User login
Patients with non-advanced LC. Boxed warning for montelukast. The happy hypoxic. COVID-19 and pulmonary vasculature.
Interventional chest and diagnostic procedures
Impact of COVID-19 pandemic in patients with non-advanced LC
The COVID-19 pandemic has challenged the way we screen for, diagnose, and treat lung cancer.1, 2 Knowing that these patients are at higher risk of respiratory failure, and that COVID-19 causes poor outcomes in cancer patients,1,3,4 valid concerns regarding viral transmission to patients and health-care workers have hampered the expedited care this population needs.
In recent months, efforts to manage the pandemic have been herculean. With the goal of limiting transmission, expert panels have offered guidance including limiting access to medical facilities, decreasing aerosolizing procedures, and prioritizing curative treatments.2,5 In general, lung cancer screening should be delayed, and patients with highly suspicious localized pulmonary lesions could receive empiric regimens, surgery, or stereotactic radiotherapy.1,3-5
The conundrum occurs when diagnostic bronchoscopy is required for staging, acquiring tissue for targeted therapy, or a moderate-risk pulmonary nodule with indeterminate PET-CT and/or high-risk for CT-guided biopsy. Thoughtful balancing of risks and benefits depends on patient comorbidities, hospital resources – such preprocedural COVID screening, adequate protective personal equipment- and rate of local viral prevalence.6,7 Delaying diagnosis and staging could lead to progression of cancer and preclude curative or adjuvant therapy for appropriate candidates. Furthermore, we should not dismiss the appalling psychological impact of delayed care on our patients.
While the pandemic continues and challenges arise in the care of patients with lung cancer, the value of a multidisciplinary input and individualized care cannot be overstated, with focus on providing the best care possible while both minimizing transmission and increasing the chances of acceptable outcomes.
Jose De Cardenas MD, FCCP – Steering Committee Member
Abdul Hamid Alraiyes MD, FCCP – Steering Committee Member
References
1. Mazzone PJ, et al. Chest. 2020;158(1):406-415. doi: 10.1016/j.chest.2020.04.020.
2. Banna G, et al. ESMO Open. 2020;5(2):e000765. doi: 10.1136/esmoopen-2020-000765.
3. Liang W, et al. Lancet Oncol. 2020;21(3):335-337. doi: 10.1016/S1470-2045(20)30096-6.
4. Singh AP, et al. JCO Oncol Pract. 2020 May 26;OP2000286. doi: 10.1200/OP.20.00286.
5. Dingemans AC, et al. J Thorac Oncol. 2020;15(7):1119-1136. doi: 10.1016/j.jtho.2020.05.001.
6. Wahidi MM, et al. J Bronchology Interv Pulmonol. 2020 Mar 18. doi: 10.1097/LBR.0000000000000681.
7. Pritchett MA, et al. J Thorac Dis. 2020;12(5):1781-1798. doi: 10.21037/jtd.2020.04.32.
Pediatric chest medicine
FDA strengthens the boxed warning for montelukast
Early this year the Food and Drug Administration (FDA) updated the boxed warning for montelukast (Singulair), related to the potential for serious mental health side effects, such as agitation, aggressive behavior, depression, hallucinations, and suicidal thoughts and actions. Since its approval in 1998, montelukast is part of the therapeutic approach for persistent asthma in children age 1 year and older, allergic rhinitis from 6 months and older, and exercises induced bronchospasm in children age 6 years and older. In 2018, around 2.3 million children younger than 17 years received a prescription for montelukast.
The FDA reviewed data from their Sentinel System comparing children receiving montelukast vs inhaled corticosteroids, and this study failed to demonstrate significant increased risk of hospitalized depressive disorders, outpatient depressive disorders, self-harm, or suicide. However, a focused evaluation by the FDA of suicides identified 82 cases of completed suicides associated with montelukast, and 19 of these cases were in children younger than 17 years of age.
Post-marketing case reports submitted to the FDA, published observational and animal studies were evaluated along with the Sentinel System study that led to the new recommendations.
Finally, on March 4, 2020, the FDA updated the Singulair®/montelukast black box warning, focusing on the importance of advising patients and caregivers about the potential for serious neuropsychiatric side effects and advice to immediately discontinue use if symptoms occurred. The warning contains a strong recommendation to reserve use of Singulair®/montelukast to patients with allergic rhinitis who have an inadequate response or intolerance to alternate therapies.
