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DEFINITION OF ASTHMA ASTHMA is a chronic inflammatory disorder of the airways in which many cells, in particular mast cells, eosinophils, and T lymphocytes, and their products (mediators, cytokines) play a role; The inflammation causes an increase in airway responsiveness to a variety of stimuli widespread but variable airflow limitation that is at least partially reversible either spontaneously or with treatment. Clinical symptoms: recurrent episodes of wheezing, breathlessness, chest tightness, and cough particulary at night and/or in the early morning. . A.Bręborowicz-2006 The reasons for the increase in the prevalence of ASTHMA changes in indoor environment – higher exposure to HDM – high quantities of cockroaches – increasing humidity (prevention of heat loss) changes in outdoor environment – urbazniztion – heavy pollution ‘Hygenic hypothesis’ of asthma/atopy development - less infections (hygenic style of life, vaccination) lead to decrease stimulation of TH1 population of lymphocytes and predominance of TH2 population; this population responsible for overproduction of IgE and atopic background A.Bręborowicz-2006 PATHOGENESIS OF ASTHMA AIRWAY INFLAMMATION ABNORMAL NEURAL CONTROL HORMONAL IMBALANCE PSYCHOLOGICAL DISTURBANCES TYPES OF ASTHMA ALLERGIC = ATOPIC = EXTRINSIC ASTHMA IgE - DEPENDENT Th2 LYMPHOCYTE DEPENDENT MECHANISMS NONALLERGIC = NONATOPIC = INTRINSIC ASTHMA IgE - INDEPENDENT Th2 LYMPHOCYTE DEPENDENT MECHANISMS A.Bręborowicz-2006 AIRWAY INFLAMMATION IN ASTHMA A pivotal role in the generation of an immune response is activation of T lymphocytes by antigen presented by APC (dendritic cells, macrophages, B lymphocytes). T lymphocytes initiate immunological cascade. Their products - CYTOKINES - modulate the function of large number of target cells. Cytokines are responsible for differentiation, migration, accumulation and activation of inflammatory cells such as: eosinophils, mast cells, neutrophils, B lymphocytes. Cells activated by cytokines release mediators and other cytokines. Mediators contributes to the development of the characteristic pathological events that occur in asthma. A.Bręborowicz-2006 PATHOLOGICAL CHANGES IN ASTHMA SWELLING OF THE AIRWAY WALL – OEDEMA – CELLULAR INFILTRATION CONTRACTION OF SMOOTH MUSCLE MUCUS PLUG FORMATION – EPITHELIAL CELL DAMAGE AND SHEDDING (CELL DEBRIS) – INCREASED MUCUS SECRETION – EXUDED SERUM PROTEINS AIRWAY WALL REMODELLING - increase in smooth muscle - vascular proliferation - collagen deposition - increase in bronchial glands A.Bręborowicz-2006 ABNORMAL NEURAL CONTROL OF AIRWAYS autonomic nerves influence the tone of the airway smooth muscle, airway secretion, blood flow, mikrovascular permeability and the migration and release of inflammatory cells the autonomic nervous system consists of: sympathetic, parasympathetic and non-adrenergic non-cholinergic (NANC) nervous system several nonspecific stimuli provoke reflex bronchoconstriction by activating the sensory receptors; in asthmatic patients the airway response develops at lower level of stimulation and the intensity of the airflow limitation response is more severe A.Bręborowicz-2006 ASTHMA DEVELOPMENT Environmental factors Genetic background FACTORS THAT EXACERBATE ASTHMA TRIGGERS ALLERGENS RESPIRATORY INFECTIONS EXERCISE AND HYPERVENTILATION WEATHER SULFUR DIOXIDE FOODS, ADDITIVES, DRUGS A.Bręborowicz-2006 CLINICAL MANIFESTATION Natural history of asthma ASTHMA EXACERBATION ASTHMA FREE PERIOD REMISSION SYMPTOMS dry cough feeling of chest tightness audible musical wheezing followed by dyspnoea (patient describes dyspnoea as both expiratory and inspiratory) increased work of breathing difficulties in walking, even talking duration - minutes, hours, days the expectoration of viscous sputum A.Bręborowicz-2006 ONSET: acute or insidious SIGNS sitting position, leaning forward using the arms paleness, cyanosis sweat hyperinflation of the chest tachypnoe, tachycardia pulsus paradoxus - reduction in pulse volume during inspiration use of accessory muscles of respiration increased