentially toxic for children 6 and younger. The actual dosage should be considered by the doctor according to the patient’s condition. Patients aged 2 or younger are recommended to use a nebulizer solution dosage of 0.2 to 0.6 mg/kg/day.15 

Tremors and nervousness are the predominant adverse events found in children from 2 to 6. Albuterol has a mild effect on heart rate by increasing it, so albuterol is not prescribed when the heart rate is above 180 every minute.14 Other adverse events may also occur, like nausea, fever, bronchospasm, vomiting, headache, dizziness, cough, and allergic reactions.

Long-acting bronchodilators (e.g., salmeterol)

Salmeterol is an example of a long-acting bronchodilator, and it is usually used to relieve asthma symptoms. Salmeterol can be used in patients above 4 years old, but its safety and efficacy require further study in patients under the age of four. Salmeterol activates β2-adrenergic receptors, allowing bronchial muscle relaxation, hence widening the airway and increasing airflow. Reducing inflammation is a side benefit of salmeterol as it reduces the secretion of inflammatory regulators by mast cells. The special molecular structure allows a longer action on the β2-adrenergic receptors, so that the drug is effective for a longer period, up to 12 hours.16 

Salmeterol is given through oral inhalation in the form of aerosol or powder. According to the National Institute for Health and Care Excellence (NICE), the dosage for children between 5-11 years old is 50 micrograms twice daily, and the dosage for children between 12-17 years old is 50 micrograms twice daily but can increase up to 100 micrograms twice daily according to the severity of symptoms, whether it is used as a treatment of asthma or prevention of bronchospasm.17

NICE also suggested common side effects like headache, palpitations, muscle cramps, and some uncommon side effects like skin reactions, insomnia, chest pain, and hypokalaemia.17

Anticholinergic bronchodilators (e.g., ipratropium)

Apart from the beta-2 receptor agonists, anticholinergics are another type of bronchodilator with a different working mechanism. Anticholinergic bronchodilators block cholinergic nerves on airway muscles, so these nerves don’t secrete chemicals that cause muscle contraction, therefore widening the airway.1

Ipratropium is an acetylcholine antagonist that blocks cholinergic receptors on airway smooth muscle contraction dilating bronchioles. Ipratropium is administered through oral inhalation or intranasal inhalation. The dosage for children under the age of 6 should be limited to 0.25 mg every 20 minutes up to 3 doses for moderate to severe asthma exacerbation. The dosage can be increased up to 0.5 mg every 20 minutes as needed up to 3 hours if the patient is between 6 and 12 years old and the maximum 0.5mg can be given to children older than 13.18 The dosage varies according to the symptoms that need to be treated so it is important to consult the doctor’s advice. Common side effects of Ipratropium include throat and nasal complaints, gastrointestinal motility disorder, and headache. Eye pain and vision disorder may occur if sprayed near the eyes.19 

Administration considerations

The dosage for each patient varies according to their age, body weight, and the severity of the symptom. It is suggested that patients should rinse their mouth with water after oral inhalation to reduce the side effects in the mouth.18 

The administration of bronchodilators occurs through inhaler devices like a nebulizer. 

A reason to prioritise the adaptation of devices for infants and children is their narrower airways compared to adults. This anatomical difference poses a challenge in facilitating the effective delivery of drug particles to the lower airways.

Paediatric inhalers often incorporate spacers or masks to enhance the effectiveness of drug delivery, ensuring that infants and children receive the medication directly into their airways.20 

Summary

Bronchodilators are a series of drugs that aim to relax the bronchial muscle and widen the airway to recover breathing. Bronchodilators can be long-acting and short-acting, and they target beta-2 receptors on smooth airway muscles or interact with cholinergic nerves to achieve their therapeutic effect. Beyond bronchodilator therapy, considering lifestyle factors, and developing alternative therapies, a future patient-centric care model contributes to comprehensive and effective paediatric respiratory care.

References

  • NHS. Bronchodilators [Internet]. nhs.uk. 2017. Available from: https://www.nhs.uk/conditions/bronchodilators/#:~:text=Bronchodilators%20are%20a%20type%20of
  • Gallacher DJ, Hart K, Kotecha S. Common respiratory conditions of the newborn. Breathe [Internet]. 2016 Mar;12(1):30–42. Available from: https://breathe.ersjournals.com/content/12/1/30
  • Ng G, da Silva O, Ohlsson A. Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Cochrane Database of Systematic Reviews. 2016 Dec 13;
  • Lung Diseases In Children | Chronic & Common Diseases |ELF [Internet]. European Lung Foundation. Available from: https://europeanlung.org/en/information-hub/lung-conditions/lung-disease-in-children/
  • Centers for Disease Control and Prevention. Most recent national asthma data [Internet]. Centers for Disease Control and Prevention. 2022. Available from: https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm
  • Lizzo JM, Cortes S. Pediatric Asthma [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551631/
  • CDC. Common asthma triggers [Internet]. Centers for Disease Control and Prevention. 2022. Available from: https://www.cdc.gov/asthma/triggers.html
  • Coleman A, Gern JE. Viral-Induced Wheeze and Asthma Development. Allergy, Immunity and Tolerance in Early Childhood [Internet]. 2016;65–82. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173475/#bib2
  • Justice NA, Le JK. Bronchiolitis [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441959/
  • GOV.UK. Interactive Health Atlas of Lung conditions in England (INHALE): February 2022 update [Internet]. GOV.UK. 2022. Available from: https://www.gov.uk/government/statistics/interactive-health-atlas-of-lung-conditions-in-england-inhale-2022-update/interactive-health-atlas-of-lung-conditions-in-england-inhale-february-2022-update
  • Erickson EN, Mendez MD. Pediatric Bronchiolitis [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519506/
  • Agarwal AK, Raja A, Brown BD. Chronic Obstructive Pulmonary Disease (COPD) [Internet]. National Library of Medicine. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559281/
  • Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database of Systematic Reviews. 2014 Jun 17;
  • Rocha G. Inhaled Pharmacotherapy for Neonates: A Narrative Review. Turkish Archives of Pediatrics. 2021 Dec 29;57(1):5–17.
  • Johnson DB, Bounds CG. Albuterol [Internet]. Nih.gov. StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482272/
  • Adams BS, Nguyen H. Salmeterol [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557453/
  • British National Formulary (BNF). Salmeterol [Internet]. NICE. National Institute for Health and Care Excellence; Available from: https://bnf.nice.org.uk/drugs/salmeterol/
  • Saab H, Aboeed A. Ipratropium [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544261/
  • British National Formulary for Children (BNFC). Ipratropium bromide [Internet]. bnfc.nice.org.uk. National Institution for Health and Care Excellence (NICE); [cited 2024 Jan 19]. Available from: https://bnfc.nice.org.uk/drugs/ipratropium-bromide
  • Everard ML. Inhaler Devices in Infants and Children: Challenges and Solutions. Journal of Aerosol Medicine. 2004 Jun;17(2):186–95.

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Shiyi Liang

Medical Biosciences, Imperial College London

Shiyi has several years of experience as a writer for health articles and science reviews. Shiyi has engaged actively in diverse research projects, spanning topics from neuroscience to endocrinology, demonstrating her meticulous approach and passion for research. She is eagerly anticipating more opportunities to delve into the realms of research and science. Furthermore, Shiyi is dedicated to creating informative scientific videos.

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