Endy Dominguez Silveyra, MD - Fellow-in-Training Member
References
1. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. FDA Drug Safety Communication, March 4, 2020.
2. Neuropsychiatric events following montelukast use: A propensity score matched analysis. Sentinel, Sept. 27, 2019.
Pulmonary physiology, function, and rehabilitation
The happy hypoxic
In early December 2019, the novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified. Over the ensuing months, SARS-CoV-2 would cause a wide range of pulmonary symptoms from cough and mild shortness of breath to acute respiratory distress syndrome (ARDS) with severe hypoxia that puzzled intensivists worldwide.
One such mystifying presentation was finding patients with critically low oxygen levels who did not appear to be short of breath. This concept was dubbed “happy or silent hypoxemia.” Novel mechanisms of the SARS-Co-V-2 virus on the respiratory system have been proposed to explain this paradox, but recent literature suggests that foundational pulmonary physiology concepts can explain most of these findings.1
Breathing is centrally controlled by the respiratory center in the brain stem and is influenced mainly by dissolved carbon dioxide and pH.2 Hypercapnia is, therefore, a powerful stimulus to breathe and increase minute ventilation. It can cause dyspnea if this demand is not met.3
Hypoxia, on the other hand, is less powerful and does not evoke dyspnea until the PaO2 drops below 60 mm Hg.4 Hypercapnia potentiates this response: the higher the PaCO2, the higher the hypoxic response. Patients with a PaCO2 of 39 mm Hg or less may not experience dyspnea even when hypoxia is severe.1
Other possible explanations for silent hypoxemia include the poor accuracy of the pulse oximeter for estimating oxygen saturation of less than 80%,1 especially in the critically ill5 and the leftward shift of the oxygen dissociation curve due to fever, making the oxygen saturation lower for any given PaO2.1
In conclusion, the clinical management of COVID-19 pneumonia with a broad range of clinical features presents many unknowns, but it is reassuring to find an anchor in good old pulmonary physiology concepts.5
It is back to the basics for us all and that might be a good thing.
Oriade Adeoye, MD – Fellow-in-Training Member
References
1. Tobin MJ, et al. Am J Respir Crit Care Med. 2020;202(3):356-360. doi: 10.1164/rccm.202006-2157CP.
2. Vaporidi K, et al. Am J Respir Crit Care Med. 2020;201(1):20-32. doi: 10.1164/rccm.201903-0596SO.
3. Dhont S, et al. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5.
4. Weil JV, et al. J Clin Invest. 1970;49(6):1061-1072. doi:10.1172/JCI106322.
5. Tobin MJ. Am J Respir Crit Care Med. 2020;201(11):1319-1320. doi:10.1164/rccm.202004-1076ED.
Pulmonary vascular disease
COVID-19 and pulmonary vasculature: an intriguing relationship
Hypoxemia is the cardinal symptom in patients with severe coronavirus disease-2019 (COVID-19). However, hypoxemia disproportionate to radiographic opacities has led to growing suspicion that involvement of pulmonary vasculature (PV), leading to shunt physiology, may be a driver of this marked hypoxemia.
The virus’s affinity for PV is explained by presence of angiotensin-converting enzyme 2 receptor, which serves as the functional receptor for SARS-CoV-2, on pulmonary endothelium (Provencher, et al. Pulm Circ. 2020 Jun 10;10[3]:2045894020933088. doi: 10.1177/2045894020933088).
This increased affinity predisposes PV to pathologic effects of SARS-CoV-2, noted in COVID-19 patients’ autopsies, which revealed pulmonary endothelial injury and abnormal vessel growth (intussusceptive angiogenesis). These changes, along with profound inflammatory response, further predispose the PV to thrombosis and microangiopathy in COVID-19 (Ackermann, et al. N Engl J Med. 2020 Jul 9;383[2]:120-128).
These autopsy results also explain the radiologic findings of PV in COVID-19. Dual energy CT scanning, used to evaluate lung perfusion in these patients, has demonstrated PV thickening, mosaicism, and pulmonary vessel dilation; the latter likely occurring due to aberrations in physiologic hypoxic pulmonary vasoconstriction (Lang, et al. Lancet. 2020 Apr 30;S1473-3099[20]30367).
