1. Chronic Obstructive Pulmonary Disease (COPD)
פרופ' רפאל ברויאר
מכון הריאה
ביה"ח האוניברסיטאי הדסה עין-כרם

2. Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD)
Asthma
Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency

3. Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD)
Asthma
Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency

4. Relative Mortality, Leading Causes of Death in the US, 1980-2010
Proportion of 1980 Rate
U.S. Centers for Disease Control (CDC)

5. Leading Causes of Death in the US, 2010
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

6. COPD Clinical presentation Pathophysiology Management strategy
Treatment

7. אבחנה של COPD Airflow obstruction that is irreversible
FEV1 / FVC < 70%

8. Chronic Obstructive Pulmonary Disease (COPD)
גורמי סיכון:
עישון - אקטיבי ופסיבי
זיהום אוויר
חשיפות תעסוקתיות לאבק/עשן
גורמים גנטיים (חסר ב alpha-1-antitrypsin).

9. COPD ועישון
עישון הוא הגורם העיקרי – אם אין עישון – יש לחשוב על אבחנה אחרת!
בכלל האוכלוסיה – ככל שאדם עישן יותר "שנות קופסא" – FEV1 יורד.
גם הסיכון למחלה תלוי ב”מינון” (שנות קופסה).

10. רמזים מרכזיים לאבחנה של COPD
מאפיינים מרכזיים:
גיל > 50
קוצר נשימה (דיספניאה) – פרוגרסיבי / קבוע.
שיעול פרודוקטיבי כרוני.
חשיפה לגורמי סיכון – בעיקר עישון

11. COPD: Traditional Classification
Emphysema Phenotype The Pink Puffer
Chronic Bronchitis Phenotype The Blue Bloater
Irreversible airflow obstruction

12. COPD—Emphysema Phenotype
The Pink Puffer

13. 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."

14. Centriacinar Emphysema
Emphysema Pathology
Bullous Emphysema
Centriacinar Emphysema

15. Emphysema Pathology
Normal lung
Emphysematous lung

16. 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.

17. COPD – Emphysema Phenotype תפקודי ריאה
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.
היפוקסמיה קלה עם Pco2 תקין.

18. Effect of Emphysema on Diffusion Capacity

19. Emphysema- CXR היפראינפלציה, חדירות יתר סרעפות שטוחות
מרווח רטרוסטרנלי גדול

20. Emphysema- HRCT
Normal
Emphysema

21. COPD—Chronic Bronchitis Phenotype
The Blue Bloater

22. 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."

23. 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).

24. COPD - Chronic Bronchitis Phenotype תפקודי ריאה
תמונה חסימתית אקספירטורית:
FEV1 מופחת, FEV1 / FVC מופחת
ללא שיפור משמעותי עם מרחיבי סימפונות
נפחי הריאה ויכולת דיפוזיה (DLCO) – תקינים

25. Chronic Bronchitis with Cor Pulmonale—CXR
ללא ממצאים משמעותיים בריאות עצמן
כלי דם ריאתיים מודגשים
לב מוגדל

26. Cor Pulmonale Phenotype in COPD

27. COPD - Cor Pulmonale Phenotype
שכיחות יותר של: היפוקסמיה קשה היפרקפניאה חמצת נשימתית כרונית.

28. Normal
Chronic
Bronchitis
Emphysema

29. COPD Clinical presentation Pathophysiology Management strategy
Treatment

30. Airway Obstruction Pathophysiology
Destruction of
peribronchial
supporting tissue
Plugging, inflammation & narrowing of airways

31. 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

32. COPD - Pathophysiology
HYPOTHESIS
Anti-Elastase
alpha-1-antitrypsin
Elastase

33. COPD - Pathophysiology
Barnes, Nat Rev 2008

34. COPD Clinical presentation Pathophysiology Management strategy
Treatment

35. COPD Management Philosophy
Relieve symptoms
Improve exercise tolerance
Improve health status
AND
Prevent disease progression
Prevent & treat exacerbations
Reduce mortality
REDUCE SYMPTOMS
REDUCE RISK

36. 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

37. COPD Management Symptoms: clinical assessment, mMRC or CAT
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

38. COPD Assessment Tool—CAT Score > 10 considered symptomatic
Symptom Assessment
COPD Assessment Tool—CAT
Score > 10 considered symptomatic

39. COPD Management Severity of airflow limitation (GOLD I-IV)
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

40. (Post Bronchodilator FEV1)
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

