You are on page 1of 53

MANAGEMENT:

ASTHMA ATTACK &


COPD EXACERBATION

Isnu PRADJOKO
Dept.of Pulmonology and Respiratory Medicine
Medical Faculty of Airlangga University / Hospital Dr. Soetomo
Surabaya
PRELIMINARY

one of the main causes of emergency


cases and hospitalizations
Understanding
of the
exacerbation / pathophysiolo
gy, treatment
ASTHMA ATTACK increased

The main reason for patients


to seek help Kaplan AG, Balter MS 2009
22 million dollars for
emergency cases
84 million dollars for
inpatient cases *

Figures rata2 inpatient


9- 10% asthma. **

* Kaplan AG, Balter MS 2009

** PDPI 2003
DEFINITION
chronic inflammatory disease involving the respiratory
GINA 2017
tract as a result of various inflammatory cells with
airway constriction is varied, characterized by wheezing
/ wheezing, shortness of breath, tightness in the chest,
coughing especially at night / early morning. The
narrowing and asthma symptoms may be reversible
either spontaneously or with treatment

Gina 2017
Flare-up = acute deterioration / sub-acute symptoms or
lung function compared to the previous normal state.
Asthma Inflammation: Cells and mediators

Source: Peter J. Barnes, MD


Its Asthma?
 Recurrent episodes of wheezing
 Nighttime cough
 Coughing or wheezing after exercise
 Coughing, wheezing or chest tightness
after exposure to allergens / pollutants
 Cold cough> 10 days
Typical spirometric (FEV1) Tracings
Volume
FEV1
normal Subject

Asthmatic (After bronchodilator)


Asthmatic (Before bronchodilator)

1 2 3 4 5
Time (sec)
Note: Each FEV1 the curve represents the highest of three repeat measurements
Pathophysiology
Hiper
RESPONSIV
edema E Hiper
SAL. SAL.NAPAS SECRETION
BREATH mucus
AIRWAY
Bronko
remodel-
constriction LING
AIR FLOW BARRIERS
VIRUS respiration / HRV BACTERIA (M.pneumonie,
C.pneumoniae
DRUG, emotional crisis Allergens, pollutants

PDPI, 2003: Gilbert TW, Denlinger LC. Role of Infection in the development and exacerbation of asthma. NIH Public Acces.Expert Rev
Respir Med. 4. 71-83.2010
CAST bronchial mucous
CAPACITY DIFFERENCES IN DEFENSE ANTIVIRUS NORMAL CELLS WITH CELL bronchial
epithelium of asthmatic bronchial epithelium
Holgate ST, Robert G. The Role of Airway Epithellium and its interaction with the Environmental Factor in Asthma Pathogenesis. Proc Am Thorac
Soc Vol 6 pp 665-659. 2009
ASTHMA CONTROL THE UGLY Psychological dysfunction (psychosis,
anxiety, depression)
History of hospitalization due to The use of bronchodilators with
asthma increasing doses reply
Psychological dysfunction (psychosis, History of use of oral corticosteroids
anxiety, depression) as controller
Cardiovascular disease and illness
Low socio-economic
chronic lung

Hodder R, Lougheed D. Management of acute asthma in adults in the emergency department: nonventilatory
management. In the Canadian Medical Association Journal, 2010.
CLINICAL
Table 1. Common asthma symptoms and signs of acute / exacerbation
(Quoted from: Hospital Physician, 2006)

SYMPTOMS AND SIGNS asthma exacerbations


Subjective Objective
dyspnea Tachypnea (weight,> 30x / min)
Cough Tachycardia (weight,> 120x / min)
wheezing Upright positioning
Tightness in the chest (chest Pulsus paradoxus (weight,> 12mmhg)
tightness) retraction sternocleidomastoid
sputum production Changes in the degree of consciousness
Crummy (exhaustion) Telegraphic speech

(Quoted from: Hospital Physician, 2006)


CLINICAL
A study has mentioned that 10% of patients with acute 1
asthma do not feel short of breath, but just felt a cough
and wheezing obtained.

