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PROFESSOR OF CHEST DISEASES MANSOURA FACULTY OF MEDICINE 2009
BY DR ESSAM EL-GAMAL
Chronic inflammatory disorder of the airways in which many cells play a role including mast cells, eosinophils and Tlymphocytes. Chronic inflammation is associated with :
- Airway hyperresponsiveness that → recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. - Widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.
Asthma is a chronic inflammatory disorder associated with BHR + widespread variable AWO.
BHR Airway inflammation
: Asthma Triggers
Host Factors Genetic - Atopy - BHR Gender Obesity
Environmental Factors . Allergens (indoor, outdoor).
. Air Pollution with irritants. . Occupational sensitizers. . Tobacco smoke. . RT Infections. . Diet. www.MansFans.com
allergic hypersensitivity affecting parts of the body not in direct contact with the allergen. Associated with : - a strong hereditary component. - elevated serum levels of total and allergen-specific IgE, → positive skinprick tests to common allergens. Includes atopic dermatitis, allergic rhinitis, conjunctivitis, and asthma.
Common Allergens & Irritants :
Allergens Irritants • Food. • Secondhand sk. • Pollen / Molds. • Strong odors. • Animals/Pets. • Ozone. • Cockroaches. • Chem compounds • Dust.
Viruses and other pathogens
?Is it Asthma
Recurrent episodes of wheezes. Recurrent cough at night. Wheeze or cough after exercise. Wheeze, cough or chest tightness after exposure to airborne allergens or pollutants. Colds “go to the chest” or take > 10 days to clear
Grass , عشبpine , صنوبرoak trees. بلوط Transported by wind and can get indoors during pollen season. Close windows during pollen season. Weather-strip doors and windows.
Found everywhere, too small to be seen. Live in soft bedding, in warm, humid places. Feed on dead skin cells. Mites & mite droppings can trigger asthma.
Skin flakes, urine, and saliva of warm blooded animals trigger asthma. Triggers remain inside for several Mns after an animal is removed.
A type of fungus. Grow on damp surfaces by releasing spores. Grow on organic materials: wood, drywall, carpet, foods, wallpaper.
Other Indoor Triggers: Household Products
Vapors from cleaning solvents paint, liquid bleach, mothballs, glue. Spray deodorants, perfume. bleach, pesticides, oven cleaners, aerosol spray products.
Pathogenesis of Asthma
Immunologic mechanism. Neural mechanism. Genetic mechanism.
1) Immunologic Mechanism : Occur in atopic pts due to Immediate R : Ag/Ab R on the surface of MC → cell disruption & release of mediators (histamine, bradykinin) → BC.
Late R : PAF & MBP → oedema & cell infiltratin of br wall. MCP & eosinophils and lymphocytes : play role in the inflam reaction in BA.
2) Neural Mechanism : .ANS plays a role in the control of airway contraction, relaxation and secretions. . Symp NS → BD. . Parasymp NS → BC and ↑↑ secretions. . NANC system →inhib innervation to AW smooth Ms (BD), neurotransmitter is VIP.
3) Genetic Mechanism :
BA occurs in families, heredity may play a role in determination of BHR.
Association of the ADAM33 gene with asthma and BHR :
Genome scan (of 460 Caucasian families) identified a locus on chromosome 20p13 (ADAM33). ADAM proteins are membrane bound metalloproteases with diverse funtcions; eg. Release of cytokines. It will shed light on molecular pathway involved & new ttt strategies.
Histologic Features In Asthma
Shedding of airway epithelium. Collagen deposition of in basal membrane. Hyperplasia of goblet cells. Hypertrophy of smooth muscles.
Inflammatory cell infiltration (N,E,L).
What happens during an ?asthma episode
Airways narrow due to : . tightening of the ASM . swelling of inner lining. . ↑↑ mucous production. www.MansFans.com
History and patterns of symptoms. Measurements of lung function : - Spirometry - Peak expiratory flow
Measurement of airway responsiveness. Measurements of allergic status to identify risk factors.
: C/P of Bronchial Asthma
Symptoms : recurrent attacks of : Breathlessness and chest tightness. Chest Wheezes. Cough more at night. Signs : during asthma attacks : Tachycardia>120/min,tachpnea>30/min. Pulsus paradoxus > 20 mm Hg. Cyanosis. Inability to speak in sentences. Use of accessory respiratory muscles. Chest wheezes or Silent chest.
