Asthma

Asthma and COPD mortality

Mathers, PLos Med 2006

Prevalence of astma (A) and asthmatic symptoms (B) between 1965 and 2005 in children and young adults

250 200 150 100 50 0

Asthma morbidity in Hungary

incidence Új betegek prevalence Összes regisztrált 3000 2000 1000 0 2013, OKTPI

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

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 viscid

Asthma

- an 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

Asthma – variable nature

allergenes, viruses cold weather, exercise

increases

Use os releaver, symptom time Asthma control

decreases Exacerbation Exacerbation

Prevalence

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.

Phenotypes

Wenzel, Lancet 2006

House dust mite (Dermatophagoides pteronyssimus)

Inflammatory 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

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, 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.

„The September epidemic” (Ontario, Canada, 2001-2004) Johnston & Sears, Thorax 2006

MODERN VIEW OF ASTHMA Allergen

Macrophage Mast cell

Mucus hyperplasia

Th2 cell

Mucus plug

Neutrophil Eosinophil

Nerve activation Epithelial shedding New vessels Plasma leak Oedema Subepithelial fibrosis Sensory nerve activation Cholinergic reflex Bronchoconstriction Hypertrophy/hyperplasia

Inflammatory and immune cells involved in asthma

Typical pathologic features: epithel shedding + basement membrane thickening After ICS Before ICS

Effect of inhaled steroid in asthma

Laitinen LA, et al. J Allergy Clin Immunol 1992;90(1):32-42

Infect theory Th1 – Th2 imbalance

Asztma and COPD 2

Characteristics

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

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)

Dyscrinia

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

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

Diagnostics -Lung function 1.

- Between the attacks: may be normal - During the attacks: obstruction (PEF, FEV 1 decreased) - Patients with - normal lung function: provocation test - obstruction: pharmacodynamic test

Metacholin provocation test

bronchial hyperreactivity

Pharmacodynamic test

reversible obstruction

Lung function 2

.

Provocation test

*Specific provocation

-allergen challenge (rarely done, can be dangeorus) 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 LF

Pharmacodynamic test:

baseline obstr.lung function resolved in 15 min due to inh. bronchodilatator

Differencial diagnostics I.

Respiratory • COPD • Large airway obstruction – Foreign body – Tumor • Pulmonary embolism • Eosinophil pneumonia • Chronic cough – Bronchitis simplex – Sinusitis – Tracheitis – Dyskinesis Non-respiratory • CHF • Gastroesophageal reflux (GERD) • Chronic cough – Drug-induced (ACE inhibitor,  -blocker)

Differencial diagnostics II.

• X-ray (chest, sinuses) • Rhinoscopia • Oesophageal pH monitoring • Bronchoscopy • Echocardiography • Lung scintigraphy (V/Q scan)

Asthma diff. dg.1./A COPD

61 years old man

Farmacodynamic test:

prae post FVC: 2,00 (47%)- 1,89 (44%) FEV 1 : 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

68 years old man Asthma diff. dg.1./B COPD/ Emphysema

Lung function FVC: 3,05 86% FEV 1 :1,03 37% VC:3,56 96% FRC:5,93 171% RV: 4,27 173% RV/TLC%: 55% DLCO: 1,6 20% Blood gas analysis pH: 7,42 pO 2 : 66,6 Hgmm pCO 2 :37,2 Hgmm Sat: 93%

Asthma diff.dg 2. Tumor of big airway

Asthma diff.dg 3.Heart failure

IV. Chronic

severe

III.

Chronic

moderate

II.

Chronic

mild

I.

Epizodic Asthma severity

Sympotms Day Night Folyamatos, naponta többször folyamatos gyakori Exercise capacity Folyamatosan korlátozott Lung function (FEV 1 or PEF) FEV 1  60% PEF variability  30%  Minden nap napi tünetek agonista  1 hét minden nap Hetente többször, de nem minden nap  1/hét, de  1/nap  2/hó Havonta többször, de nem minden héten  1 hét, a rohamok tünetmentesség PEF normál  2/hó Panaszok idején fizikai terhelhetőség  FEV 1  60-80 % PEF variability  30% Nagyobb fizikai terhelés köhögést és bronchospazmust provokál Hosszabb futás köhögést és bronchospazmust provokál FEV 1  80% PEF variability  30% FEV 1  80% PEF variability  20%

Treatment 1.

1. Controllers (Anti-inflammatory)

*ICS, inhaled corticosteroid

: (budenosid, fluticasone, beclomethason, ciclesonide) *oral or intravenous corticosteroids (prednisone, methylprednisolone, hydrocortisone) *leukotriene inhibitors (montelukast, zafirlukast, pranlukast) *LABA(long acting beta-2 agonists) – salmeterol, formoterol

Treatment 2.

2 . Releavers (bronchodilators ) *beta-2 agonist: - short-acting (SABA): inhaled (salbutamol, terbutalin, formoterol) *aminophylline or theophylline (I.v) *anticholinergics (ipratropium)

1. step p.r.n. SABA GINA 2009 : treatment decrease increase 2. step

Choose one

ICS low dose

3. step 4. step

p.r.n. SABA

5. step

Choose one

ICS low dose + LABA

Copmbine one or more

ICS moderate or high dose + LABA

Combine one or more

oral corticosteroid (small dose) Anti IgE

Preventive treatment

antileukotriens ICS moderate or high dose antileukotriens ICS low dose + antileukotrien ICS low dose + theophyllin, antileukotrien theophyllin

Severity of asthma exacerbations I.

dyspnea Talks in Mild Moderate Walking Can lie down sentences Talking Prefers sitting phrases Severe At rest Hunched forward words Resp.arrest

alertness Respirator y rate Increased Usually agitated Increased Usually agiteted >30/min Drowsy or confused

Severity of asthma exacerbations II.

Accesory muscles wheeze Pulse rate Pulsus paradoxus Mild not moderate <100 Absent <10mmHg Moderate usually loud 100-120 10-25 mmHg Severe Resp.arrest

usually Usually loud >120 Paradox thoraco abdominal movement Abscence of wheeze bradycardi a >25mmHg Abscence musc.fatig.

Severity of asthma exacerbations III.

PEF Mild >80% Moderate Severe 60-80% <60% Resp.arrest

PaO2 PaCO2 SaO2 >95% >60mmHg <60mmHg <45mmHg >45mmHg 91-95% <90%

Treatment of acute exacerbation