Sufferers are usually aware of these asthma attacks 1


when FEV1 has reached 50% or more of normal values or
when the residual volume reaches up to 200% of normal
1
A fact in the study, the results obtained, 90% of people
who feel they are asymptomatic, it turns out 40% of them
obtained wheezing.
2

1.Young DJ, Salzman GA. Asmaticus status in adult Patients.Clinical Review Article in Hospital Physician. 2006
2.Kotaru C, McFadden ER. Acute exacerbations of asthma. In Asthma and chronic obstructive pulmonary diseases. Basic
ASSESSMENT AND EVALUATION
MANAGEMENT BEGINS WITH asthma exacerbations WEIGHT RATING
DEGREE OF ATTACKS AND EVALUATION WHICH COVERS FATAL
ASTHMA RISK FACTOR *
Oxygenation and bronchodilators
FIRST *
DIAGNOSIS asthma exacerbations **
1. Upper airway obstruction
2. Foreign body aspiration
3. The vocal cords dysfunction syndrome
4. pulmonary edema
5. Acute exacerbations of COPD
6. Conversion reaction hysterik

* Jain DG, SK Singal, Clark RK. Understanding and managing Acute Severe Asthma and Difficult. In Clinical Medicine. Journal of Indian Academy of
Clinical Medicine. Vol.7.2006
** Hodder R, Lougheed D. Management of acute asthma in adults in the emergency department: nonventilatory management. In the Canadian
Medical Association Journal, 2010.
EVALUATION exacerbations
AX • Onset, causal, severity , respons for therapy (pre emergency
room), history of diseases, and hospitalisation, and comorbid

• Assess the severity of exacerbations and overall patient status, including

P.D. awareness, fluid status, cyanosis, respiratory distress and wheezing


• Identify possible complications, such as pneumonia, pneumothorax, and
pneumomediastinum
• Pulmonary serial function measurements performed on arrival, and repeated 30 and
60 minutes after initial therapy, are essential in assessing the severity of
LFT exacerbations.
• In severe and life-threatening exacerbations of asthma, lung function tests in triage
are not recommended.

• Generally patients with asthma exacerbations do not require laboratory testing

Lab • Indicated for the detection of respiratory failure, theophylline toxicity, or a concession
that complicates the treatment of asthma (cardiovascular disease, pneumonia, or
diabetes)
15
Camargo CA, Rachelefsky G. Managing Asthma exacerbations in the Emergency Department. Summary of the National
Asthma Education and Prevention Program Expert Panel. Proc Am Thorac Soc. Vol.6.357-366. 2009
WEIGHT DISTRIBUTION DEGREE OF ASTHMA ATTACK

PDPI 2003
PEAKFLOW
METER
Aim Management
exacerbations Asthma
record: increasingly fast treatment starts, increasingly easy resolve attack
medications
Pre-hospital
Inhalation β2 agonists brief 2-4 puffs every 1 hour 20 min
pd first. After the first hour, the dose of β2 agonist depending on
the severity of exacerbations. In mild exacerbations followed by 2-
4 puffs every 3 to 4 hours. Exacerbations are in need 6-10 puffs in
1 to 2 hours. Oral glucocorticoids should be given

oxygenation Handling in RS
Saturation is maintained a minimum 92%

Β2 AGONISTS SHORT
The main drug, per inhalation is highly recommended, the first 1 hour
continuous pd
Giving dg anticholinergics provide improved lung function and reduce the
number of hospitalizations
GINA 2012
FUNDAMENTAL THERAPY
PD ASTHMA ATTACK
Beta 2-agonists
RELAXATION
bronchial smooth
muscle

REDUCE THE MAST


Increased clearance
CELL MEDIATOR
MUKOSILIER RELEASE
DECREASE vascular
permeability
Systemic corticosteroids
• SINCE THE START BE CONSIDERED FOR GRANTED ON ALL
DEGREES exacerbations

OTHER THERAPY
• Recommended in severe non-response to pd β2
MgSO4 agonist and systemic corticosteroids
• Consideration of efective, safe, cheap

• Considered if there is suspected


AB bacterial infectionbila curiga ada
infeksi bakterial

Xantine
Inhaled Corticosteroids (Evidence B)
• MORE SECURE THAN SYSTEMIC STEROIDS
• ICS give effect that more fast (1-2jam) when be given in
dose multiple with interval time <30 minute for 90-120 minute,

Change value PEFR before and after administration


250
steroid
200
150
PEFR

Nebules
100 IV

50
0
0 20 40 60 120 180 240 300 360
Nebules 80,3 129 148 161 174 183 194 208 213
IV 71,6 111 134 147 166 174 182 185 192
Time (minute)