Definition : an exaggeration of normal variation in the pulse during respiration, in which the pulse becomes weaker as one inhales & stronger as one exhales. Occurs in several conditions including : asthma, COPD, cardiac tamponade, pericarditis, chronic sleep apnea and croup. Detection : by measuring variation of SBP with respiration : . Normal SBP variation (with respiration) is considered to be ≤10 mmHg. . Pulsus paradoxus is an inspiratory reduction in systolic pressure > 10 mmHg.
:CLASSES OF ASTHMA SEVERITY
once per week > brief ( few hr: few days) asymptomatic between EXB times per month 2 > ≥ 80% OPV, variability < 20%
once per week ≤ but < once per day may affect activity and sleep times per month 2 < ,OPV 80% ≤ variability < 20%
Night Symptoms FEV1 or PEF
CLASSES OF ASTHMA SEVERITY:
Symptoms EXB Night Symptoms FEV1 or PEF
daily use of SABA affect activity & sleep once per week < to < 80% 60% < OPV variability > 30%
continuous; physical activities limited frequent frequent OPV 60% => variability > 30%
Levels of Asthma Control
Characteristic Daytime symptoms Limitations of activities Nocturnal symptoms / awakening Need for rescue / “reliever” ttt Lung function ((PEF or FEV1 Exacerbation Controlled
None ( ≤/ wk) None
Partly controlled (Any present in (any wk
twice / wk > Any
None (≤( / wk
twice /wk > OPV or 80% < personal best on any day One or more / y
≥3 features of partly controlled asthma in any week
1 in any week
Investigation In Bronchial Asthma:
ww w .M an sF an s. co m
Pulmonary function tests. Chest X-ray. ABG. Serum IgE. Detection of allergen. Sputum Exam. Others : CBC, ECG.
Pulmonary function tests In Bronchial Asthma
Obstructive Hypoventilation : • FEV1 < 80% OPV & FEV1/FVC < 65%. • Coved pattern of F-V loop : maximal exp begins & ends at higher lung volumes & lower flow rates than normal.
Reversibility of AWO: ∀ ↑ FEV1 ≥ 12% (↑ 200 mLs) after 2 puffs of SABA.
Pulmonary function tests In Bronchial Asthma
PEFR Variability : . Shows > 20% diff ( ) the highest & lowest values with morning dipping. . Used to monitor EXB : to assess their severity and guide management decisions.
Bronchoprovocation Challenge Test : . With methacholine histamine or exercise in cases with normal spirometry.
OBSTRUCTIVE & RESTRICTIVE HYPOVENTILATION
OBSTRUCTIVE FEV1/ FVC RATIO LUNG VOLUMES F-V LOOP Reduced . FEV1 markedly ↓ . FVC decreased . VC normal or ↓ RESTRICTIVE Normal or ↑ . FEV1 markedly ↓ . FVC markedly ↓ . VC moderately ↓
witch's hat appearance www.MansFans.com
Peak Flow Meter
How to use PEF meter: Stand up or sit up straight. Slide indicator to base of meter. Take in deep breath. Place mouthpiece in mouth and seal lips around it. Blow out as hard and fast as you can (one quick blow). Repeat process 2 times more. Select highest number of the 3 efforts.
:MANAGEMENT OF ASA
A E R O S O L TH E R A P Y A F T E R 2 0 M IN P E FR > 7 0 % -----> D IS C H A R G E < 7 0 % ----> R E P E A T A F T E R 2 0 M IN P E FR > 7 0 % -----> D IS C H A R G E < 7 0 % ----> R E P E A T A F T E R 2 0 M IN P E FR > 7 0 % -----> D IS C H A R G E < 7 0 % -----> IV C S T
:MANAGEMENT OF ASA
PEFR < 70% 40 - 70 % IV C S T 6 0 M IN ---> A E R O S O L 2 5 -4 0 % IV C S T < 25 % IV C S T IN T U B A T IO N M V A D M IT T O IC U
> 7 0 % -----> D IS C H A R G E < 7 0 % ------> A D M IT
A D M IT T O H O S P IT A L
Flow-volume curve variations
Flow-volume curves from (A) a healthy person. (B) severe obstruction (emphysema). (C) severe restriction (interstitial fibrosis). (D) upper airways obstruction (tracheal stenosis). (E) poor effort.
Investigation In Bronchial :Asthma
CXR : . May show a cause or C/O of BA : pneumonia, pnx, collapse, # ribs. ABG : . For hypoxemia, hypercapnia and need of MV. Total serum IgE : . ↑ in cases with atopy. Detection of Allergen : . Serum specific IgE, skin prick test, BPT using inhaled allergens.
