Asthma Handout PDF

1 Asthma Asthma is a chronic obstructive lung disease characterised by intermittent airways obstruction, chronic inflammation and hyperreactivity. It is defined by a history of symptoms such as wheeze, cough, shortness of breath and chest tigh...

1 Asthma Asthma is a chronic obstructive lung disease characterised by intermittent airways obstruction, chronic inflammation and hyperreactivity. It is defined by a history of symptoms such as wheeze, cough, shortness of breath and chest tightness that vary in severity and over time. Epidemiology It is estimated that 339 million people have asthma globally. It is the most common chronic condition to affect children (World Health Organisation (WHO) 2020). In the UK 5.4 million people currently receive treatment for asthma (1.1 million children); however, there are many people thought to be undiagnosed or misdiagnosed. Although prevalence has dropped since the 90’s, the UK has a 50% higher asthma mortality rate than any European country (Asthma and Lung UK 2020). Asthma prevalence is higher in more economically developed countries but death rates are worse in less economically developed countries (WHO 2020). More males have childhood asthma, but more females have persistent asthma to adulthood, or develop asthma in adulthood (Asthma and Lung UK 2022). Pathophysiology Asthma is characterised by episodic hyperreactivity of the medium to small airways to various known or unknown triggers which causes chronic airway inflammation, airway smooth muscle contraction (known as bronchospasm/bronchoconstriction) mucosal oedema (from local vascular fluid leak) and mucus hypersecretion; these factors lead to widespread airway obstruction (narrowing). Airway inflammation is the hallmark of asthma with presence of infiltrated eosinophils or neutrophils (white blood cells associated with immunity) and inflammatory mediators such as leukotrienes and prostaglandins. Mucus hypersecretion can occur during an asthma episode due to goblet gland hypertrophy and hyperplasia. The resultant secretions are often viscid and light in colour. Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022  2 Pathophysiology of sensitisation 50 - 60% of all patients with asthma demonstrate allergic asthma (sometimes called atopic or extrinsic asthma) - where first exposure to certain allergens (triggers) sets off a cascade of complex events, known as sensitisation, which leads to airway narrowing. This is a simplified explanation of the process (see Figure 1 and subsequent text). Figure 1. Sensitisation 1. Allergen/stimuli/virus IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII Airway epithelium IIIIIIIIIIIIII 2. Attracts T helper 2 (Th2 cells) These:  Attract inflammatory/immune cells to the area (mast cells, eosinophils, Th basophils, neutrophils) by release of 2 Interleukin IL 3, 4, 5, 13 Mast cell  Stimulate B lymphocytes to make Immunoglobulin E (IgE) Immunoglobulin IgE 3. IgE attaches to receptors on mast cells 4. The allergen now binds to the mast cell. This is ‘primed’ for re-exposure 5. On re-exposure to the same allergen/trigger: Mast cells and other inflammatory/immune cells release inflammatory mediators This causes suchand an early as histamine, late stage response: prostaglandins, leukotrienes and interleukins Early – allergen directly stimulates airway mediators smooth muscle →bronchoconstriction (5-15 mins) Late (3-12 hours)  smooth muscle constriction (bronchospasm)  mucus hypersecretion  vascular permeability causing oedematous mucosa/epithelium Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 3 Sensitisation An allergen/antigen/trigger arrives on the respiratory epithelium. This attracts T Helper 2 cells (TH2 Thymus humoral immunity cells) to the area which then attract inflammatory cells such as mast cells, neutrophils, basophils and eosinophils by the release of interleukins (e.g. IL5). Th2 cells also stimulate B lymphocyte cells to make IgE immunoglobulins which fit perfectly onto receptor sites on the mast cells. The allergen now binds to the mast cells too. The mast cell is now said to be ‘primed’. On re-exposure to the same allergen, antigen or stimuli, the primed mast cells degranulate and release histamine. Other inflammatory mediators such as prostaglandins, leukotrienes and interleukins (IL-3, IL-4 and IL-5) are also released. These cause airways narrowing through stimulation of bronchial smooth muscle causing bronchoconstriction and also airway inflammation and oedema, but this is a late response occurring 3-12 hours after allergen exposure. The allergen can also act directly and immediately on bronchial smooth muscle in the airway wall leading to bronchospasm within 5-15 minutes of exposure – during the early phase of asthma exacerbation. This early phase abates quickly. With continued exposure to the allergen further changes occur such as hypertrophy and hyperplasia of smooth muscle cells, mucus gland hypertrophy and hypersecretion, and mucosal oedema as a result of increased vascular permeability. It is important to consider these phases of response so that a patient with an acute asthma exacerbation can be monitored for an appropriate