chronic obstructive lung disease latest

2. CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
Presenter- Dr Abdirisak jacda (IMR1)
Moderator- Dr abdulaziz (Internist, fellow)

3. Outline
 Definition
 Epidemiology
 Pathophysiology
 Diagnosis
 Clinical feature
 management

4. Definition
 COPD is a common preventable and treatable disease that
 characterized by persistent respiratory symptoms and airflow
limitation that is due to airway and/or alveolar abnormalities
usually caused by significant exposure to noxious particles or
gases and influenced by host factors including abnormal lung
development.

5. Cont.
 Chronic bronchitis:- chronic productive cough for 3 months in
each of 2 successive years in a patient in whom other causes
of chronic cough are excluded
 Emphysema – structural changes including permanent air
space enlargement with destruction of airspace walls with out
obvious fibrosis

6. Cont.
 Asthma COPD Overlap- age >40 years , persistent airflow
obstruction and a history of asthma or evidence of partial
bronchodilator reversibility

7. Prevalence
 Prevalence of COPD
 Estimated 384 million COPD cases in 2010.
 Estimated global prevalence of 11.7% (95% CI 8.4%–15.0%).
 Three million deaths annually.
 With increasing prevalence of smoking in developing countries, and aging
populations in high-income countries, the prevalence of COPD is
expected to rise over the next 30 years.

8. Prevalence
 By 2030 predicted 4.5 million COPD related deaths annually
 COPD is currently the 4th leading cause of death in the world
Now it’s the third

9. Risk factors
 Cigarette smoking-
 In absence of genetic environmental or occupational exposure >10-15
pack years
 Associated with higher prevalence of respiratory symptoms and lung
function abnormalities and increased annual rate of decline in FEV1 and
greater COPD mortality
 ETS, marijuana and other types of tobacco are also associated with
COPD
 Indoor smoke exposure
 Burning wood and other biomass fuel
 25% of death from COPD in low income countries is due to indoor
exposure
 Outdoor air pollution
 Occupational exposure
 Organic and in organic dusts, chemicals and fumes

10. Risk factor cont.
 Age and sex
 Genetics
 AATD, gene encoding MMP-12 and glutathione S transferase
 Lung growth and development
 Socioeconomic status
 Asthma and airway hyper-reactivity
 Chronic bronchitis
 Infections
 Severe childhood respiratory infection, TB, HIV

11. Pathogenesis

12. Pathology
 Large airway
 Mucus gland enlargement
 Goblet cell hyperplasia
 Squamous metaplasia of bonchi
 Smooth muscle hypertrophy and hyper
reactivity
 Small airway
 The major site of increased resistance
 Goblet cell metaplasia
 Luminal narrowing
 Reduced surfactant
 Inflammation
 Vessels
 Due to chronic hypoxic vasoconstriction of
pulmonary arteries
 Increased medial thickness
 Concentric intimal fibrosis
 Lung parenchyma
 Destruction of gas-exchanging air spaces,
i.e., the respiratory bronchioles, alveolar
ducts, and alveoli.
 Large numbers of macrophages
accumulate in respiratory bronchioles of
essentially all smokers-roughly five times
as many macrophages as nonsmokers.
 Neutrophils and T lymphocytes,
particularly CD8+ cells, are also increased
in the alveolar space of smokers

13. Emphysema
 Proximal
acinar(centrilobular)
 Abnormal dialtion or
destruction of the respiratory
bronchiole the central portion
of acinus

14.  Panacinar –all parts of
acinus
 Diffuse panacinar
emphysema is seen in A1AT
deficiency

15.  Distal acinar (paraseptal)
 predominantly alveolar ducts
are affected
 when it occurs alone is
usually associated with
spontaneous pneumothorax


17. Pathophysiology
 Hyperinflation
 Air trapping with increased RV and RV/TLC ratio
 Late stage progressive hyperinflation (increased TLC)
 Airflow obstruction
 Persistent and does not show large response to bronchodilator
unlike asthma
 Gas exchange
 Non uniform ventilation and VQ mismatch
 Pao2 usually near normal until the FEV1 is < 50% of predicted
 Paco2 is not expected to increase until the FEV1 is <25% of
predicted
 Cor pulmonale and pulmonary HTN-FEV1<25% and PaO2<

