‫‪Chronic Obstructive‬‬
‫‪Pulmonary Disease‬‬
‫)‪(COPD‬‬
‫פרופ' רפאל ברויאר‬
‫מכון הריאה‬
‫ביה"ח האוניברסיטאי הדסה עין‪-‬כרם‬
Obstructive Pulmonary Disease
 Chronic obstructive pulmonary disease
(COPD)
 Asthma
 Bronchiectasis
 Cystic fibrosis
 Bronchiolitis obliterans
 Alpha-1-antitrypsin deficiency
Obstructive Pulmonary Disease
 Chronic obstructive pulmonary
disease (COPD)





Asthma
Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency
Relative Mortality,
Leading Causes of Death in the US, 1980-2010
Proportion of
1980 Rate
U.S. Centers for Disease Control (CDC)
Leading Causes of Death in the US, 2010
1
Heart disease
595,444
2
Cancer
573,855
3
Chronic lower respiratory disease (COPD)
137,789
4
Cerebrovascular disease (stroke)
129,180
5
Accidents
118,043
6
Alzheimer’s Disease
83,308
7
Diabetes
68,905
8
Nephritis, nephrotic syndrome, nephrosis
50,472
9
Influenza & pneumonia
50,003
10
Suicide
37,793
11
Septicemia
34,843
12
Chronic liver disease & cirrhosis
31,802
13
Essential hypertension & hypertensive renal disease
26,577
14
Parkinson’s disease
21,963
Pneumonitis due to solids & liquids
17,001
U.S. CDC, 2012
COPD