length if time. Non-allergic asthma The pathophysiology of the triggering of non-allergic asthma is poorly understood. It does not involve an allergic or immune response like allergic asthma. It is thought that a trigger, for example a viral illness, causes Cytokines to attract neutrophils to the airway. This leads to airway inflammation and hyperreactivity, as well as mucus production and therefore is similar to allergic asthma in the gross airway changes. This type of asthma tends to occur in adults over the age of 30 years. Other triggers for non-allergic asthma include emotions, exercise, dry air, hyperventilation and smoke. It is also closely linked to occupational asthma. Non-allergic asthma is uncommon in childhood but can occur with viral respiratory infections. Airway remodelling Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 4 See Figure 2. Over time, the process described above causes chronic inflammation which contributes to airway structural changes termed 'remodelling'. In response to inflammation, collagen fibres are laid down causing epithelial fibrosis and basement membrane thickening. Epithelial blood vessels proliferate and vasodilate (angiogenesis) leading to greater epithelial thickening and oedema (through increased vascular permeability). The epithelium can become denuded (stripped) so that the cilia are damaged and removed. This reduces mucociliary clearance leading to build up of mucus and cough. Ultimately the airways narrow which can be intermittent or become so pronounced that it leads to fixed permanent airway narrowing which fails to respond to drug therapy. Figure 2. Airway remodelling How Asthma affects the mechanics of breathing Airway narrowing causes expiratory airflow resistance to increase leading to a reduced expiratory airflow. It takes longer for an expiration to occur and often some inspired tidal volume (TV) air remains trapped in the alveoli causing an increase in residual volume (the volume of air remaining in the lung after forced expiration) and functional residual capacity (the amount of air remaining in the lung after a TV expiration). This is more noticeable on exercise and exertion because the respiratory rate increases – therefore, the time for expiration reduces and patients find Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 5 themselves inspiring again long before expiration is complete. As the inspiratory volumes are greater than the expiratory volumes, air trapping in the alveoli occurs and lung hyperinflation will result. Eventually, the trapped air will increase lung volume so much that breathing occurs near total lung capacity which is very difficult to maintain. In order to achieve an adequate minute volume (tidal volume x respiratory rate) the respiratory rate must increase to compensate for the reduced tidal volume. Again, this is more pronounced during activity. The respiratory muscles are also affected by asthma. The increased expiratory airflow resistance increases the LOAD on the expiratory accessory muscles (the abdominals and internal intercostals) as they try to force air out against resistance of the narrowed airways. Lung hyperinflation flattens the diaphragm and alters the alignment of the intercostal muscles putting these muscles at a mechanical disadvantage through alteration of the fibre length-tension relationship, making normal inspiratory muscle function difficult and fatigue of these muscles more likely. The respiratory muscle CAPACITY is thus reduced and the work of breathing increases. Reduced blood oxygen levels known as hypoxaemia, as a result of alveolar hypoventilation (from air trapping) also reduces the oxygenation of these muscles. In this way, the respiratory muscles are likely to fatigue. This is more pronounced during exercise, as the respiratory muscles have to work harder and their oxygen demand increases. NB As patients have to force trapped air out of the lungs on expiration by use of their expiratory accessory muscles this effort causes the intrapleural pressure to increase (become less negative) which in turn increases airways resistance leading to a steeper pressure drop in the airways and therefore the equal pressure point narrowing (see learning materials on EPP for more) occurs in the small airways. This increases asthma airways resistance even more, worsening the patient’s problem. Aetiology/Predisposing factors Asthma is a complex condition. Many environmental and genetic factors have been associated with the disorder leading to numerous clinical presentations (phenotypes) and severities. Extrinsic asthma (atopic or allergic asthma - related to TH2 immunity dominance). In this type of asthma, the airways overreact to normally harmless substances like pollen. This is the most Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 6 common type of asthma and is often inherited and therefore commonly diagnosed in childhood before the age of 10 years. There is a genetic predisposition to developing Immunoglobulin E antibodies on exposure to allergens such as dust mites, pollen, animal dander and mould spores which stimulate an inflammatory process in the airways. Any sputum produced contains