Clinical Practice Guidelines for Traumatic Brain Injury 2556Utai Sukviwatsirikul
Clinical Practice Guidelines for Traumatic Brain Injury 2556
แนวทางเวชปฏิบัติกรณีสมองบาดเจ็บ (Clinical Practice Guidelines for Traumatic Brain Injury) พิมพ์ครั้งที่ 1 2556
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Clinical Practice Guidelines for Traumatic Brain Injury 2556Utai Sukviwatsirikul
Clinical Practice Guidelines for Traumatic Brain Injury 2556
แนวทางเวชปฏิบัติกรณีสมองบาดเจ็บ (Clinical Practice Guidelines for Traumatic Brain Injury) พิมพ์ครั้งที่ 1 2556
http://pni.go.th/pnigoth/wp-content/uploads//2013/10/Clinical-Practice-Guidelines-for-Traumatic-Brain-Injury.pdf
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Internal medicine review for national license examination 2 Santi Silairatana
Internal Medicine review, with focus on pulmonary medicine and critical care medicine including pneumonia, asthma, COPD, tuberculosis, and sepsis & septic shock. Intended to be used for medical students.
แนวทางการจัดการความเสี่ยงที่ส่งผลต่อต้นทุนการจัดการสินค้าคงคลัง
ของร้านขายยา CDE ในจังหวัดขอนแก่น
The Approach of Risk Management that Affecting the
Inventory Management Cost of CDE Drugstore in Khonkaen Province
Best Practice in Communication
ราชวิทยาลัยกุมารแพทย์แห่งประเทศไทย สมาคมกุมารแพทย์แห่งประเทศไทย
บรรณาธิการ วินัดดา ปิยะศิลป์ วันดี นิงสานนท์
ISBN 978-616-91972-1-8
Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea ...Utai Sukviwatsirikul
Saccharomyces boulardii in the prevention of antibiotic-associated
diarrhoea in children: a randomized double-blind placebo-controlled
trial
M. KOTOWSKA, P. ALBRECHT & H. SZAJEWSKA
Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland
Accepted for publication 24 November 2004
1. Real life practice in COPD
รศ.พญ. เบญจมาศ ช่วยชู
สาขาวิชาโรคระบบการหายใจและวัณโรค
ภาควิชาอายุรศาสตร์ คณะแพทยศาสตร์ศิริราช
พยาบาล
มหาวิทยาลัยมหิดล
19 July 2013
5. Barnes PJ and Celli BR. Eur Respir J 2009; 33: 1165–1185
Systemic effects and comorbidities
of COPD
โรคปอดอุดกั้นเรื้อรังไม่ได้เป็นโรคที่
เกิดปัญหาเฉพาะในปอดเพียงอย่าง
เดียว
6. Definition
• “Systemic effects”
extrapulmonary manifestations which is the
consequence of COPD
• “Comorbidities”
highly prevalent diseases in COPD (e.g. cardiovascular,
metabolic, muscular, and bone disorders) in aged
patients represent the co-ocurrence.
Alvar Agustı´ A and Faner R. Proc Am Thorac Soc Vol 9, Iss. 2, pp 43–46, May 1, 2012
7. Aging
• Almost one-half of people aged > 65 years have > 3
chronic medical conditions, and one-fifth have five or
more
• Aging itself is associated with a chronic low-grade
inflammatory status and the theory that systemic
inflammation is the common driver of chronic diseases
would explain the high prevalence of chronic diseases
with increasing age
• This so-called “inflamm-aging” seems to be the
consequence of lifelong antigenic exposure leading to
genetic modifications
Nussbaumer-Ochsner Y and Rabe KF. Chest 2011;139;165-173
34. นิยามของภาวะกำาเริบเฉียบพลัน
(COPD exacerbation)
GOLD
“An event in the natural course of
the disease characterized by a
change in the patient’s baseline
dyspnea, cough, and/or sputum
that is beyond normal day-to-day
variations, is acute in onset, and
may warrant a change in regular
medication in a patient with
underlying COPD.”