Clinical presentation
Pathophysiology
Management strategy
Treatment
COPD ‫אבחנה של‬
 Airflow obstruction
that is irreversible
 FEV1 / FVC < 70%
‫‪Chronic Obstructive Pulmonary Disease‬‬
‫)‪(COPD‬‬
‫‪ ‬גורמי סיכון‪:‬‬
‫–עישון‬
‫‪ -‬אקטיבי ופסיבי‬
‫– זיהום אוויר‬
‫– חשיפות תעסוקתיות לאבק‪/‬עשן‬
‫– גורמים גנטיים (חסר ב ‪.)alpha-1-antitrypsin‬‬
‫‪ COPD‬ועישון‬
‫‪ ‬עישון הוא הגורם העיקרי –‬
‫אם אין עישון – יש לחשוב על אבחנה אחרת!‬
‫‪ ‬בכלל האוכלוסיה – ככל שאדם עישן יותר "שנות‬
‫קופסא" – ‪ FEV1‬יורד‪.‬‬
‫‪ ‬גם הסיכון למחלה תלוי ב”מינון” (שנות קופסה)‪.‬‬
‫רמזים מרכזיים לאבחנה של ‪COPD‬‬
‫‪ ‬מאפיינים מרכזיים‪:‬‬
‫– גיל > ‪50‬‬
‫– קוצר נשימה (דיספניאה) –‬
‫פרוגרסיבי ‪ /‬קבוע‪.‬‬
‫– שיעול פרודוקטיבי כרוני‪.‬‬
‫– חשיפה לגורמי סיכון – בעיקר עישון‬
COPD: Traditional Classification
 Emphysema Phenotype
The Pink Puffer
 Chronic Bronchitis Phenotype
The Blue Bloater
 Irreversible airflow obstruction
COPD—
Emphysema
Phenotype
The Pink Puffer
COPD – Emphysema Phenotype
“An anatomical alteration of the lung
characterized by an abnormal
enlargement of the air spaces distal to
the nonrespiratory bronchioles,
accompanied by destructive changes of
the alveolar walls."
Emphysema Pathology
Bullous Emphysema
Centriacinar Emphysema
Emphysema Pathology
Normal lung
Emphysematous lung
‫‪COPD – Emphysema Phenotype‬‬
‫‪Clinical Features‬‬
‫‪ ‬סמפטומים‪:‬‬
‫– ‪Dyspnea‬קוצר נשימה פרוגרסיבי‪.‬‬
‫– שיעול לא בולט‪.‬‬
‫– מיעוט (יחסי) בזיהומים ריאתיים‪.‬‬
‫‪ ‬בדיקה גופנית‪:‬‬
‫–‬
‫–‬
‫–‬
‫–‬
‫–‬
‫–‬
‫רזים‪ ,‬חולשת שרירים )‪.(asthenia‬‬
‫חזה חביתי‪ ,‬טכיפניאה‪.‬‬
‫ללא כיחלון בולט ("ורודים")‪.‬‬
‫ירידה דיפוזית בקולות הנשימה‪ ,‬אקספיריום מוארך‪.‬‬
‫סרעפות נמוכות‪.‬‬
‫קולות לב מרוחקים‪.‬‬
‫‪ ‬אק"ג‪ :‬ציר ימני‪ ,‬קומפלקסים קטנים‪.‬‬
‫‪COPD – Emphysema Phenotype‬‬
‫תפקודי ריאה‬
‫‪ ‬תמונה חסימתית אקספירטורית‪:‬‬
‫– ‪ FEV1‬מופחת‪ FEV1 / FVC ,‬מופחת‪.‬‬
‫– למרבית החולים אין שיפור משמעותי עם מרחיבי‬
‫סימפונות‪.‬‬
‫‪ ‬היפראינפלציה ולכידת אוויר‪:‬‬
‫– ‪ RV ,TLC‬ו‪ RV / TLC-‬מוגברים‪.‬‬
‫‪ ‬ירידה ביכולת הדיפוזיה של חמצן‪:‬‬
‫– ‪ DLCO‬מופחת‪.‬‬
‫– היפוקסמיה קלה עם ‪ Pco2‬תקין‪.‬‬
Effect of
Emphysema
on Diffusion
Capacity
‫‪Emphysema- CXR‬‬
‫היפראינפלציה‪ ,‬חדירות יתר‬
‫מרווח רטרוסטרנלי גדול‬
‫סרעפות שטוחות‬
Emphysema- HRCT
Normal
Emphysema
COPD—Chronic
Bronchitis
Phenotype
The Blue Bloater
COPD – Chronic Bronchitis Phenotype
" A clinical disorder characterized by
excessive mucus secretion... chronic or
recurrent productive cough... on most
days for a minimum of three months in
the year for not less than two
successive years."
‫‪COPD - Chronic Bronchitis Phenotype‬‬
‫‪Clinical Features‬‬
‫‪ ‬סמפטומים‪:‬‬
‫– שיעול יצרני כרוני‪ ,‬שפע ליחה "מוגלתית"‬
‫– זיהומים ריאתיים והתלקחויות תכופות‪.‬‬
‫– קוצר נשימה (מתגבר בהתלקחויות)‪.‬‬
‫‪ ‬בדיקה גופנית‪:‬‬
‫– עודף משקל‪.‬‬
‫– נטיה לכיחלון‪.‬‬
‫– אקספיריום מוארך עם צפצופים‪.‬‬
‫– סימנים של אי‪-‬ספיקת לב ימנית‬
‫(‪.)Cor Pulmonale‬‬
‫‪COPD - Chronic Bronchitis Phenotype‬‬
‫תפקודי ריאה‬
‫‪ ‬תמונה חסימתית אקספירטורית‪:‬‬
‫– ‪ FEV1‬מופחת‪ FEV1 / FVC ,‬מופחת‬
‫– ללא שיפור משמעותי עם מרחיבי סימפונות‬
‫‪ ‬נפחי הריאה ויכולת דיפוזיה )‪ – (DLCO‬תקינים‬
‫‪Chronic Bronchitis with Cor Pulmonale—CXR‬‬
‫ללא ממצאים משמעותיים בריאות עצמן‬
‫כלי דם‬
‫ריאתיים‬
‫מודגשים‬
‫לב מוגדל‬
Cor Pulmonale
Phenotype in
COPD
‫‪COPD - Cor Pulmonale Phenotype‬‬
‫‪ ‬שכיחות יותר של‪:‬‬
‫היפוקסמיה קשה‬
‫היפרקפניאה‬
‫חמצת נשימתית כרונית‪.‬‬
Normal
Chronic
Bronchitis
Emphysema
COPD




