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Chronic Obstructive Pulmonary Disease (COPD) פרופ' רפאל ברויאר מכון הריאה...
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Transcript of Chronic Obstructive Pulmonary Disease (COPD) פרופ' רפאל ברויאר מכון הריאה...
Chronic Obstructive Pulmonary Disease
(COPD)
פרופ' רפאל ברויארמכון 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)
1 Heart disease 595,4442 Cancer 573,855
3 Chronic lower respiratory disease (COPD) 137,7894 Cerebrovascular disease (stroke) 129,1805 Accidents 118,0436 Alzheimer’s Disease 83,3087 Diabetes 68,9058 Nephritis, nephrotic syndrome, nephrosis 50,4729 Influenza & pneumonia 50,00310 Suicide 37,79311 Septicemia 34,84312 Chronic liver disease & cirrhosis 31,80213 Essential hypertension & hypertensive renal disease 26,57714 Parkinson’s disease 21,963
Pneumonitis due to solids & liquids 17,001
Leading Causes of Death in the US, 2010
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
- אקטיבי ופסיבי עישון–
זיהום אוויר –חשיפות תעסוקתיות לאבק/עשן–).alpha-1-antitrypsin(חסר ב גורמים גנטיים –
COPDועישון
– עישון הוא הגורם העיקרי
אם אין עישון – יש לחשוב על אבחנה אחרת!
בכלל האוכלוסיה – ככל שאדם עישן יותר יורד.FEV1"שנות קופסא" –
.(שנות קופסה) ”גם הסיכון למחלה תלוי ב”מינון
COPDרמזים מרכזיים לאבחנה של
:מאפיינים מרכזיים50גיל > –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 PhenotypeThe 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 PathologyBullous Emphysema Centriacinar Emphysema
Emphysema Pathology
Normal lung Emphysematous lung
COPD – Emphysema PhenotypeClinical Features
:סמפטומים–Dyspnea.קוצר נשימה פרוגרסיבישיעול לא בולט.–מיעוט (יחסי) בזיהומים ריאתיים.–
:בדיקה גופנית).astheniaרזים, חולשת שרירים (–חזה חביתי, טכיפניאה.–ללא כיחלון בולט ("ורודים").–ירידה דיפוזית בקולות הנשימה, אקספיריום מוארך.–סרעפות נמוכות.–קולות לב מרוחקים.–
:ציר ימני, קומפלקסים קטנים.אק"ג
:תמונה חסימתית אקספירטורית–FEV1 ,מופחת FEV1 / FVC .מופחת
למרבית החולים אין שיפור משמעותי עם מרחיבי –סימפונות.
:היפראינפלציה ולכידת אוויר–TLC, RV-ו TLC / RV.מוגברים
:ירידה ביכולת הדיפוזיה של חמצן– DLCO.מופחת
תקין.Pco2היפוקסמיה קלה עם –
COPD – Emphysema Phenotypeתפקודי ריאה
Effect of Emphysema on Diffusion Capacity
Emphysema- CXR היפראינפלציה, חדירות יתר
סרעפות שטוחות מרווח רטרוסטרנלי גדול
Emphysema- HRCT
Normal Emphysema
COPD—Chronic Bronchitis PhenotypeThe 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."