Clinical diagnosis
Chest 2000;117;398S-401S
35. Bach PB. et al. Ann Intern Med. 2001;134:600-620.
36. Exacerbations
• Respiratory symptoms were classified as
– “major” symptoms (dyspnea, sputum purulence, sputum amount)
– “minor” symptoms (wheeze, sore throat, cough, and symptoms
of a common cold which were nasal congestion /discharge)
• Exacerbations were defined as the presence for at least
two consecutive days of increase in
– any two “major” symptoms or
– increase in one “major” and one “minor” symptom
according to criteria modified from Anthonisen and
colleagues
• The first of the two consecutive days was taken as the
day of onset of exacerbation.
Am J Respir Crit Care Med Vol 161. pp 1608–1613, 2000
37. Severity of exacerbations
• Moderate : treatment with systemic
corticosteroids or antibiotics or both
• Severe: Hospitalization
38. Hansel TT and Barnes PJ, Lancet 2009; 374: 744–55
Physiology of exacerbations in a hypothetical regular
smoker with COPD by stage of severity
42. Frequent exacerbators represent stable COPD phenotype
- independent of severity
ECLIPSE 3 year data
492
296
210
409
117
63
778
79
23
0%
20%
40%
60%
80%
100%
Year 1 Year 2 Year 3
≥2 Exacerb./Yr 1 Exacerb./Yr 0 Exacerb./Yr
• Proportion of subjects experiencing ≥2 exacerbations/year increases year-on-year
• Stable population provides potential to understand the cause(s) of the phenotype
Hurst et al. N Engl J Med 2010
43. The ‘frequent exacerbator phenotype’:
Frequency/severity by GOLD Category
7
18
33
22
33
47
0
10
20
30
40
50
GOLD II
(N=945)
GOLD III
(N=900)
GOLD IV
(N=293)
%ofpatients
p<0.01
Hospitalised for exacerbation in yr 1 Frequent exacerbations (2 or more)
ECLIPSE 1 year data Hurst et al. N Engl J Med 2010
47. Exacerbations/year
> 2
1
0
mMRC 0-1
CAT < 10
GOLD 4
mMRC >2
CAT >10
GOLD 3
GOLD 2
GOLD 1
SAMA prn
or
SABA prn
LABA
or
LAMA
ICS + LABA
or
LAMA
Manage Stable COPD:
PharmacologicTherapy
FIRST CHOICE
A B
DC
ICS + LABA
or
LAMA
55. Post-dose (hours)
ChangeinFEV1
(%)
Ipratropium + Albuterol
Albuterol
Ipratropium
COMBIVENT Inhalation Aerosol Study Group. Chest. 1994;105:1411-1419. Reproduced with permission from American College of Chest Physicians.
Short-acting Bronchodilators:
Onset and Duration of Action
P<0.001 for the combination versus each agent alone
N=534
57. Potential Side Effects of COPD Therapy:
Anticholinergic Agents
• Side effects are less common
versus systemic agents (e.g.,
atropine)
• Dry mouth is most commonly
reported adverse event
• Urinary retention may be a
problem for patients with bladder
outlet disease
Rennard SI. Lancet. 2004;364:791-802.
58. Sustained-release theophylline
• Narrow safety margin (10 -20 µg/ml)
(monitoring of theophylline blood level may be necessary)
• 400 µg/day (low dose 200 µg/day)
• Side effects
– CNS : seizures
– CVS : hypotension, arrhythmia
– GI : Nausea & vomiting
Theodur® , Nuelin SR®
หักครึ่งได้ห้ามบดห้ามเคี้ยว
63. Wongsurakiat P, Maranetra KN, Wasi C, Kositanont U, Dejsomritrutai W, Charoenratanakul S.
Acute Respiratory Illness in Patients With COPD and the Effectiveness of Influenza Vaccination:
A Randomized Controlled Study. CHEST 2004; 125:2011–2020
65. Pulmonary rehabilitation
Evidence A
• Improves exercise capacity
• Reduces the perceived intensity of breathlessness
• Improves health-related quality of life
• Reduces the number of hospitalizations and days in the hospital
• Improve recovery after hospitalization for an exacerbation
• Reduces anxiety and depression associated with COPD
Evidence B
• Strength and endurance training of the upper limbs improves arm function
• Benefits extend well beyond the immediate period of training
• Improves survival
• Enhances the effect of long-acting bronchodilators
Evidence C
• Respiratory muscle training can be beneficial, especially when combined
with general exercise training
GOLD 2013
66. Components of pulmonary rehabilitation
• Patient assessment
• Exercise training (strongest level of
evidence for benefit)
• Education
• Nutritional intervention
• Psychosocial support
Ries AL et al. Chest. 2007;131:4S-42S.