Clinical presentation
Pathophysiology
Management strategy
Treatment
Airway Obstruction Pathophysiology
Destruction of
peribronchial
supporting tissue
Plugging, inflammation &
narrowing of airways
Findings in Human BAL Studies
 Smokers’ BAL contain 4-5 times more neutrophils
than non-smokers
 Neutrophils in BAL fluid are the main source of
elastase
 Cigarette smoke and neutrophils suppress antielastase activity
 Conclusion: Quantity and activity of elastase
is increased in smokers
COPD - Pathophysiology
HYPOTHESIS
Anti-Elastase
Elastase
alpha-1-antitrypsin
COPD - Pathophysiology
Barnes,
Nat Rev
2008
COPD




Clinical presentation
Pathophysiology
Management strategy
Treatment
COPD Management Philosophy
 Relieve symptoms
 Improve exercise tolerance
 Improve health status
REDUCE
SYMPTOMS
AND
 Prevent disease progression
 Prevent & treat exacerbations
 Reduce mortality
REDUCE
RISK
COPD Management
 To determine disease severity & guide therapy,
assess:
– Symptoms
– Severity of airflow limitation
– Risk of exacerbation
– Presence of comorbidities
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011
COPD Management
 To determine disease severity & guide therapy,
assess:
– Symptoms: clinical assessment, mMRC or CAT
– Severity of airflow limitation
– Risk of exacerbation
– Presence of comorbidities
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011
Symptom Assessment
COPD Assessment Tool—CAT
Score > 10 considered symptomatic
COPD Management
 To determine disease severity & guide therapy,
assess:
– Symptoms (clinical assessment, mMRC or CAT)
– Severity of airflow limitation (GOLD I-IV)
– Risk of exacerbation
– Presence of comorbidities
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011
Grading COPD Severity
CHARACTERISTICS
(Post Bronchodilator FEV1)
STAGE
FEV1 / FVC
< 70%
I
Mild
FEV1 ≥ 80% predicted
II
Moderate
50% ≤ FEV1 ≤ 80% predicted
III
Severe
30% ≤ FEV1 ≤ 50% predicted
IV
Very
Severe
FEV1 ≤ 30% predicted
COPD Management
 To determine disease severity & guide therapy,
assess:
– Symptoms (clinical assessment, mMRC or CAT)
– Severity of airflow limitation (GOLD I-IV)
– Risk of exacerbation (frequency/year)
– Presence of comorbidities
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011
Definition of COPD Exacerbation
 Symptoms worsening beyond daily variations
– Cough / sputum / dyspnea
 Leads to change in medications
 Cause:
– Viral infection
– Bacterial infection
– Pollutants
 Diagnosis based on clinical presentation
Exacerbations—Critical Events in the
Natural History of COPD
 Poor quality of life
 Accelerated loss of lung function
 Exacerbations  increased risk future exacerbations
 Increased risk of hospitalization
 All-cause 3-year mortality after hospitalization up to
49% (GOLD 2011)
Probability of survival
Frequency of COPD Exacerbation & Survival
Time (months)

Prospective study, cohort 304 males, exacerbations requiring hospitalization,
5-year follow-up
Soler-Cataluῆa, Thorax 2005
Hurst et al, ECLIPSE, NEJM 2010
Frequent Exacerbator Phenotype
Pats with no
exacerbation
Pats with ≥2
exacerbations
Year 1
Year 2
Year 3
Hurst et al, ECLIPSE, NEJM 2010
Treatment of COPD Exacerbations
Treat early aggressively to minimize duration,
prevent recurrence
 Short-acting inhaled bronchodilators
(Ventalin, +/- Aerovent, as needed)
 Systemic corticosteroids
 Antibiotics
 Noninvasive ventilation
7 days
COPD: Antibiotic treatment
 Pathogens:
– Streptococcus pneumonia
– Haemophilus influenza
– Moraxella catarrhalis
 Antibiotics:
– Cefuroxime, beta-lactam, macrolides,
doxycycline
Impact of COPD Exacerbations
Impact on
Accelerated
symptoms &
lung function
quality of life
decline
Exacerbations
Increased
economic
costs
Increased
mortality
 Treat early aggressively to minimize duration,
prevent recurrence
COPD Management
 To determine disease severity & guide therapy,
assess:
– Symptoms (clinical assessment, mMRC or CAT)
– Severity of airflow limitation (GOLD I-IV)
– Risk of exacerbation (frequency / year)
– Presence of comorbidities
Global Initiative for Chronic Obstructive Lung Disease (GOLD)
Systemic Manifestations & Comorbidities
 Cardiovascular
disease