Investigation In Bronchial :Asthma
Sputum Exam : . May show eosinophilia, Curchman spirals, Charcot-Leyden crystals and Creola bodies. CBC : . Eosinophilia in allergic diseases, Leucocytosis in infection.
Yellow-white wavy long threads represent bronchial casts composed of : - shed epithelium. - spiral aggregates of eosinophils. - mucus. in a fibril network.
Breakdown product of eosinophils. Appear : slender and pointed and stain purplishred in the trichrome stain.
: Creola Bodies
compact clumps or strips of columnar epithelial cells shed from the bronchus.
considered and excluded. These include: • Chronic rhino-sinusitis. • Recurrent viral lower RTI. • TB. • COPD. • GERD. • FB aspiration. • Primary ciliary dyskinesia syndrome. • Cystic fibrosis. • Congenital malformation causing narrowing of the intrathoracic airways. • Congenital HD. • Immune deficiency.
Alternative causes of recurrent wheezing (Other (D. Dx
COMPLICATIONS OF ACUTE SEVERE ASTHMA
Pneumothorax, pneumomediastinum, pneumopericardium, subcutaneous emphysema. ABPA. Rib Fracture. Respiratory Failure. tracheoesofageal fistula (with MV). Death.
GINA GUIDELINES FOR Stepwise Approach to Therapy : G-IN-A : Global Initiative for Asthma Management
GINA GUIDELINES FOR Stepwise Approach to Therapy :
PRN : Quick Relievers : iSABA : given PRN
Daily or increasing use indicates need for long-term control therapy. Intensity of ttt depends on severity of EXB.
NB : Step 1 Intermittent asthma : no LTC.
Daily : Long-term Control Therapy: ICS and other drugs in schedule
GINA GUIDELINES FOR Stepwise Approach to Therapy : Daily LTC
Step 2 Mild ICS/LD OR Cromolyn OR nedocromil OR Persistent SR–theo OR LTM ICS/MD OR Step 3 ICS/LD-MD + iLABA (OR SR-theo) Moderate Persistent - If needed ↑ dose (ICS/HD, iLABA) asthma - Consider refrral to a specialist ICS/HD + all : Step 4 LABD:iLABA OR SR_theo OR oral LABA Severe Persistent Oral CT: long-term. Asthma - Recommended refrral to a specialist.
Stepwise Approach to Therapy : Maintaining Control
Multiple long-term-control medications, include oral corticosteroids
> 1 Long-term-control medications
1 Long-term-control medication : anti-inflammatory STEP 1 Quick-relief medication :PRN
Step down if possible s Step up if necessary s Pat education & environm control at every step s Recommend referral to specialist at Step 4; s consider referral at Step 3
Step 1 Treatment : Mild Intermittent
1) Daily Long-Term Control : Not needed 2) PRN Quick Relief –iSABA : PRN – use, or use > 2 / wk, may indicate need for long-term-control – Intensity of ttt depends on severity of EXB
Step 2 Treatment : Mild Persistent
1) Daily Long-Term Control – Anti-inflammatory s ICS (low dose) or s Cromolyn or nedocromil OR – SR theophylline (to STEP 2 serum conc 5-15 mcg/mL) is an alternative but not preferred. – Leukotriene modifier may be considered
Step 2 Treatment : Mild Persistent (continued)
2) PRN Quick Relief s iSABA : PRN s Daily or increasing use indicates need STEP 2 for long-termcontrol s Intensity of ttt depends on severity www.MansFans.com of EXB
Step 3 Treatment : Moderate Persistent
1) Daily Long-Term Control s ICS (medium dose) OR s ICS (low-to-medium dose) AND s LABA or SR theophylline. IF NEEDED, increase to: s ICS (medium-to-high dose) and LABA. Consider referral to a specialist
Step 3 Treatment : Moderate Persistent(continued
PRN Quick Relief s iSABA : PRN s Daily or increasing use indicate need for longterm-control therapy s Intensity of ttt depends on severity of EXB
Step 4 Treatment : Severe Persistent
1) Daily Long-Term Control s ICS (high dose) AND s Long-acting bronchodilator – iLABA OR – SR theophylline OR – LABA tablets AND s Long term Oral CST Recommend referral to a specialist
Step 4 Treatment : Severe Persistent ( continued)
2) PRN Quick Relief s iSABA : PRN s Daily or increasing use indicates need for long-term control therapy s Intensity of ttt depends on severity of EXB.
those who care for the patients can be taught to“ ”.manage cases well with what is available
E Parry The Tropical Health & Education Trust London Thorax1997;52:589
Without actions asthma drugs are available only for rich patients and for animals in rich countries!