Atika Sari, Faisal Yunus, et al, RSFriendship 2003


OTHER THERAPY
• Combination helium-oxygen,
Heliox Breathable

Leukotrien • still little data role on


modifier asthma attacks

Aggressive hydration is not recommended for adults,


but may be suitable for infants and children who are
dehydrated as a result of an increased respiratory rate
and decreased oral intake. **

Sedatives = BANS *
ATTENTION
Respiratory failure intubation
* GINA 2010
**Camargo CA, Rachelefsky G. Managing Asthma exacerbations in the Emergency Department. Summary
of the National Asthma Education and Prevention Program Expert Panel. Proc Am Thorac Soc. Vol.6.357-
Managing exacerbations in primary care
PRIMARY CARE Patient presents with acute or sub-acute asthma exacerbation

Is it asthma?
ASSESS the PATIENT Risk factors for asthma-related death?
Severity of exacerbation?

Or MILD MODERATE SEVERE Life-threatening


Talks in phrases, Prefers Talks in words, sits hunched
sitting to lying, not agitated forwards, agitated Drowsy, confused
Increased respiratory rate Respiratory rate> 30 / min or silent chest
Accessory muscles not used Accessory muscles in use
Pulse rate of 100-120 bpm Pulse rate> 120 bpm URGENT
O2 saturation (on air) of 90-95% O2 saturation (on air) <90%
START
PEF> 50%TREATMENT
predicted or best PEF ≤50% predicted or best
SABA 4-10 puffs by pMDI + spacer,
repeat every 20 minutes for 1 hour TRANSFER TO ACUTE
WORSENING CARE FACILITY
prednisolone: adults 1 mg / kg, max.
50 mg, children 1-2 mg / kg, max. 40 mg
While waiting: give inhaled
Controlled oxygen (If available): target SABA and ipratropium bromide,
saturation of 93-95% (children: 94-98%) O2, Systemic corticosteroids
CONTINUE TREATMENT with SABA as needed
WORSENING
ASSESS RESPONSE AT 1 HOUR (Or Earlier)
Improving

ASSESS FOR DISCHARGE Arrange at DISCHARGE


symptoms improved, not needing SABA reliever: continue as needed
PEF improving, and> 60-80% of personal controller: start, or step up. Check inhaler
best or predicted technique, adherence
oxygen saturation> 94% room air prednisolone: continue, usually for 5-7 days
(3-5 days for children)
Resources at home adequate
Follow-up: within 2-7 days
FOLLOW UP
reliever: reduce to as-needed
controller: continue higher dose for short term (1-2 weeks) or long term (3 months), Depending
on the background to exacerbation
Risk factors: check and correct modifiable risk factors that may have Contributed to exacerbation,
Including inhaler technique and adherence
Action plan: Is it understood? Was it used appropriately? Does it need modification?
GINA 2017 Box 4-3 (1/7)
PRIMARY CARE Pacient with acute / sub-acute asthma exacerbation

Is this asthma?
ASSESS the PATIENT Asthma distinguished high risk of death?
The severity of exacerbations

Or MILD MODERATE SEVERE Life-threatening


Talk in the phrase, cut no Speak in words, agitasi
unconscious
agitation RR> 30 / min or silent chest
RR increased The use of accessory muscles
A breathing muscle - Pulse > 120 bpm
Pulse 100-120 bpm O2 saturation (on air) <90% URGENT
O2 saturation (on air) of 90-95% PEF ≤50% prediksi
PEF> 50% prediksi
START Terapi TRANSFER TO ACUTE
SABA 4-10 puffs by pMDI + Spacers, CARE FACILITY
reset each 20 minutes for 1 hour
worsening While waiting: inhalcare SABA and
prednisolone:
ipratropium bromide, O2, Systemic
Controlled oxygen (If available): target corticosteroids
saturation of 93-95% (children: 94-98%)

GINA 2017 Box 4-3 (4/7) ©©Global


GlobalInitiative
Initiativefor
forAsthma
Asthma
START Therapy
SABA 4-10 puffs by pMDI + Spacers, TRANSFER TO ACUTE
reset each 20 minutes for 1 hour
CARE FACILITY
prednisolone: WORSENING
While waiting: inhalcare SABA and
Controlled oxygen (If available): target
ipratropium bromide, O2, Systemic
saturation of 93-95% (children: 94-98%)
corticosteroids