– Pulmonary hypertension

– Ischemic heart disease

– Congestive heart failure
– Stroke
Lung cancer
Diabetes, metabolic syn
Osteoporosis
Skeletal muscle
dysfunction
 Depression
Percent with Condition
COPD—Independent Risk Factor for
Cardiovascular Morbidity
Higher Rates of Hospitalization Due To Comorbidities
18
16
16.5
15
Percent of Subjects
14
12
12.6
COPD
11
10
10.2
8
10.2
9.8
9.5
No COPD
7
6
4
2.9
2
3.6
3
1.6
0
Hypertension
IHD
Diabetes
Pneumonia
CHF
RF
2.6
0.4
PVD
1
TM
Reproduced with permission of Chest, from “Comorbidity and Mortality in COPD Related Hospitalizations in the United
States, 1979 to 2001,” Holguin F et al, Vol 128, pp 2005-2011, Copyright © 2005.
Higher Mortality Rates Due to Cormorbidities
In Hospital Mortality (as % of discharges)
40
IHD = ischemic heart disease
CHF = congestive heart failure
RF = respiratory failure
PVD = pulmonary vascular disease
TM = thoracic malignancy
37
35
30
25
25
COPD
22.5
22
No COPD
19
20
14
15
12
10
10
13
12
11
8.5
10
6.5
5
5
3
0
RF
Pneumonia Heart Failure
IHD
Hypertension
TM
Diabetes
PVD
Holguin et al Chest 2005
Comorbidity in COPD
Traditional View
 Airflow obstruction & emphysema affect
gas exchange  systemic implications
Current Debate
 Is airways compromise the central
disease process?
OR
 Is it one manifestation of a “systemic”
inflammatory state with multiple organ
compromise?
COPD




Clinical presentation
Pathophysiology
Management strategy
Treatment
COPD Risk Assessment
GOLD IV
Frequency of Exacerbations
C
D
≥2
A
B
1
GOLD III
GOLD II
GOLD I
0
mMRC 0-1
CAT < 10
Risk of Exacerbation
Severity of Obstruction
mMRC > 2
CAT > 10
Increasing Symptoms (mMRC or CAT score)
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011
COPD Treatment
Smoking
Cessation
Short-Term
↓ cough, sputum
↑ lung function
Long-Term
↑ survival
↑ QOL
↓ lung function
↓cormorbidities
COPD Risk and Smoking Cessation
FEV1 (% of value at age 25)
100
Never smoked
or not
susceptible to
smoke
75
Smoked
regularly and
susceptible to
effects of smoke
50
Stopped
smoking at
45 (mild
COPD)
Disability
25
Death
0
25
50
75
Stopped
smoking at
65 (severe
COPD)
Age (years)
Fletcher CM, Peto R. BMJ. 1977;1:1645-1648
COPD Treatment
Short-Term
Influenza,
Pneumococcal
Immunization
Long-Term
↓ exacerbation
frequency
COPD Treatment
Bronchodilators:
Long-acting
Beta2 Agonist or
Anti Cholinergic
Combination:
Inhaled
Corticosteroid &
Long-acting
Beta2 Agonist
Short-Term
↓ airflow obstruction
↓ hyperinflation
↑ exercise endurance
↑ tremors, dry mouth
Long-Term
↑ Quality of life
↓ exacerbations
↓ airflow obstruction
↓ hyperinflation
↓ dyspnea
↑ exercise tolerance
↑ Quality of life
↑ possibly survival
↓ exacerbations
↑ risk of pneumonia
Symptom- and Risk-Based Treatment Paradigm
MANY SYMPTOMS, HIGH RISK OF EXACERBATIONS
1: Combination inhaled corticosteroid/longacting beta2 agonist or long-acting
anticholinergic
1: Combination inhaled corticosteroid/longacting beta2 agonist or long-acting
anticholinergic
2: Combination 2 long-acting bronchodilators
or combination inhaled corticosteroid / longacting anticholinergic
2: Combination inhaled corticosteroid/longacting beta2 agonist, long-acting
anticholinergic
3: May add phosphodiesterase-4 inhibitor or
short-acting bronchodilator and theophylline
or carbocysteine
FEW SYMPTOMS, LOW RISK OF EXACERBATIONS
1: Short-acting bronchodilator
MORE SYMPTOMS, LOW RISK OF EXACERBATIONS
1: Long-acting bronchodilators recommended
2: Combination of short-acting bronchodilators 2: Combination of long-acting bronchodilators
/ introduce long-acting bronchodilator
in patients with severe breathlessness
INCREASING SYMPTOMS
Global Initiative for
COPD (GOLD) 2011
INCREASING EXACERBATIONS
INCREASING AIRWAYS OBSTRUCTION
FEW SYMPTOMS, HIGH RISK OF EXACERBATIONS
COPD Treatment
Short-Term
Oxygen Therapy ↑ exercise endurance
Long-Term
↑ survival
Oxygen Therapy Improves Survival
"The more
hours, the
better!"
Lancet 2003 362:1053-1061
Indications for Oxygen Therapy
 PaO2 <55 mm Hg or SaO2 ≤88%
 Milder hypoxemia – In the presence of cor pulmonale or hematocrit >55%
 Normoxemic at rest but desaturation
during exercise or sleep
Oxygen Therapy





