COPD - DEFINITION, PATHOPHYSIOLOGY AND MANAGEMENT

COPD

1. DR. AMMAR SABIR SIDDIQUI, ASSISTANT PROFESSOR, DEPARTMENT OF MEDICINE, IIMSR, LUCKNOW Chronic obstructive pulmonary disease

2. DEFINITION Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, sputum production and/or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction.

3. Burden Of COPD Global prevalence is 10.8% (11.8% in men, 8.5 % in women) . P revalence of COPD increased steeply with age, with the highest prevalence among those > 60 years. Globally, 3 million deaths each year due to COPD . 3 rd leading cause of death 5 th leading cause of reduced DALY (disability-adjusted life years) (2013) . In India NCDs were estimated to have accounted for 53% of all deaths and 44% of disability-adjusted life-years (DALYs) lost in 2005. Of these chronic respiratory disease accounted for 7% deaths and 3% DALYs lost

4. Pathogenesis GETomics : Complex and dynamic interaction between G enes and E nvironment over the life T ime Genes Environment Lifetime

5. ENVIRONMENTAL RISK FACTORS

6. Genetic factors To date, hundred of genetic variants are discovered with a link to COPD ( including genes encoding matrix metalloproteinase 12 (MMP-12), glutathione S-transferase, the alpha-nicotinic acetylcholine receptor, and the hedgehog interacting protein (HHIP) Most important genetic mutation is SERPINA1 which encodes for alfa-1 antitrypsin (AATD) PiZZ (homozygous) genotype in 0.14% patients of COPD. There is controversy in link of heterozygotes (MZ & SZ) with the development of COPD

7. Pathobiology Inflammatory changes Inflammation within large and small airways and in terminal space of lung Proteinases released by inflammatory cells damage ECM (extracellular matrix) around airways, vasculature and alveoli. Structural changes Structural cell death leading to extensive loss of small airways, vascular pruning ,and alveolar destruction Disordered repair of elastin and other ECM leads to air space enlargement and emphysema.

8. Pathobiology

9. COPD Normal lung tissue (A) COPD lung tissue with severe emphysema showing a small airway with extensive loss of alveolar attachments. (B) normal lung tissue with a small airway with normal parenchyma A B

10. Pathophysiology Airflow obstruction and gas trapping caused by a mixture of small airways disease (which increases airway resistance) and parenchymal destruction (emphysema, that reduces the normal elastic recoil of the lung parenchyma). Hyperinflation S tatic hyperinflation: due to the loss of elastic lung recoil (as a consequence of emphysema) D ynamic hyperinflation: as a consequence of airflow obstruction when ventilatory demands are increased and expiratory times are reduced

11. Gas exchange abnormalities resulting in different degrees of arterial hypoxemia, without or with hypercapnia. also leads to decreased lung diffusing capacity ( Dlco ) Pulmonary hypertension Centrilobular emphysema in chronic smoker (70 pack year) Panlobular emphysema with severe Paraseptal emphysema in 56 yr female alfa-1 AT deficiency. (37 pack year smoking history)

12. FEV1 Trajectories over lifetime

13. How does emphysema lead to obstruction Elastic recoil - generates the pressure responsible for flow under conditions of dynamic compression. Loss of tethering caused by alveolar wall destruction in emphysema - airway collapse Pressure-volume curve shifts upwards and leftwards. West, J. B., Luks, A., & West, J. B. (2017).  West's pulmonary pathophysiology: The essentials. Chapter 4 : Obstructive diseases

14. The posteroanterior (A) and lateral (B) chest x-rays of a 71-year-old female with emphysema show increased lung volumes with flattened hemidiaphragms on the lateral examination (arrow) and increase in the retrosternal space (arrowhead ). The normal retrosternal airspace is less than 2.5 cm. A prominent pulmonary artery on the posteroanterior view (dashed arrow) reflects secondary pulmonary hypertension.

15. Etiotypes of COPD COPD G- genetically determined COPD (AATD) COPD D- COPD due to abnormal lung development (e.g.premature birth) Environmental COPD – COPD C - cigarette smoking COPD P -pollution and biomass exposure COPD I -COPD due to childhood infections,tuberculosis COPD A –COPD and asthma COPD U –COPD of unknown cause

16. Medical History 1. History of exposure to risk factors, such as smoking and environmental exposures (household/outdoor). 2. Past medical history, including early life events (prematurity, low birthweight, maternal smoking during pregnancy, passive smoking exposure during infancy), asthma, allergy, sinusitis, or nasal polyps; respiratory infections in childhood; HIV; tuberculosis. 3. Family history of COPD or other chronic respiratory disease. 4. History of more frequent or prolonged “winter colds,” . 5. History of exacerbations or previous hospitalizations for respiratory disorder. 6. Impact of disease on patient’s life.