eosinophils (inflammatory cells). People with allergic asthma often have food allergies too, for example milk and eggs and there is often a family history of rhinitis, eczema and hay fever, especially on the maternal side. Intrinsic asthma, (non-atopic or non-allergic - related to TH1 immunity dominance and neutrophils). This accounts for 10-30% of asthma and is Intrinsic. It frequently develops in adults and is termed late-onset asthma. There is no allergic response with normal IgE/eosinophil levels. It is more common in females later in life. Symptoms are not associated with an allergic reaction but other types of trigger. Environmental pollutants, chemicals, perfumes, cigarette smoke, cleaning products, hot, humid or cold conditions, emotions, respiratory infections or drug sensitivity (aspirin, non- steroidal anti-inflammatory drugs) can all be causative, but the cause may be unknown. Some people demonstrate exercised- induced asthma which can indicate poorly controlled asthma (for example medication or inhaler technique ineffective or poor patient compliance with treatment) or cardiovascular deconditioning. When exercising, the increased rate and depth of breathing leads to dehydration of the epithelium and cold air in the conducting bronchi. This stimulates the epithelium to release inflammatory mediators. Intrinsic asthma may be idiopathic (cause unknown) making treatment by removal of the irritant/trigger impossible. Occupational asthma occurs on exposure to a particular workplace substance e.g. isocyanates (paint chemical), foam moulding, wood, latex rubber or flour dust Symptoms improve away from the work place e.g. holidays and weekends. A reduction in peak flow rates (PEF) of > 20% whilst at work is considered diagnostic. This is often classed as being related to Intrinsic, non- allergic asthma. Predisposing factors Gender In young children wheeze is more common in boys as they have relatively small airways compared to girls, however, asthma is Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 7 more persistent into adulthood in girls. Boys quite commonly ‘grow out’ of the condition in adolescence possibly due to hormonal influences are relatively large airways following puberty. Low birth weight or preterm babies These babies are more susceptible to asthma due to their smaller airways and immature respiratory system. Wheezy infant It is common for preschool children to present with a wheeze. Often this is due to a viral respiratory infection (commonly Respiratory Syncytial virus – RSV - which causes bronchiolitis). Symptoms subside once the infection abates. Children who present with wheeze over the age of 2.5 years are more likely to have persistent asthma into later life. Maternal smoking and prenatal stress These factors increase the risk of asthma in a mother’s offspring. Anxiety This is often associated with asthma and can predispose or worsen asthma but is also linked with Hyperventilation Syndrome which can be misdiagnosed as asthma. Obesity This causes greater circulating inflammatory mediators and therefore has links with asthma. A high body mass index may also compromise cardiovascular aerobic fitness thus worsening asthma symptoms such as wheeze and shortness of breath. Hygiene hypothesis It is thought that modern high standards of hygiene/sanitation/immunisation/antibiotics can reduce childhood exposure to allergens and stimuli so that first exposures later in life cause a more pronounced response in the airway thus sparking sensitisation. We have 2 types of immunity: Type I (associated with viral/bacterial infections and autoimmunity) and Type 2 (associated with allergy). The foetus has a dominance of Type 2 because Type 1 might risk rejecting the mother through an autoimmune response. After birth, exposure to pathogens, germs etc. helps develop Type I immunity to balance the immune systems, however, with sanitisation this process can be impaired leading to Type II allergic dominance. Even though there are several asthma phenotypes the type of clinical features can be similar, though their severity can vary. Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 8 Clinical Features Wheeze is caused by narrowing of the medium/small airways due to bronchial smooth muscle constriction (due to mediators released from inflammatory cells stimulating bronchial smooth muscle receptors), inflammatory changes in the airway wall (such as mucosal oedema) and mucus hypersecretion (from hypertrophied mucus glands). Airway narrowing causes the expiratory airflow to become more turbulent and airway walls to vibrate creating a musical, often high-pitched or polyphonic (multiple-pitched) sound. In mild cases, the wheeze may be limited to the end-expiration phase, as the smaller airways constrict late in expiration. As the severity of airway narrowing increases, the wheeze can become continuous throughout the respiratory cycle (inspiration and expiration). Most ominous is a 'silent chest' where wheezing ceases due to extreme airway narrowing (so very little airflow in or out). This is a medical emergency and medical help and review should be sought urgently. Wheeze can be worse at night