Aim: PaO2 60-70mm Hg or SatO2 >88%
Nasal masks 1-2L/min
Venturi masks 24%, 28%, 35%
Monitor SatO2, PaCO2 and pH
If hypoxemia persists or CO2 retention worsens:
optimize bronchodilators, consider using assisted
noninvasive ventilation
Noninvasive Ventilation
 If hypoxemia persists or CO2 retention
worsens:
– Optimize bronchodilators and consider using assisted
noninvasive ventilation
COPD Treatment
Pulmonary
Rehabilitation
Short-Term
Long-Term
↓ dynamic hyperinflation ↑ QOL
↓ functional dyspnea
↑ possibly survival
↑ exercise endurance
Pulmonary Rehabilitation
 Goals: Reduce symptoms, improve quality of life,
and increase participation in daily activities
 Program includes:
– Exercise training (tolerance and muscle strength)
– Nutrition counseling
– Education
Pulmonary Rehabilitation
 Components:
– Exercise training
(bicycle ergometry/treadmill & upper limb exercises)
– Education
– Nutrition counseling
– Smoking cessation
 8-12 week duration
 Beneficial in a wide range of disability
Benefits of Pulmonary Rehabilitation in COPD








Improves exercise capacity
Improves recovery from exacerbation
Improves QOL
Reduces perceived intensity of breathlessness
Reduces hospitalizations, days in hospital
Reduces anxiety & depression
Benefits beyond immediate training period
May improve survival
 Acute reversibility of airways obstruction in
response to bronchodilator is a poor predictor
of benefit to FEV1 after 1 year

SF BUILD THIS SLIDE UP
Exercise Tolerance & Survival in COPD






365 patients, 2 centers, 19942005
Smoking history >10 years
FEV1/FVC < 0.70
171 deaths (47%, 43±24 mo),
respiratory failure (majority),
cardiovascular disease (9%),
lung cancer (18%), other causes
(23%)
Nonsurvivors older, more
severe airflow limitation, lower
mean exercise capacity
6MWD best predictor of allcause mortality
Cote & Celli et al, Chest 2007
Survival probability
Exercise Capacity & Survival in COPD
1.0
0.8
0.6
0.4
0.2
0
>350 m
<350 m
0
12
24
36
48
60
72
84
96
F/U (months)
 Exercise tolerance predicts survival in COPD
Cote & Celli et al, Chest 2007
COPD Phenotypes
 Emphysema-hyperinflation Dyspnea, exercise intolerance,
hyperinflation
 Chronic bronchitis Cough & sputum 3 mos/yr, 2 yr
 Frequent exacerbator ≥ 2 exacerbations / year
 Cor pulmonale