New Zealand. Sunday Star. Times January 4,2004 Photo : Kevin Stent
New changes in asthma medications
Leukotriene modifiers now have a more prominent role as controller treatment in asthma, particularly in adults. LABA alone are no longer presented as an option for add- on treatment at any step of therapy, unless accompanied by ICS. Monotherapy with cromones is no longer given as an alternative to monotherapy with a low dose of ICS in adults. Some changes have been made to the tables of equipotent daily doses of ICS for both children and adults.
How serious is it, as a health ? problem
A very common AW disease. About 155 million individuals worldwide are affected. Number one chronic illness among children and young adults From 1979 to 1996, the no. of children dying from asthma increased 300%
What is asthma ?
Caused by hypersensitivity of airways to a number of triggers Dust-pollen-smoke-cold air-excercise The airways are obstructed leading to difficulty in breathing Can lead to death in severe cases Usually associated with atopy, elevated IgE in serum and bronchial hyper- responsiveness
ACUTE SEVERE ASTHMA pt is alert, distressed hot sweats, pale wants to sit up says few words hyperinflation with insp & exp movements audible wheezes tachycard., P alternans
TERMINAL ASTHMA drowsy, confused cold sweats, cyanosed wants to lie down can not speak hyperinflation with no expansion silent chest bradycar., no pulsus
. Normal Loop → rapid rise to the PEFR, followed by a nearly linear fall. . Obstructive → maximal exp begins & ends at higher lung volumes and lower flow rates than normal → coved pattern. . Restrictive → lung volumes & flow rates are ↓ but the flow in relation to lung volume is > normal → witch's hat" appearance with a steep descending limb.
LEVELS OF ASTHMA CONTROL
CHARACTERISTIC CONTROLLED All of the) (following None (twice /wk ≥) None (twice /wk ≥) None Non Normal None PARTLY CONTROLLED Any measure) (present in any wk twice /wk ≤ features/wk 3 ≤ of partly controlled asthma UNCONTROLLED
Need For Reliever ttt Nocturnal Symptoms Limitations Of Activity (PFT (PEF or FEV1 EXB
twice /wk ≤ Any Any OPV 80% > One /year ≤
One in any wk
Definition : an allergic hypersensitivity affecting parts of the body not in direct contact with the allergen. Associated with : 1 - a strong hereditary component. 2 - elevated serum levels of total and allergen-specific IgE, → positive skinprick tests to common allergens. Includes atopic dermatitis, allergic rhinitis, conjunctivitis, and asthma. Atopic syndrome can be fatal in serious allergic reactions such as anaphylaxis, due to reaction to food or environment.
How to elicit the sign : Can be measured by listening to Korotkoff sounds during blood pressure measurement -- slowly decrease cuff pressure to SBP level where sounds are first heard during expiration. Then, cuff pressure is slowly lowered further until Korotkoff sounds are heard throughout the respiratory cycle, during both inspiration and expiration. If the pressure difference between hearing the first sounds and hearing them throughout the respiratory cycle is > 10mmHg, it can be classified as pulsus paradoxus.
Airway Hyperresponsiveness Genetic*
Allergens,Chemical sensitisers, Air pollutants, Virus infections
Exercise, Cold Air
SYMPTOMS Cough Wheeze Dyspnoea
:Mucous plug in asthma
The Tests Reasons for Additional Tests
Patient has symptoms spirometry normal or – Assess diurnal variation of peak flow over 1 but is near normal. to 2 weeks.
– Refer to a specialist for bronchoprovocation with methacholine , histamine, or exercise; negative test may hel rule out asthma. Suspect infection, large airway lesions, heart disease, or obstruction by foreign object – Chest x-ray
Suspect coexisting chronic obstructive pulmonary – Additional pulmonary function studies disease, restrictive defect, or central airway – Diffusing capacity test obstruction Suspect other factors contribute to asthma (These are not diagnostic tests for asthma.) – Allergy tests—skin or in vitro – Nasal examination – Gastroesophageal reflux assessment
Subcutaneous emphysema ·Significant reduction of breath sounds suggesting mucus plugging or pneumothorax. ·Pulsus paradoxus greater than 20 mm Hg ·Agitation Unable to lie flat PEF after therapy less than 50%.