41. COPD Management Risk of exacerbation (frequency/year)
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

42. 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

43. 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)

44. Frequency of COPD Exacerbation & Survival
Probability of survival
Time (months)
Prospective study, cohort 304 males, exacerbations requiring hospitalization, 5-year follow-up
Soler-Cataluῆa, Thorax 2005

45. Hurst et al, ECLIPSE, NEJM 2010

46. Frequent Exacerbator Phenotype
Pats with no exacerbation
Pats with ≥2 exacerbations
Year Year Year 3
Hurst et al, ECLIPSE, NEJM 2010

47. 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

48. COPD: Antibiotic treatment
Pathogens:
Streptococcus pneumonia
Haemophilus influenza
Moraxella catarrhalis
Antibiotics:
Cefuroxime, beta-lactam, macrolides, doxycycline

49. Impact of COPD Exacerbations
Accelerated
lung function
decline
Impact on
symptoms &
quality of life
Increased mortality
Exacerbations
Increased economic costs
Treat early aggressively to minimize duration, prevent recurrence

50. COPD Management Presence of comorbidities
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

51. Systemic Manifestations & Comorbidities
Cardiovascular disease
Pulmonary hypertension
Ischemic heart disease
Congestive heart failure
Stroke
Lung cancer
Diabetes, metabolic syn
Osteoporosis
Skeletal muscle dysfunction
Depression

52. COPD—Independent Risk Factor for Cardiovascular Morbidity
Percent with Condition

53. 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 , Copyright © 2005.

54. Higher Mortality Rates Due to Cormorbidities
IHD = ischemic heart disease
CHF = congestive heart failure
RF = respiratory failure
PVD = pulmonary vascular disease
TM = thoracic malignancy
Speaker notes
A recent evaluation of the USA National Hospital Discharge Survey analyzed more than 47 million hospital discharges for COPD (8.5% of all hospitalisations) that occurred in the USA from 1979 to 2001.
The prevalence and in-hospital mortality of many conditions were greater in hospital discharges with any mention of COPD versus those that did not mention COPD.
A hospital diagnosis of COPD was associated with a higher rate of age-adjusted, in-hospital mortality for pneumonia, hypertension, heart failure, respiratory failure, and thoracic malignancies.
In contrast, a hospital diagnosis of COPD was not associated with a greater prevalence of hospitalisation or in-hospital mortality for acute and chronic renal failure, HIV, gastrointestinal hemorrhage, and cerebrovascular disease.
References
Holguin F, Folch E, Redd SC, Mannino DM. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to Chest. 2005;128:
Holguin et al Chest 2005

55. Comorbidity in COPD Traditional View Current Debate
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?

56. COPD Clinical presentation Pathophysiology Management strategy
Treatment

57. COPD Risk Assessment C D B A ≥2 Risk of Exacerbation 1 GOLD IV
GOLD III
GOLD II
GOLD I
Severity of Obstruction
Risk of Exacerbation ≥2 1
Frequency of Exacerbations C D A B
Increasing Symptoms (mMRC or CAT score)
mMRC 0-1
CAT < 10
mMRC > 2
CAT > 10
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011

58. COPD Treatment Smoking Cessation Short-Term ↓ cough, sputum
↑ lung function
Long-Term
↑ survival
↑ QOL
↓ lung function
↓cormorbidities

59. COPD Risk and Smoking Cessation
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
Age (years)
FEV1 (% of value at age 25)
Speaker Notes
The set of curves on this slide shows the risks for death and disability for smoking and nonsmoking men.
The slide shows the effects that smoking, and stopping smoking, can have on FEV1 in a man who is liable to develop COPD if he smokes.
Reference
Fletcher C, Peto R. The natural history of chronic airflow obstruction. BMJ. 1977;1:
Fletcher CM, Peto R. BMJ. 1977;1:

60. COPD Treatment ↓ exacerbation frequency
Influenza, Pneumococcal Immunization
Short-Term
Long-Term
↓ exacerbation frequency

61. COPD Treatment Short-Term Long-Term
Bronchodilators: 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
↓ dyspnea
↑ exercise tolerance
↑ possibly survival
↑ risk of pneumonia

62. 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
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 C D
Increasing Airways Obstruction
Increasing Exacerbations A B
Increasing Symptoms
Global Initiative for COPD (GOLD) 2011

