understanding COPD and its phenotypesphenotype .pptx

This ppt is regarding COPD Phenotypes

1. Chronic Obstructive Pulmonary Disease : Phenotypes ‘‘Chronic obstructive pulmonary disease and phenotypes: a state-of-the-art.’’ Alexandru Corlateanu et al Pulmonology Volume 26, Issue 2 Dr. Rahul Kumar Gupta SR PCCM

2. Phenotypes ! Aim Classification into distinct prognostic and therapeutic subgroups for both clinical and research purposes . Establishing a common language facilitate understanding of disease and management

3. Systematic biology approaches :interrelationships between clinical phenotypes and their environmental, genetic, molecular, and cellular basis .

4. Definition Phenotype has to be a subgroup with a great impact in the prognosis ( symptoms, exacerbations, response to therapy, rate of  disease progression, or death ). COPD phenotype should be able to classify patients into distinct subgroups that provide prognostic information and allow to better determine appropriate therapy that alters clinically meaningful outcomes

5. History F irst idea of conceptualizing the different types of phenotypes by Snider , in 1989 . N onproportional Venn diagram : classic 3 subgroups of COPD.

6. Non-proportional Venn diagram of COPD adapted from Am J Respir Care Med (ATS,1995) Patients with asthma whose airflow obstruction is completely reversible (subset 9) are not considered to have COPD. Because in many cases it is virtually impossible to differentiate patients with asthma whose airflow obstruction does not remit completely from persons with chronic bronchitis and emphysema who have partially reversible airflow obstruction with airway hyper reactivity, patients with unremitting asthma are classified as having COPD (subsets 6, 7 and 8). Chronic bronchitis and emphysema with airflow obstruction usually occur together (subset 4,5 ) Some patients may have asthma associated with these two disorders (subset 8). Individuals with asthma who have been exposed to chronic irritation, as from cigarette smoke, may develop chronic productive cough, which is a feature of chronic bronchitis (subset 6). Persons with chronic bronchitis and/or emphysema without airflow obstruction (subsets 1, 2 ) are not classified as having COPD. Patients with airway obstruction (10) due to diseases with known aetiology or specific pathology such as cystic fibrosis or obliterative bronchiolitis (subset 10) are not included in this definition. The subsets comprising COPD are shaded.

7. Proportional Venn diagram presenting the different phenotypes within the Wellington Respiratory Survey study population. The large black rectangle represents the full study group. The clear circles within each coloured area represent the proportion of subjects with COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC) <0.7). The isolated clear circle represents subjects with COPD who did not have an additional defined phenotype of asthma, chronic bronchitis or emphysema.

8. Old classifications of phenotypes A . ( Patients with chronic bronchitis, inflammatory phenotype, frequent exacerbator, systemic manifestations and with co-morbidities) B. (Patients with emphysema, pronounced lung hyperinflation and without frequent exacerbations).

9. Classification of COPD phenotypes Widely accepted COPD phenotypes  Emerging COPD phenotypes  Chronic Bronchitic Emphysematous Asthma-COPD-Overlap Frequent exacerbator Rare exacerbator  Pulmonary cachexia phenotype Overlap COPD and bronchiectasis Upper lobe-predominant Emphysema Phenotype The fast decliner phenotype The comorbidities or systemic phenotype α1- Antitrypsin Deficiency No smoking COPD 

10. FEV1/FVC  < 0.70 ratio definition of COPD leaves a large proportion of subjects with physiological abnormalities that also manifest respiratory symptoms but do not satisfy the COPD diagnostic criteria, the patients will need to be approached from multiple dimensions (clinical, physiological, imaging and endotyping ).

11. Vestbo et al… (2014) Suggested the following phenotypes: Asthma Bronchial hyper responsiveness Bronchodilator reversibility Emphysema Hyperinflation Cachexia Chronic bronchitis Frequent exacerbations systemic inflammation T his classification has changed over the years since the original idea.

