Download presentation
Presentation is loading. Please wait.
1
Attila Somfay Dept.Pulmonology, University of Szeged, Deszk, Hungary
Asthma Attila Somfay Dept.Pulmonology, University of Szeged, Deszk, Hungary
2
Medical history of D.B. 30-year-old woman, school teacher
Complaints for 20 years: periods of S.O.B., particularly in the August-October period, but also during exercise (tennis), cold air exposure (skie) or under stress (exams). Severity changes considerably time to time, with frequent attacks of wheezing, between attacks no complaints Never smoked Mother also had asthma
3
Acute admission Severe attack which responded poorly to BD drugs and inhaled CS. Exhausted, dehydrated, very anxious On examination: dyspneic, orthopneic, accessory muscles of respiration were active Lungs hyperinflated, musical rhonchi in all areas HR: 110/min with pulsus paradoxus Sputum scant and viscous
4
Definition of asthma - inflammatory disorder of the airways, characterized by periodic attacks of wheezing, shortness of breath, chest tightness, and coughing, tipically during the night and early morning. - a condition characterized by recurrent attacks of bronchoconstriction and excessive mucus production, in response to a variety of factors. - the attacks releave spontaneously or by bronchodilators - chronic inflammation results in bronchial hyperreactivity
5
DEFINITION OF 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. NEW! Wenzel, Lancet 2006
6
Asthma and COPD mortality
Mathers, PLos Med 2006 Future worldwide mortality from chronic obstructive pulmonary disease. Projections based on estimates provided by the World Health organization. [ 3 ] . It is estimated that by 2030, 7.3 million people will die from COPD and asthma worldwide. IHD ischemic heart disease, CVD cerebrovascular disease, COPD chronic obstructive pulmonary disease
7
Prevalence of astma (A) and asthmatic symptoms (B)
between 1965 and 2005 in children and young adults
8
Asthma morbidity in Hungary
Prevalence Incidence 14 629 15 836 OKTPI, 2016
9
Asthma – variable nature
allergenes, viruses cold weather, exercise increases Use os releaver, symptom time Asthma control Many of the factors that contribute to the development and persistence of asthma also lead to variability. This variability is often beyond the control of either the patient or physician. The variable nature of asthma means that most patients experience periods of good asthma control and periods of worsening asthma symptoms. Bronchial hyperresponsiveness is a characteristic feature of asthma and leads to episodes of coughing, wheezing, chest tightness and breathing difficulties. Asthma exacerbations can be triggered by various stimuli including allergens, infections, environmental factors and exercise. During exacerbations, patients tend to use their reliever medication to control their symptoms without also increasing their anti-inflammatory medication as they should. Changes to the controller medication dose are usually only made if asthma worsening persists long enough for the patient to make a visit to the physician. However, without additional controller therapy, inflammation may increase — leading to airway obstruction that, in turn, may lead the patient to be hospitalised or seek emergency room treatment, which often involves a course of oral steroids. decreases Exacerbation Exacerbation
10
Prevalence Concomittant diseases
3-5% of adults and 7-10% of children. *Half of the people with asthma develop it before age 10 and most develop it before age 30. Asthma symptoms can decrease over time, especially in children. Concomittant diseases Many people with bronchial asthma have an individual and/or family history of allergies such as hay fever (allergic rhinitis) or eczema. Others have no history of allergies or evidence of allergic problems.