or early morning (which may be due to the diurnal rhythm of hormones such as cortisol and melatonin or due to bedding allergens). Patients can be wheeze-free much of the time as asthma is episodic. Some patients may describe chest tightness which is often a result of wheeze and narrowed/obstructed airways. Cough occurs due to inflammatory mediators (such as histamine from mast cells) released during exposure to an allergen. These irritate cough receptors in the airway wall. Bronchoconstriction and hypersecretion of mucus can also contribute to coughing by stimulation of cough receptors. The cough is usually episodic and non-productive - often occurring at night or after exercise. This may be due to diurnal factor, relative narrowing of the airways during sleep/recumbency and less mucociliary clearance when flat/immobile. In severe episodes, tenacious sputum plugs/casts can cause coughing and difficulty expectorating. Here the cough may be wet/moist. In airway remodelling the cilia and respiratory epithelium can become denuded with loss of normal mucociliary action and build of mucus which causes cough by stimulating cough receptors. Cough may be the only presenting feature in some cases. Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 9 Breathlessness is a very common asthma symptom. It occurs for several reasons. Firstly, because airways are narrowed (from airway smooth muscle tightening, hypersecretion of mucus, mucosal oedema (from vascular leak) and airway inflammation) this means it is difficult to fully empty the lungs on expiration before the next inspiration comes along. The reduced airway diameter causes an increased resistance to the expiratory flow. Eventually, air becomes trapped in the alveoli and small airways causing hyperinflation of the lungs. This makes full exhalation of tidal volume increasingly difficult. Eventually lung volume keeps rising, with increases in residual volume and functional residual capacity. This trapped air is not useful air but rather physiological dead space i.e. ‘old’ air that cannot contribute to gas exchange. Breathing soon occurs near total lung volume, which is difficult and effortful. The person attempts to inhale when the lungs are already hyperinflated causing a sensation of inspiratory dyspnoea (breathlessness) though the main defect is still reduced expiratory airflow. Alveolar ventilation is severely compromised as oxygen is absorbed but not replenished causing a low V/Q ratio and therefore a low partial pressure of arterial oxygen in the blood - hypoxaemia. If hyperinflation is severe the diaphragm will be flattened instead of dome-shaped (at the end of expiration). The length-tension of the muscle is therefore changed and it is at a mechanical disadvantage, altering the biomechanics of breathing. The internal intercostal muscles are also at a disadvantage as the ribs are more horizontal in hyperinflation. This makes the work of breathing much harder causing the inspiratory accessory muscles to work to lift the sternum and upper ribs in an attempt to improve inspiration, also leading to a sense of breathlessness. This is worsened by reduced delivery of oxygen to the respiratory muscles from a low V:Q and hypoxaemia. On exercise, this situation is worsened because the demand for oxygen by the exercising muscles causes the respiratory rate to increase. This not only increases the work of breathing (and oxygen demand by the respiratory muscles) but also further reduces the time for expiration occur – thus more hyperinflation. Retained secretions may occur due to hypersecretion of mucus from mucous gland hypertrophy and hyperplasia (increase number of glands) which occurs in the late stage of an asthma episode (12- 24 hours after the trigger). In severe asthma airway remodelling may occur where there is permanent hypertrophy and hyperplasia of the goblet and mucous glands leading to chronic mucus in the Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 10 airways. The respiratory epithelium may also be denuded leading to cilial stripping and reduced mucociliary clearance causing mucus to build up, usually as very thick plugs which are very difficult to cough and clear. Oxygen saturations SpO2 This percentage of haemoglobin saturated with oxygen may be reduced in asthma due to poor ventilation of the alveoli (alveolar hypoventilation) from air trapping and airway obstruction as described under breathlessness above. Oxygen in the alveoli is absorbed but not replenished on the subsequent inspiration because of increased physiological dead space. So although the lungs are full of air – it is redundant from a gas exchange perspective. Pulse oximetry is used to monitor oxygen saturations in severe exacerbations. The aim is to keep the Sp02 at more than 94% with supplemental oxygen administered if the SpO2 falls below this. Arterial blood gases ABGs may be taken if a person’s SpO2 has fallen below 92% or if clinical deterioration occurs. Type 1 respiratory failure may be seen where the Pa02 falls below 8 kPa (due to reduced alveolar gas exchange from alveolar hypoventilation) with PaC02 normal or reduced (due to C02 being ‘blown off’ from an increased