67. Establishing pulmonary rehabilitation
program
Funding and promotion
• Where possible, dedicated funding should be
sought to establish a PRP
• Costing estimates vary depending upon the
health-care system, existing infrastructure and
equipment, staffing and duration of the program
• Low cost programs in existing facilities have
been shown to be effective
• Lack of resources ought not to deter clinicians
from seeking to establish a PRP
Jenkins S. Respirology.2010;15:1157–73
68. Conclusions I
• Spirometry is required to make diagnosis of
COPD: post-bronchodilator FEV1/FVC < 0.7
• Assessment of COPD:
– symptoms: CAT, mMRC scale, CCQ
– degree of airflow limitation: post-bronchodilator FEV1
% pred (stage 1-4)
– risk of exacerbations: previous exacerbation, severe
COPD
– Comorbidities: cardiovascular disease, osteoporosis,
anxiety/depression, DM
69. Conclusions II
• Combined assessment of symptoms and risk of
exacerbations is the basis for non-
pharmacologic and pharmacologic management
of COPD
– Smoking cessation
– Influenza vaccination
– Pulmonary rehabilitation
– Bronchodilators + Inhaled corticosteroids
72. Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using
spirometry
Assess risk of exacerbations
Assess comorbidities
GOLD revised 2011
73. Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using
spirometry
Assess risk of exacerbations
Assess comorbidities
GOLD revised 2011
74. COPD Assessment Test (CAT)
Modified Medical Research Council Dyspnea
Scale (mMRC scale)
Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD: assess symptoms
GOLD revised 2011
77. Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using
spirometry
Assess risk of exacerbations
Assess comorbidities
GOLD revised 2011
78. Global Strategy for Diagnosis, Management and Prevention of COPD
Classification of Severity of Airflow Limitation in COPD*
In patients with FEV1/FVC < 0.70:
GOLD 1: Mild FEV1> 80% predicted
GOLD 2: Moderate 50% < FEV1< 80% predicted
GOLD 3: Severe 30% < FEV1< 50% predicted
GOLD 4: Very Severe FEV1< 30% predicted
*Based on Post-Bronchodilator FEV1
GOLD revised 2011
79. Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using
spirometry
Assess risk of exacerbations
Assess comorbidities
GOLD revised 2011
80. Global Strategy for Diagnosis, Management and Prevention of COPD
Assess Risk of Exacerbations
High risk of exacerbations
> 2 exacerbations within the last year or
FEV1 < 50 % of predicted value
GOLD revised 2011
81. Frequent exacerbators represent stable
COPD phenotype - independent of severity
ECLIPSE 3 year data
492
296
210
409
117
63
778
79
23
0%
20%
40%
60%
80%
100%
Year 1 Year 2 Year 3
≥2 Exacerb./Yr 1 Exacerb./Yr 0 Exacerb./Yr
• Proportion of subjects experiencing ≥2 exacerbations/year increases year-on-year
• Stable population provides potential to understand the cause(s) of the phenotype
Hurst et al. N Engl J Med 2010
82. The ‘frequent exacerbator phenotype’:
Frequency/severity by GOLD Category (1)
7
18
33
22
33
47
0
10
20
30
40
50
GOLD II
(N=945)
GOLD III
(N=900)
GOLD IV
(N=293)
%ofpatients
p<0.01
Hospitalised for exacerbation in yr 1 Frequent exacerbations (2 or more)
ECLIPSE 1 year data Hurst et al. N Engl J Med 2010
83. Global Strategy for Diagnosis, Management and Prevention of COPD
Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using
spirometry
Assess risk of exacerbations
Assess comorbidities
GOLD revised 2011
84. Global Strategy for Diagnosis, Management and Prevention of
COPD
Assess COPD Comorbidities
COPD patients are at increased risk for:
• Cardiovascular diseases
• Osteoporosis
• Respiratory infections
• Anxiety and Depression
• Diabetes
• Lung cancer
These comorbid conditions may influence
mortality and hospitalizations and should be
looked for routinely, and treated appropriately.
