penyakit paru obstruk kronis gold . ilmu penyakit dalam

1. PPOK

2. Definisi
PPOK
Penyakit paru obstruktif kronik (PPOK) adalah penyakit yang
umum, dapat dicegah dan diobati ditandai dengan gejala respirasi
yang persisten dan obstruksi SN disebabkan karena kelainan pada
SN dan/atau alveolar yang biasanya akibat dari pajanan partikel
atau gas berbahaya
• © 2020 Global Initiative for Chronic Obstructive Lung Disease

3. Diagnosis PPOK
© 2020 Global Initiative for Chronic Obstructive Lung Disease
GEJALA
Sesak napas
Batuk kronis
Produksi sputum
FAKTOR RISIKO
Faktor host
Tembakau
Pekerjaan
Polusi dalam/luar ruangan
SPIROMETRI: dibutuhkan untuk menegakkan
diagnosis

4. DEFINITION
• Kondisi paru-paru heterogen yang ditandai
dengan gejala pernapasan kronis (dispnea,
batuk, produksi dahak) karena kelainan
saluran udara (bronkitis, bronkiolitis)
dan/atau alveoli (emfisema) yang
menyebabkan obstruksi aliran udara yang
terus-menerus, seringkali progresif

5. CAUSES AND RISK FACTOR
• Gene
• Environment
• T – Lifetime
• tobacco smoking
• inhalation of toxic particles
• gases from household
• outdoor air pollution, etc
• host factors (abnormal lung development and
accelerated lung aging)
damage the lungs
And/or
Alter their
development/aging process

6. CAUSES AND RISK FACTOR(2)
• Genetic risk : mutations in the SERPINA1 gene,
leading to α1-antitrypsin deficiency

7. DIAGNOSTIC CRITERIA
• Presence of non-fully reversible airflow limitation
(FEV1/FVC < 0.7 post-bronchodilation)
• Pre-COPD/PRISm (Preserved Ratio Impaired
Spirometry):
- Structural lung lesions (emphysema)
- Physiological abnormalities (including low-normal
FEV1, gas trapping, hyperinflation, reduced lung
diffusing capacity and/or rapid FEV1 decline)
- without airflow obstruction (FEV1/FVC ≥ 0.7 post-
bronchodilation)

8. CLINICAL PRESENTATION
• Dyspnea
• Activity limitation
• Cough with or without sputum production
• May experience acute events characterized by
increased respiratory symptoms called exacerbations

12. ENVIROMENTAL RISK FACTOR
• Cigarette smoking
• Biomass exposure
• Occupational exposure: organic & inorganic dusts,
chemical agents & fumes, pesticide
• Air pollution: particulate matter (PM), ozone, oxides
of nitrogen or sulfur, heavy metals, and other
greenhouse gases

13. GENETIC FACTOR
• mutations in the SERPINA1 gene that leads to the
hereditary deficiency of α-1 antitrypsin (AATD)
• matrix metalloproteinase 12 (MMP-12)
• glutathione S-transferase
• alpha-nicotinic acetylcholine receptor
• hedgehog interacting protein (HHIP).

15. • Dysanapsis:anthropometric mismatch of airway tree
calibre relative to lung volume

16. • Young COPD = 20-50 yrs, significant structural and
functional lung abnormalities
• Pre-COPD: respiratory symptoms and/or other
detectable structural and/or functional abnormalities,
in the absence of airflow obstruction on forced
spirometry
• PRISm: preserved ratio (FEV1/FVC ≥ 0.7 after
bronchodilation) but impaired spirometry (FEV1 <
80% of reference, after bronchodilation)

17. • Asthma and airway hyper-reactivity – RF COPD
• Chronic bronchitis: MUC5B levels markedly increase
due to submucosal gland hyperplasia and airway
occlusion can occur
• Infection
- CB: Pseudomonas aeruginosa -> associated with
accelerated FEV1 decline
- TB
- HIV

18. • Sex: women may be more susceptible to the harmful
effects of smoking than men
• Socioeconomic status

19. PATHOBIOLOGY
• Pathological : airways, lung parenchyma, and pulmonary
vasculature
• Inflammatory change: >>> macrophages in peripheral
airways, lung parenchyma and pulmonary vessels,
together with increased activated neutrophils and
increased lymphocytes 🡪 multiple inflammatory
mediators 🡪 attract inflammatory cells from the
circulation (chemotactic factors), amplify the
inflammatory process (via proinflammatory cytokines),
and induce structural changes (via growth factors)
• Inflammatory change: Increased oxidative stress (e.g.,
hydrogen peroxide, 8- isoprostane)