12. Weatherall et al… U sed a cluster analysis to explore the clinical phenotypes in a community population with airways disease. A nalysis included 175 subjects and 5 clinical phenotypes were identified: 1 ) Severe and markedly variable airflow obstruction with features of atopic asthma, chronic bronchitis, and emphysema 2) Features of emphysema alone 3) Atopic asthma with eosinophilic airways inflammation 4) Mild airflow obstruction without other dominant phenotypic features 5) Chronic bronchitis in nonsmokers.

13. ECLIPSE- Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study I ncluded 2138 patients The exacerbation frequency was followed over a period of 3 years. provided significant information about the susceptibility of certain patients to develop exacerbations . Conclusion – Airflow limitation alone does not provide an accurate measure of disease severity ECLIPSE confirms Exacerbations become more frequent and more severe as COPD severity increases . Frequent exacerbator is an independent disease phenotype . Patients with moderate COPD may be frequent exacerbators (22%) Exacerbation in prior year is the best predictor of occurrence of exacerbation Exacerbation rate must be integrated in GOLD guidelines

14. S tudy by the Phenotype and Course of COPD J. Garcia- Aymerich , F.P. Gómez, M. Benet, E.  Farrero , X.  Basagaña , À  Gayete ,  et al. Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes S ub classified groups of COPD patients with exacerbations. 342 subjects with COPD who were hospitalized with their first exacerbation, were identified as belonging to 3 distinct COPD groups : 1) “severe respiratory COPD” characterized by airflow limitation (mean FEV1, 38% of predicted value) 2 ) “moderate respiratory COPD” marked by milder degrees of airflow limitation (mean FEV1, 58% of predicted value) 3 ) “systemic COPD” with similar milder airflow limitation but with a greater proportion of comorbidities such as obesity, cardiovascular disease and diabetes mellitus.

15. Han and collaborators… Used CT data of COPD Gene study ( Multicenter observational study designed to identify genetic factors with COPD .) Conclusion - B oth bronchial wall thickness and total lung emphysema percentage were predictive factor of COPD exacerbation frequency in a continuous way independently of severity airflow limitation. As airflow worsens, the symptoms increase but this varies greatly among individual patients.

16. Nishimura et al…. 5-year prospective follow-up study of patients with COPD in Japan to identify variables that might influence the rate of COPD progression evaluated lung function and CT scan results at baseline and twice-yearly lung function and clinical outcomes over the follow-up period. It resulted in a cohort with 3 groups 1 ) sustained lung function 2 ) slow rate of lung function decrease [30mL/year decrease in FEV1] 3 ) rapid rate of lung function decrease [60ml/year decrease in FEV1] patients with sustained lung function had less evidence of emphysema and a higher number of circulating eosinophils, in comparison with those rapid progressors who had the highest ratio of emphysema demonstrated on CT scans and a lowest transfer coefficient for carbon monoxide .

17. Kume et al…. prospective clinical study examined the prevalence of airway eosinophilia and airway responsiveness in COPD patients who have neither symptoms nor past medical history of asthma and also explored the association of these pathophysiological features of asthma in the management for COPD. sputum qualitative and quantitative analysis in patients with COPD GOLD stage 1-3. Sputum eosinophils were observed in 65 subjects of 129 (50.4%) using qualitative analysis. Airway hyperresponsiveness was developed in 46.9% of these subjects, and the exacerbations were more frequently in lower-grade airway eosinophilia without ciclesonide than higher-grade airway eosinophilia with ciclesonide. These entities are characteristic features of asthma, but they may develop in the subset of patients with COPD who do not present any symptoms related to asthma or a previous diagnosis of asthma .

