15.3.5 Atopy (asthma) Flashcards
Hygiene Hypothesis of for the increase of allergies
One of the hypothesis is the Hygiene Hypothesis which hypothesizes that children living in a more hygienic environment changes their microbial exposure. The less microbial exposure the patient has, the more likely they are to develop allergic and autoimmune diseases. However, this theory has not been proven.
Define:
Allergy
Atopy
Asthma
Allergy:
- a hypersensitivity reaction as a result of immunological mechanisms
- Can be cell mediated or antibody mediated
- IgE
Atopy:
- Personal or familial tendency to become sensitised to an allergen and produce IgE antibodies
- Development of atopic diseases
Asthma:
- Chronic inflammation
- increased airway hyper-reactivity
- Reversible airway obstruction
Define
Hypersensitivity
Immune tolerance
Sensitization
Hypersensitivity
- Objectively reproducible symptoms or signs after exposure to an allergen (food/drug/aeroallergen) at a dose which is tolerated by most people
Immune tolerance
- Absence of active immune reaction to an antigen
Sensitization
- Positive test to an allergen
- This does not equate to allergy unless there is a clinical reaction
Cell and Coombs classification of hypersensitivity reactions
Slide 7
Nomenclature of allergic diseases
Slide 8
Pathogenesis of allergy
- allergy only happen when you have clinical response to second exposure of antigen
- Allergy occurs when the body is exposed to an allergen, but tolerance to the allergen does not develop.
- An antigen enters the body – largely through the neonatal or infant gut – and is presented by antigen presenting cells to T-cells which cause them to differentiate into Th2 calls. Th2 cells then cause B
- Cells to produce IgE. Th2 cells also induce B-cell and T-cell memory response.
- At this point the body has developed sensitization to the allergen.
- Regulatory mechanisms can prevent any further reactions with future exposures to the allergens.
- If the regulatory mechanisms work the patient will develop tolerance to the allergen. This means that with future exposures, there will be no clinical symptoms in the patient.
- If regulatory mechanisms fail, at re-exposure with the same antigen, there is cross-linking on IgE bound to mast cells which cause the mast-cell to degranulate and release histamine. This will cause clinical allergy syndromes. These include allergic rhinitis/conjunctivitis, asthma, eczema, food allergy and anaphylaxis.
- It is important to note that our testing to allergens tests for sensitization and not allergy. Interpretation of these tests requires a clinical response along with a positive test result.
Asthma
- Asthma is an inflammatory disease with multiple phenotypes. About half of cases are atopic asthma, other phenotypes include exercise induced -, aspirin induced - and occupational asthma.
- Atopic asthma usually presents in early life, in patients with other atopic diseases. The patients would display sensitization to inhaled allergens. They have an IgE-mediated reaction to these inhaled allergens resulting in mucous secretion, bronchoconstriction and inflammation.
- The hallmark pathological feature is eosinophilic airway inflammation with resultant airway remodelling. This inflammation results in airway hyper-responsiveness, variable airway obstruction (which is reversible) and clinical symptoms (such as wheeze, cough, tight chest and difficulty breathing).
Risk factors for Wheezing
Slide 12
- exposure to smoke is perinatal and postnatal RF for wheezing (not asthma)
- The most prominent risk-factor pre- and postnatally is exposure to tobacco smoking.
- Babies who are delivered via caesarean section have a higher risk than those born via normal vertex delivery, as maternal vaginal flora improve the infant’s gut microbiome
- There are many genetic markers which are also a risk factor for wheezing
- Postnatally, early exposure to viral infections such as the very common RSV and Rhinovirus increase the risk for patients to start wheezing
- Breastfeeding is a protective factor against wheezing early in life, however it may not prevent the development of asthma.
Aetiology of recurrent wheeze
- Recurrent wheeze has a multifactorial aetiology: a combination of genetic predisiposition, environmental exposures and viral infections
- Genetic predisposition includes: family history of asthma and other atopic diseases
- Environmental exposures include: exposure to aeroallegens such as pollen, house dustmites, pet dander, grasses, trees. Other exposures such as smoke exposure in the home, exposures to gas or fire fumes,
- Viral exposures to various viruses such as RSV, adenovirus, influenza, para-influenza etc
- One in 3 children will wheeze at least once before their 3rd birthday.
Wheezing phenotypes
- Episodic viral wheeze
➡️Specific episodes associated with a viral infection - Multiple-trigger wheeze
➡️Specific episodes, may be associated with viral infections
➡️Also associated with one or more of the following:
>Smoke exposure
>Allergen exposure
>Exercise
>Excessive emotion (crying, laughing)
Pre-school wheezers
- Most children with a preschool wheeze will be as a result of viral infections (clinically we call this diagnosis bronchiolitis)– most commonly RSV, Rhinovirus, parainfluezna, influenza etc
- Wheezing is caused by turbulent airflow through narrowed airways, causing vibration of the airways. This narrowing can either because of mucus in the lumen of the airway, or because of muscle spasm of the airways/bronchospasm.
- The most common mechanism of preschool wheezers is secondary to mucus production because of the viral infection. The mucus blocks causes airway narrowing, which results in the wheezing. This is why bronchodilators do not work in children with bronchiolitis.
- BUT not every child who has a preschool wheeze has viral induced wheezing…
Commonest causes of recurrent wheezing in pre-school children
slide 18
- On this screen you will see many of the common causes of recurrent wheezing. When you are seeing a pre-school patient with recurrent wheezing, you need to consider that the aetiology might not only be related to the respiratory system.
- While viral induced wheezing is incredible common, you have to consider other causes as well. Congenital lung abnormalities such as laryngomalacia, vocal-cord paresis and vascular rings and slings to name few, should be considered especially in children under 1 year of age. Other infectious diseases such as tuberculosis can cause wheezing as a result of TB lymph nose causing airway obstruction. The most common aspiration syndrome is caused my GORD, but others include tracheo-oesophageal fistula, laryngeal clefts and swallowing in-coordination. Cardiac failure is a very common cause of wheezing in children, and often mimics viral wheezing.
Important to note is that asthma is bottom of the list in pre-school wheezers. So always check for other causes before diagnosing asthma.
What is asthma
- Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation.
- It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation.
Wheeze more likely to be due to asthma
- Family history of asthma and/or allergies
- Personal history of atopic diseases and/or food allergy
- Children with asthma also usually have a family history of atopic diseases or asthma, as well as a personal history of atopic diseases, and food or drug allergy, along with their recurrent episodes of wheeze.
Symptoms of other atopic diseases
- Cough, wheeze, tight chest, difficulty breathing
- Runny nose, itchy nose, sneezing, snoring
➡️allergic rhinitis - Itchy eyes, with watery discharge
➡️allergic conjunctivitis - Dry, itchy skin
➡️eczema - Allergic reactions to food or medication
➡️food and drug allergy