COPD w bronchiectasis HRCT diagnosis, airways colonization?
Mixed asthma-COPD Increased reversibility of obstruction
COPD-eosinophilia
Comorbidities & systemic inflammation ↑ biomarkers
(C-reactive protein, serum alymoid A, IL-6, IL-8, tumor necrosis factor α, leukocytes)
 α1 antitrypson
Phenotype-Specific COPD Treatment
Treatment
Roflumilast
Phenotype
Frequent exacerbator
(≥ 2 / yr)
Azithromycin
Frequent exacerbator
(≥ 2 / yr)
Benefit
↓ exacerbations
↑ quality of life
↑ lung function
↓ exacerbations
↑ QOL
Chronic antibiotic COPD with
bronchiectasis
↓ exacerbations
↓ eradicate colonizing
microorganisms
↓ chronic inflammation
Inhaled
corticosteroids
↑ lung function
COPD-eosinophilia
and
Mixed asthma-COPD
COPD Treatment
Treatment
Lung Volume
Reduction
Surgery /
Bronchoscopy
Phenotype
Predominantly upper
lobe emphysema
Benefit
↑ exercise capacity
Lung
Transplantation
With failure of
medical treatment,
select patients
↓ exacerbations
↑ quality of life
↑ lung function
COPD – Conclusions
 COPD: underdiagnosed; high & rising mortality
 Dyspnea, chronic cough, +/- sputum, risk factors
 consider COPD
 Diagnosis by spirometry: FEV1 / FVC < 70%
 Treatment of stable COPD: consider symptoms,
severity of obstruction, frequency of exacerbations
 Manage exacerbations: bronchodilators,
corticosteroids, +/- antibiotics
COPD – Conclusions
 High rates of comorbidities
 Rehabilitation: a standard of care to break the
cycle of dyspnea, fear, anxiety, increasing
inactivity
 A heterogeneous disease: the future is
phenotype-specific treatment
Obstructive Pulmonary Disease
 Chronic obstructive pulmonary disease
(COPD)
 Asthma




Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency
Bronchitis
Emphysema
Asthma
Other
Airways Obstruction
Differential Diagnosis:
COPD and Asthma
COPD
ASTHMA
 Onset in mid-life

 Symptoms slowly progressive

 Long smoking history

 Dyspnea during exercise
 Largely irreversible airflow
limitation
Onset early in life (often
childhood)
Symptoms vary from day to day
Symptoms at night/early
morning
 Allergy, rhinitis, and/or eczema
also present
 Family history of asthma
 Largely reversible airflow
limitation
COPD – Differential Diagnosis
History
Chronic
Bronchitis
Emphysema
Asthma
Smoking
+
+
+/-
Productive
Cough
Main
complaint
May be
absent
Common
(usually
nocturnal)
Dyspnea
May be
absent
Main
complaint
Episodic
Exacerbations
++
-
++
Allergy
-
-
Common
COPD - Differential Diagnosis
Physical Examination
Chronic
Bronchitis
Emphysema
Asthma
Barrel Chest
+/-
+
Rare
Prolonged
Expiration
+
+
+
Decreased
Breathing
Sounds
In severe
exacerbation
Typical
In severe
exacerbation
Wheezing
+/-
Rare
-/+/++
Cyanosis
++
+/-
In severe
exacerbation
Weight Loss
-
In advanced
disease
-
COPD - Differential Diagnosis
PFT
Pulmonary Function
Component
Chronic
Bronchitis
Emphysem
a
Asthma
FEV1
Normal/


