Asthma

14.3 Asthma



Adam Jaffé



Definition


The word ‘asthma’ is a derivative of the Greek verb aazein, meaning ‘to pant’. In an attempt to describe it more precisely, the Global Initiative for Asthma (GINA) has defined asthma as ‘a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment’. Although this is a complex definition and is of limited practical value in making the diagnosis in an individual, it highlights the interplay between inflammation, airway hyper-responsiveness, obstruction and clinical symptoms.



Burden of asthma


Asthma is estimated to affect 300 million people worldwide. Although the burden of asthma continues to increase in some countries, its prevalence is stabilizing and even declining in others. In the UK the prevalence of asthma is 1 in 11, and in Australia it is 1 in 9 children. The International Study of Asthma and Allergies in Childhood (ISAAC) has identified Australia, along with the UK, New Zealand and the Republic of Ireland, as having a relatively high prevalence of asthma in children compared with other countries. It is one of the commonest presentations to the primary physician and emergency department. In most developed countries the mortality rate remains low, but death still occurs in childhood. Like many respiratory diseases, the prevalence of asthma is higher in Indigenous children.


The return to school after the summer holidays is associated with a peak in hospital admissions; this occurs in February in the southern hemisphere, and in October in countries in the northern hemisphere, and is likely to be caused by the spread of viruses such as rhinovirus in the classroom.



Age of onset


The onset of asthma can occur at any age, including within the first few years of life; children under 4 years of age are more likely to be hospitalized or to seek medical attention. However, the diagnosis of asthma is particularly difficult in the preschool child as there are many different wheezing phenotypes in this age group (see Chapter 14.4). It is often difficult to distinguish young children who wheeze with upper respiratory tract viral infections from those with intermittent asthma. The importance of this distinction is that those with virus-induced wheeze will usually get better by 6 years of age.


The Asthma Predictive Index is a helpful guide in the clinical setting for predicting whether children under 3 years of age with recurrent wheeze will develop asthma when older. Children are at a high risk of developing asthma if they have either:



one of:


• parental history of asthma (particularly maternal)

• eczema

• sensitization to aeroallergens

or two of:


• allergic rhinitis

• > 4% eosinophilia

• food allergies

• wheezing in circumstances not related to upper respiratory tract infections.


Pathogenesis




Genes


The cause of asthma is multifactorial and complicated, and involves an interaction between genetic determinants and environmental stimuli (Table 14.3.1). Although asthma has been known to run in families, the inheritance pattern remains unclear. Asthma is polygenic and, although many potential candidate genes have been discovered, no single gene accounts for more than 10% of the susceptibility of an individual for developing asthma. Boys generally have smaller airways than girls and tend to suffer more from asthma. However, after adolescence the prevalence is higher in females.


Table 14.3.1 Factors involved in the pathogenesis of asthma


















Host Environment
Innate immunity

• Hygiene hypothesis

 Allergens

• Aeroallergens (house dust mite, cockroaches, Alternaria)

Genetic candidates

• β2-adrenoreceptor


• Tumour necrosis factor α


• Interleukin-4


• Interleukin-4 receptor


• Clara cell protein


• CD14


• β-chain of IgE receptor


• RANTES (a chemokine) promoter polymorphism


• ADAM33 (a disintegrin and matrix metalloproteinase domain-containing protein 33)

 Respiratory infections

• Viruses (e.g. RSV) (association but causation not yet proven)

  Environmental tobacco smoke

• In utero causes smaller airways and increased wheeze in early life


• Continued exposure associated with increased asthma severity

Sex

• More prevalent in boys


• From puberty, more prevalent in females

 Air pollution (association but causation not fully proven)
Low intake of antioxidants (association but causation not yet proven)
Low intake of omega-3 fatty acids (association but causation not yet proven)
Obesity (via inflammatory mediators)
Chlorinated swimming pools in infancy (association but causation not yet proven)
Paracetamol (controversial – association in utero and first 12 months of life but causation not proven)

Ig, immunoglobulin; RANTES, regulated upon activation, normal T cell expressed and secreted; RSV, respiratory syncytial virus



Allergy


The role of allergy in asthma is very important and more than 80% of people with asthma have an allergy. Sensitization and chronic exposure to aeroallergens such as house dust mite, cockroach and animal dander are implicated in the development of asthma; however, this research area remains confusing as there is evidence that early exposure to animals such as dogs may be protective.



Hygiene hypothesis


This is another explanation for why children develop asthma. At birth, there is an overexpression of the T-helper cell type 2 (Th2) pathway. Th2 cells produce cytokines (interleukin (IL)-4, -5, -6, -9 and -13) that mediate allergic inflammation, and this pathway is associated with the development of atopy and asthma. Factors that favour the Th2 phenotype include antibiotic use, diet, urban environment and lifestyle, and sensitization to allergens. Exposure to environmental stimuli such as lipopolysaccharide stimulates the immune system to develop along the Th1 pathway with expression of IL-2 and interferon-γ. Having older siblings or living in a rural environment also favours the expression of the Th1 phenotype; these children generally do not develop an allergic phenotype.



Viruses


Although viruses such as human rhinovirus C cause asthma exacerbations, it is increasingly recognized that exposure to viruses may lead to the development of asthma. Some researchers have demonstrated that babies exposed to winter viruses are more likely to develop asthma later in life. The role of respiratory syncytial virus (RSV) is important but controversial. Infection with RSV is certainly associated with the development of asthma, but whether it causes asthma directly or is simply a marker for those likely to develop asthma remains to be elucidated.


Most children with asthma have an underlying immunoglobulin (Ig) E-mediated eosinophilic response, but it is increasingly being recognized that there are other phenotypes such as neutrophilic asthma. This has potential implications with regard to therapy, as children with neutrophilic asthma may benefit from medications such as macrolides. Future research will help to define better the different phenotypes and causes of asthma in children.



Clinical features


The diagnosis of asthma is likely in children with the following symptoms, particularly if they occur at night or early in the morning or have identified triggers:



• Wheeze – the main symptom is wheeze which is a musical note caused by turbulent air flow and is usually, but not always, present in children with asthma. Parents often mistake wheeze for other sounds such as stertor or rattle, so it is important to ensure that parents understand what is meant by the term ‘wheeze’ (see Chapter 14.4)


• Cough


• Difficulty breathing


• Chest tightness.

Related posts:

  1. Sudden unexpected death in infancy
  2. Birth defects, prenatal diagnosis and teratogens
  3. Neural tube defects, large heads and hydrocephalus
  4. The newborn infant: stabilization and examination

Stay updated, free articles. Join our Telegram channel
Tags:
Aug 4, 2016 | Posted by in PEDIATRICS | Comments Off on Asthma

Full access? Get Clinical Tree
Get Clinical Tree app for offline access