סמפטומים:שיעול יצרני כרוני, שפע ליחה "מוגלתית"–זיהומים ריאתיים והתלקחויות תכופות.–קוצר נשימה (מתגבר בהתלקחויות).–
:בדיקה גופניתעודף משקל.–נטיה לכיחלון.–אקספיריום מוארך עם צפצופים.–סימנים של אי-ספיקת לב ימנית –
)Cor Pulmonale.(
COPD - Chronic Bronchitis PhenotypeClinical Features
:תמונה חסימתית אקספירטורית–FEV1 ,מופחת FEV1 / FVC מופחת
ללא שיפור משמעותי עם מרחיבי סימפונות–) נפחי הריאה ויכולת דיפוזיהDLCO – (תקינים
COPD - Chronic Bronchitis Phenotype תפקודי ריאה
Chronic Bronchitis with Cor Pulmonale—CXR
משמעותיים בריאות ללא ממצאיםעצמן
לב מוגדל
כלי דם ריאתיים מודגשים
Cor Pulmonale Phenotype in COPD
COPD - Cor Pulmonale Phenotype
:שכיחות יותר שלהיפוקסמיה 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 anti-elastase activity
Conclusion: Quantity and activity of elastase is increased in smokers
alpha-1-antitrypsinElastase
Anti-Elastase
COPD - PathophysiologyHYPOTHESIS
COPD - Pathophysiology
Barnes, Nat Rev 2008
COPD Clinical presentation Pathophysiology Management strategy Treatment
Relieve symptoms Improve exercise tolerance Improve health status
AND Prevent disease progression Prevent & treat exacerbations Reduce mortality
REDUCE SYMPTOMS
REDUCE RISK
COPD Management Philosophy
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
COPD Assessment Tool—CATScore > 10 considered symptomatic
Symptom Assessment
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
STAGE CHARACTERISTICS(Post Bronchodilator FEV1)
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)
Prospective study, cohort 304 males, exacerbations requiring hospitalization, 5-year follow-up
Soler-Cataluῆa, Thorax 2005
Frequency of COPD Exacerbation & SurvivalP
roba
bili
ty o
f sur
viva
l
Time (months)
Hurst et al, ECLIPSE, NEJM 2010
Frequent Exacerbator Phenotype
Hurst et al, ECLIPSE, NEJM 2010
Pats with no exacerbation
Pats with ≥2 exacerbations
Year 1 Year 2 Year 3
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
Acceleratedlung function
decline
Impact on symptoms&
quality of life
Increased mortality
Exacerbations
Increased economic
costs
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) 2011
Systemic Manifestations & Comorbidities
Cardiovascular disease – Pulmonary hypertension– Ischemic heart disease – Congestive heart failure– Stroke
Lung cancer Diabetes, metabolic syn Osteoporosis Skeletal muscle
dysfunction Depression
COPD—Independent Risk Factor for Cardiovascular Morbidity
Pe
rce
nt w
ith C
on
diti
on
16.5
15
10.211
9.8
7
3 2.6
12.6
10.29.5
2.93.6
1.6 0.4 10
2
4
6
8
10
12
14
16
18
Hypertension IHD Diabetes Pneumonia CHF RF PVD TM
Pe
rce
nt o
f Su
bje
cts
COPD
No COPD
Higher Rates of Hospitalization Due To Comorbidities
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
37
25
22.5
19
1312
11
5
22
14
1012
8.56.5
10
3
0
5
10
15
20
25
30
35
40
RF Pneumonia Heart Failure IHD Hypertension TM Diabetes PVD
In H
osp
ital M
ort
alit
y (a
s %
of d
isch
arg
es)
COPD
No COPD
IHD = ischemic heart diseaseCHF = congestive heart failureRF = respiratory failurePVD = pulmonary vascular diseaseTM = thoracic malignancy
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
Risk
of E
xace
rbati
on≥2
1
0
Frequency of Exacerbations
COPD Risk Assessment
C D
A B
Increasing Symptoms (mMRC or CAT score)
mMRC 0-1CAT < 10
mMRC > 2CAT > 10
GOLD IV
GOLD III
GOLD II
GOLD I
Severity of Obstruction
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
Fletcher CM, Peto R. BMJ. 1977;1:1645-1648
FE
V1
(% o
f va
lue
at a
ge
25)
Smoked regularly and
susceptible to effects of smoke
Never smoked or not susceptible to smoke
Stopped smoking at 45 (mild COPD)
Stopped smoking at 65 (severe COPD)
Disability
Death
25
50
75
100
0
Age (years)25 50 75
COPD Treatment
Influenza, Pneumococcal Immunization
Short-Term Long-Term↓ exacerbation
frequency
Short-Term Long-TermBronchodilators: Long-acting Beta2 Agonist or Anti Cholinergic
↓ airflow obstruction↓ hyperinflation↑ exercise endurance↑ tremors, dry mouth
↑ Quality of life↓ exacerbations
Combination: Inhaled Corticosteroid & Long-acting Beta2 Agonist
↓ airflow obstruction↓ hyperinflation↓ dyspnea↑ exercise tolerance
↑ Quality of life↑ possibly survival↓ exacerbations↑ risk of pneumonia
COPD Treatment
Symptom- and Risk-Based Treatment Paradigm
FEW SYMPTOMS, HIGH RISK OF EXACERBATIONS
1: Combination inhaled corticosteroid/long-acting beta2 agonist or long-acting anticholinergic
2: Combination 2 long-acting bronchodilators or combination inhaled corticosteroid / long-acting anticholinergic