FEV1 after
Bronchodilator
 /No
change
 /No
change

Residual Volume
(RV)
Normal/ 

Normal/ 
Total Lung Capacity
(TLC)
Normal

Normal
Diffusion Capacity
(DLCO)
Normal

Normal
COPD - Differential Diagnosis
Complications
Chronic
Bronchitis
Emphysema
Asthma
Common
Common
During
exacerbation
Erythrocytosis
Common
In advanced
disease
Rare
Hypercarbia
Common
End-stage
disease
In severe
exacerbation
Cor-pulmonale
Common
In advanced
disease
Rare
Hypoxemia
Obstructive Pulmonary Disease
 Chronic obstructive pulmonary disease
(COPD)
 Asthma
 Bronchiectasis
 Cystic fibrosis
 Bronchiolitis obliterans
 Alpha-1-antitrypsin deficiency
‫‪Bronchiectasis - Definition‬‬
‫‪ ‬מצב בו דלקות וזיהומים גורמים נזק לדרכי‬
‫האוויר‪ ,‬כך שאלו הופכים למעוותים‬
‫‪ ‬ריר מצטבר בדרכי האוויר וקיים קושי לסלקו‬
‫בשל פגיעה במנגנוני סילוק ההפרשות של‬
‫דרכי האוויר‬
‫‪ ‬התוצאה – זיהומים חוזרים וקשים‬
Bronchiectasis - Pathology
Bronchiectasis - Etiology
 Recurrent bronchial infections
– Airway obstruction (localized) caused by foreign
body, benign tumor
– Post-infectious (measles, pertussis, S. aureus, TB)
 Immune deficiency- hypoglobulinemia, leukocyte
dysfunction
 Cystic fibrosis
 Ciliary dyskinesia (Kartagener's syndrome)
 Allergic bronchopulmonary aspergillosis
Bronchiectasis - Clinical Features





Chronic productive cough
Coarse crackles, clubbing
Hemoptysis
Obstructive lung disease
Respiratory failure
Bronchiectasis - Diagnosis
 Chest x-ray
 Bronchography
 High-resolution CT
Bronchiectasis
Chest x-ray
Bronchiectasis
Bronchography
Bronchiectasis
High-resolution
CT
Bronchiectasis - Treatment





Antibiotics (p. aeruginosa, s. aureus)
Vaccinations
Physiotherapy
Bronchodilators
Surgery for localized disease
Obstructive Pulmonary Disease
 Chronic obstructive pulmonary disease
(COPD)
 Asthma
 Bronchiectasis
 Cystic fibrosis
 Bronchiolitis obliterans
 Alpha-1-antitrypsin deficiency
Obstructive Pulmonary Disease
 Chronic obstructive pulmonary disease
(COPD)
 Asthma
 Bronchiectasis
 Cystic fibrosis
 Bronchiolitis obliterans
 Alpha-1-antitrypsin deficiency
‫‪Bronchiolitis Obliterans - Definition‬‬
‫‪ ‬תהליך הצטלקות כרוני של דרכי האוויר הקטנות‬
‫של הריאה‪.‬‬
‫‪ ‬בעקבות כך ‪ -‬הרס פרוגרסיבי של דרכי אוויר אלו‬
‫המביאה להתפתחות מחלת ריאות חסימתית‪.‬‬
‫‪ ‬מדובר בהתהליך בלתי הפיך בעיקרו‪.‬‬
Bronchiolitis Obliterans - Etiology





Inhalation of toxic fumes (smoke)
Connective tissue disease (RA)
Post BMT, lung & heart-lung transplant
Drugs (eg., gold, penicillamine)
Consequent to respiratory infections
(adenovirus, mycoplasma)
 Cryptogenic
Cryptogenic Bronchiolitis Obliterans
Clinical Features
 Onset: months to years
 Dyspnea and cough with minimal
sputum production
 Normal breathing sounds, occasionally
rhonchi
 CXR= normal or hyperinflation,
 CT= mosaic attenuation, ground-glass
pattern
Bronchiolitis Obliterans
Inspiratory & Expiratory HRCT
)‫מוזאיקה (אוויר כלוא‬
‫זכוכית חול‬
Obstructive Pulmonary Disease
 Chronic obstructive pulmonary
disease (COPD)
 Asthma
 Bronchiectasis
 Cystic fibrosis
 Bronchiolitis obliterans
 Alpha-1-antitrypsin
deficiency
‫‪Alpha-1-Antitrypsin Deficiency‬‬
‫‪ 5% ‬מחולי אמפיזמה‬
‫‪ ‬רמות האנזים בחולים קטנות מ‪35%-‬‬
‫‪ ‬הגנוטיפ התקין מכונה ‪ PiMM‬והפגום ‪PiZZ‬‬
‫‪ ‬הביטויים הקליניים‪:‬‬
‫– אמפיזמה‬
‫– שחמת והפטומה‪.‬‬
‫‪ ‬טיפול – תחליף האנזים )‪(Zymera‬‬