18. Pathogenesis
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19. January 7, 2023
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20. January 7, 2023
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21. Pathology , Pathogenesis & Pathophysiology
 Pathology
 Chronic inflammmation
 Structural changes
 Pathogenesis
 Oxidative stress
 Protease anti protease imbalance
 Inflammatory cells & Inflammatory mediators
 Peribronchial and interstitial fibrosis
 pathophysiology
 Airflow limitation and gas trapping
 Gas exchange abnormalities
 Mucus hypersecreation
 Pulmonary hypertension January 7, 2023
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22. Clinical features
 Symptoms
 Variable over time more worse in the morning
 Dyspnea- exertional
 Chronic cough
 Sputum production
 Fatigue
 Wheezing
 weightloss
 History of smoking or other risk factors
 Comorbid diseases
 Lung ca, bronchiectasis, CVD, depression
 Family history

23. Physical examination
 In the early stages : normal
 Signs of active smoking, including an
odor of smoke or nicotine staining of
fingernails
 A prolonged expiratory phase and
expiratory wheezing
 Signs of hyperinflation include a
barrel chest and enlarged lung
volumes with poor diaphragmatic
excursion
 Use of accessory muscles of
respiration
 Sitting in the characteristic “tripod”
position
 Cyanosis, visible in the lips and nail
beds
 Marked cachexia
 Paradoxical inward movement of the
rib cage with inspiration (hoover’s
sign)
 Signs of overt right heart failure
 Clubbing of the digits is not a sign
of COPD
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24. Diagnosis

26. Other tests
 Alpha-1 antitrypsin deficiency (AATD) screening.
 Lung Volumes
 Diffusing capacity for carbon monoxide (DLCO)
 6-minute walk test (6MWT
 computed tomography
 Arterial blood gases (ABGs)
 Erythrocytosis ( CBC)
 Sputum gram stain and culture

27. Pulmonary function test
 Spirometry
 is required to make the diagnosis
 Irreversible or partially reversible air flow limitation
 the presence of a post-bronchodilator FEV1/FVC < 0.70 confirms
the presence of persistent airflow limitation
 FEV1/FEV6
 PEF- underestimates the degree of obstruction in COPD and
low PEF is not also specific for airway limitation

28. Cont.
Lung volumes and diffusing capacity.
 Increased RV with increased RV/TLC later increased TLC
 Measurement of DLCO (functional impact of emphysema
in COPD)
 Done for patients with hypoxemia, breathlessness out of
proportion to airflow limitation and evaluation for LVRS
Exercise testing and assessment of physical activity
Is a powerful indicator of health status impairment and
predictor of prognosis

29. Imaging

30. -Signs of lung hyperinflation
flattened diaphragm and
an increase in the volume of
the retrosternal air space
hyperlucency of the lungs,
and
 rapid tapering of the
vascular markings.

31. CT
For lung cancer risk
assessment
For concomitant disease
assessement
Complication assessment
For lung volume reduction
surgery eligibility
assessment
 For patients being
evaluated for lung
transplantation

32. Biomarkers
 The evidences are difficult to interpret
 Some studies suggested C-reactive protein (CRP) and
procalcitonin in restricting antibiotic usage during exacerbations
 Observed sputum color remains highly sensitive and specific for a high
bacterial load during Exacerbations
 Blood eosinophils- guides use of corticosteroids especially in the
prevention of some exacerbations.

33. Assessment of severity
 GOLD staging
 BODE index
 COPD foundation systems
 Combined COPD assessment tool

34. GOLD

37. The refined ABCD assessment tool
 Spirometry in conjunction with patient symptoms and
exacerbation history remains vital for the diagnosis, prognostication and consideration of
other important therapeutic approaches.
 In the refined assessment scheme, patients should undergo spirometry to determine
the severity of airflow limitation (i.e., spirometric grade).
 then undergo assessment of either dyspnea using mMRC or symptoms using CATTM.
 history of exacerbations (including prior hospitalizations) should be recorded.