Despite PV’s involvement, only few cases of COVID-19 have been reported in patients with pulmonary arterial hypertension (PAH) , leading to the hypothesis that pre-existing vascular changes may have a protective effect in PAH patients (Horn, et al. Pulm Circ. 2020;10(2):1-2).
The above discussion details the complex and multifaceted relationship between COVID-19 and PV which underscores the value of understanding this interaction further and may prove to be insightful for discovering potential therapeutic targets in COVID-19.
Humna Abid Memon, MD – Fellow-in-Training Member
Interventional chest and diagnostic procedures
Impact of COVID-19 pandemic in patients with non-advanced LC
The COVID-19 pandemic has challenged the way we screen for, diagnose, and treat lung cancer.1, 2 Knowing that these patients are at higher risk of respiratory failure, and that COVID-19 causes poor outcomes in cancer patients,1,3,4 valid concerns regarding viral transmission to patients and health-care workers have hampered the expedited care this population needs.
In recent months, efforts to manage the pandemic have been herculean. With the goal of limiting transmission, expert panels have offered guidance including limiting access to medical facilities, decreasing aerosolizing procedures, and prioritizing curative treatments.2,5 In general, lung cancer screening should be delayed, and patients with highly suspicious localized pulmonary lesions could receive empiric regimens, surgery, or stereotactic radiotherapy.1,3-5
The conundrum occurs when diagnostic bronchoscopy is required for staging, acquiring tissue for targeted therapy, or a moderate-risk pulmonary nodule with indeterminate PET-CT and/or high-risk for CT-guided biopsy. Thoughtful balancing of risks and benefits depends on patient comorbidities, hospital resources – such preprocedural COVID screening, adequate protective personal equipment- and rate of local viral prevalence.6,7 Delaying diagnosis and staging could lead to progression of cancer and preclude curative or adjuvant therapy for appropriate candidates. Furthermore, we should not dismiss the appalling psychological impact of delayed care on our patients.
While the pandemic continues and challenges arise in the care of patients with lung cancer, the value of a multidisciplinary input and individualized care cannot be overstated, with focus on providing the best care possible while both minimizing transmission and increasing the chances of acceptable outcomes.
Jose De Cardenas MD, FCCP – Steering Committee Member
Abdul Hamid Alraiyes MD, FCCP – Steering Committee Member
References
1. Mazzone PJ, et al. Chest. 2020;158(1):406-415. doi: 10.1016/j.chest.2020.04.020.
2. Banna G, et al. ESMO Open. 2020;5(2):e000765. doi: 10.1136/esmoopen-2020-000765.
3. Liang W, et al. Lancet Oncol. 2020;21(3):335-337. doi: 10.1016/S1470-2045(20)30096-6.
4. Singh AP, et al. JCO Oncol Pract. 2020 May 26;OP2000286. doi: 10.1200/OP.20.00286.
5. Dingemans AC, et al. J Thorac Oncol. 2020;15(7):1119-1136. doi: 10.1016/j.jtho.2020.05.001.
6. Wahidi MM, et al. J Bronchology Interv Pulmonol. 2020 Mar 18. doi: 10.1097/LBR.0000000000000681.
7. Pritchett MA, et al. J Thorac Dis. 2020;12(5):1781-1798. doi: 10.21037/jtd.2020.04.32.
Pediatric chest medicine
FDA strengthens the boxed warning for montelukast
Early this year the Food and Drug Administration (FDA) updated the boxed warning for montelukast (Singulair), related to the potential for serious mental health side effects, such as agitation, aggressive behavior, depression, hallucinations, and suicidal thoughts and actions. Since its approval in 1998, montelukast is part of the therapeutic approach for persistent asthma in children age 1 year and older, allergic rhinitis from 6 months and older, and exercises induced bronchospasm in children age 6 years and older. In 2018, around 2.3 million children younger than 17 years received a prescription for montelukast.
The FDA reviewed data from their Sentinel System comparing children receiving montelukast vs inhaled corticosteroids, and this study failed to demonstrate significant increased risk of hospitalized depressive disorders, outpatient depressive disorders, self-harm, or suicide. However, a focused evaluation by the FDA of suicides identified 82 cases of completed suicides associated with montelukast, and 19 of these cases were in children younger than 17 years of age.
Post-marketing case reports submitted to the FDA, published observational and animal studies were evaluated along with the Sentinel System study that led to the new recommendations.