MANY SYMPTOMS, HIGH RISK OF EXACERBATIONS
1: Combination inhaled corticosteroid/long-acting beta2 agonist or long-acting anticholinergic
2: Combination inhaled corticosteroid/long-acting 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
2: Combination of short-acting bronchodilators / introduce long-acting bronchodilator
MORE SYMPTOMS, LOW RISK OF EXACERBATIONS
1: Long-acting bronchodilators recommended
2: Combination of long-acting bronchodilators in patients with severe breathlessness
A B
C D
INCR
EASI
NG
AIR
WAY
S O
BSTR
UCT
ION
INCR
EASI
NG
EXA
CERB
ATIO
NS
INCREASING SYMPTOMS Global Initiative for COPD (GOLD) 2011
COPD Treatment
Short-Term Long-TermOxygen Therapy ↑ exercise endurance ↑ 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
Short-Term Long-TermPulmonary Rehabilitation
↓ dynamic hyperinflation↓ functional dyspnea↑ exercise endurance
↑ QOL↑ possibly survival
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
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
Benefits of Pulmonary Rehabilitation in COPD
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, 1994-
2005 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 all-cause mortality
Cote & Celli et al, Chest 2007
Exercise tolerance predicts survival in COPD
Cote & Celli et al, Chest 2007
Exercise Capacity & Survival in COPD
F/U (months)
Surv
ival
pro
babi
lity
1.00.80.60.40.20
0 12 24 36 48 60 72 84 96
>350 m
<350 m
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 TreatmentTreatment Phenotype BenefitRoflumilast Frequent exacerbator
(≥ 2 / yr)↓ exacerbations↑ quality of life↑ lung function
Azithromycin Frequent exacerbator (≥ 2 / yr)
↓ exacerbations↑ QOL
Chronic antibiotic COPD with bronchiectasis
↓ exacerbations↓ eradicate colonizing
microorganisms↓ chronic inflammation
Inhaled corticosteroids
COPD-eosinophilia and Mixed asthma-COPD
↑ lung function
COPD Treatment
Treatment Phenotype BenefitLung Volume Reduction Surgery / Bronchoscopy
Predominantly upper lobe emphysema
↑ 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
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
COPD – Conclusions
Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD)
Asthma Bronchiectasis Cystic fibrosis Bronchiolitis obliterans Alpha-1-antitrypsin deficiency
Emphysema
AsthmaBronchitis
Other
Airways Obstruction
Differential Diagnosis: COPD and Asthma
COPD Onset in mid-life
Symptoms slowly progressive
Long smoking history
Dyspnea during exercise
Largely irreversible airflow limitation
ASTHMA 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 DiagnosisHistory
Asthma EmphysemaChronic Bronchitis
+/- + + Smoking
Common (usually
nocturnal)
May be absent
Main complaint
Productive Cough
EpisodicMain
complaintMay be absent
Dyspnea
++ - ++ Exacerbations
Common - - Allergy
COPD - Differential DiagnosisPhysical Examination
Asthma EmphysemaChronic
Bronchitis
Rare + +/- Barrel Chest
+ + +Prolonged Expiration
In severe exacerbation Typical In severe
exacerbation
Decreased BreathingSounds
-/+/++ Rare +/- Wheezing
In severe exacerbation +/- ++ Cyanosis
- In advanced disease - Weight Loss
COPD - Differential DiagnosisPFT
Asthma Emphysema
Chronic Bronchitis
Pulmonary Function Component
Normal/ FEV1
/No change
/No changeFEV1 after
Bronchodilator
Normal/ Normal/ Residual Volume (RV)
Normal Normal Total Lung Capacity (TLC)
Normal NormalDiffusion Capacity
(DLCO)
COPD - Differential DiagnosisComplications
Asthma EmphysemaChronic
Bronchitis
During exacerbation
Common Common Hypoxemia
RareIn advanced
diseaseCommon Erythrocytosis
In severe exacerbation
End-stage disease
Common Hypercarbia
RareIn advanced
diseaseCommon Cor-pulmonale
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 לדרכיהאוויר, כך שאלו הופכים למעוותים
ריר מצטבר בדרכי האוויר וקיים קושילסלקו בשל פגיעה במנגנוני סילוק
ההפרשות של דרכי האווירהתוצאה – 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
BronchiectasisChest 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 האווירהקטנות של הריאה.
בעקבות כך - הרס פרוגרסיבי של דרכי אוויראלו 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 ObliteransClinical 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 ObliteransInspiratory & 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-35%רמות האנזים בחולים קטנות מ הגנוטיפ התקין מכונהPiMM והפגום
PiZZ :הביטויים הקליניים
אמפיזמה–שחמת והפטומה.–
) טיפול – תחליף האנזיםZymera (