1. Dr Lamya Abd Alkarem Consultant physician, MRCP Member of Royal College of Physicians London, Edinburgh, Glasgow

2. Asthma is characterised by  chronic airway inflammation  increased airway hyper-responsiveness leading to symptoms of wheeze, cough, chest tightness and dyspnoea. It is characterised functionally by the presence of airflow obstruction which is variable over short periods of time, or is reversible with treatment.

3. The prevalence of asthma increased steadily in Western lifestyle and in developing countries. Current estimates suggest that 300 million people world- wide suffer from asthma an additional 100 million may be diagnosed with asthma by 2025. In childhood, asthma is more common in boys, but following puberty females are more frequently affected. The socio-economic impact of asthma is enormous, particularly when poor control leads to days lost from school or work, hospital admissions and, for some patients, a premature death.

4. The aetiology of asthma is complex multiple environmental and genetic determinants are implicated 1- The hygiene hypothesis proposes that decreased infections in early life bias the immune system towards an allergic phenotype. T lymphocytes may differentiate into two distinct subsets: Th1 and Th2. In infancy, a shift occurs from the in utero Th2 bias towards a Th1 response necessary for fighting viral and bacterial infection.

5. Reduction in childhood infections favours persistence of a Th2 bias directing the immune system towards an allergic type of response. In support of this hypothesis, day care attendance (which presumably increases exposure to childhood infections) is associated with lower rates of atopy, wheeze and asthma in later childhood Other infections such as respiratory syncytial virus, appear to increase the risk of developing asthma

6. The association between atopy-a propensity to produce IgE-and asthma suggests that sensitisation and exposure to allergens is an important risk factor.  Warm, humid, centrally heated homes favour multiplication of house dust mites and this may contribute to childhood asthma.  Many patients with asthma appear sensitised to pets such as cats and dogs however, the relationship between pet exposure and the development of asthma is complex with some studies suggesting that pet exposure in early life may protect against asthma

7. 3- Interest in probiotics as a potential therapy has been fuelled by observations that higher levels of Lactobacillus in the gut may protect against the development of atopic disease. 4- The increase in asthma may also be linked to the rise of obesity in Western society through mechanical mechanisms such as gastro-oesophageal reflux

8. Shared genetic traits, modification of the immune system by diet, or alteration of airway responsiveness by hormones are, alternative explanations. However, the development of asthma, the course of the disease and the response to treatment appear to be under genetic as well as environmental control.

9. The inhalation of an allergen in a sensitised atopic asthmatic patient results in a two-phases bronchoconstrictor response. A- The inhaled allergen rapidly interacts with mucosal mast cells via an IgE-dependent mechanism resulting in the release of mediators such as histamine and the cysteinyl leukotrienes with resulting bronchoconstriction

10. B- In persistent asthma B- In persistent asthma : a chronic and complex inflammatory response ensues Characterised by an influx of numerous inflammatory cells, the transformation and participation of airway structural cells the secretion of cytokines, chemokines and growth factors

12. Airflow limitation Usually reverses spontaneously or with treatment Airway hyper-reactivity (AHR) Exaggerated bronchoconstriction to a wide range of non-specific stimuli, e.g. exercise, cold air Airway inflammation Eosinophils, lymphocytes, mast cells, neutrophils Associated oedema Smooth muscle hypertrophy and hyperplasia Thickening of basement membrane Mucous plugging and epithelial damage.

13. Other factors are likely to be important including the  behaviour of airway smooth muscle  the degree of airway narrowing  the influence of neurogenic mechanisms. With increasing severity and chronicity of the disease, remodelling of the airway occurs Leading to fibrosis of the airway wall, fixed narrowing of the airway and a reduced response to bronchodilator medication

15. Asthma is not a uniform disease but a dynamic clinical syndrome with a variety of features. Typical symptoms include recurrent episodes of wheezing, chest tightness, breathlessness and cough. Common precipitants include  exercise  cold weather  exposure to airborne allergens  pollutants  viral upper respiratory tract infections (beware the cold that 'goes to the chest' or takes more than 10 days to clear).