GOLD revised 2011
86. Relieve symptoms
Improve exercise tolerance
Improve health status
Prevent disease progression
Prevent and treat exacerbations
Reduce mortality
Reduce
symptoms
Reduce
risk
Global Strategy for Diagnosis, Management and Prevention of COPD
Manage Stable COPD: Goals of Therapy
87. Avoidance of risk factors
- smoking cessation
- reduction of indoor pollution
- reduction of occupational exposure
Influenza vaccination
Global Strategy for Diagnosis, Management and Prevention of
COPD
Manage Stable COPD: All COPD Patients
88. Global Strategy for Diagnosis, Management and Prevention of COPD
Combined Assessment of COPD
Risk
(GOLDClassificationofAirflowLimitation)
Risk
(Exacerbationhistory)
> 2
1
0
(C) (D)
(A) (B)
mMRC 0-1
CAT < 10
4
3
2
1
mMRC>2
CAT >10
Symptoms
(mMRC or CAT score))
89. Exacerbationsperyear
> 2
1
0
mMRC 0-1
CAT < 10
GOLD 4
mMRC >2
CAT >10
GOLD 3
GOLD 2
GOLD 1
SAMA prn
or
SABA prn
LABA
or
LAMA
ICS + LABA
or
LAMA
Global Strategy for Diagnosis, Management and Prevention of COPD
Manage Stable COPD: PharmacologicTherapy
FIRST CHOICE
A B
DC
ICS + LABA
or
LAMA
90. Global Strategy for Diagnosis, Management and Prevention of COPD
Manage Stable COPD: PharmacologicTherapy
(Medications in each box are mentioned in alphabetical order, and
therefore not necessarily in order of preference.)
Patient First choice Second choice Alternative Choices
A
SAMA prn
or
SABA prn
LAMA
or
LABA
or
SABA and SAMA
Theophylline
B
LAMA
or
LABA
LAMA and LABA
SABA and/or SAMA
Theophylline
C
ICS +LABA
or
LAMA
LAMA and LABA
PDE4-inh.
SABA and/or SAMA
Theophylline
D
ICS + LABA
or
LAMA
ICS andLAMA or
ICS + LABA and LAMA or
ICS+LABA and PDE4-inh.or
LAMA and LABA or
LAMA and PDE4-inh.
Carbocysteine
SABA and/or SAMA
Theophylline
93. Post-dose (hours)
ChangeinFEV1
(%)
Ipratropium + Albuterol
Albuterol
Ipratropium
COMBIVENT Inhalation Aerosol Study Group. Chest. 1994;105:1411-1419. Reproduced with permission from American College of Chest Physicians.
Short-acting Bronchodilators:
Onset and Duration of Action
P<0.001 for the combination versus each agent alone
N=534
95. Potential Side Effects of COPD Therapy:
Anticholinergic Agents
• Side effects are less common
versus systemic agents (e.g.,
atropine)
• Dry mouth is most commonly
reported adverse event
• Urinary retention may be a
problem for patients with bladder
outlet disease
Rennard SI. Lancet. 2004;364:791-802.