39. The refined ABCD assessment tool
January 7, 2023
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40. BODE index
 BODE index
 Assess individual risk of death
 Can also be used to assess therapeutic response to treatment
 COPD foundation system
 Contains seven domains with therapeutic implication

41. BODE INDEX-SURVIVAL PREDICTION

42. Treatment
 Goals
 Reduce symptom
 Relieve symptom
 Improve exercise tolerance
 Improve health status
 Reduce risk
 Prevent disease progression
 Prevent and treat exacerbation
 Reduce mortality

43. Management
 Smoking cessation
 Vaccination
 Pharmacologic therapy
 Non pharmacologic therapy

44. Smoking cessation GOLD
 Approximately 40% of COPD patients are current smokers
 With effective methods long term quit success rate is upto 25%
 Has the greatest impact on altering natural course of the
disease
 Reduces the rate of decline in lung function(FEV1) and
improves survival
 5As-Ask , Advise, Assess , Assist ,Arrange
 Pharmacologic therapy includes
 nicotine replacement therapy, bupropion , vareniciline

46. Vaccination
© 2017 Global Initiative for Chronic Obstructive Lung Disease
 Efluenza vaccination can reduce serious illness (such as
lower respiratory tract infections requiring hospitalization) and
death in COPD patients.
 Pneumococcal vaccinations, PCV13 and PPSV23, are
recommended for all patients ≥ 65 years of age

47. vaccinations

48. Pharmacologic therapy
 Bronchodilators
 Beta 2 agonists
 Relax airway smooth muscle
 Improve FEV1 and symptoms
 In general, bronchodilators are the primary treatment for almost all
patients with COPD and are used for symptomatic benefit and to
reduce exacerbations.
 In symptomatic patients, both regularly scheduled use of long-
acting agents and as-needed short-acting medications are indicated.
 Toxicity is dose related

49. Pharmacologic Therapy

50. Pharmacologic Therapy…..

51.  LABA
 LABAs show duration of action of 12 or more hours and do not
preclude additional benefit from as-needed SABA therapy.
 The most common side effects are muscle tremor and
palpitation
 There is a small fall in plasma potassium due to increased
uptake by skeletal muscle cells, but this effect does not usually
cause any clinical problem.

52. Anti-muscarinic drugs
 Blocks the effect of Ach (bronchoconstriction and mucus secretion) on M3
receptors
 SAMA
 Ipratropium and oxitropium
 Improve lung function and reduce symptoms
 also block the inhibitory neuronal receptor M2, which potentially can cause
vagally induced bronchoconstriction
 LAMA
 Tiotropium, aclidinium, glycopyrrolate, umeclidinium
 Has prolonged binding to M3 receptors
 Improves symptom, response to rehabilitation , exacerbation and hospitalization
 ADRs- dry mouth in elderly patients, urinary retention and glaucoma

53. Methylxanthines
 Modest bronchodialator effect
 Theophylline metabolized by cyt p450 and clearance
decreases with age
 Thephylline with salmeterol has greater improvement in FEV1
and breathlessness than salmeterol alone.
 Effect on exacerbation is controversial
 Toxicity is dose related and has narrow therapeutic ratio
 ADR- Nausea, tremor, tachycardia
 No mortality benefit or progression change

54. Combination bronchodilator therapy
 Increase the degree of bronchodilation with a lower risk of side-
effects compared to increasing the dose of a single
bronchodilator.
 Combinations of SABAs and SAMAs are superior compared
to either medication alone in improving FEV1 and symptoms.
 Formetrol and tiotropium better FEV1 improvement than
each medication alone.
 Improve lung function

56. Anti-inflammatory agents
Inhaled corticosteroids (ICS)
 COPD-associated inflammation has limited responsiveness to
corticosteroids.
 Regular treatment with ICS alone does not modify the long-term
decline of FEV1 nor mortality in patients with COPD.
 In patients with moderate to very severe COPD and exacerbations, an
ICS combined with a LABA is more effective than either component alone
in improving lung function, health status and reducing exacerbation

57. Cont.
 Blood eosinophil count-
 has a continuous relationship and predict the magnitude of the effect
of ICS (added on top of regular maintenance bronchodilator treatment)
in preventing future exacerbations.
 No and/or small effects are observed at lower eosinophil counts(< 100
cells/Μl)
 increasing effects observed at higher eosinophil counts. (> 300
cells/μL)

58. Cont.
• Effect of ICS containing regimens is higher in patients with high
exacerbation risk (≥ 2 exacerbations and / or 1 hospitalization in the
previous year).
• Triple therapy (LABA/LAMA/ICS)
 the step up in triple therapy can occur by various approaches and has
been shown to improve lung function, patient reported outcomes and
reduce exacerbations when compared to LAMA alone, LABA/LAMA and
LABA/ICS.
 OCS
 for acute management of exacerbations
 they have no role in the chronic treatment

59. ADR of ICS
 Local side effects
 hoarseness (dysphonia) and
 oral candidiasis- which may be reduced with the use of a
largevolume spacer device.
 systemic side effects from lung absorption-
 many studies have demonstrated that ICS have minimal systemic
effects
 At the highest recommended doses, there may be some
suppression of plasma and urinary cortisol concentrations, but there
is no convincing evidence that long-term treatment leads to impaired
growth in children or to osteoporosis in adults.