18. Taiwan Obstructive Lung Disease study R etrospective , multicenter research study which assessed medical records from patients with COPD over 40 years P atients with asthma were excluded, and demographic data, lung function, symptom scores and frequency of acute exacerbations were recorded and analyzed . Evaluated the differences between patients with and without wheezing . From 1096 patients with COPD, only 424 (38.7%) had wheezing phenotype, and from this group they had more acute exacerbations within the past year analyzed than the non-wheezing group. The postbronchodilator FEV1 was lower in wheezing patients ( p <0.001) associating these patients with a worse COPD phenotype in comparison to those without that symptom.

19. Korean cohort study made by Ji et al. Even though smoking is a major risk factor for COPD, more than ¼ of COPD patients are non-smokers. N ear a cement plant, observed smokers and non-smokers by a cutoff of a 5 pack-year smoking history N on-smoker (n=49) group resulted in younger patients with a superior BMI vs. the smoker group (n=11) ( p <0.05 ). S mokers group had more emphysema than non-smokers but with a borderline statistical significance ( p =0.051 ). T obacco smoke exposure was highly associated with an emphysema phenotype, while exposure to biomass (i.e. cement) exhibited less emphysema and more air trapping and more structural lung changes on volumetric CT scans

20. COPD phenotypes in biomass smoke- versus tobacco smoke-exposed Golpe et al Spain…. O bserved 499 patients diagnosed with COPD by smoking or biomass exposure. Male gender was higher in the tobacco group (92.1%) and there was more frequency of emphysema among the tobacco users. Prevalence of chronic bronchitis and exacerbations, comorbidities and hospital admission rate were equal between both groups. P.G. Camp et al Mexico City….. women in the tobacco group had more significantly marked emphysema than in the biomass group. And in the biomass group these women had more air trapping than the tobacco group. A revision by Torres-Duque et al  reinforces the fact that wood smoke is a completely different phenotype .

21. Biomass smoke exposure WHO estimates that, or household air pollution, is responsible for 4.3 million deaths annually globally. biomass exposure shows greater reduction in mid-expiratory flow and less pronounced markers of emphysema like air trapping . I n biomass smoke exposure there is thickening of the basement membrane and lymphocytic predominance in a bronchoalveolar lavage fluid and some visualization of bronchial anthracofibrosis

22. Definitions Widely accepted COPD phenotypes Chronic Bronchitic  The presence of productive cough more than 3 months per year in two or more consecutive years  Emphysematous  Presence of emphysema confirmed on imaging  Asthma-COPD-Overlap  Persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD(typically is asthmatic smoker)  Frequent exacerbator  Presence of frequent exacerbations (two or more per year)  Rare exacerbator  Presence of rare exacerbations (no or just one exacerbation) 

23. . Emerging COPD phenotypes COPD phenotype  Definition  Pulmonary cachexia phenotype  Body Mass Index lower than 21kg/m2  Overlap COPD and bronchiectasis  HRCT confirmation of bronchiectasis and definite COPD diagnosis  Upper lobe-predominant emphysema phenotype  CT findings consistent of predominant upper lobe emphysema  The fast decliner phenotype  Rapid decline of lung function  The comorbidities or systemic phenotype  High comorbidities burden, predominantly cardiovascular and metabolic  α1- antitrypsin deficiency  Genetic condition caused by deficiency of α1-Antitrypsin  No smoking COPD  Induced by biomass exposure 

24. studies were often performed in unselected populations of COPD and it is possible that different results could have been detected in selected subpopulations . there is a real need for larger studies to identify variables other than lung function to improve the risk assessment in patients with COPD. will benefit the clinicians for a development of COPD management guidelines.

25. Out come 2019 GOLD guidelines management of stable COPD was redefined: groups A, B, C, D are now used just for informing the initial treatment only . Regarding follow-up, two outcomes are proposed: dyspnea and exacerbations, with different individualized treatment algorithms. Blood eosinophil count is introduced as a biomarker for the likelihood to treatment with an inhaled corticosteroids .