Treatment: First-line Drugs
Oxygen to keep SaO2 > 92% Inhaled Beta2 Agonists: Salbutamol (Albuterol) MDI: 4-8 puffs (100 ug/puff) q15-20 min with spacer, increase by one puff q 30-60 sec Wet Nebulizer: 2.5-5 mg (0.5-1 ml) in 2.5 ml normal saline q15-20 min
Corticosteroids Oral: prednisone 40-60 mg Intravenous: methylprednisolone 125 mg bolus then 120-180 mg/day in 3-4 divided doses for 48 hrs
Vital Signs Heart Rate Respiratory Rate Peak Expiratory Flow Rate (PEF) or FEV1 Oxygen Saturation Respiratory Status Lung auscultation Assess accessory muscle use Chest X-Ray has low yield in acute exacerbations Assessment if patient in extremis Arterial Blood Gas
Step 1: Initial Assessment
Step 2: Initial Management
Inhaled Short-acting Beta Agonist (Nebulized Albuterol) One dose up to every 20 minutes for one hour Anticholinergic (Ipratropium bromide or Atrovent)
Indication: FEV1 or PEF <50% of predicted (Severe)
Add to Nebulized Albuterol
Systemic Corticosteroid IV Indication : Severe episode (FEV1 or PEF <50% predicted)
No immediate response
Oxygen indication Oxygen Saturation <91% Consider Additional measures for severe exacerbation
Repeat measures in step 1
Step 3: Reassess
Moderate episode ( PEF 60-80% of predicted )
Nebulized Albuterol hourly Consider Systemic Corticosteroids Continue management for 1-3 hours while improving Severe episode ( PEF <60% predicted ) Nebulized Albuterol hourly or continuous Consider adding ipratroprium bromide to nebulizer Oxygen Systemic Corticosteroids Prednisone 1-2 mg/kg/day qd-bid Maximum: 40-60 mg/day for 5-10 days No tapering needed if use less than 2 weeks
Emergency Room Management of Asthma
,O2 to keep Sat >91% nebulized b2 agonists up to every 20 min Systemic steroids and Ipratropium in severe cases
• • •
Good Response PEF > 70%
Partial Response PEF 50-70%
Continue 1-2 hrs
Poor Response PEF <50%
Disch arge Home
Admit to the Hospital
Managing Exercise-Induced ( Bronchospasm(EIB )(continued
• • •
Short-acting inhaled beta2-agonists used shortly before exercise last 2 to 3 hours Salmeterol may prevent EIB for 10 to 12 hours Cromolyn and nedcromil are also acceptable A lengthy warmup period before exercise may preclude medications for patients who can tolerate it Long-term-control therapy, if appropriate
Hospitalized patients: 1 mg / kg of prednisone equiv. / 6 – 12 hrs for 48 hrs or FEV1 or PEFR reaches 50 % of predicted or of baseline then decrease dose to 60-80 mg / d. to achieve PEF 70 % ICS to be started at beginning of tapering If patient discharged from ER : 40 mg x 5 d.
short courses: • 0.5 – 1 mg / kg / d prednisone in a single or bid dose ( 40-60 mg / d for 5-10 days ) Bid regimen decreases side effects 1 more week of a reduced dose can be added relatively little dose-related toxicity ( mood disturb. – increased appet. – loss of glucose control in DM – candidiasis – cough )
Longer courses : for more protracted bouts of severe asthma slower rate for tapering
( avoid exacerbations & adrenal suppression ) repeated efforts to decrease dose to min. needed alternate days is preferred Alternate days : in severe persistent asthma ( high dose ICS )
In ER: 125 mg stat decreases rate of return to er In ward : 40-60 mg qid
• 1st line therapy for persistent asthma • High concentration directly to site of inflammation • Therapeutic index of drugs greatly enhanced leading to less side effects Members: beclomethasone flunisolide fluticasone triamcinolone budesonide
• MDI PROPER TECHNIQUE INHALATION CHAMBER DRUG POWDER INHALERS NON – CFC PERPELLANT SYST. • NEBULIZERS
• 400 – 1000 ug of beclomethasone dipropionate or equivalent • Increase dose as necessary guided by: symp. ( frequency of B2 agonists – signs of poorly controlled asthma ) PEF 50-100 % till symp. Are controlled In case of: severe symp. – night awakening – PEFR > 65% of predicted give a short course of OCS
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