96. Sustained-release theophylline
• Narrow safety margin (10 -20 µg/ml)
(monitoring of theophylline blood level may be necessary)
• 400 µg/day (low dose 200 µg/day)
• Side effects
– CNS : seizures
– CVS : hypotension, arrhythmia
– GI : Nausea & vomiting
Theodur® , Nuelin SR®
หักครึ่งได้ห้ามบดห้ามเคี้ยว
100. Pulmonary rehabilitation
Evidence A
• Improves exercise capacity
• Reduces the perceived intensity of breathlessness
• Improves health-related quality of life
• Reduces the number of hospitalizations and days in the hospital
• Reduces anxiety and depression associated with COPD
Evidence B
• Strength and endurance training of the upper limbs improves arm function
• Benefits extend well beyond the immediate period of training
• Improves survival
• Improve recovery after hospitalization for an exacerbation
• Enhances the effect of long-acting bronchodilators
Evidence C
• Respiratory muscle training can be beneficial, especially when combined
with general exercise training
GOLD revised 2011
101. Conclusions I
• Spirometry is required to make diagnosis of
COPD: post-bronchodilator FEV1/FVC < 0.7
• Assessment of COPD:
– symptoms: CAT, mMRC scale
– degree of airflow limitation: post-bronchodilator FEV1
% pred (stage 1-4)
– risk of exacerbations: previous exacerbation, severe
COPD
– Comorbidities: cardiovascular disease, osteoporosis,
anxiety/depression, DM
102. Conclusions II
• Combined assessment of symptoms and risk of
exacerbations is the basis for non-
pharmacologic and pharmacologic management
of COPD
– Smoking cessation
– Influenza vaccination
– Pulmonary rehabilitation
– Bronchodilators + Inhaled corticosteroids
104. Establishing pulmonary rehabilitation
program
Funding and promotion
• Where possible, dedicated funding should be
sought to establish a PRP
• Costing estimates vary depending upon the
health-care system, existing infrastructure and
equipment, staffing and duration of the program
• Low cost programs in existing facilities have
been shown to be effective
• Lack of resources ought not to deter clinicians
from seeking to establish a PRP
Jenkins S. Respirology.2010;15:1157–73
105. Minimum requirement Optional
Pulse oximeter Weights machine/multigym
Polar heart rate monitor Stationary cycle
Sphygmomanometer Spirometer
Odometer (for walking test/track) Glucometer
Stopwatch Inspiratory muscle training device
Walking track/treadmill Rollator
Hand weights
Stairs/step
Portable oxygen and nasal prongs
Jenkins S. Respirology.2010;15:1157–73
Equipment required for a pulmonary rehabilitation program
106. Program setting
• Inpatient pulmonary rehabilitation
• Outpatient pulmonary rehabilitation
• Home-based rehabilitation
ATS/ERS statement on pulmonary rehabilitation. Am J Respir Crit Care Med.2006;173:1390–413
107. Outpatient pulmonary rehabilitation
• is the most widely available of settings and may be
hospital or community based
• Potential advantages include cost-effectiveness, a safe
clinical environment, and availability of trained staff
• The majority of studies describing the benefits of
pulmonary rehabilitation are derived from hospital-based
outpatient programs
ATS/ERS statement on pulmonary rehabilitation. Am J Respir Crit Care Med.2006;173:1390–413
โรงพยาบาลแม่พริก (Community based)โรงพยาบาลศิริราช (Hospital based)
108. Specificity of exercise training
• Lower extremity training is traditionally focused
– Cycling or walking
• Upper limb exercises should also be incorporated into
the training program because many daily activities
involve upper extremities
– e.g. arm cycle ergometer, free weights, and elastic
bands
• Upper limb exercise training reduces dyspnea during
upper limb activities and reduces ventilatory
requirements for arm elevation
ATS/ERS statement on pulmonary rehabilitation. Am J Respir Crit Care Med.2006;173:1390–413
111. Endurance training
• Cycling or walking exercises is the most commonly
applied
• High levels of intensity (60% maximal work rate)
• Total effective training > 30 minutes
• Interval training may be a reasonable alternative in case
difficult to achieve the target time or intensity
• Interval training results in significantly lower symptom
scores despite high absolute training loads, thus
maintaining the training effects
ATS/ERS statement on pulmonary rehabilitation. Am J Respir Crit Care Med.2006;173:1390–413
The recommendations of the ACSM include that the minimum duration of a session
is 20 minutes effective exercise training
112. Strength (or resistance) training
• Improve muscle mass and strength than endurance
training
• two to four sets of 6 to 12 repetitions at intensities
ranging from 50 to 85% of one repetition maximum
• Strength training may also result in less dyspnea during
the exercise period, thereby making this strategy easier
to tolerate than aerobic training
• Combination of endurance and strength training is
probably the best strategy to treat peripheral muscle
dysfunction in chronic respiratory disease, because it
results in combined improvements in muscle strength
