History and exam
Key diagnostic factors
common
presence of risk factors
Associated with asthma: allergic sensitisation; atopic disease; respiratory tract infections in early life; serum eosinophilia; family history of asthma or atopy; gene polymorphisms and epigenetics; passive or active cigarette smoking; vaping; maternal smoking in pregnancy; abnormal lung function and airway hyper-responsiveness; indoor and outdoor air pollution; low socio-economic status; pesticide exposure.
wheezing episode triggers
Factors, in addition to respiratory infection, that may trigger episodes of wheeze include change in weather, environmental tobacco smoke, exercise, and emotion.
increased work of breathing
During symptomatic episodes tachypnoea, recessions (or retractions), and accessory muscle recruitment may be present depending on the severity of the episode.
features of atopic disease
Features of atopic disease on examination include flexural eczema. Other non-specific features such as oedema and tearing of the conjunctiva, and boggy nasal mucous membranes, are non-specific.[126]
Other diagnostic factors
common
age >3 years
Transient infantile wheezing may be difficult to distinguish from asthma during the initial few years of life. In transient infantile wheezing, symptoms resolve in the preschool years.
dry night-time cough
Cough may accompany wheeze during symptomatic episodes, but the symptom is often misdiagnosed as asthma in children. It requires careful review of the history and the exclusion of alternative causes.[102][110]
The presence of a dry night-time cough is suggestive of asthma, but subjective parental reports can be unreliable.[102] Isolated cough in the absence of other symptoms is rarely asthma.[109] A moist cough suggests an alternative diagnosis or a concurrent viral or bacterial infection, and when chronic, suggests the presence of protracted bacterial bronchitis.[109][128][129]
dyspnoea on exertion
Dyspnoea may accompany wheeze and cough during symptomatic episodes but is rarely present on its own.
expiratory wheezing
During symptomatic episodes a widespread polyphonic wheeze is typically present. Localised wheeze suggests an alternative diagnosis such as inhaled foreign body.
Auscultation sounds: Expiratory wheeze
Auscultation sounds: Polyphonic wheeze
uncommon
chest wall deformity
In persistent asthma, chest wall deformity (Harrison's sulci or hyperinflation) may be present, although this is now rarely seen.
Risk factors
strong
allergic sensitisation
Exposure and sensitisation to aeroallergens (e.g., house dust mites or pollens) and certain foods is a recognised risk factor for developing asthma (e.g., a positive skin prick test to house dust mites or specific pollens).[28]
atopic disease
Atopic disease (e.g., eczema, atopic dermatitis, allergic rhinitis, and food allergy) is strongly associated with asthma. Progression from eczema/atopic dermatitis to allergic rhinitis to subsequent asthma has been termed 'the allergic march', although these temporal associations between allergic phenotypes may evolve along multiple pathways.[18][25][26][27]
Atopy is associated with increased asthma severity.[18][32][46][47][48] Atopic children show a stronger association between viral respiratory illness and asthma or wheeze.[29]
respiratory tract infections in early life
URTIs and lower respiratory tract infections in early life increase the risk of later asthma, particularly when caused by respiratory syncytial virus or rhinovirus.[30][31]
One meta-analysis of 150,000 European school-age children revealed that early-life URTI (croup, whooping cough, ear/throat infection, rhinitis) was associated with an increased risk of asthma, and that early-life LRTI (bronchitis, bronchiolitis, pneumonia) was associated with increased risk of both asthma and worse lung function.[30]
Respiratory syncytial virus (RSV) or human rhinovirus (RV) in early life increases the risk of recurrent wheeze and asthma in later childhood.[31] Chlamydia pneumoniae IgE and Mycoplasma pneumoniae IgM have also been associated with increased risk of asthma and exacerbations.[49][50]
serum eosinophilia
family history of asthma or atopy
The majority of children with asthma have a positive family history of asthma or atopy.
gene polymorphisms and epigenetics
Multiple gene polymorphisms have been associated with the development of childhood asthma.[20][21][22][23]
These include genes for nitric oxide synthase (NOS), cytokines (e.g., IL-13, IL-4,IL-4R, TNF-α), beta-2 adrenergic receptor (ADRB2), and the vitamin D receptor (VDR).[20][22][23][54][55][56]
Genetic risk likely interacts with environmental exposures in early childhood (e.g., allergens, viral infections, and tobacco smoke) to increase the risk of asthma and wheeze.[18][22] Epigenome-wide association studies indicate that environmental exposures during the antenatal and early childhood periods are associated with asthma through, for example, differential methylation among genes known to be involved in asthma.[57]
passive or active cigarette smoking
Environmental tobacco smoke is a recognised risk factor for impaired lung growth, infantile wheeze, and asthma exacerbation.[32][33] Passive and active smoking cause poor asthma control and increase other respiratory symptoms such as cough, wheeze, and dyspnoea.
Asthma risk may be enhanced by interactions between obesity and second-hand smoke.[34]
vaping
maternal smoking in pregnancy
abnormal lung function and airway hyper-responsiveness
indoor and outdoor air pollution
Outdoor air pollution is associated with an increased risk of both asthma and loss of asthma control in children, especially traffic-related air pollution with exposure to NO₂ and particulate matter ≤2.5 micrometres (PM2.5).[18][37][40][58] Antenatal exposure to traffic-related air pollution, particularly from the second trimester, has been associated with an increased risk of asthma development among children and adolescents.[59]
Indoor air pollutants associated with an asthma diagnosis and symptoms include volatile organic compounds (e.g., household products, cleaning agents, glue, personal care products, building materials like formaldehyde, and vehicle emissions) and particulate matter (e.g., smoking, cooking, heating, candles).[60][61]
low socio-economic status
Socio-economically disadvantaged groups are more likely to live in areas with the poorest air quality and worst housing conditions, while being exposed to more psychosocial stress and having poorer diets.[44] These factors increase the risk of asthma, poor asthma control, and acute exacerbations.
weak
male sex
obesity
Associated with an increased risk of asthma or an asthma phenotype, particularly among children who experience rapid weight gain.[18][64]
Children with obesity and asthma have greater severity, poorer control, and more frequent exacerbations than children with asthma and a healthy weight.[65][66][67]
Asthma risk may be enhanced by interactions between obesity and both outdoor and indoor air pollutants.[34]
gastro-oesophageal reflux disease (GORD)
Observational studies show a weak association between GORD and poorly controlled asthma.[68]
One Cochrane review found that treatment for GORD moderately improved lung function and use of rescue medication in patients with moderate-to-severe asthma and comorbid GORD; however, the effect of GORD treatment on exacerbations and hospital utilisation is uncertain.[69]
obstructive sleep apnoea (OSA)
There is emerging evidence for a bi-directional link between asthma and OSA in both adults and children.[70]
The prevalence of OSA in individuals with asthma is approximately two to three times higher than in the general population.[71]
Both conditions share risk factors including obesity, rhinitis, and GORD.[72]
assisted reproductive technologies
There is an increased risk of asthma in children conceived using assisted reproductive technologies.[73]
cesarean section
There is an increased risk of wheezing in infancy and childhood among children born by cesarean section compared with vaginal delivery.[74] This is probably due to the lower neonatal stress, reduction in associated hormone and cytokine release, and loss of maternal microbiome transfer normally associated with vaginal delivery.[75]
intestinal microbiota
A greater relative abundance of Bacteroidaceae, Clostridiaceae, and Enterobacteriaceae and a lower relative abundance of Bifidobacteriaceae and Lactobacillaceae is associated with asthma.[76]
acid-suppressive drug use in pregnancy and childhood
paracetamol use in pregnancy
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