percussion note auscultation: prolonged expiration, wheezing, rhonchi, silent lung barrel chest deformity, Harrison sulci, clubbing of the fingers A.Bręborowicz-2006 ASTHMA EQUIVALENT – COUGH VARIANT ASTHMA - the cough at night or induced by exercise, cold air or laughter – COUGH PREDOMINANT ASTHMA – WHEEZY BRONCHITIS A.Bręborowicz-2006 ASTHMA IN EARLY LIFE INFANTILE ASTHMA significant number of asthmatic children demonstrates first obstructive episodes early in life – 30% < 1yr of age – 50-55% < 2 yr of age – 80% < 5 yr of age A.Bręborowicz-2006 ASTHMA IN EARLY LIFE INFANTILE ASTHMA wheezing - associated lower respiratory tract illnesses in infants and young children are extremly common; a large number of anatomical and physiological factors predisposes to obstruction but only part of infants develops recurrent symptoms; there are many causes of recurrent and persistent wheezing but their prevalence is low; however before asthma diagnosis is establish other alternative diagnoses should be excluded. A.Bręborowicz-2006 Infantile asthma - criteria of diagnosis 3 wheezy episodes (independent of atopy) 2 wheezy episodes with atopic background (positive family or individual history) 1 wheezy episode induced by exposure to allergen A.Bręborowicz-2006 GINA recommendation recurrent wheezing (wheezy bronchitis) other causes excluded positive response to therapy DIAGNOSIS OF ASTHMA A.Bręborowicz-2006 1. Case history characteristics of asthma episode, frequency, duration, severity types of triggers (precipitating, agravating) the onset of the disease atopic history environmental history previous and current therapy response to medication impact of disease on child, family, school attendence psychosocial evaluation of patient/family general medical history of child 2. Physical examination A.Bręborowicz-2006 3. lung function tests considerable (more than 20%) variabilty of peak flow rate or FEV1 over short period of time daily variability= PEF evening - PEF morning 1/2 (PEF even. + PEF morn.) x 100 response to bronchodilator when obstruction (improvement of at least 15-20% in PEF or FEV1) measurement of bronchial hyperresponsiveness (decreasing of at least 15-20% in PEF or FEV1 after non-specific provocation) basic spirometry - assessment of degree of obstruction A.Bręborowicz-2006 4. assessment of allergy SERUM IgE measure of the allergy predisposition and their degree the concentration is age dependent total concentration specific IgE level - against specific antigens; not more sensitive than skin test, results independent of therapy, skin lesions, dermographism, no risk of excessive (allergic/anaphylactic) reaction normal values does not exclude allergy A.Bręborowicz-2006 4. assessment of allergy SKIN TESTS background - recovery of IgE on the surface of patient mast cells; interaction between allergen and IgE leads to releasing of histamine and other mediators, which acts on specific receptors in small vessels, causing increasing permeability and dilatation and axon reflex stimulation technique: prick/puncture or intradermal, small quantity of allergenic extract is introduced into the skin A.Bręborowicz-2006 4. assessment of allergy SKIN TESTS two control tests should be always performed: negative control - for exclusion of nonspecific reaction on pricking or solution used in production of extracts; positive control - for assessment of skin reactivity size of skin weal recorded after 15 min. - measuring the mean diameter, positive test - a wheal at least 3 mm greater than negative control A.Bręborowicz-2006 Allergen SPECIFIC IgE The advantages: safety - high degree of precision - standardization - lack of dependence on the skin reactivity and medication The disadvantages: - lack of immediately available results - high costs •Supplement to skin testing when the clinical significance of result is doubt •If immunotherapy is considered and lack of convincing history to confirm positive skin prick tests (concerns mites and moulds) A.Bręborowicz-2006 5. other tests CHEST X - ray normal in asymptomatic asthma, necessary to exclude other diseases acute asthma - hyperinflation and diagnosis of complication BLOOD EOSINOPHIL COUNT increased count in about 50% of astma patients predictive for responsiveness to therapy measure of the severity, indicates steroid requirement SPUTUM EOSINOPHILIA positive > 20% of the total leucocytes usually present in symptomatic asthma A.Bręborowicz-2006 5. other tests DIFFERENTIAL DIAGNOSIS A.Bręborowicz-2006 Classification of asthma severity Intermittent asthma – intermittent symptoms < 1 time a week – brief exacerbation – nightime asthma symptoms 1- 2 times a month – asymptpmatic and normal lung function between exacerbation: PEF variability < 20% FEV1 > 80% predicted Mild persistent asthma – symptoms 1 time a week or more, but < 1 time per day – exacerbation may affect activity and sleep – nightime asthma symptoms > 2 times a month – PEF variability 20-30%, FEV1 > 80% predicted A.Bręborowicz-2006 Classification of asthma severity Moderate persistent asthma – symptoms daily – exacerbations affect activity and sleep – nightime asthma symptoms >1 time a week – PEF variability > 30%, FEV1 60 - 80% predicted Severe persistent asthma – continous symptoms – frequent exacerbations – frequent nightime asthma symptoms – PEF variability > 30%, FEV1 <60% predicted A.Bręborowicz-2006 Asthma management program Educate patients to develop partnership in asthma management Assess and monitor asthma severity with both symptoms reports and measurements of lung function Avoid and control asthma triggers Establish individual medication plans for long term management Establish plans for managing exacerbation Provide regular follow up care A.Bręborowicz-2006 Goals for successful management of asthma Achieve nad maintain control of symptoms Prevent asthma exacerbations Maintain pulmonary function as close to normal level possible Maintain normal activity levels, including exercise Avoid adverse effects from asthma medications Prevent development of irreversible airflow limitation Prevent asthma mortality A.Bręborowicz-2006 General principles of long term asthma therapy Chronic therapy Dependence of intensity of therapy on severity of asthma Priority of anti-inflammatory drugs Short acting bronchodilators as first line rescue medication Long acting bronchodlators associated with anti-inflamatory therapy in moderate and severe asthma A.Bręborowicz-2006 General principles of long term asthma therapy Priority of inhaled medication Establishment of individual therapy Written instruction Complementary function of antihistamines A.Bręborowicz-2006 Asthma medication – preventers Inhaled corticosteroids (potential side effects in high doses) Sodium cromoglycate (very safe but only weakly antiinflammatory) Nedocromil sodium A.Bręborowicz-2006 Asthma medication controllers Leukotriene antagonists (good safety profile, responders and nonresponders) Slow release theophylline (narrow therapeutic window) Long acting inhaled (or oral) beta2 agonists ????????? (not antiinflammatory, but steroid sparing) A.Bręborowicz-2006 Asthma medication - relievers Short acting beta 2 agonists Muscarinic receptor antagonists anticholinergics Systemic corticosteroids Rapid release teophylline (short acting) A.Bręborowicz-2006 GINA NHLBI/WHO Report 2002 Choice of therapy EPISODIC asthma b2 agonist as needed * prevention of EIA cromones GKS ih b2 agonists Anti- leukotriens A.Bręborowicz-2006 GINA NHLBI/WHO Report 2002 Choice of therapy MILD asthma b2 agonist as needed * chronic antiinflammatory therapy budezonid up to 400ug Cromones Slow released theophylline Anti-leukotriens A.Bręborowicz-2006 Choice of therapy MODERATE asthma b2 agonists as needed * budezonid 400 - 800ug + Long acting b2 agonists Anti - leukotriens or budezonid > 800 ug A.Bręborowicz-2006 Slow released theophylline Choice of therapy SEVERE Asthma b2 agonists as needed * budezonid > 800 ug + Slow-released theophylline + + A.Bręborowicz-2006 Long acting b2 agonists GKS systemic + + Anti-leukotriens Asthma exacerbation Short acting beta 2 agonists Systemic corticosteroids Muscarinic receptor antagonists Theophylline Monitoring Oxygen Hydratation A.Bręborowicz-2006