20. PATHOBIOLOGY
• Inflammatory change: ↑macrophage, ↑neutrophil,
↑lymphocytes
Oxidative stress: ↑ hydrogen peroxide, 8-isoprostane
• Structural changes: Peribronchiolar fibrosis and
interstitial opacities

21. PATOPHYSIOLOGY
• Airflow obstruction and gas trapping
- Measured by spirometry
- Airflow obstruction -> small airway disease (↑airway
resistance) & parenchymal destruction (emphysema)
• Pulmonary gas exchange abnormalities -> V/Q
missmatch
• Pulmonary hypertension
• Exacerbations
• Multimorbidity

22. PATOPHYSIOLOGY
• Airflow obstruction and gas trapping
- Measured by spirometry
- Airflo
• Pulmonary gas exchange abnormalities
• Pulmonary hypertension
• Exacerbations
• Multimorbidity

24. DIAGNOSIS AND ASSESSMENT
• Dyspnea, chronic cough or sputum production, a
history of recurrent lower respiratory tract infections
and/or a history of exposure to risk factors for the
disease +
• FEV1/FVC < 0.7

25. DIAGNOSIS AND ASSESSMENT
• Dyspnea: sense of increased effort to breathe, chest
heaviness, air hunger, or gasping
• Chronic cough
• Sputum production
• Wheezing and chest tightness
• Fatigue
• Additional clinical features in severe disease: Weight
loss, muscle mass loss, and anorexia, ankle swelling,
depression and/or anxiety

29. SPIROMETRY

31. INITIAL ASSESSMENT

36. ADDITIONAL INVESTIGATIONS
• Lung volume : gas trapping -> static hyperinflation -
> documented by body pletysmography, or less
accurately by helium dilution lung volume
measurement
• Carbon monoxide diffusing capacity of the lung
(DLco):
- DLco < 60% predicted – associated with increased
symptoms, decreased exercise capacity, worse health
status
- DLco <80% predicted (as a marker of emphysema)
signal an increased risk for developing COPD over
time

37. • Oximetry and ABG measurement: SpO2 < 92% 🡪
measure ABG
• Exercise testing and assessment of physical activity:
Walking test (paced shuttle walk test & self-paced 6-
minute walk test) 🡪 assessing disability and risk of
mortality

38. IMAGING
• Chest X-Ray: sign of lung hyperinflation (flattened
diaphragm & increase in the volume of the
retreosternal air space), hyper lucency of the lungs,
and rapid tappering of the vascular markings
• CT

40. ALPHA-1 ANTITRYPSIN DEFICIENCY
(AATD)
• Young < 45yrs + panlobular basal emphysema
• Delay -> older, typical distribution of emphysema
(centrilobular apical)
• Low concentration (<20% normal) -> highly
suggestive of homozygous deficiency

41. BIOMARKERS
• Blood eosinophil count > 300cells/ul -> COPD at
higher risk of exacerbations -> more likely benefit to
preventive treatment wih ICS

43. EVIDENCE SUPPORTING PREVENTION
AND MAINTENANCE THERAPY
• Smoking Cessation
- Nicotine replacement products : nicotine gum,
inhaler, nasal spray, transdermal patch, sublingual
tablet, lozenge
KI: recent myocard infarct, stroke
- E-Cigarette
Adv effect: Severe acute lung injury (vaping-associated
lung injury), eosinophilic pneumonia, alveolar
hemorrhage, respiratory bronchiolitis
• asd

44. • Pharmacological products: Bupropion and
nortriptyline

46. VACCINATION
• Influenza vaccine
• Pneumococcal: conjugated (PCV20 or PCV15) and
pollysaccharide (PPSV23) -> > 65 th
-19-64yrs: if have an underlying medical condition such
as chronic lung disease (COPD, emphysema, asthma),
cigarette smoking, solid organ tranplant
-If never received conjugate /previous pneu vacc
unknown -> PCV15 followd by PPSV23 OR one dose
PCV20
- Adults who have only received PPSV23 may receive a
PCV (PCV20/PCV15) > 1 yr after their last PPSV23
dose
• Tdap, COVID-19