11
Asthma phenotypes Wenzel, Nature Med 2012
Theoretical grouping of emerging asthma phenotypes based on the distinction between TH2-high asthma and non-TH2 asthma. TH2 asthma consists of both early- and later-onset disease over a range of severities. It is likely that the majority of early-onset allergic asthma is mild but that an increasing complexity of immune processes leads to greater severity. Later-onset eosinophilic asthma without traditional allergic elements is more likely to be severe, whereas EIA is a milder form of TH2 asthma. Non-TH2 asthma includes very late–onset, obesity-associated asthma as well as smoking-related and neutrophilic asthma, and asthma in which affected individuals show little inflammation. The intensity of the colors represents the range of severity; the relative sizes of the subcircles suggest relative proportions of affected individuals. Wenzel, Nature Med 2012
12
Symptom – inflammation relationship
Haldar, AJRCCM 2008
13
Mediators Effects Inflammatory cells Structural cells Mast cell
eosinophil Th2 basophil neutrophil platelet Structural cells Epithel Smooth muscle Endothel Fibroblast Nerves Mediators Histamin Leukotrienes Prostanoids PAF Kinins Adenosin Endothelins NO Cytokines Chemokines Growth factors Effects Brochospasm Plasma exsudation Mucus secretion AHR Structural changes
14
Etiology * In sensitive individuals, asthma symptoms can be triggered by inhaled allergens (allergy triggers) such as pet dander, dust mites, cockroach allergens, pollens. * Asthma symptoms can also be triggered by respiratory infections (virus!), exercise, cold air, tobacco smoke and other pollutants, stress, food or drug allergies. * Aspirin and other non-steroidal anti-inflammatory medications (NSAID) provoke asthma in some patients.
15
House dust mite (Dermatophagoides pteronyssimus)
16
„The September epidemic”
(Ontario, Canada, ) Johnston & Sears, Thorax 2006 Érzéklehető késés van az őszi tünetcsúcsokban: az iskolások az elsődleges vektorok a későbbi korcsoportok asztma exacerbációja szempontjából, mind a fiatalabb, mind az idősebb korcsoportban
17
MODERN VIEW OF ASTHMA Allergen Macrophage Mast cell Th2 cell
Neutrophil Eosinophil Mucus plug Epithelial shedding Nerve activation Subepithelial fibrosis Plasma leak Oedema Sensory nerve activation Mucus hypersecretion hyperplasia Vasodilatation New vessels Cholinergic reflex Bronchoconstriction Hypertrophy/hyperplasia
18
Inflammatory and immune cells
involved in asthma Thymic stromal lymphopoetin
19
Infect theory Th1 – Th2 imbalance
20
Typical pathologic features: epithel shedding + basement membrane
thickening After ICS Before ICS
21
Effect of inhaled steroid in asthma
•A cross-section of the airway wall taken from an asthmatic patient who had received only symptomatic treatment with a b2-agonist, viewed through an electron microscope, reveals severe damage to the epithelium (E) and an intense inflammatory reaction under the basement membrane (BM). Several types of inflammatory cells can be identified, including lymphocytes (L), eosinophils (Eo) and degranulated mast cells (M). •Following 3 months treatment of this patient with inhaled budesonide (Pulmicort®), examination of a new specimen of airway wall cross-section shows healing of the epithelium and suppression of the inflammatory reaction under the basement membrane. Laitinen LA, et al. J Allergy Clin Immunol 1992;90(1):32-42
22
Asztma and COPD 1.
23
Differences in airway obstruction
COPD Asthma
24
Asztma and COPD 2
25
Clinical characteristics of asthma
26
Symptoms 1. *Most people with asthma have periodic wheezing attacks separated by symptom-free periods. *Some asthmatics have chronic shortness of breath with episodes of increased shortness of breath. *Asthma attacks can last minutes to days, and can become dangerous if the airflow becomes severely restricted
27
Cough, Wheezing, Dyspnoe - usually begins suddenly - episodic
Symptoms 2. Cough, Wheezing, Dyspnoe - usually begins suddenly - episodic - may be worse at night or in early morning - aggravated by exposure to cold air, by exercise, by reflux - resolves spontaneously or by bronchodilators - cough with or without sputum (dyscrinia) - breathing that requires increased work - intercostal retractions - abnormal breathing pattern: exhalation (breathing out) more than twice as long as inspiration (breathing in)
28
(because sputum scant and viscous)
Dyscrinia (because sputum scant and viscous)
29
*bluish color to the lips and face *severe anxiety
Symptoms 3. Emergency symptoms *extremely difficult breathing *bluish color to the lips and face *severe anxiety *rapid pulse (pulsus paradoxus) *sweating *decreased level of consciousness (severe drowsiness or confusion) during an asthma attack
30
Lung sounds are usually normal between episodes.