63. COPD Treatment Short-Term Long-Term Oxygen Therapy
↑ exercise endurance
↑ survival

64. Oxygen Therapy Improves Survival
"The more hours, the better!"
Lancet :

65. 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

66. 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

67. Noninvasive Ventilation
If hypoxemia persists or CO2 retention worsens:
Optimize bronchodilators and consider using assisted noninvasive ventilation

69. COPD Treatment Short-Term Long-Term Pulmonary Rehabilitation
↓ dynamic hyperinflation
↓ functional dyspnea
↑ exercise endurance
↑ QOL
↑ possibly survival

70. 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

71. 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

72. 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

73. 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

74. Exercise Tolerance & Survival in COPD
365 patients, 2 centers,
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

75. Exercise Capacity & Survival in COPD
F/U (months)
Survival probability
1.0
0.8
0.6
0.4
0.2
>350 m
<350 m
Exercise tolerance predicts survival in COPD
Cote & Celli et al, Chest 2007

76. 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

77. Phenotype-Specific COPD Treatment
Benefit
Roflumilast
Frequent exacerbator (≥ 2 / yr)
↓ exacerbations
↑ quality of life
↑ lung function
Azithromycin
Frequent exacerbator
(≥ 2 / yr)
↑ QOL
Chronic antibiotic
COPD with bronchiectasis
↓ eradicate colonizing microorganisms
↓ chronic inflammation
Inhaled corticosteroids
COPD-eosinophilia
and
Mixed asthma-COPD

78. COPD Treatment Treatment Phenotype Benefit
Lung 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

79. 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

80. 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

81. Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD)
Asthma
Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency

82. Emphysema
Asthma
Bronchitis
Other
Airways Obstruction

83. Differential Diagnosis: COPD and Asthma
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 83

84. COPD – Differential Diagnosis History
Asthma
Emphysema
Chronic Bronchitis
+/- +
Smoking
Common (usually nocturnal)
May be absent
Main complaint
Productive Cough
Episodic
Dyspnea ++ -
Exacerbations
Common
Allergy

85. COPD - Differential Diagnosis Physical Examination
Asthma
Emphysema
Chronic Bronchitis
Rare +
+/-
Barrel Chest
Prolonged Expiration
In severe exacerbation
Typical
Decreased Breathing
Sounds
-/+/++
Wheezing ++
Cyanosis -
In advanced disease
Weight Loss

86. COPD - Differential Diagnosis PFT
Asthma
Emphysema
Chronic Bronchitis
Pulmonary Function Component 
Normal/
FEV1 
 /No change
FEV1 after Bronchodilator
Normal/ 
Residual Volume (RV)
Normal
Total Lung Capacity (TLC)
Diffusion Capacity (DLCO)

87. COPD - Differential Diagnosis Complications
Asthma
Emphysema
Chronic Bronchitis
During exacerbation
Common
Hypoxemia
Rare
In advanced disease
Erythrocytosis
In severe exacerbation
End-stage disease
Hypercarbia
Cor-pulmonale

88. Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD)
Asthma
Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency

89. 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

90. Bronchiectasis - Pathology

91. 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

92. Bronchiectasis - Clinical Features
Chronic productive cough
Coarse crackles, clubbing
Hemoptysis
Obstructive lung disease
Respiratory failure

93. Bronchiectasis - Diagnosis
Chest x-ray
Bronchography
High-resolution CT

94. Bronchiectasis
Chest x-ray

95. Bronchiectasis
Bronchography

96. Bronchiectasis
High-resolution CT
BETTER CT AVAIL IN PAT TZ Z844321

97. Bronchiectasis - Treatment
Antibiotics (p. aeruginosa, s. aureus)
Vaccinations
Physiotherapy
Bronchodilators
Surgery for localized disease

98. Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD)
Asthma
Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency

99. Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD)
Asthma
Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency

100. 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.

101. 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

102. 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

103. Bronchiolitis Obliterans Inspiratory & Expiratory HRCT
מוזאיקה (אוויר כלוא)
זכוכית חול

104. Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD)
Asthma
Bronchiectasis
Cystic fibrosis
Bronchiolitis obliterans
Alpha-1-antitrypsin deficiency

105. Alpha-1-Antitrypsin Deficiency
5% מחולי אמפיזמה
רמות האנזים בחולים קטנות מ-35%
הגנוטיפ התקין מכונה PiMM והפגום PiZZ
הביטויים הקליניים:
אמפיזמה
שחמת והפטומה.
טיפול – תחליף האנזים (Zymera)