respiratory rate typical in more severe asthma episodes). In very severe life-threatening asthma, there may be Type II respiratory failure (Pa02 < 8 kPa and CO2 > 6 kPa) because the work of breathing is so high. The high work of breathing is high due to resistance to expiratory airflow, and air trapping/hyperinflation which alters the biomechanics of breathing as described above. A high respiratory rate is stimulated by hypoxaemia/hypoxia – low oxygen levels in the blood/tissues. This increases respiratory muscle fatigue and eventually causes the ventilatory pump to fail allowing C02 to build up. Cyanosis Nail beds, lips and mucosal membranes may become blue in severe or life-threatening asthma due to low partial pressure of oxygen in blood and tissue - hypoxaemia and hypoxia respectively. Severe airways narrowing resulting from smooth muscle constriction, airway inflammation and hypersecretion of mucus causing mucus plugging can eventually lead to serious air trapping in the alveoli and poor oxygen gas exchange. A low V/Q exists with areas of perfused but unventilated alveoli. Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 11 Heart rate This can increase in severe asthma episodes (increased to 110 – 140 bpm according to age) due to lowered arterial blood oxygen (from alveolar hypoventilation and air trapping), side effects of β2-antagonists medication (bronchodilators that widen airways such as Ventolin) and anxiety. In severe asthma a drop in systolic blood pressure may be seen. This is because of lung hyperinflation. As the lung volume increases it pulls open the pulmonary blood vessels allowing more blood to flow and pool in the lungs. This reduces the blood volume returning to the left side of the heart and thus reduces left ventricular filling and subsequent force of ventricular contraction (Starling’s law) – this equates to a drop in systolic blood pressure. Expiratory accessory muscle use (abdominals and internal intercostals) occurs during acute asthma episodes to overcome the resistance to expiratory airflow from airway narrowing. If the work of breathing is very high due to hyperinflation, then the inspiratory accessory muscles may also act to try and get air in to the lungs (sternocleidomastoid, scalenes, pectorals) to compensate for the diaphragm’s mechanical disadvantage. Bucket handle action may be reduced if the lungs are very hyperinflated (due to air trapping) as there is little room for greater lung/chest expansion. The inspiratory muscles may also be compromised by an abnormal length-tension relationship leading to less effective contraction. Pump handle action may increase due to the accessory muscles of inspiration working harder to compensate for the diaphragm by lifting the upper ribs and sternum. Respiratory rate may be raised to try and preserve minute ventilation (tidal volume x respiratory rate) as tidal volumes are reduced in lung hyperinflation (as the lungs are already overinflated leaving little room for more inspired air to enter). Also, a low partial pressure of oxygen in the blood will stimulate chemoreceptors to increase respiratory rate in an attempt to increase alveolar oxygenation. Respiratory rate is especially increased during exercise as oxygen demand of the tissues increases. Unfortunately, there is less time for expiration which only serves to increase air trapping and all the problems associated with more hyperinflation. Auscultation may be normal as asthma is episodic but widespread wheeze may be heard, ranging in severity from only end-expiratory Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 12 to throughout the respiratory cycle. A prolonged expiratory phase is present during exacerbations due to expiratory airflow obstruction. A 'silent chest', as referred to above, is an ominous sign requiring immediate medical intervention. Coarse crackles may be heard if there are retained secretions. Sputum associated with asthma is often very viscous and mucoid (white or clear). Chest x-ray is normal in 75% of diagnosed asthmatics. Radiology is not needed routinely. It can eliminate complications such as pneumonia or pneumothorax, and should be performed in deteriorating life-threatening asthma or if ventilation is required. CXRs may show signs of hyperinflation due to air trapping in the alveoli (flattened diaphragm, > 6 anterior ribs visible, horizontal rib angles and a tall, narrow mediastinum/heart - squashed from overinflated lungs, and darker air-filled lung fields). There may be bronchial thickening from airway remodelling. Spirometry (lung function tests) is a test of airflow obstruction and indicates the degree of airway calibre/narrowing from bronchospasm, oedema, inflammation and mucus hypersecretion in asthma. The test involves breathing in maximally to Total lung capacity and then forcefully exhaling into a mouthpiece of a spirometry machine. The Forced Expiratory Volume in 1 second (FEV1) – the volume of air which is forcefully exhaled in the first second following maximal inspiration, and the Forced Vital Capacity (FVC) – the total volume of air forcefully exhaled following a maximal inhalation. The ratio between these, the Forced expiratory ratio FER, is calculated by dividing the measured FEV1 by the measured FVC. Normally this is > 0. 