and whole body endurance, without unduly increasing
training time
ATS/ERS statement on pulmonary rehabilitation. Am J Respir Crit Care Med.2006;173:1390–413
113. Intensity of exercise
• > 60% of the peak exercise capacity
• A Borg score of 4 to 6 for dyspnea or fatigue is usually a
reasonable target
• Alternatively, heart rate at the gas exchange threshold or
power output has also been used to target training
intensity
ATS/ERS statement on pulmonary rehabilitation. Am J Respir Crit Care Med.2006;173:1390–413
115. Lower limb endurance training – walking, cycling
• Training the muscles of ambulation is a mandatory
• Walking, ground-based or utilizes a treadmill, is an
essential component as it is an important activity in daily
life
• Training using a cycle ergometer is also beneficial as this
modality imposes a greater specific load on the
quadriceps muscles than walking
• Supervised ground-based walking training results in a
significantly greater increase in walking endurance
capacity compared with supervised cycle based training
Jenkins S. Respirology.2010;15:1157–73
116. Tests and measurements recommended for patient
assessment
Exercise capacity - Field-based walking test*
Tests most commonly used:
– six-minute walk test (6MWT)
– Incremental shuttle walk test (ISWT)
– Endurance shuttle walk test (ESWT)
• Measures recorded before a PRP should be the best of two
tests
• Two 6MWTs do not appear to be required at post-program
assessment
• 6MWT and ISWT can be used to prescribe initial training
intensity
MID
• 6MWT: ranges from 25 to 54 m, approximately 10% of the
6MWD measured before commencing the PRP
• ISWT: approximately 48 m
• ESWT: unknown
Jenkins S. Respirology.2010;15:1157–73
MID = minimal important difference in patients with COPD
PRP = pulmonary rehabilitation program
* - Indicates that the assessment is essential
137. Global Strategy for Diagnosis, Management and Prevention of COPD
Risk Factors for COPD
Lung growth and development
Gender
Age
Respiratory infections
Socioeconomic status
Asthma/Bronchial
hyperreactivity
Chronic Bronchitis
Genes
Exposure to particles
Tobacco smoke
Occupational dusts, organic
and inorganic
Indoor air pollution from
heating and cooking with
biomass in poorly ventilated
dwellings
Outdoor air pollution
GOLD revised 2011
138. Diagnosis of exacerbations
• A worsening of the following two or more major symtoms for at
least 2 consecutive days
• Dyspnea
• Sputum volume
• Sputum purulence
• Or
• A worsening of any 1 major symptom together with an increase
in any one of the following minor symptoms for at least 2
consecutive days
• Sore throat
• Colds (nasal discharge and/or nasal congestion)
• Fever without other cause
• Cough
• Wheeze
Editor's Notes
COPD is a complex disease with pulmonary and extrapulmonary manifestations
The link between these domains of the disease is unclear.
The individual capability of dealing with this inflammatory burden and developing protective mechanisms seems to modulate individual susceptibility to common causes of morbidity and mortality in elderly people
Dx asthma ที่ ศิริราช age 52 yr. smoking 20 p-y
Notes
The management of COPD depends on the stage of disease:
Management of mild-to-moderate COPD involves the avoidance of risk factors to prevent disease progression and pharmacotherapy as needed to control symptoms [p32/col1/par1/ln4–7]
Severe and very severe COPD often require the integration of several different disciplines, a variety of treatment approaches and a commitment of the clinician to the continued support of the patient as the illness progresses. [p32/col1/par1/ln7–11]
In addition to patient education, health advice and pharmacotherapy, COPD patients may need specific counselling about smoking cessation, instruction in physical exercise, nutritional advice and continued nursing support. [p32/col1/par1/ln11–14]
Not all approaches are needed for every patient, and assessing the potential benefit of each approach at each stage of the illness is a crucial aspect of effective disease management. [p32/col1/par1/ln15–19]
Reference
GOLD Guidelines (Updated 2007). Available at http://goldcopd.com.
If you were a frequent exacerbator in year 1, chance are that you would also be a frequent exacerbator in year 2 and 3
THIS SLIDE CONTAINS 3 BUILDS
Frequent exacerbators (those reporting 2 or more exacerbations per year) is more common in the very severe GOLD Category but almost ¼ of GOLD Category 2 subjects are frequent exacerbators and 7% of patients in GOLD Category 2 have been hospitalised in year 1 of the study
Speaker Notes
In a 12-week prospective, double-blind, parallel-group evaluation, 534 patients with moderately severe stable COPD received by metered-dose inhaler a combination of β2-adrenergic agonist albuterol plus ipratropium or either agent separately.
Results on days 1, 29, 57, and 85 showed that the combination treatment was statistically superior to either single agent alone in peak effect on FEV1, in the effect during the first 4 hours after dosing, and in total AUC for the FEV1 response.