47. VACCINATION

48. PHARMACOLOGICAL THERAPY FOR
STABLE COPD
• Bronchodilators
- Beta2 agonist
Relax airway smooth muscle by stimulating beta2
adrenergic receptors
SABA: wears off within 4-6 hrs
LABA: 12/more hrs
Adv effect: tachycardia, cardiac rhythm disturbances,
somatic tremor, hypokalemia, mild falls in PaO2

49. PHARMACOLOGICAL THERAPY FOR
STABLE COPD
• Antimuscarinic
- Blocks bronchoreceptor effect on acethylcoline on M3
muscarinic receptors expressed in airway smooth muscle
- SAMA (ipratropium&oxitropium): block the inhibitory
neural receptor M2 -> vagally induced
bronchoconstriction
- LAMA (tiotropium, aclidinium, glycopyronium bromide,
umeclidinium): prolonged binding to M3 muscarinic
receptors, with faster dissociaton from M2 muscarinic
receptr -> prolonging duration bronchodilator effect
- Adv effect: dryness of mouth, bitter-metallic taste,
cardiovascular events (ipratropium bromide), glaucoma
(use of solutions with a facemask)

50. PHARMACOLOGICAL THERAPY FOR
STABLE COPD
• Methylxanthines
- Theophylline
- Adv effect: toxicity is dose related -> atrial and
ventricular arrhythmias, grand mal convulsions,
headaches, insomnia, nausea, heartburn

51. PHARMACOLOGICAL THERAPY FOR STABLE COPD

52. • Combination bronchodilator therapy: LABA+LAMA
• Anti inflammatory drugs
• ICS
- ICS alone: does not modify the long term decline of
FEV1 or mortality
- ISC+LABA: more effective than either component
alone
- Adv effect: modifies airway microbiome (higher
prevalece of oral candidiasis, hoarse voice, skin
bruising, pneumonia)

56. • Triple therapy (LABA+LAMA+ICS): superior when
compared to LAMA alone, LABA+LAMA, LABA+ICS
• Oral glucocorticoids: SE: steroid myopathy (muscle
weakness, decreased functionality, respiratory failure
in people with very severe COPD)
• PDE4 inh: roflumilast
- Adve effect: diarrhea, nausea, reduced appetite, weight
loss, abdominal pain, sleep disturbance, headache

57. • Antibiotics: continues use -> no effect on the frequency
of exacerbations
- Azithromycin (250mg/day or 500mg three times a week)
or erythromycin (250mg two times per day) for 1 yr in
patients prone to exacerbations->reduced the risk of
exacerbations compared to usual care
• Mucolytic (mucokinetics, mucoregulators) and
antioxidant agents (N-acetylcysteine, carbocysteine,
erdosteine)
- Mucolytic -> reduce exacerbations
- Erdosteine may have a significant effect on
(mild)exacerbations irrespective of concurrent treatment
with ICS

58. • Other drugs with potentioal to reduce exacerbations
- IL-5 monoclonal antibody (mepolizumab) & anti IL-5
receptor-α antibody (benralozumab) : 15-20% reduction
in the rate of exacerbations but the effect was not always
statistically significant

62. • Lung transplantation
- Should be refeered for consideraton of receiving lung
transplantation: proggresive disease despite max
medical treatment, not candidates for LVRS, BODE index
5 to 6, PaCO2 >50 mmHg (6.6 kPa) and/or PaO2 < 60
mmHg(8 kPa) and FEV1 <25%,
- Should be considered for listing for lung
transplantation: BODE index > 7, FEV1 < 15-20%, and
had > 3 severe exacerbations during the previous tear, 1
severe exacerbations with hypercapnic respiratory
failure, or have moderate to severe pulmonary
hypertension

65. LTOT indicated
- PaO2 < 55
mmHg/SaO2 <
88% with or
wothout
hypercapnia
confirmed twice
over a three-
week period –
or –
- PaO2 55-60
mmHg or SaO2
88% if ther is
evidence of
pulmonary
hypertension,
peripheral
edema
suggesting CHF,
or polycythemia
(Ht > 55%)

68. • Exacerbations: increased dyspnea and/pr cough and
sputum that worsens in < 14 days which may be
accompanied by tachypnea and/pr tachycardia and is
often associated with increased local and systemic
inflammation caused by infection, pollution, or other
insult to the airways

69. • Currently, exacerbations are classified after the event
has occurred as:
- Mild (treated with SABD only)
- Moderate (treated with SABD and oral corticosteroid
+ antibiotics) or
- Severe (patient requires hospitalization or visits the
emergency room). Severe exacerbations may also be
associated with acute respiratory failure