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Emerging role of biologics in COPD: A new direction
Airways Disorders Network
Asthma and COPD Section
Remodeling of airways and destruction of parenchyma by immune and inflammatory mechanisms are the leading cause of lung function decline in patients with COPD. Type 2 inflammation has been recognized as an important phenotypic pathway in asthma. However, its role in COPD has been much less clear, which had been largely associated with innate immune response.1
Activation of Interleukin (IL)-25, IL-33, thymic stromal lymphopoietin (TSLP) produces type 2 cytokines IL-4, IL-5, and IL-13, either by binding to ILC2 or by direct Th2 cells resulting in elevated eosinophils in sputum, lungs, and blood, as well as fractional exhaled nitric oxide.2 The combined inflammation from this pathway underpins the pathological changes seen in airway mucosa, causing mucous hypersecretion and hyperresponsiveness.
Prior trials delineating the role of biologics, such as mepolizumab and benralizumab, showed variable results with possible benefit of add-on biologics on the annual COPD exacerbations among patients with eosinophilic phenotype of COPD.3
More recently, the BOREAS trial evaluated the role of dupilumab as an add-on therapy for patients with type 2 inflammation-driven COPD established using blood eosinophil count of at least 300/mL at initial screening.4 Dupilumab is a human monoclonal antibody that blocks combined IL-4 and IL-13 pathways with a broader effect on the type 2 inflammation. It included patients with moderate to severe exacerbations despite maximal triple inhaler therapy with blood eosinophilia. Patients with asthma were excluded. This 52-week trial showed reduction in annual moderate to severe COPD exacerbations, sustained lung function improvement as measured by prebronchodilator FEV1, and improvement in patient-reported respiratory symptoms.4 Evaluation of sustainability of these results with therapy step-down approaches should be explored.
References
1. Scanlon & McKenzie, 2012.
2. Brusselle et al, 2013.
3. Pavord et al, 2017.
4. Bhatt et al, 2023.
Airways Disorders Network
Asthma and COPD Section
Remodeling of airways and destruction of parenchyma by immune and inflammatory mechanisms are the leading cause of lung function decline in patients with COPD. Type 2 inflammation has been recognized as an important phenotypic pathway in asthma. However, its role in COPD has been much less clear, which had been largely associated with innate immune response.1
Activation of Interleukin (IL)-25, IL-33, thymic stromal lymphopoietin (TSLP) produces type 2 cytokines IL-4, IL-5, and IL-13, either by binding to ILC2 or by direct Th2 cells resulting in elevated eosinophils in sputum, lungs, and blood, as well as fractional exhaled nitric oxide.2 The combined inflammation from this pathway underpins the pathological changes seen in airway mucosa, causing mucous hypersecretion and hyperresponsiveness.
Prior trials delineating the role of biologics, such as mepolizumab and benralizumab, showed variable results with possible benefit of add-on biologics on the annual COPD exacerbations among patients with eosinophilic phenotype of COPD.3
More recently, the BOREAS trial evaluated the role of dupilumab as an add-on therapy for patients with type 2 inflammation-driven COPD established using blood eosinophil count of at least 300/mL at initial screening.4 Dupilumab is a human monoclonal antibody that blocks combined IL-4 and IL-13 pathways with a broader effect on the type 2 inflammation. It included patients with moderate to severe exacerbations despite maximal triple inhaler therapy with blood eosinophilia. Patients with asthma were excluded. This 52-week trial showed reduction in annual moderate to severe COPD exacerbations, sustained lung function improvement as measured by prebronchodilator FEV1, and improvement in patient-reported respiratory symptoms.4 Evaluation of sustainability of these results with therapy step-down approaches should be explored.
References
1. Scanlon & McKenzie, 2012.
2. Brusselle et al, 2013.
3. Pavord et al, 2017.
4. Bhatt et al, 2023.
Airways Disorders Network
Asthma and COPD Section
Remodeling of airways and destruction of parenchyma by immune and inflammatory mechanisms are the leading cause of lung function decline in patients with COPD. Type 2 inflammation has been recognized as an important phenotypic pathway in asthma. However, its role in COPD has been much less clear, which had been largely associated with innate immune response.1
Activation of Interleukin (IL)-25, IL-33, thymic stromal lymphopoietin (TSLP) produces type 2 cytokines IL-4, IL-5, and IL-13, either by binding to ILC2 or by direct Th2 cells resulting in elevated eosinophils in sputum, lungs, and blood, as well as fractional exhaled nitric oxide.2 The combined inflammation from this pathway underpins the pathological changes seen in airway mucosa, causing mucous hypersecretion and hyperresponsiveness.
Prior trials delineating the role of biologics, such as mepolizumab and benralizumab, showed variable results with possible benefit of add-on biologics on the annual COPD exacerbations among patients with eosinophilic phenotype of COPD.3
More recently, the BOREAS trial evaluated the role of dupilumab as an add-on therapy for patients with type 2 inflammation-driven COPD established using blood eosinophil count of at least 300/mL at initial screening.4 Dupilumab is a human monoclonal antibody that blocks combined IL-4 and IL-13 pathways with a broader effect on the type 2 inflammation. It included patients with moderate to severe exacerbations despite maximal triple inhaler therapy with blood eosinophilia. Patients with asthma were excluded. This 52-week trial showed reduction in annual moderate to severe COPD exacerbations, sustained lung function improvement as measured by prebronchodilator FEV1, and improvement in patient-reported respiratory symptoms.4 Evaluation of sustainability of these results with therapy step-down approaches should be explored.