The graph in this slide shows the percent change above test day baseline in FEV1 response on day 85. The combination produced a significantly greater change than either agent alone (P&lt;0.001 for each comparison).
Additional Information
The mean peak percent increases in FEV1 over baseline on the four test days were 31 to 33 percent for the combination, 24 to 25 percent for ipratropium, and 24 to 27 percent for albuterol. The differences between the combination and its components were statistically significant on all test days.
The AUC0-4 means for the combination were 21 to 44 percent greater than the ipratropium mean values and 30 to 46 percent greater than for albuterol.
Reference
COMBIVENT Inhalation Aerosol Study Group. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. An 85-day multicenter trial. Chest. 1994;105:1411-1419.
Speaker Notes
Systemic side effects can occur from inhaled β2-agonists, including palpitations and tremor most commonly, and additionally hypokalaemia and ventricular arrhythmias.
The systemic effects are mediated by drug absorbed through the lung and also by drug deposited in the pharynx and swallowed.
Additional Information
Although there are some differences, all of these bronchodilators currently used to achieve bronchodilation are selective for the β2 receptor. These adrenoceptors are also present in the heart where they mediate a complex array of effects.
It is thus likely that cardiac effects of currently used β2-agonists are due to these cardiac receptors, rather than to lack of selectivity.
Reference
Rennard SI. Treatment of stable chronic obstructive pulmonary disease. Lancet. 2004;364:791-802.
Speaker Notes
Dry mouth is the most common symptom reported with the anticholinergic agent tiotropium, probably due to systemic absorption.
Urinary retention could be a problem, especially for those with concurrent bladder outlet disease.
Local effects can occur if tiotropium is accidentally sprayed directly into the eye.
Additional Information
Currently used inhaled anticholinergics are quaternary amines, and side-effects are markedly less than with systemic anticholinergics, such as atropine.
Reference
Rennard SI. Treatment of stable chronic obstructive pulmonary disease. Lancet. 2004;364:791-802.
Proposed mechanism of corticosteroid resistance in COPD patients. Stimulation of normal alveolar macrophages activates NF-κB and other transcription factors to switch on histone acetyltransferase leading to histone acetylation and subsequently to transcription of genes encoding inflammatory proteins, such as tumor necrosis factor-α (TNF-α) and IL-8. Corticosteroids reverse this by binding to glucocorticoid receptors (GR) and recruiting HDAC-2. This reverses the histone acetylation induced by NF-κB and switches off the activated inflammatory genes. In COPD patients, cigarette smoke activates macrophages, as in normal subjects, but oxidative stress (acting through the formation of peroxynitrite) impairs the activity of HDAC-2. This amplifies the inflammatory response to NF-κB activation but also reduces the anti-inflammatory effect of corticosteroids, as HDAC-2 is now unable to reverse histone acetylation. MMP = matrix metalloproteinase.
Increase PaO2 &gt; 60 mmHg, SaO2 &gt; 90%
,which will preserve vital organ function by ensuring adequate delivery of oxygen
If you were a frequent exacerbator in year 1, chance are that you would also be a frequent exacerbator in year 2 and 3
THIS SLIDE CONTAINS 3 BUILDS
Frequent exacerbators (those reporting 2 or more exacerbations per year) is more common in the very severe GOLD Category but almost ¼ of GOLD Category 2 subjects are frequent exacerbators and 7% of patients in GOLD Category 2 have been hospitalised in year 1 of the study
Speaker Notes
In a 12-week prospective, double-blind, parallel-group evaluation, 534 patients with moderately severe stable COPD received by metered-dose inhaler a combination of β2-adrenergic agonist albuterol plus ipratropium or either agent separately.
Results on days 1, 29, 57, and 85 showed that the combination treatment was statistically superior to either single agent alone in peak effect on FEV1, in the effect during the first 4 hours after dosing, and in total AUC for the FEV1 response.
The graph in this slide shows the percent change above test day baseline in FEV1 response on day 85. The combination produced a significantly greater change than either agent alone (P&lt;0.001 for each comparison).
Additional Information
The mean peak percent increases in FEV1 over baseline on the four test days were 31 to 33 percent for the combination, 24 to 25 percent for ipratropium, and 24 to 27 percent for albuterol. The differences between the combination and its components were statistically significant on all test days.