17. SPIROMETRY Forced spirometry measures the – the volume of air forcibly exhaled from the point of maximal inspiration (forced vital capacity, FVC); the volume of air exhaled during the first second of this maneuver (forced expiratory volume in one second, FEV1); and the ratio of these two measurements (FEV1/FVC).

18. Considerations in performing spirometry…. Preparation- Well trained supervisor Maximal patient effort Performance- Expiratory volume/time tracs should be smooth and free from irregularities. Pause between inspiration and expiration is less than 1 second. Largest value of FVC and FEV1 to be considered. Bronchodilation- 400mcg beta2 agonist/160mcg short acting anticholinergic is given. 4. Evaluation

19. Role of spirometry in COPD Diagnosis Assessment of severity of airflow obstruction Follow up assessment Therapeutic decisions Identification of rapid decline

20. Additional investigations Physiological – Lung volumes : by Plethysmography or Helium dilutional method DLco Pulse Oximetry and ABG Exercise testing : 6 min walking test Imaging – Chest X-ray HRCT thorax: to rule out other causes of dyspnea e.g. bronchiectasis

21. Contd….. Alpha-1 antitrypsin levels: <20% of normal concentration suggests homozygous deficiency. D. Biomarkers : e.g. absolute eosinophil count . E. Composite scores : e.g. BODE index for COPD survival (BMI, Obstruction, Dyspnea And Exercise )

22. Impulse Oscillometry An advanced spirometry technique, patient friendly and does not require any tedious and exhaustive breathing maneuver.  Simple, noninvasive method requiring only passive patient cooperation. It allows for the evaluation of lung function through the measurement of both airway resistance and airway reactance. It has much higher sensitivity than FEV1 and peak expiratory flow. IOS can detect subtle changes in the small airway function even in the setting of normal spirometry The frequencies of the waves delivered in IOS ranges from 5 to 30 Hz. * While frequencies higher than 30 Hz can cause discomfort to the patient, the parameters measured at <5 Hz are influenced by breath dynamics.

23. STEPS OF IOS INTERPRETATION IF INCREASED→ TOTAL AIRWAY RESISTANCE INCREASED IF INCREASED→ LARGER AIRWAY RESISTANCE INCREASED SMALLER AIRWAY RESISTANCE INCREASED If X5insp Is More Negative → Restrictive Pathology If X5exp Is More Negative → Obstructive Pathology

24. INTERPRETATION WITH PARAMETERS Increase R5,increase R19/20, Normal R5 - R19/20 -> Central airway obstruction Increase R5, Normal R19/20, Increase R5,R19/20-> Peripheral airway obstruction Increase R5, increase R19/20, Increase R5 - R19/20-> Total airway obstruction More negative X5 and increase Fres with normal R -> Restrictive disease Response to bronchodilator - Significant change in R5 (40%), X5 (50%), Ax (80%) & Fres (leftward shift) -> Reversible obstruction Increase R5, more negative Xs and increase Fres - Peripheral airway obstruction Normal R5, more negative X5 and 1 Fres - Restrictive lung disease Increase R5, & increase R19/20 with normal Xs & Fres - Central airway obstruction

25. Initial assessment of COPD

26. Classification of airflow severity in COPD

27. Modified m MRC dyspnea scale

28. CAT (COPD ASSESSMENT TEST)

29. Combined COPD assessment (GOLD) In 2011, GOLD proposed combined assessment of COPD Based on – Levels of symptoms ( mMRC or CAT) Severity of airflow obstruction (GOLD grades 1-4) Frequency of exacerbation EARLIER GOLD 2023 Earlier C D A B E B A 1or more severe exacerbation leading to hospitalization or 2 or more moderate exacerbation 0 or1 moderate exacerbation (not leading to hospitalization )

30. What’s new in GOLD 2023 and 2024? Proposed taxonomy / etio -types of COPD The ABCD assessment tool has been revised to ABE assessment tool Classification of severity of COPD exacerbation Vaccine recommendations for people with COPD . Therapeutic intervention to reduce COPD mortality

31. Management STABLE COPD EXACERBATION OF COPD

32. MANAGEMENT OF STABLE COPD Reduce Risk factors Pharmacological Non pharmacological Maintenance and follow up Smoking cessation Reduces exposure to household and outdoor pollution Education Self management Nutritional supplement Palliative care Oxygen therapy Ventilatory support Interventional bronchoscopy and surgery

33. Initial Pharmacological Treatment Group B LABA + LAMA Group A BRONCHO-DIALATOR Group E LABA + LAMA Consider LABA + LAMA+ICS WHEN BLOOD EOS ≥300 mMRC-0-1, CAT SCORE <10 mMRC -≥2 CAT SCORE >10 ≥2 Moderate Exacerbations or ≥1 leading to Hospitalization 0-1 moderate Exacerbation Not leading to hospitalization

34. PHARMACOLOGICAL THERAPY Anti Inflammatory drugs Bronchodilator Antibiotics Azithromycin [250mg/day or 500 mg three times per week Erythromycin 250 mg / day X 1 year Mucolytics agents Other pharmacological agents – alpha 1 antitrypsin augmentation therapy

