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Can be caused by infection or exposure to allergens.

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Baby: chest retraction + nasal flaring
Use of intercostal muscles

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Multiple ways:
- Child runs 6 min on treadmill (<160 bmp)
- Cold air
- Isocapnic hyperventilation
- Aerosol challenge with hypertonic solutions

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Extrinsic asthma: external factor as cause (dust mite, animals, pollen, fungi)
- In childhood often accompanied with eczema (...% gets rid of it later) --> atopic triad: asthma,  eczema and rhinitis
- diagnosis: skin prick test

Intrinsic asthma: non-atopic (could be occupational asthma)
- caused by immune system

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- Overall increase in prevalence
- 15% of population
- Geographical variation: more common in developed countries
- 2025: expect to have 4 million individuals with asthma

Hygiene hypothesis: growing up in clean environment predisposes IgE response to allergens. You don't make antigens to allergens.
--> Might not be the case, because maybe the dirty environment is less detected (usually non-developed countries)

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3 am: narrowest

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Right side: low molecular weight compounds
Left side: high molecular weight compounds

Both triggers will lead to the same response.

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If not treated properly it can become irreversible (airway wall remodeling) and develop into COPD.

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- PEFR: diurnal variation --> asthma is variable (changes during the day) + measures histamine/ metacholine provocation + see if treatment is working
- Spirometry: assess reversibility --> >15% improvement of FEV1 or PEFR after bronchodilator
- DLCO: normal in asthma

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Genetic factors
- Genes (predisposition) that control production of cytokines
- IgE production
- production of mast cells and eosinophils
(don't need to know the specific genes)

Environmental factors
- Hygiene hypothesis
- Smoking exposure --> influences IgE production
- Childhood exposure to allergens

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A common chronic condition → cause not fully understood

Symptoms include:

-       Wheezing

-       Chest tightness

-       Cough

-       Shortness of breath

-       (Symptoms can be worse at night)

Commonly starts in childhood (3-5 y.o.) → may worsen / improve in adolescence

How to explain improvement:
- Just happens (no explanation)
- When managed well during childhood--> prevents development
- Growth of the bronchi when getting older

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- lumen is smaller
- epithelial denudation and shedding
- mucus production
- invagination of airway mucosa due to smooth muscle contraction
- more bloodvessels
- neuronal proliferation --> more muscle contraction

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1. Airflow limitation → usually reversible spontaneously OR with treatment (not reversible with chronic asthma due to airway wall remodeling)

2. Airway hyper-responsiveness (AHR)→ to a wide range of stimuli

3. Bronchial inflammation

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All patients suffering with severe airflow limitation should undergo a formal trial of corticosteroids

Prednisolone 30mg orally should be given daily for 2 weeks, with lung function measured before and immediately after the course

A substantial improvement (>15%) in FEV1 confirms presence of reversible element

Indicates that the administration of inhaled steroids will prove beneficial to the patient

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Occupational sensitisers: (15% of cases)
- Low-molecular-weight compounds (e.g. bleach, isocyanates)
Reactive chemicals bond chemically to epithelial cells to      activate them + provide haptens recognized by T-cells.
- High-molecular-weight compounds (e.g. flour, organic dust)
Involving IgE antibodies and mast cells.

Non-specific factors:
- Cold air and exercise: release histamine, prostaglandins and leukotrienes from mast cells and stimulation of neural reflexes when epithelial lining fluid gets dry.
- Pollution: worsening of symptoms due to tobacco smoke, car fumes, solvents, strong perfumes, or high concentrations of airborne dust Asthma exacerbation in certain seasons: Summer: higher concentrations of ozone, particulates & NO₂

Winter: higher concentrations of particulates, NO₂ & SO₂

- Diet: need to take extra fruit and vegetables for antioxidants and other protective molecules. Genetic variation in antioxidants.
- Emotion: can be psychosomatic--> asthma attacks can be very stressful (explanation for the positive correlation).
- Drugs
- NSAIDs (5% of patients): blocks Cox-pathway->prevent synthesis of prostaglandins (protect stomach, women: open cervix during delivery and menstruation)  -->  progression of leukotrienes  KNOW HOW THEY ACT AND EFFECT OF MOLECULES PRODUCED BY THIS PATHWAY!
- Beta blockers: cause bronchial spasms
- Allergen induced asthma:
- immediate: after contact with allergens, immediate reaction of 15 min peak and duration of 1 hour.
- late phase/ dual: After initial reaction, reaction is prolonged and can recur.

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Laura copy + paste

Order of giving the drugs:
1. SABA
2. SABA +  low dose ICS
3. LABA + low dose ICS
4. LABA + increasing dose of ICS

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To detect airway hyper-responsiveness (AHR)

Demonstrated by asking the patient to inhale increasing concentrations of histamine or methacholine

Patients with coughing as symptom

Induces transient airflow limitation in susceptible individuals

Severity of AHR is determined by Provocation Dose (PD) or Concentration (PC) of agonist

Patients with asthma will react to very low doses of methacholine

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Don't need to know up to molecules, but cell detail.

Eniek/ Laura: copy + paste explanation of this.

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Measures amount of airway inflammation.
Mostly used in children.

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Used for eosinophil count (raised in asthma patients).
- better if you find it in sputum to diagnose

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Shows no specific diagnosic features, but:
- trapped air (lower, how much ribspaces you count)
- underlying cause of asthma
- flatted diaphragm
- overinflation in acute, chronic and severe asthma

Exclude pneumothorax, pneumonia or detect allergic bronchopulmonary aspergillosis and infiltration.

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Should be performed in ALL cases of asthma to help identify allergic trigger factors

Allergen-specific IgE can be measured in serum IF skin-prick test facilities are not available / patient is taking antihistamines / no suitable allergen extracts are available

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When occupational asthma is suspected:
- need to find specific allergens that provokes reaction