The AUC0-4 means for the combination were 21 to 44 percent greater than the ipratropium mean values and 30 to 46 percent greater than for albuterol.
Reference
COMBIVENT Inhalation Aerosol Study Group. In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone. An 85-day multicenter trial. Chest. 1994;105:1411-1419.
Speaker Notes
Systemic side effects can occur from inhaled β2-agonists, including palpitations and tremor most commonly, and additionally hypokalaemia and ventricular arrhythmias.
The systemic effects are mediated by drug absorbed through the lung and also by drug deposited in the pharynx and swallowed.
Additional Information
Although there are some differences, all of these bronchodilators currently used to achieve bronchodilation are selective for the β2 receptor. These adrenoceptors are also present in the heart where they mediate a complex array of effects.
It is thus likely that cardiac effects of currently used β2-agonists are due to these cardiac receptors, rather than to lack of selectivity.
Reference
Rennard SI. Treatment of stable chronic obstructive pulmonary disease. Lancet. 2004;364:791-802.
Speaker Notes
Dry mouth is the most common symptom reported with the anticholinergic agent tiotropium, probably due to systemic absorption.
Urinary retention could be a problem, especially for those with concurrent bladder outlet disease.
Local effects can occur if tiotropium is accidentally sprayed directly into the eye.
Additional Information
Currently used inhaled anticholinergics are quaternary amines, and side-effects are markedly less than with systemic anticholinergics, such as atropine.
Reference
Rennard SI. Treatment of stable chronic obstructive pulmonary disease. Lancet. 2004;364:791-802.
Proposed mechanism of corticosteroid resistance in COPD patients. Stimulation of normal alveolar macrophages activates NF-κB and other transcription factors to switch on histone acetyltransferase leading to histone acetylation and subsequently to transcription of genes encoding inflammatory proteins, such as tumor necrosis factor-α (TNF-α) and IL-8. Corticosteroids reverse this by binding to glucocorticoid receptors (GR) and recruiting HDAC-2. This reverses the histone acetylation induced by NF-κB and switches off the activated inflammatory genes. In COPD patients, cigarette smoke activates macrophages, as in normal subjects, but oxidative stress (acting through the formation of peroxynitrite) impairs the activity of HDAC-2. This amplifies the inflammatory response to NF-κB activation but also reduces the anti-inflammatory effect of corticosteroids, as HDAC-2 is now unable to reverse histone acetylation. MMP = matrix metalloproteinase.
Increase PaO2 &gt; 60 mmHg, SaO2 &gt; 90%
,which will preserve vital organ function by ensuring adequate delivery of oxygen
Cycling or walking exercises is the most commonly applied
Optimally, the approach consists of relatively long exercise sessions at high levels of intensity (60% maximal work rate)
The total effective training time should ideally exceed 30 minutes
Interval training may be a reasonable alternative in case difficult to achieve the target time or intensity
Interval training is a modification of endurance training where the longer exercise session is replaced by several smaller sessions separated by periods of rest or lower intensity exercise
Interval training results in significantly lower symptom scores despite high absolute training loads, thus maintaining the training effects
Improve muscle mass and strength than endurance training
two to four sets of 6 to 12 repetitions at intensities ranging from 50 to 85% of one repetition maximum
Strength training may also result in less dyspnea during the exercise period, thereby making this strategy easier to tolerate than aerobic training
Combination of endurance and strength training is probably the best strategy to treat peripheral muscle dysfunction in chronic respiratory disease, because it results in combined improvements in muscle strength and whole body endurance, without unduly increasing training time
&gt; 60% of the peak exercise capacity is empirically considered sufficient to elicit some physiologic training effects, although higher percentages are likely to be more beneficial and are often well tolerated
In clinical practice, symptom scores can be used to adjust training load; these scores are anchored to a stable relative load and can be used throughout the training program
A Borg score of 4 to 6 for dyspnea or fatigue is usually a reasonable target
Alternatively, heart rate at the gas exchange threshold or power output has also been used to target training intensity
in daily life. Training using a cycle ergometer is also
beneficial as this modality imposes a greater specific
load on the quadriceps muscles than walking.95
However, supervised ground-based walking training
results in a significantly greater increase in walking
endurance capacity compared with supervised cyclebased
training.