Finally, on March 4, 2020, the FDA updated the Singulair®/montelukast black box warning, focusing on the importance of advising patients and caregivers about the potential for serious neuropsychiatric side effects and advice to immediately discontinue use if symptoms occurred. The warning contains a strong recommendation to reserve use of Singulair®/montelukast to patients with allergic rhinitis who have an inadequate response or intolerance to alternate therapies.
Endy Dominguez Silveyra, MD - Fellow-in-Training Member
References
1. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. FDA Drug Safety Communication, March 4, 2020.
2. Neuropsychiatric events following montelukast use: A propensity score matched analysis. Sentinel, Sept. 27, 2019.
Pulmonary physiology, function, and rehabilitation
The happy hypoxic
In early December 2019, the novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified. Over the ensuing months, SARS-CoV-2 would cause a wide range of pulmonary symptoms from cough and mild shortness of breath to acute respiratory distress syndrome (ARDS) with severe hypoxia that puzzled intensivists worldwide.
One such mystifying presentation was finding patients with critically low oxygen levels who did not appear to be short of breath. This concept was dubbed “happy or silent hypoxemia.” Novel mechanisms of the SARS-Co-V-2 virus on the respiratory system have been proposed to explain this paradox, but recent literature suggests that foundational pulmonary physiology concepts can explain most of these findings.1
Breathing is centrally controlled by the respiratory center in the brain stem and is influenced mainly by dissolved carbon dioxide and pH.2 Hypercapnia is, therefore, a powerful stimulus to breathe and increase minute ventilation. It can cause dyspnea if this demand is not met.3
Hypoxia, on the other hand, is less powerful and does not evoke dyspnea until the PaO2 drops below 60 mm Hg.4 Hypercapnia potentiates this response: the higher the PaCO2, the higher the hypoxic response. Patients with a PaCO2 of 39 mm Hg or less may not experience dyspnea even when hypoxia is severe.1
Other possible explanations for silent hypoxemia include the poor accuracy of the pulse oximeter for estimating oxygen saturation of less than 80%,1 especially in the critically ill5 and the leftward shift of the oxygen dissociation curve due to fever, making the oxygen saturation lower for any given PaO2.1
In conclusion, the clinical management of COVID-19 pneumonia with a broad range of clinical features presents many unknowns, but it is reassuring to find an anchor in good old pulmonary physiology concepts.5
It is back to the basics for us all and that might be a good thing.
Oriade Adeoye, MD – Fellow-in-Training Member
References
1. Tobin MJ, et al. Am J Respir Crit Care Med. 2020;202(3):356-360. doi: 10.1164/rccm.202006-2157CP.
2. Vaporidi K, et al. Am J Respir Crit Care Med. 2020;201(1):20-32. doi: 10.1164/rccm.201903-0596SO.
3. Dhont S, et al. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5.
4. Weil JV, et al. J Clin Invest. 1970;49(6):1061-1072. doi:10.1172/JCI106322.
5. Tobin MJ. Am J Respir Crit Care Med. 2020;201(11):1319-1320. doi:10.1164/rccm.202004-1076ED.
Pulmonary vascular disease
COVID-19 and pulmonary vasculature: an intriguing relationship
Hypoxemia is the cardinal symptom in patients with severe coronavirus disease-2019 (COVID-19). However, hypoxemia disproportionate to radiographic opacities has led to growing suspicion that involvement of pulmonary vasculature (PV), leading to shunt physiology, may be a driver of this marked hypoxemia.
The virus’s affinity for PV is explained by presence of angiotensin-converting enzyme 2 receptor, which serves as the functional receptor for SARS-CoV-2, on pulmonary endothelium (Provencher, et al. Pulm Circ. 2020 Jun 10;10[3]:2045894020933088. doi: 10.1177/2045894020933088).
This increased affinity predisposes PV to pathologic effects of SARS-CoV-2, noted in COVID-19 patients’ autopsies, which revealed pulmonary endothelial injury and abnormal vessel growth (intussusceptive angiogenesis). These changes, along with profound inflammatory response, further predispose the PV to thrombosis and microangiopathy in COVID-19 (Ackermann, et al. N Engl J Med. 2020 Jul 9;383[2]:120-128).
These autopsy results also explain the radiologic findings of PV in COVID-19. Dual energy CT scanning, used to evaluate lung perfusion in these patients, has demonstrated PV thickening, mosaicism, and pulmonary vessel dilation; the latter likely occurring due to aberrations in physiologic hypoxic pulmonary vasoconstriction (Lang, et al. Lancet. 2020 Apr 30;S1473-3099[20]30367).