References
1. Scanlon & McKenzie, 2012.
2. Brusselle et al, 2013.
3. Pavord et al, 2017.
4. Bhatt et al, 2023.
Hot or cold – impact on asthma and COPD
Airways Disorders Network
Asthma & COPD Section
Earlier works investigating effects of temperature and humidity changes on the airway in patients with asthma are insightful (Strauss, et al. 1978). Heat can irritate asthmatic airways that are already hyperreactive. Cold air can remove airway moisture. Similar mechanisms with warm/hot air can affect airway inflammation in COPD. In addition, poor air quality often occurs during extreme heat events and can affect patients with COPD.
Seasonal variation in COPD exacerbations was demonstrated by the TORCH study, where a two-fold increase in COPD exacerbations and hospitalizations was noted during the winter months in both northern and southern regions of the world. This trend was not observed in tropical countries with average annual temperatures of >18 °C (64 °F). Factors accounting for this variation may include greater risk of viral infections, increased host susceptibility, and more time spent indoors, along with impact of temperature variation on lung function (Jenkins, et al. 2012). This effect was accompanied by variation in the treatment choices with antibiotics alone or in combination with steroids. A trend towards combined antibiotics and steroids was noted during winters.
Ideal conditions for patients with COPD to minimize risk for exacerbation would be home humidity between 30% and 50% with indoor temperature of 21°C at least 9 hours per day in living areas (Osman, et al. 2008).
Outdoor activities during extreme temperatures should be avoided. Air conditioning and/or humidifiers can be helpful in modifying influences.
Maria Azhar, MD
Section Fellow-in-Training
Richard George Barbers, MD, FCCP
Section Chair
References
Jenkins CR, et al. Seasonality and determinants of moderate and severe COPD exacerbations in the TORCH study. Eur Respir J. 2012;39(1):38-45.
Osman LM, et al. Home warmth and health status of COPD patients. Eur J Public Health. 2008;18(4):399-405.
Strauss RH, et al. Influence of heat and humidity on the airway obstruction induced by exercise in asthma. J Clin Invest. 1978;61(2):433-40.
Airways Disorders Network
Asthma & COPD Section
Earlier works investigating effects of temperature and humidity changes on the airway in patients with asthma are insightful (Strauss, et al. 1978). Heat can irritate asthmatic airways that are already hyperreactive. Cold air can remove airway moisture. Similar mechanisms with warm/hot air can affect airway inflammation in COPD. In addition, poor air quality often occurs during extreme heat events and can affect patients with COPD.
Seasonal variation in COPD exacerbations was demonstrated by the TORCH study, where a two-fold increase in COPD exacerbations and hospitalizations was noted during the winter months in both northern and southern regions of the world. This trend was not observed in tropical countries with average annual temperatures of >18 °C (64 °F). Factors accounting for this variation may include greater risk of viral infections, increased host susceptibility, and more time spent indoors, along with impact of temperature variation on lung function (Jenkins, et al. 2012). This effect was accompanied by variation in the treatment choices with antibiotics alone or in combination with steroids. A trend towards combined antibiotics and steroids was noted during winters.
Ideal conditions for patients with COPD to minimize risk for exacerbation would be home humidity between 30% and 50% with indoor temperature of 21°C at least 9 hours per day in living areas (Osman, et al. 2008).
Outdoor activities during extreme temperatures should be avoided. Air conditioning and/or humidifiers can be helpful in modifying influences.
Maria Azhar, MD
Section Fellow-in-Training
Richard George Barbers, MD, FCCP
Section Chair
References
Jenkins CR, et al. Seasonality and determinants of moderate and severe COPD exacerbations in the TORCH study. Eur Respir J. 2012;39(1):38-45.
Osman LM, et al. Home warmth and health status of COPD patients. Eur J Public Health. 2008;18(4):399-405.
Strauss RH, et al. Influence of heat and humidity on the airway obstruction induced by exercise in asthma. J Clin Invest. 1978;61(2):433-40.
Airways Disorders Network
Asthma & COPD Section
Earlier works investigating effects of temperature and humidity changes on the airway in patients with asthma are insightful (Strauss, et al. 1978). Heat can irritate asthmatic airways that are already hyperreactive. Cold air can remove airway moisture. Similar mechanisms with warm/hot air can affect airway inflammation in COPD. In addition, poor air quality often occurs during extreme heat events and can affect patients with COPD.
Seasonal variation in COPD exacerbations was demonstrated by the TORCH study, where a two-fold increase in COPD exacerbations and hospitalizations was noted during the winter months in both northern and southern regions of the world. This trend was not observed in tropical countries with average annual temperatures of >18 °C (64 °F). Factors accounting for this variation may include greater risk of viral infections, increased host susceptibility, and more time spent indoors, along with impact of temperature variation on lung function (Jenkins, et al. 2012). This effect was accompanied by variation in the treatment choices with antibiotics alone or in combination with steroids. A trend towards combined antibiotics and steroids was noted during winters.
Ideal conditions for patients with COPD to minimize risk for exacerbation would be home humidity between 30% and 50% with indoor temperature of 21°C at least 9 hours per day in living areas (Osman, et al. 2008).
Outdoor activities during extreme temperatures should be avoided. Air conditioning and/or humidifiers can be helpful in modifying influences.
Maria Azhar, MD
Section Fellow-in-Training
Richard George Barbers, MD, FCCP
Section Chair
References
Jenkins CR, et al. Seasonality and determinants of moderate and severe COPD exacerbations in the TORCH study. Eur Respir J. 2012;39(1):38-45.
Osman LM, et al. Home warmth and health status of COPD patients. Eur J Public Health. 2008;18(4):399-405.
Strauss RH, et al. Influence of heat and humidity on the airway obstruction induced by exercise in asthma. J Clin Invest. 1978;61(2):433-40.