Signs and tests Listening to the chest (auscultation) during an episode reveals wheezing. Lung sounds are usually normal between episodes. Tests may include: *pulmonary function tests *chest X-ray *allergy testing by skin testing or serum tests (IgE) *arterial blood gas *eosinophil count
31
- Between the attacks: may be normal
Diagnostics -Lung function 1. - Between the attacks: may be normal - During the attacks: obstruction (PEF, FEV decreased) - Patients with - normal lung function: provocation test - obstruction: pharmacodynamic test
32
Metacholin provocation test bronchial hyperreactivity
34
Pharmacodynamic test reversible obstruction
35
Lung function 2. Provocation test
*Specific provocation-allergen challenge (rarely done, neber in routine,can be dangeorus – anaphylaxis, suffocation) inhalation causes prompt and sign. bronchoconstriction *rapid decline in FEV1: lasts: 15 min.- 1 hour *=early asthmatic reaction (EAR)=early phase response *After this phase resolves (spontaneously or with -agonist), the FEV1 reaches a level to the pre-chall. baseline. *6-24 hours after exposure to the allergen bronchoconstriction can be developed=late asthmatic response (LAR). The decline in FEV1 may be less severe. *Aspecific provocation (histamin, metacholin): *Exercise test – 6-8 min run, pre/post spirometry Pharmacodynamic test:baseline obstr.lung function, resolved in 15 min due to inh. bronchodilator (salbutamol)
36
Differencial diagnostics I.
Respiratory Non-respiratory COPD Large airway obstruction Foreign body Tumor VCD Pulmonary embolism Eosinophil pneumonia Chronic cough Bronchitis simplex Sinusitis Tracheitis Dyskinesis CHF Gastroesophageal reflux (GERD) Chronic cough Drug-induced (ACE inhibitor, -blocker)
37
Differencial diagnostics II.
X-ray (chest, sinuses) Oesophageal pH monitoring Bronchoscopy, Laryngoscopy Echocardiography CT angiography, V/Q scan
38
Vocal cord dysfunction
39
Irreversible obstructive pulmonary disease
Asthma diff. dg.1./A COPD Farmacodynamic test: prae post FVC: 2,00 (47%)- 1,89 (44%) FEV1: 0,93 (28%)- 0,88 (26%) FRC:5,29 (150%)- 5,09 (144%) RV: 4,65 (201%)- 4,57 (198%) Raw: 6,01-6,19 (<2,24) Irreversible obstructive pulmonary disease 61 years old man
40
Asthma diff. dg.1./B COPD/Emphysema Lung function 68 years old man
FVC: 3, % FEV1:1, % VC:3, % FRC:5, % RV: 4, % RV/TLC%: % DLCO: 1, % 68 years old man Blood gas analysis pH: 7,42 pO2: 66,6 Hgmm pCO2:37,2 Hgmm Sat: 93%
41
Asthma diff.dg 2. Tumor in large airways
42
Asthma diff.dg 3.Heart failure
43
Asthma severity Sympotms Day Night Exercise capacity Lung function
(FEV1 or PEF) IV. Chronic severe Folyamatos, naponta többször folyamatos gyakori Folyamatosan korlátozott FEV1 60% PEF variability30% III. Chronic moderate Minden nap napi tünetek agonista 1 hét minden nap Panaszok idején fizikai terhelhetőség FEV1 % II. Chronic mild Hetente többször, de nem minden nap 1/hét, de 1/nap 2/hó Nagyobb fizikai terhelés köhögést és bronchospazmust provokál FEV1 80% PEF variability30% Intermittent, epizodic Havonta többször, de nem minden héten 1 hét, a rohamok között 2/hó tünetmentesség PEF normál Hosszabb futás köhögést és bronchospazmust provokál FEV1 80% PEF variability20%
44
What to treat…
45
Controllers (Anti-inflammatory)
Treatment 1. Controllers (Anti-inflammatory) - ICS, inhaled corticosteroid: (budenosid, fluticasone, beclomethason, ciclesonide) - leukotriene inhibitors (montelukast, zafirlukast, pranlukast) - LABA(long acting beta-2 agonists) – salmeterol, formoterol – only with ICS - xantin derivates (teophyllin) - Biological therapy: omalizumab (anti IgE) mepolizumab (anti IL-5)
46
Treatment 2. Releavers (bronchodilators )
- beta-2 agonist: short(fast)-acting (SABA): inhaled (salbutamol, terbutalin, formoterol) - aminophylline or theophylline (I.v) - anticholinergics inhaled (ipratropium)
47
GINA 2017
48
Severity of asthma exacerbations I.