Despite PV’s involvement, only few cases of COVID-19 have been reported in patients with pulmonary arterial hypertension (PAH) , leading to the hypothesis that pre-existing vascular changes may have a protective effect in PAH patients (Horn, et al. Pulm Circ. 2020;10(2):1-2).
The above discussion details the complex and multifaceted relationship between COVID-19 and PV which underscores the value of understanding this interaction further and may prove to be insightful for discovering potential therapeutic targets in COVID-19.
Humna Abid Memon, MD – Fellow-in-Training Member
Interventional chest and diagnostic procedures
Impact of COVID-19 pandemic in patients with non-advanced LC
The COVID-19 pandemic has challenged the way we screen for, diagnose, and treat lung cancer.1, 2 Knowing that these patients are at higher risk of respiratory failure, and that COVID-19 causes poor outcomes in cancer patients,1,3,4 valid concerns regarding viral transmission to patients and health-care workers have hampered the expedited care this population needs.
In recent months, efforts to manage the pandemic have been herculean. With the goal of limiting transmission, expert panels have offered guidance including limiting access to medical facilities, decreasing aerosolizing procedures, and prioritizing curative treatments.2,5 In general, lung cancer screening should be delayed, and patients with highly suspicious localized pulmonary lesions could receive empiric regimens, surgery, or stereotactic radiotherapy.1,3-5
The conundrum occurs when diagnostic bronchoscopy is required for staging, acquiring tissue for targeted therapy, or a moderate-risk pulmonary nodule with indeterminate PET-CT and/or high-risk for CT-guided biopsy. Thoughtful balancing of risks and benefits depends on patient comorbidities, hospital resources – such preprocedural COVID screening, adequate protective personal equipment- and rate of local viral prevalence.6,7 Delaying diagnosis and staging could lead to progression of cancer and preclude curative or adjuvant therapy for appropriate candidates. Furthermore, we should not dismiss the appalling psychological impact of delayed care on our patients.
While the pandemic continues and challenges arise in the care of patients with lung cancer, the value of a multidisciplinary input and individualized care cannot be overstated, with focus on providing the best care possible while both minimizing transmission and increasing the chances of acceptable outcomes.
Jose De Cardenas MD, FCCP – Steering Committee Member
Abdul Hamid Alraiyes MD, FCCP – Steering Committee Member
References
1. Mazzone PJ, et al. Chest. 2020;158(1):406-415. doi: 10.1016/j.chest.2020.04.020.
2. Banna G, et al. ESMO Open. 2020;5(2):e000765. doi: 10.1136/esmoopen-2020-000765.
3. Liang W, et al. Lancet Oncol. 2020;21(3):335-337. doi: 10.1016/S1470-2045(20)30096-6.
4. Singh AP, et al. JCO Oncol Pract. 2020 May 26;OP2000286. doi: 10.1200/OP.20.00286.
5. Dingemans AC, et al. J Thorac Oncol. 2020;15(7):1119-1136. doi: 10.1016/j.jtho.2020.05.001.
6. Wahidi MM, et al. J Bronchology Interv Pulmonol. 2020 Mar 18. doi: 10.1097/LBR.0000000000000681.
7. Pritchett MA, et al. J Thorac Dis. 2020;12(5):1781-1798. doi: 10.21037/jtd.2020.04.32.
Pediatric chest medicine
FDA strengthens the boxed warning for montelukast
Early this year the Food and Drug Administration (FDA) updated the boxed warning for montelukast (Singulair), related to the potential for serious mental health side effects, such as agitation, aggressive behavior, depression, hallucinations, and suicidal thoughts and actions. Since its approval in 1998, montelukast is part of the therapeutic approach for persistent asthma in children age 1 year and older, allergic rhinitis from 6 months and older, and exercises induced bronchospasm in children age 6 years and older. In 2018, around 2.3 million children younger than 17 years received a prescription for montelukast.
The FDA reviewed data from their Sentinel System comparing children receiving montelukast vs inhaled corticosteroids, and this study failed to demonstrate significant increased risk of hospitalized depressive disorders, outpatient depressive disorders, self-harm, or suicide. However, a focused evaluation by the FDA of suicides identified 82 cases of completed suicides associated with montelukast, and 19 of these cases were in children younger than 17 years of age.