61. Mucolytics
 In COPD patients not receiving inhaled corticosteroids, regular
treatment with mucolytics such as carbocysteine and N-acetylcysteine
may reduce exacerbations and modestly improve health status
 No mortality benefit

62. Phosphodiesterase 4 inhibitors
 Reduce inflammation by preventing breakdown of intracellular
cAMP
 Roflumilast
 No bronchodialtor effect
 Reduce moderate to severe exacerbation treated with systemic
corticosteroids in patients with chronic bronchitis, severe to very
severe COPD, and a history of exacerbations
 Has also impact on lung function when added on LABA or patients
on LABA/ICS and poor control
 ADR – diarrhea nausea weight loss headache

63. Antibiotics
 Regular use of some antibiotics may reduce exacerbation rate.
 Azithromycin (250 mg/day or 500 mg three times per week) or
erythromycin (250 mg two times per day)
 Adverse effects
 Increased incidence of bacterial resistance,
 Prolongation of QTc interval,
 Impaired hearing tests.

65. Group A
• All should be offered
bronchodilator(SABA/LABA) based on its
effect on breathlessness.
 This should be continued if benefit is
documented
Group B
 Initial therapy should consist of a LABA
 LABA Superior to SABA taken PRN.
 For patients with severe breathlessness
initial therapy with two bronchodilators
may be considered.
Group C
 Initial therapy should consist of a single
long acting bronchodilator
 LAMA was superior to the LABA
regarding exacerbation prevention
Group D
 In general, therapy can be started with a
LAMA as it has effects on both
breathlessness and exacerbations.
 LAMA/LABA for severe symptoms
 An advantage of LABA/ LAMA over
LAMA for exacerbation prevention has
not been consistently demonstrated, so
the decision to use LABA/LAMA as initial
treatment should be guided by the level
of symptoms

66. Follow up
Dyspnea
 For patients with persistent breathlessness or exercise limitation on
long acting bronchodilator monotherapy/ the use of two
bronchodilators is recommended.
 If the addition of a second long acting bronchodilator does not
improve symptoms, treatment could be stepped down again to
monotherapy. Switching inhaler device can also be considered.
 For patients with persistent breathlessness or exercise limitation on
LABA/ICS treatment, LAMA can be added to escalate to triple
therapy.
 Switching from LABA/ICS to LABA/ LAMA should be considered
if the original indication for ICS was inappropriate or if ICS side
effects warrant discontinuation

67. Non-Pharmacologic Treatment
► Education and self-management
► Physical activity
► Pulmonary rehabilitation programs
► Exercise training
► Self-management education
► End of life and palliative care
► Nutritional support
► Vaccination
► Oxygen therapy

68. Non-Pharmacologic Treatment

69. Exacerbation scenarios
1. Persistent exacerbations on LABA monotherapy, escalation
to either LABA/LAMA or LABA/ICS is recommended.
2. For patients with one exacerbation per year, a peripheral
blood level ≥ 300 eosinophils/μL identifies patients more
likely to respond to LABA/ICS treatment.
3. For patients with ≥ 2 moderate exacerbations per year or at
least one severe exacerbation, LABA/ICS treatment can be
considered at blood eosinophil counts ≥ 100 cells/μL,
4. ICS effects are more pronounced in patients with greater
exacerbation frequency and/or severity.