Mild Moderate Severe Resp.arrest dyspnea Walking Can lie down Talking Prefers sitting At rest Hunched forward Talks in sentences phrases words alertness Usually agitated Usually agiteted Drowsy or confused Respiratory rate Increased >30/min
49
Severity of asthma exacerbations II.
Mild Moderate Severe Resp.arrest Accesory muscles not usually Paradox thoraco-abdominal movement wheeze moderate loud Usually loud Abscence of wheeze Pulse rate <100 >120 bradycardia Pulsus paradoxus Absent <10mmHg 10-25 mmHg >25mmHg Abscence musc.fatig.
50
Severity of asthma exacerbations III.
Mild Moderate Severe Resp.arrest PEF >80% 60-80% <60% PaO2 >60mmHg <60mmHg PaCO2 <45mmHg >45mmHg SaO2 >95% 91-95% <90%
51
Treatment of asthma exacerbation
SABA DPI, MDI: 4-10 puff ( g salbutamol ) 20 min, repeat max. 3 times Improves No improvement Mild exacrebation Severe exacerbation Some impovement Moderate exacerbation
52
Further treatment Mild exacerbáció Roham oldódik, PEF! 100-200 g SABA
4-6 h for 2-3 days inh. steroid dose:2x for 2-4 weeks Moderate exacerb. iv. or per os 40 mg methylprednisolon, continue for 5-7 days Severe excerbation O2, iv mg methylprednisolon, (iv. xantin), +SABA/SAMA transfer to ED
53
Hospital treatment (above the previous ones, if needed)
54
DEFINITION OF SEVERE ASTHMA
When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming uncontrolled or that remains uncontrolled despite this therapy. F. Chung et al, ERJ 2014.
55
HETEROGENEITY OF EOSINOPHILIC ASTHMA
- Brusselle G. et al, Nature Medicine 2013.
56
DEFINITION OF UNCONTROLLED ASTHMA
At least one of the following: Poor symptom control: ACQ consistently > 1.5, ACT < 20 Frequent severe exacerbations: two or more bursts of systemic CS in the previous year Serious exacerbations: at least one hospitalisation or ICU stay in the previous year Airflow limitation: after appropriate bronchodilator withold FEV1 < 80% predicted F. Chung et al, ERJ 2014.
57
terápia rezisztens asztma (~50%)
Difficult to treat vs. severe, refracter asthma Nem (alul) kezelt Nehezen kezelhető Refrakter Not (under) treated Severe refrakter, terápia rezisztens asztma (~50%) Diff.to treat Difficult to treat: Not asthma Poor compliance Comorbidities, environmental factors, triggers Dolan CM et al. Ann Allergy Asthma Immunol 2004; 92: 32-9. Moore WC et al. J Allergy Clin Immunol 2007; 119:
58
F. Chung et al, ERJ 2014.
Similar presentations