35. Use of anti-inflammatory agents Long term mono-therapy with ICS is not recommended (Evidence A) Long term treatment with ICS may be considered with LABA for patients with history of exacerbations despite appropriate treatment with long acting bronchodilators (Evidence A) Long term therapy with oral corticosteroids not recommended (Evidence A) In patients with severe airflow limitation, chronic bronchitis, and exacerbations addition of PDE-4 inhibitor (Roflumilast) to long acting bronchodilators with or without ICS (Evidence B)

36. Classification of Exacerbation Mild [No respiratory failure] Moderate [Acute respiratory failure - Non life threatening] Severe [Acute respiratory failure- L ife threatening] Respiratory rate ≤24/min[20-30 /min] >24/min[>30 /min] >24/min[>30 /min] Accessory muscle use Absent Present Present Mental status Normal Normal Altered Hypoxemia Improved with supplemental oxygen (FiO2: 24-35 % ) Improved with supplemental oxygen (FiO2 > 35 % ) Not improved even with supplemental oxygen (FiO2 > 40 % ) PaCO2 Normal 50-60 mmHg >60 mmHg (pH < 7.2)

37. Management of Exacerbation

38. Factors to consider when use ICS Strongly favour use-History of hospitalization for exacerbation ≥2moderate exacerbation of COPD per year Blood eosinophils count ≥300 cells/micro L History of, or concomitant asthma Favours use-1 moderate exacerbation of COPD per year Blood eosinophils count 100 to <300 cells/micro L Against use -repeated pneumonia Blood eosinophils count <100 cells/micro L History of mycobacterial infection

39. If LABA+LAMA+ICS fails….. Add roflumilast. This may be considered in patients with an FEV1 < 50% predicted and chronic bronchitis. Add a macrolide. The best available evidence exists for the use of azithromycin, especially in those who are not current smokers . Withdrawing ICS can be considered if pneumonia or other considerable side-effects develop .

40. Commonly used medications in COPD

41. Commonly used medications in COPD

42. Overview of management DIAGNOSIS On the basis of Symptoms Risk factors Spirometry INITIAL ASSESSMENT Categorise into GOLD 1- 4 (FEV1) and ABE(CAT, mMRC , exacerbations) Smoking status Comorbidities ADJUST Pharmacotherapy Non-pharmacological therapy INITIAL MANAGEMENT Smoking cessation Vaccination Lifestyle and exercise Initial pharmacotherapy Self management education Management of comorbidities REVIEW Symptoms Exacerbations Smoking status & other risk factors Inhaler techniques and adherence Physical activity Need for pulmonary rehabilitation Need for oxygen, NIV, intervention, palliation Vaccination Spirometry (at least annually)

43. FOLLOW UP PHARMACOLOGICAL TREATMENT If appropriate Maintain it Assess response to initial treatment If not appropriate Assess inhaler technique and adherence Consider predominant treatable trait to target (Dyspnoea or exacerbation) and treat accordingly Assess response, adjust and review

44. Inhalation of drugs Choice of inhaler device has to be individually tailored and depends on access, cost, patient’s ability and preference It is essential to demonstrate proper inhalational technique when prescribing a device Inhaler technique (and adherence) should be assessed before changing present therapy

45. Indications of Hospitalisation Symptoms like worsening of resting dyspnoea, high respiratory rate, decrease oxygen saturation, confusion, drowsiness Presence of cyanosis, peripheral edema Failure to respond to initial medication Serious comorbidities like heart failure, arrhythmias etc. Insufficient home support

46. Supplemental oxygen to COPD Patient Arterial hypoxemia –Pao2 ≤55 mm hg or Sao2 <88% Or Pao2 > 55 but <60 mm hg with right heart failure Prescribe supplemental oxygen and titrate to keep Sao2 ≥ 90 % Recheck in 60 to 90 days to assess If supplemental oxygen still needed If prescribed supplemental oxygen is effective

47. Indications of Mechanical Ventilation At least one of the following Respiratory acidosis (PaCO2 >45 mmHg and arterial pH ) Severe dyspnoea with clinical signs like use of accessory muscles, retraction of intercostal spaces, paradoxical motion of abdomen Persistent hypoxemia despite supplemental oxygen therapy   Unable to tolerate NIV or NIV failure Diminished consciousness, psychomotor agitation Massive aspiration or persistent vomiting Inability to remove respiratory secretions Hemodynamic instability Severe ventricular or supraventricular arrhythmias INDICATIONS OF NIV

48. Vaccination in COPD

49. Interventional therapy in stable COPD Bullectomy Bronchoscopic interventions-endobronchial valves, lung coils Lung volume reduction surgery Bronchoscopic intervention under study- cryospray,targeted lung denervation technology Lung transplantation

50. THANK YOU