CONTINUE Terapi with SABA if needed


WORSENING
EVALUATION OF RESPONSES 1 hour or more early
Improving

ASSESS FOR DISCHARGE


symptoms improved, not needing SABA
PEF improving, and> 60-80% of personal
best or predicted
oxygen saturation> 94% room air
Resources at home adequate

GINA 2017 Box 4-3 (5/7) © Global Initiative for Asthma


START Terapi TRANSFER TO ACUTE
SABA 4-10 puffs by pMDI + Spacers, CARE FACILITY
reset each 20 minutes for 1 hour
deteriorate While waiting: inhalcare SABA and
prednisolone:
ipratropium bromide, O2, Systemic
Controlled oxygen (If available): target corticosteroids
saturation of 93-95% (children: 94-98%)

CONTINUE TREATMENT with SABA if needed


deteriorate
EVALUATION OF RESPONSES 1 hour or more early
Improving

CURRENT REPATRIATION
EVALUATION FOR REPATRIATION reliever: fill in when needed
Symptoms improved, SABA can be stopped controller: be started or the dose was increased
PEF improved, and > 60-80% of the best from the previous, Check technique using the
predictors appliance and compliance
oxygen saturation> 94% room air prednisolone: lanjjutkan, especially 5-7 day
(3-5 day for children)
Preparation for the home meet
Follow-up: for 2-7 days

GINA 2017 Box 4-3 (6/7) © Global Initiative for Asthma


Managing exacerbations in acute care settings
INITIAL ASSESSMENT Are any of the following present?
A: Airway B: Breathing C: circulation Drowsiness, Confusion, Silent chest

NO
YES

Further Triage BY CLINICAL STATUS Consult ICU, start SABA and O2,
According to worst feature and prepare the patient for
intubation

Or MILD MODERATE SEVERE


Talks in phrases Talks in words
Prefers sitting to lying Sits hunched forwards
not agitated agitated
Increased respiratory rate Respiratory rate> 30 / min
Accessory muscles not used Accessory muscles being used
Pulse rate of 100-120 bpm Pulse rate> 120 bpm
O2 saturation (on air) of 90-95% O2 saturation (on air) <90%
Short-acting beta2-agonists Short-acting beta2-agonists
PEF> 50% predicted or best PEF ≤50% predicted or best
Consider ipratropium bromide ipratropium bromide
Controlled O2 to maintain Controlled O2 to maintain
saturation of 93-95% (94-98% of children) saturation of 93-95% (94-98% of children)
oral corticosteroids Oral or IV corticosteroids
Consider IV magnesium
Consider high-dose ICS
If continuing deterioration, treat as
severe and re-aassess for ICU

CLINICAL ASSESS PROGRESS FREQUENTLY


MEASURE LUNG FUNCTION
Patients in all one hour after initial treatment

FEV1 or PEF 60-80% of predicted or FEV1 or PEF <60% of predicted or


personal best and symptoms improved personal best, or lack of clinical response
SEVERE
MODERATE
Continue treatment as above
Consider for discharge planning and reassess frequently

GINA 2017 Box 4-4 (1/4)


INITIAL ASSESSMENT Are there any of these symptoms?
A: Airway B: Breathing C: circulation Sleepy, confusedSilent chest

NO
YES

clinical status consul ICU, start SABA and O2,


and preparation for intubation

Or MILD MODERATE SEVERE


Talk in the phrase Speak in words
Posisi sitting or lying down Crouched position
no agitation Agitasi
respiratory rate increase Respiratory rate> 30 / min
No use of a breathing muscle The use of a breathing muscles
pulse 100-120 bpm Pulse rate> 120 bpm
O2 saturation (on air) of 90-95%
O2 saturation (on air) <90%
PEF> 50% prediksi
PEF ≤50% prediction