75 – 0.8. ( or 75-80%). In asthma it is 80% predicted; in Asthma it is < 80% predicted. This may be normal between asthma episodes. In asthma, airway obstruction slows/limits expiratory airflow so that less air leaves the lungs in the first second and more air is retained by the lung (thus greater functional residual capacity). Peak expiratory flow rate PEF is a measure of the maximum airflow achieved during a forced expiration from maximal inspiration. It is a simple test that is useful for monitoring any changes in asthma severity according to airway calibre. Patients can monitor and record this on a daily basis to help predict the onset of an asthma episode. It is not a sensitive measure for all patients. PEF Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 13 can also be useful during diagnosis (see below). PEF may be reduced (from personal best) during an asthma episode or just preceding it. This is due to airway narrowing/obstruction as described above which causes resistance to expiratory flow rate. Exercise tolerance is often reduced in people with asthma. During an asthma episode it is reduced due to an increased work of breathing from mechanisms described above such as lung hyperinflation leading to abnormal biomechanics of breathing and increased respiratory muscle work (to overcome airway narrowing/obstruction and resistance to airflow). During exercise, the respiratory rate increases to try and improve alveolar oxygenation, however, this rate leaves less time for expiration which only serves to increase air trapping and worsen alveolar hypoventilation. The resultant reduced arterial oxygen is unable to meet the demands of the exercising skeletal muscles and respiratory muscles. This leads to muscle fatigue and reduced exercise tolerance. Avoidance of exercise is common as it is a trigger for asthma in some people but also causes breathlessness – a symptom in common with asthma, therefore fear of exercise exists. This leads to deconditioning of the cardiovascular system and skeletal muscles, which can be detrimental for exercise tolerance. Mental State Patients may become agitated and anxious during asthma episodes due to fear, hypoxia or β2-agonist side effect (increased heart rate and shaking). However, in late severe asthma episodes there may be lowered consciousness which may indicate hypercapnia (high PaCO2) and Type II respiratory failure. Diagnosis Diagnosing asthma is often difficult as the exact causes and pathophysiological mechanisms are not fully understood. There is no gold standard diagnostic test, so diagnosis is based on a characteristic pattern/history of episodic symptoms and demonstration of variable expiratory airflow limitation through objective testing. Features supporting asthma diagnosis:  More than one of the following symptoms: - wheeze, cough, breathing difficulty, chest tightness.  Particularly if these symptoms: Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 14 - occur over the course of 24 hours, are seasonal, nocturnal or worse in the morning, or occur in response to triggers or exercise  Patient history of atopic/allergic disorders e.g. rhinitis  Family history of atopic disorders or asthma  Widespread polyphonic expiratory wheeze on auscultation  Improvement in lung function and/or symptoms with bronchodilators/inhaled corticosteroid therapy.  Unexplained low FEV1 Diagnostic investigations *NB you do not need to know this in detail for PSPE Not all of these will be used for every patient. These are ordered in preference for diagnosis.  Spirometry test of airflow obstruction - Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio – the Forced expiratory ratio (FER) - normal > 0. 75 – 0.8, possible asthma 20% variability from baseline measurement supports asthma in adults. Morning dips in PEF are also suggestive of asthma.  Bronchial challenge test - measures airway hyper- responsiveness. Patients inhale substances that induce bronchoconstriction such as histamine or mannitol. Exercise can be also be used as an indirect stimuli e.g. modified shuttle run - physios may be involved here. Spirometry is performed before and after these provocation tests to see if there is a reduction in FER. Drops of approximately 15-20% (for mannitol) support asthma diagnosis. These test are usually only performed if other diagnostic measures are inconclusive. NB These investigations cannot be performed in children < 5 years. Diagnosis is based on symptom history, clinical judgement and response to drug therapy. Asthma Classification *NB you do not need to know this in detail for PSPE Sarah Pierrepoint [email protected] October 2015 Version 5 October 2022 15 a) Based on disease severity Key resource: Global Strategy for Asthma management and prevention update 2022 Intermittent Symptoms less than once a week. Brief exacerbations. Nocturnal symptoms no more than twice a month. FEV1 or PEF >80% predicted Mild persistent Symptoms more than once a week but less than daily. Exacerbations may affect sleep/activities. Nocturnal symptoms more than twice a month. FEV1 or PEF