26. Proposal of pharmacological treatment of COPD according to clinical phenotypes Treatment of COPD by clinical phenotypes: putting old evidence into clinical practice Marc Miravitlles et al European Respiratory Journal 2013 41: 1252-1256;  DOI:  10.1183/09031936.00118912

27. Chronic Obstructive Pulmonary Disease Phenotypes: Implications for Care From the Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN

28. GOLD 2021 KEY CHANGES SUMMARY Genetic factors New sentence and reference about AATD PiZZ genotypes in European populations. Prevalence of 0.12% in COPD in Europe.

29. Pharmacotherapies for smoking cessation Four new paragraphs have been added on e-cigarettes/vaping. e-cigarettes/vaping – efficacy remain controversial Long term health effect largely unknown Vaping associated lung injury reported in case series Severe lung injury , eosinophilic pneumonia, alveolar hemorrhage, occasionally death D ata showed that vitamin E acetate an additive is strongly linked to EVALI outbreak following its identification out break have decreased Neutrophilic inflammation, airway irritability , mucus hyper secretion seen in animal modal Long term risk to be define

30. Vaccinations Addition of information about CDC recommendation for Tdap ( dTaP / dTPa ) vaccination to protect against pertussis (whooping cough), in those adults with COPD who were not vaccinated in adolescence .

31. Methylxanthines A new sentence has been added to the adverse effects section on interactions between Methylxanthines and commonly used medications . Erythromycin Ciprofloxacin Allopurinol Cimetidine Serotonin uptake inhibitor fluvoxamine 5 lipoxygenase inhibitor zileuton

32. Combination bronchodilator therapy A new sentence has been added about the EMAX trial ( Maltais et al. 2019 ) from trial Umeclidinium / vilanterol consistently provides early and sustained improvements in lung function and symptoms and reduces the risk of deterioration/treatment failure versus umeclidinium or salmeterol in symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids. These findings suggest a potential for early use of dual bronchodilators to help optimize therapy in this patient group.

33. Triple therapy (LABA/LAMA/ICS) Incorporate new findings on triple therapy and mortality .

34. Mucolytic and antioxidant agents section has been changed to state that erdosteine may have a significant effect on (mild) exacerbations irrespective of concurrent treatment with inhaled corticosteroids.

35. Other drugs with potential to reduce exacerbations New sentences have been added on the use of beta-blockers in COPD patients who do not have a cardiovascular indication for their use

36. Issue related to inhaled delivery and pulmonary rehabilitation pharmacist-led interventions1 and lay health coaching can improve inhalation technique and adherence in COPD patients. New paragraphs on HFOT oxygen supplementation during exercise and pulmonary rehabilitation.

37. Palliative treatment of dyspnea Ventilatory Support Acupuncture/acupressure may improve dyspnea Benefits of NIV in the stable COPD patient… clear benefit of CPAP in patient with OSA and COPD

38. Physical activity Two new sentences added to incorporate new evidence about physical activity.

39. Antibiotics A new paragraph on procalcitonin has been added.

40. Respiratory support Two new sentences on HFO.

41. Lung Cancer A new section on COPD and lung cancer has been added Emphysema on CT > airflow obstruction , are independent risk factor Other then smoking , chronic inflammation, genetics , DNA methylation are risk factor

42. Heart failure Sentence on ß1-blocker Treatment with ß1-blockers improves survival in heart failure and is recommended in patients with heart failure who also have COPD. Selective ß1-blockers should be used, and only used, to treat patients with COPD for approved cardiovascular indications; not solely for the purpose of preventing exacerbations of COPD.

43. Ischemic heart disease (IHD) During , and for at least 90 days after, acute COPD exacerbations there is an increased risk of cardiovascular events (death, myocardial infarction, stroke, unstable angina, and transient ischemic attack) in patients at high risk of concomitant IHD. Hospitalization for an acute COPD exacerbation has been associated with 90-day mortality of acute myocardial infarction, ischemic stroke, and intracranial hemorrhage.

44. C ognitive impairment in patients with COPD A new section added Prevalence 32-56% Present across all range of spirometry Increased risk of hospitalization

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