17. Asthma characteristically displays a diurnal pattern, with symptoms and PEF (peak expiratory flow) being worse in the early morning. 1- Patients with mild intermittent asthma are usually asymptomatic between exacerbations exacerbations occur during viral respiratory tract infections or after exposure to allergens. 2- In persistent asthma the pattern is one of chronic wheeze and breathlessness Particularly when asthma is poorly controlled, symptoms such as cough and wheeze disturb sleep and have led to the use of the term 'nocturnal asthma'. '

18. 3- Cough may be the dominant symptom in some patients and the lack of wheeze or breathlessness may lead to a delay in reaching the diagnosis of so-called 'cough-variant asthma 4- In some circumstances the appearance of asthma relates to the use of medications.  Beta-adrenoreceptor antagonists (β-blockers-even when administered topically as eye drops) may induce bronchospasm.  Aspirin and other non-steroidal anti-inflammatory drugs are associated with asthma in about 10% of patients.

19. This is believed to reflect a shift in the metabolism of arachidonic acid from the cyclo-oxygenase pathway generating prostaglandins, towards the lipo-oxygenase pathway generating cysteinyl leukotrienes Aspirin-sensitive asthma is often associated with rhinosinusitis and nasal polyps

20. Occupational asthma is now the most common form of occupational respiratory disorder Accounts for around 5% of all adult-onset asthma This should be considered in all adult asthmatics of working age, particularly if symptoms improve during time away from work, e.g. weekends or holidays. Atopic individuals and smokers appear to be at increased risk. Early diagnosis and removal from exposure leads to a significantly improved prognosis and may result in cure.

21. The recognition of occupational asthma has important medico-legal implications should prompt screening of the workplace as other employees may also have developed the disease.

22. The diagnosis of asthma is made on the basis of a compatible clinical history combined with the demonstration of variable airflow obstruction. Pulmonary function tests and Peak flow meters are inexpensive and widely available Provide a simple and straightforward method of confirming the diagnosis.

23. 1-Ideally patients should be instructed to record peak flow readings after rising in the morning and before going to bed A diurnal variation in PEF (the lowest values typically being recorded in the morning) of more than 20% is considered diagnostic and the variability provides some indication of disease severity A trial of corticosteroids (e.g. 30 mg daily for 2 weeks) may be useful in documenting the improvement in PEF

24. 2-The measurement of FEV 1 and VC by spirometry allows the demonstration of airflow obstruction Following the administration of a bronchodilator, confirms the diagnosis when a 15% (and 200 ml) improvement in FEV 1 is noted. Spirometry is also particularly helpful in monitoring the severity of airflow obstruction in patients with impaired lung function

25. 3-Enhanced bronchoconstriction (AHR) to a variety of direct and indirect stimuli including exercise, cold air, dusts, smoke and chemicals such as histamine and methacholine, is an integral part of the definition of asthma helpful in patients presenting with normal lung function

26. 4- For patients whose symptoms are prominently related to exercise, an exercise test may be followed by a drop in PEF or FEV 1.

27. Compatible clinical history plus either/or: FEV 1 ≥ 15% (and 200 ml) increase following administration of a bronchodilator/trial of corticosteroids > 20% diurnal variation on ≥ 3 days in a week for 2 weeks on PEF diary FEV 1 ≥ 15% decrease after 6 mins of exercise

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29. Radiological examination is generally unhelpful in establishing the diagnosis May point to alternative diagnoses. Acute asthma is accompanied by hyperinflation, and lobar collapse may be seen if mucus has occluded a large bronchus. Flitting infiltrates, on occasion accompanied by lobar collapse, suggest asthma complicated by allergic bronchopulmonary aspergillosis (ABPA)

31. An elevated sputum or peripheral blood eosinophils count may be observed Serum total IgE is typically elevated in atopic asthma. Skin prick tests are simple and provide a rapid assessment of atopy. Similar information may be provided by the measurement of allergen-specific IgE

32. can be particularly difficult Two-hourly recordings of peak flow, preferably including a period of time away from work, may establish the diagnosis but are often difficult to undertake. Bronchial provocation tests with the suspected agent may be required. Skin prick tests or the measurement of specific IgE may confirm sensitivity to the suspected agent.