GINA 2017 Box 4-4 (2/4) © Global Initiative for Asthma


MILD OR MODERATE SEVERE
Speak in a phrase or sentence Speak in words
Posisi sitting or lying down Crouched position
no agitation Agitasi
respiratory rate increase Respiratory rate> 30 / min
No use of a breathing muscle The use of a breathing muscles
pulse 100-120 bpm Pulse rate> 120 bpm
O2 saturation (on air) of 90-95% O2 saturation (on air) <90%
PEF> 50% prediksi PEF ≤50% prediction
Short-acting beta2-agonists Short-acting beta2-agonists
consideration ipratropium bromide ipratropium bromide
Controlled O2 to maintain Controlled O2 to maintain
saturation of 93-95% (94-98% of children) saturation of 93-95% (94-98% of children)
oral corticosteroids Oral or IV corticosteroids
consider magnesium sulphate

GINA 2017 Box 4-4 (3/4)


Short-acting beta2-agonists
Short-acting beta2-agonists
consideration ipratropium bromide
ipratropium bromide
Controlled O2 to maintain
saturation of 93-95% (94-98% of children) Controlled O2 to maintain
saturation of 93-95% (94-98% of children)
oral corticosteroids
Oral or IV corticosteroids
consider magnesium sulphate
If it worsens, immediately consider ICU
care

EVALUATION OF CLINICAL DEVELOPMENT often as possible


Examination of lung function (if possible)
one hour after initial treatment

FEV1 or PEF <60% prediction or


FEV1 or PEF 60-80% of prediksi
no clinical improvement
MODERATE
SEVERE
Consider for discharge planning
Continue therapy as above and re-asses

GINA 2017 Box 4-4 (4/4) © Global Initiative for Asthma


ASSESSMENT REPEAT & REPATRIATION

GOOD • should be observed for 30-60 minutes to


RESPONS
ensure response stability

• When APE (PEFR) is at least 70% Prediction or best


DISCHARGE
value

• Given systemic (oral) between 3-10 days post-


CORTICO discharge.
STEROID
• Low compliance intramuscular depo is better
- GINA 2010
-Camargo CA, Rachelefsky G. Managing Asthma exacerbations in the Emergency Department. Summary of the National
Asthma Education and Prevention Program Expert Panel. Proc Am Thorac Soc. Vol.6.357-366. 2009
EDUCATION
General education: to help patients recognize and
respond to symptoms of asthma.

• A review of the use of inhaler technique

• Referral for follow-up

• Plans therapy at discharge


Camargo CA, Rachelefsky G. Managing Asthma exacerbations in the Emergency Department. Summary of the
National Asthma Education and Prevention Program Expert Panel. Proc Am Thorac Soc. Vol.6.357-366. 2009
CONCLUSION
Exacerbations of asthma Treatment of asthma
require an immediate Patients with fatal asthma exacerbation begins
treatment and strict risk factors, need more with determining the
supervision to reduce the strict supervision degree of severity of
occurrence of worsening the attack.

Primary therapies in Systemic steroid


exacerbations include delivery after
oxygen administration,
short-acting β2 agonist exacerbations is
labor, corticosteroids, & important in addition
oxygenation to education
MANAGEMENT COPD
exacerbations
Isnu PRADJOKO
Dept.of Pulmonology and respiratory Medicine
Medical Faculty of Airlangga University/HOSPITAL Dr. Soetomo
Surabaya
DIAGNOSIS AND EXECUTING
ASSESSMENT OF COPD
Three cardinal symptoms of COPD exacerbations
are characterized by: (Anthonisen criteria)
- Increased shortness.
- Production of increased sputum / sputum.
- Sputum / sputum purulence is present.
Supporting investigation
• Thoracic images useful to exclude alternative diagnoses
• Examination of Blood Gas Analysis for suspicion toward signs of acute on
chronic respiratory failure. Examination of oxygen saturationPulse
Oxymetri helpful to adjust oxygen supplementation therapy.
• Routine hematological examination
• Electro Cardiography examination to determine heart problems
• Microbiological examination of sputum. Purulensi sputum during
exacerbations sufficiently used as an indication of empiric antibiotic
therapy.
• Examination of clinical chemistry electrolytes, blood glucose levels to
search for existing comorbidities.
COPD exacerbations procedural
Mechanical ventilation: inavasif and non-invasive

principle covers
PART MANAGEMENT IN HOSPITAL
Pharmacological therapy
•bronchodilators
•corticosteroids
•Antibiotics
•additional therapy