Post-marketing case reports submitted to the FDA, published observational and animal studies were evaluated along with the Sentinel System study that led to the new recommendations.
Finally, on March 4, 2020, the FDA updated the Singulair®/montelukast black box warning, focusing on the importance of advising patients and caregivers about the potential for serious neuropsychiatric side effects and advice to immediately discontinue use if symptoms occurred. The warning contains a strong recommendation to reserve use of Singulair®/montelukast to patients with allergic rhinitis who have an inadequate response or intolerance to alternate therapies.
Endy Dominguez Silveyra, MD - Fellow-in-Training Member
References
1. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. FDA Drug Safety Communication, March 4, 2020.
2. Neuropsychiatric events following montelukast use: A propensity score matched analysis. Sentinel, Sept. 27, 2019.
Pulmonary physiology, function, and rehabilitation
The happy hypoxic
In early December 2019, the novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified. Over the ensuing months, SARS-CoV-2 would cause a wide range of pulmonary symptoms from cough and mild shortness of breath to acute respiratory distress syndrome (ARDS) with severe hypoxia that puzzled intensivists worldwide.
One such mystifying presentation was finding patients with critically low oxygen levels who did not appear to be short of breath. This concept was dubbed “happy or silent hypoxemia.” Novel mechanisms of the SARS-Co-V-2 virus on the respiratory system have been proposed to explain this paradox, but recent literature suggests that foundational pulmonary physiology concepts can explain most of these findings.1
Breathing is centrally controlled by the respiratory center in the brain stem and is influenced mainly by dissolved carbon dioxide and pH.2 Hypercapnia is, therefore, a powerful stimulus to breathe and increase minute ventilation. It can cause dyspnea if this demand is not met.3
Hypoxia, on the other hand, is less powerful and does not evoke dyspnea until the PaO2 drops below 60 mm Hg.4 Hypercapnia potentiates this response: the higher the PaCO2, the higher the hypoxic response. Patients with a PaCO2 of 39 mm Hg or less may not experience dyspnea even when hypoxia is severe.1
Other possible explanations for silent hypoxemia include the poor accuracy of the pulse oximeter for estimating oxygen saturation of less than 80%,1 especially in the critically ill5 and the leftward shift of the oxygen dissociation curve due to fever, making the oxygen saturation lower for any given PaO2.1
In conclusion, the clinical management of COVID-19 pneumonia with a broad range of clinical features presents many unknowns, but it is reassuring to find an anchor in good old pulmonary physiology concepts.5
It is back to the basics for us all and that might be a good thing.
Oriade Adeoye, MD – Fellow-in-Training Member
References
1. Tobin MJ, et al. Am J Respir Crit Care Med. 2020;202(3):356-360. doi: 10.1164/rccm.202006-2157CP.
2. Vaporidi K, et al. Am J Respir Crit Care Med. 2020;201(1):20-32. doi: 10.1164/rccm.201903-0596SO.
3. Dhont S, et al. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5.
4. Weil JV, et al. J Clin Invest. 1970;49(6):1061-1072. doi:10.1172/JCI106322.
5. Tobin MJ. Am J Respir Crit Care Med. 2020;201(11):1319-1320. doi:10.1164/rccm.202004-1076ED.
Pulmonary vascular disease
COVID-19 and pulmonary vasculature: an intriguing relationship
Hypoxemia is the cardinal symptom in patients with severe coronavirus disease-2019 (COVID-19). However, hypoxemia disproportionate to radiographic opacities has led to growing suspicion that involvement of pulmonary vasculature (PV), leading to shunt physiology, may be a driver of this marked hypoxemia.
The virus’s affinity for PV is explained by presence of angiotensin-converting enzyme 2 receptor, which serves as the functional receptor for SARS-CoV-2, on pulmonary endothelium (Provencher, et al. Pulm Circ. 2020 Jun 10;10[3]:2045894020933088. doi: 10.1177/2045894020933088).
This increased affinity predisposes PV to pathologic effects of SARS-CoV-2, noted in COVID-19 patients’ autopsies, which revealed pulmonary endothelial injury and abnormal vessel growth (intussusceptive angiogenesis). These changes, along with profound inflammatory response, further predispose the PV to thrombosis and microangiopathy in COVID-19 (Ackermann, et al. N Engl J Med. 2020 Jul 9;383[2]:120-128).