33. Induced sputum and exhaled breath allow the non- invasive assessment of airway inflammation and may prove useful in the diagnosis of asthma and assist in the monitoring of disease activity.

34. Achieve and maintain control of symptoms Prevent asthma exacerbations Maintain pulmonary function as close to normal as possible Avoid adverse effects from asthma medications Prevent development of irreversible airflow limitation Prevent asthma mortality

35. Encouraging patients to take responsibility for control of their disease should lead to improved clinical outcomes. Patient education should begin at the time of diagnosis and be revisited in subsequent consultations. Patients (or their carers) should be taught about the relationship between symptoms and inflammation The importance of key symptoms such as nocturnal waking The different types of medication The use of PEF to guide management decisions. Written action plans may prove helpful in developing these skills.

36. Cold air Exercise Emotion Allegen: house dust mite, pollen, fue Infection Smoking Pollution NSAID B blockers

37. Step 1: mild intermittent asthma  symptoms less than once a week for 3 months  fewer than two nocturnal episodes/month), Occasional use of inhaled short-acting β 2 -adrenoreceptor agonist bronchodilators as required basis However, many patients, and their physicians, under- estimate the severity of asthma and these patients should be carefully supervised. A history of a severe exacerbation should lead to a reclassification of the patient's condition as persistent asthma.

38. Patient has experienced an exacerbation of asthma in the last 2 years Regular anti-inflammatory therapy (preferably inhaled corticosteroids-ICS) should be started +inhaled β 2 - agonists taken on an as required basis uses inhaled β 2 -agonists three times a week or more reports symptoms three times a week or more is awakened by asthma one night per week.

39. 1. Add inhaled long-acting β2 agonist (LABA) 2. Assess control of asthma:  Good response to LABA - continue LABA  Benefit from LABA but control still inadequate- continue LABA and increase inhaled steroid dose to 800 mcg/day  No response to LABA stop LABA and increase inhaled steroid to 800 mcg/ day. If control still inadequate Institute trial of other therapies,  leukotriene receptor antagonist  SR theophylline

40. Consider trials of:  increasing inhaled steroid up to 2000 mcg/day  addition of a fourth drug e.g. leukotriene receptor antagonist, SR theophylline, β2 agonist tablet

41. Use daily steroid tablet in lowest dose providing adequate control Maintain high dose inhaled steroid at 2000 mcg/day* Consider other treatments to minimise the use of steroid tablets Refer patient for specialist care

42. A - Near-fatal asthma Raised P a CO 2 or immediate requirement for ventilation with raised inflation pressures. B - Life-threatening asthma i - Severe airways obstruction PEF <33% best or predicted Soft breath sounds or ‘silent chest’ Feeble respiratory effort.

43. ii - Increased work of breathing and haemodynamic stress Exhaustion Hypotension (SBP <100mmHg) Bradycardia or arrhythmia. iii Ventilation-perfusion mismatch Cyanosis Hypoxia (SpO 2 <92% and/​or P a O 2 <8kPa irrespective of inspired O 2 concentration). iv Ventilatory failure Rising P a CO 2 suggests ‘near-fatal’ asthma Confusion or coma

44. C- Acute severe asthma PEF 33-50% predicted (< 200 l/min) Respiratory rate ≥ 25/min Heart rate ≥ 110/min Inability to complete sentences in 1 breath

45. D- Brittle asthma Type 1: wide PEF variation despite intensive and regular therapy Type 2: sudden severe asthma attacks on background of apparently well-controlled asthma Admission is mandatory if any of the markers of severe, life-threatening, or near-fatal asthma are present