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

Asthma morbidity in Hungary

2013, OKTPI

incidence prevalence

050

100150200250

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

%00

0

0

1000

2000

3000

%00

0

Új betegek Ö sszes regisztrált

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 bronchialhyperreactivity

Use os releaver,symptom

increases

Asthma control

decreases

time

Exacerbation Exacerbation

allergenes,viruses

cold weather,exercise

Asthma – variable nature

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 diseasesMany 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 cellsMast cell

eosinophil

Th2

basophil

neutrophil

platelet

Structural cellsEpithel

Smooth muscle

Endothel

Fibroblast

Nerves

MediatorsHistamin

Leukotrienes

Prostanoids

PAF

Kinins

Adenosin

Endothelins

NO

Cytokines

Chemokines

Growth factors

EffectsBrochospasm

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.

Johnston & Sears, Thorax 2006

„The September epidemic”(Ontario, Canada, 2001-2004)

Eosinophil

Mast cell

Allergen

Th2 cell

MODERN VIEW OF ASTHMAMODERN VIEW OF ASTHMA

VasodilatationNew vessels

Plasma leak Oedema

Neutrophil

Mucushypersecretionhyperplasia

Mucus plug

Macrophage

BronchoconstrictionHypertrophy/hyperplasia

Cholinergic reflex

Epithelial shedding

Subepithelial fibrosis

Sensory nerve activation

Nerve activation

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 – Th2imbalance

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 testsListening 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, FEV1

decreased)- Patients with - normal lung function: provocation test

- obstruction: pharmacodynamic test

Metacholin provocation testbronchial hyperreactivity

Pharmacodynamic testreversible obstruction

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

Lung function 2.

• COPD• Large airway obstruction

– Foreign body– Tumor

• Pulmonary embolism• Eosinophil pneumonia• Chronic cough

– Bronchitis simplex– Sinusitis– Tracheitis– Dyskinesis

• CHF• Gastroesophageal

reflux (GERD)• Chronic cough

– Drug-induced (ACE inhibitor, -blocker)

Respiratory Non-respiratory

Differencial diagnostics I.

Differencial diagnostics II.

• X-ray (chest, sinuses)

• Rhinoscopia

• Oesophageal pH monitoring

• Bronchoscopy

• Echocardiography

• Lung scintigraphy (V/Q scan)

Asthma diff. dg.1./ACOPD

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

Blood gas analysis

pH: 7,42

pO2: 66,6 Hgmm

pCO2:37,2 Hgmm

Sat: 93%

Lung function

FVC: 3,05 86%

FEV1:1,03 37%

VC:3,56 96%

FRC:5,93 171%

RV: 4,27 173%

RV/TLC%: 55%

DLCO: 1,6 20%

Asthma diff. dg.1./BCOPD/Emphysema

68 years old man

Asthma diff.dg 2. Tumor of big airway

Asthma diff.dg 3.Heart failure

Asthma severitySympotms

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 napnapi tünetekagonista 1 hétminden nap

Panaszok idején fizikai terhelhetőség

FEV1 60-80 %

PEF variability30%

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%

I. Epizodic Havonta többször, de nem minden héten

1 hét,a rohamokközött 2/hó tünetmentesség PEF normál

Hosszabb futás köhögést és bronchospazmust provokál

FEV1 80%

PEF variability20%

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 2. step 3. step 4. step 5. step

p.r.n. SABA

p.r.n. SABA

Choose one Choose one Copmbine one or more

Combine one or more

Preventivetreatment

ICS low dose ICS low dose + LABA

ICS moderate or high dose + LABA

oral corticosteroid (small dose)

antileukotriens ICS moderate or high dose

antileukotriens Anti IgE

ICS low dose + antileukotrien

theophyllin

ICS low dose +

theophyllin, antileukotrien

GINA 2009 : treatmentdecreasedecrease increaseincrease

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 Increased >30/min

Severity of asthma exacerbations II.

Mild Moderate Severe Resp.arrest

Accesory muscles

not usually usually Paradox thoraco-abdominal movement

wheeze moderate loud Usually loud

Abscence of wheeze

Pulse rate <100 100-120 >120 bradycardia

Pulsus paradoxus

Absent

<10mmHg

10-25 mmHg

>25mmHg Abscence musc.fatig.

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%

Treatment of acute exacerbation