70. In patients who develop further exacerbations on LABA/LAMA
therapy
• Escálate to LABA/LAMA/ICS- If blood eosinophil counts ≥ 100
cells /μL, with a greater magnitude of response more likely with
higher eosinophil counts.
 Add Roflumilast or azithromycin- If blood eosinophils < 100
cells/μL.
 Consider stopping ICS if adverse events occur or if lack of
efficacy

71. © 2020 Global Initiative for Chronic Obstructive Lung Disease

72. Exacerbation
 Definition (GOLD,WHO, NHLBI)
 “An acute event characterized by worsening of the patient’s
respiratory symptoms that is beyond normal day-to-day variation
and leads to a change in medication”
 Acute change in one or more of
 cough increase in frequency and severity
 Sputum production (change in volume or character)
 Dyspnea increases
 On P/E- tachypnea, Respiratory distress, wheezing, altered
mentation, asterixis

73. Risk factor
 Prior exacerbation
 Advanced age
 Longer duration of COPD
 History of antibiotic therapy
 COPD related hospitalization
in the past year
 Peripheral blood eosinophil
>340 cell/microL
 Theophylline therapy
 One or more co morbidity
 Triggers
 Viral infection
 bacterial infection
 H.influenza
 Moraxella catarrhalis
 S.pneumoniae
 P.aeruginosa
 Environmental pollution
 PTE
 Unknown etiology

74.  GOLD
 Low risk- GOLD 1 or 2and /or 0-1 exacerbation per year and no
hospitalization due to an exacerbation
 High risk -GOLD 3or 4, and/or =2 exacerbation /year or .=1
hospitalization due to an exacerbation
 Other risk factors
 Pulmonary HTN
 greater percentage of emphysema on CT
 Vitamin D deficiency

75. Work up
 Pso2
 Chest x-ray
 CBC, Electrolyte,OFT
 ABG
 Covid 19 RDT/PCR
 Sputum Gram stain and
cultured
 D-dimer , lower extremity
doppler, CTA
 ECG, NT proBNP
 DDX
 Heart failure
 Cardiac arrhythmias
 Pneumonia
 Pneumothorax
 Pulmonary embolism
 Pleural effusion

76. Severity of exacerbation
 Mild
 treated with short acting bronchodilators only, SABDs
 Only one of the 3 cardinal symptoms
 Moderate
 At least 2 out of the 3 symptoms
 treated with SABDs plus antibiotics and/ or oral corticosteroids
 Severe
 patient requires hospitalization or visits the emergency room
treatment
 doesn't respond to SABA and treated with SABA,antibiotics, oral or
IV steroids

77. Management
 Indications for
hospitalization
 Acute respiratory failure
 Severe symptoms including
confusion ,drowsiness, SOB
 Onset of new physical sign
including arrhythmia, edema
cyanosis
 Co morbid illness

78.  Criteria for ICU admission
 Patients with high risk
comorbidities
 Continued need for NIV or
invasive ventilation
 Hemodynamic instability
 Need for frequent monitoring
and nebulizer treatment

79. Treatment
 General measure
 Smoking cessation
 Nutritional support
 Thromboprophhylaxis
 Oxygen therapy
 Target SpO2 88-92% or Pao2- 60-70mmHg

80.  In hospitalized patients assess for respiratory failure
 No respiratory failure-
 RR=20-30, no altered mentation, no increase in hypercarbia, hypoxia
corrected by 28-35% fio2, no use of accessory muscle
 Acute respiratory failure –non life threatening
 RR>30, no altered mentation, hypercarbia paco2 50-60mmHg, hypoxia
corrected by 28-35% fio2, there is use of accessory muscle
 Acute respiratory failure – life threatening
 RR>30, altered mentation, hypercarbia paco2 >60mmHg, hypoxia not
corrected by 40% fio2, there is use of accessory muscle

81.  SABD
 Inhaled beta agonists and muscarinic antagonists
 For severe-nebulized treatment
 Systemic sterids
 For hospitalized patients
 Reduce length of stay hastens recovery and reduce feature
exacerbation
 5-7 days vs 14 days prednisolone vs oral dexamethasone

82.  Antibiotics
 For moderate to severe
exacerbation
 No risk factor for
pseudomonas
 Levofloxacin 750m
 Ceftriaxone
 Cefotaxime
 Risk for Pseudomonas
 Levofloxacin
 Cefepime
 Ceftazidime
 Pip-tazo
 Send sputum culture
 Re evaluate after 72hr

83. COPD Vs Bronchial Asthma
COPD B. Asthma
 Older age at onset
 Significant risk factors
 TH2 cytokines
 CD8 cells
 Neutrophilic
inflamation
 Parenchymal
involvement
 Irreversible airflow
limitation
 Younger age at onset
 Other allergic
conditions
 Family history, TH1
cytokine
 CD4 cells
 Eosinophilic
inflamation
 Airway involvement
 Reversible airflow
limitation
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84. References
 Harrison 20th edition
 Uptodate online
 GOLD 2021