respiratory Support
•oxygen therapy
• Mechanical ventilation: inavasif and non-invasive
• Short-acting-bronchodilator.
• Beta 2 agonists are inhaled short Work (SABA) with or
without short-acting anticholinergic is usually the
treatment of choice for exacerbations bronkodikator. SABA
given as initial therapy for acute exacerbations. Can be
administered via MDI (equivalent to 400-800 mcg
salbutamol / puff 4-8) or nebuliser (equivalent to 2.5 mg)
• Giving Phosphodiesterase inhibitors (methylxantine)
considered when not sufficiently responds to SABA.
• Oral corticosteroids can be given in most cases of moderate to severe
exacerbations.
• The dose of prednisone 40 mg per day for 5 days is an appropriate dose
• ERS / ATS Guideline instead recommends oral corticosteroids up to <14
days. (ERS / ATS)
• according to the Thorax Journal, there have been several studies
examining the administration of systemic steroids in COPD exacerbations
with dose variations of methyl prednisolone 125 mg every 6 hours to
prednisolone 30 mg daily.
• Bronchodilators and corticosteroids can also be administered by
inhalation. Each has its advantages
• Antibiotics should be given to patients with COPD
exacerbations who have 3 cardinal symptoms
• has 2 cardinal symptoms if elevation of purulent
sputum is one of 2 symptoms or sufferers
requiring mechanical ventilation.
• Recommended recommended time is 5-10 days
according to germ maps.
ANTIBIOTIC GUIDE

LOOK FOR INTERNET


ADDITIONAL THERAPY
Erdostein
• Faizal Yunus et al, 2004 After 8 days of therapy, clinical symptoms
of sputum changes, sputum viscosity, cough difficulty, mucus
auscultation sound, frequency and cough quality and intensity of
breathing in both groups. Although not statistically significant, the
erdostein group took a shorter time and resulted in lower scores for
sputum color improvement, sputum viscosity, mucus auscultation
sound and shortness of breath compared to placebo groups. The
total clinical symptoms score in the erdostein group was lower than
in the placebo group. Average use of erdostein group rheumatism
spray was less than placebo and statistically significant.
NON PHARMACOLOGICAL THERAPY

OXYGEN THERAPY

• Oxygen is the treatment of hypoxemia and not


therapy for the claustrophobic.
• The target oxygen saturation in patients with
COPD is generally a 88% -92%. (McKay)
• Some studies indicate that hiperkapnea induced
by oxygen therapy. (MK Johnson, 2002)
mechanical ventilation
Non-Invasive or Invasive
Non-invasive to minimize the incidence of pneumonia (VAP)
self Management
Education of patients
Early recognition of symptoms of exacerbation by itself can
increase the improvement and reduce the incidence of
hospitalization.
Management of serious non-life-
threatening exacerbations of
• PerformCOPD: (GOLD,
an assessment of the2017)
severity of
symptoms, blood gas analysis, and thoracic
photographs
• Provide oxygen supplementation as well as
assess the pulse oximetry
• Give bronchodilators: increase SABA dose,
SABA and anticholinergic combination, LABA
giving if patient is stable.
Hemodinamik tidak stabil  membutuhkan vasopresor

Indications ICU Care


•Severe breathlessness with an inadequate response to
therapy
initials in the emergency ward
•Changes in mental status
•Hypoxemia persistent or worsening (PaO2 <40 mmHg) or
deterioration or severe respiratory acidosis (pH <7.25)
although with
oxygen supplements and non-invasive ventilation
•Requires invasive mechanical ventilation
•Hemodynamic unstable requires vasopressor
Indication of Invasive
Mechanical Ventilation
• Can not tolerate NIV or NIV failure
• Respiratory or cardiac arrest
• Stop breathing with loss of consciousness
• Massive aspiration
• Awareness decreases, psychomotor agitation
that can not be controlled by sedation
• Persistent inability to cleanse respiratory
secretions
Criteria returned home from
the hospital
• Can use PROFIT, either Beta 2-agonist and or
anticholinergic with or without inhaled
corticosteroids
• The patient can walk across the room
• Patients can eat and sleep without often
wake up because of shortness
• Clinically stable between 12-24 hours
SUMMARY
• COPD is a chronic airway disease that requires
attention and special treatment at the time of
exacerbation.
• Clinical assessment and distribution of
severity at exacerbations help determine the
therapy to be administered.
• Pharmacologic and nonpharmacologic
Achievement of optimal happens
35
Madison, Th 1962

36
THANK YOU
37