These autopsy results also explain the radiologic findings of PV in COVID-19. Dual energy CT scanning, used to evaluate lung perfusion in these patients, has demonstrated PV thickening, mosaicism, and pulmonary vessel dilation; the latter likely occurring due to aberrations in physiologic hypoxic pulmonary vasoconstriction (Lang, et al. Lancet. 2020 Apr 30;S1473-3099[20]30367).
Despite PV’s involvement, only few cases of COVID-19 have been reported in patients with pulmonary arterial hypertension (PAH) , leading to the hypothesis that pre-existing vascular changes may have a protective effect in PAH patients (Horn, et al. Pulm Circ. 2020;10(2):1-2).
The above discussion details the complex and multifaceted relationship between COVID-19 and PV which underscores the value of understanding this interaction further and may prove to be insightful for discovering potential therapeutic targets in COVID-19.
Humna Abid Memon, MD – Fellow-in-Training Member
Bronchoscopy and tracheostomy in the COVID-19 era
The coronavirus disease 2019 (COVID-19) pandemic has changed the way we deliver healthcare for the foreseeable future. Not only have we had to rapidly learn how to evaluate, diagnose, and treat this new disease, we have also had to shift how we screen, triage, and care for other patients for both their safety and ours. As the virus is primarily spread via respiratory droplets, aerosol-generating procedures (AGP), such as bronchoscopy and tracheostomy, are high-risk for viral transmission. We have therefore had to reassess the risk/benefit ratio of performing these procedures – what is the risk to the patient by procedure postponement vs the risk to the health-care personnel (HCP) involved by moving ahead with the procedure? And, if proceeding, how should we protect ourselves? How do we screen patients to help us stratify risk? In order to answer these questions, we generally divide patients into three categories: the asymptomatic outpatient, the symptomatic patient, and the critically ill patient.
The asymptomatic outpatient
Early in the pandemic as cases began to spike in the US, many hospitals decided to postpone all elective procedures and surgeries. Guidelines quickly emerged stratifying bronchoscopic procedures into emergent, urgent, acute, subacute, and truly elective with recommendations on the subsequent timing of those procedures (Pritchett MA, et al. J Thorac Dis. 2020 May;12[5]:1781-1798). As we have obtained further data and our infrastructure has been bolstered, many physicians have begun performing more routine procedures. Preprocedural screening, both with symptom questionnaires and nasopharyngeal swabs, has been enacted as a measure to prevent inadvertent exposure to infected patients. While there are limited data regarding the reliability of this measure, emerging data have shown good concordance between nasopharyngeal SARS-CoV-2 polymerase chain reaction (PCR) swabs and bronchoalveolar lavage (BAL) samples in low-risk patients (Oberg, et al. Personal communication, Sept 2020). Emergency procedures, such as foreign body aspiration, critical airway obstruction, and massive hemoptysis, were generally performed without delay throughout the pandemic. More recently, emphasis has been placed on prioritizing procedures for acute clinical diagnoses, such as biopsies for concerning lung nodules or masses in potentially early-stage patients, in those where staging is needed and in those where disease progression is suspected. Subacute procedures, such as inspection bronchoscopy for cough, minor hemoptysis, or airway stent surveillance, have generally been reintroduced while elective procedures, such as bronchial thermoplasty and bronchoscopic lung volume reduction, are considered elective, and their frequency and timing is determined mostly by the number of new cases of COVID-19 in the local community.
For all procedures, general modifications have been made. High-efficiency particulate air (HEPA) filters should be placed on all ventilatory circuits. When equivalent, flexible bronchoscopy is preferred over rigid bronchoscopy due to the closed circuit. Enhanced personal protective equipment (PPE) for all procedures is recommended – this typically includes a gown, gloves, hair bonnet, N-95 mask, and a face shield. Strict adherence to the Centers for Disease Control and Prevention (CDC) guidelines for postprocedure cleaning and sterilization is strongly recommended. In some cases, single-use bronchoscopes are being preferentially used, though no strong recommendations exist for this.
The symptomatic COVID-19 patient
In patients who have been diagnosed with SARS-CoV-2, we generally recommend postponing all procedures other than for life-threatening indications. For outpatients, we generally wait for two negative nasopharyngeal swabs prior to performing any nonemergent procedure. In inpatients, similar recommendations exist. Potential inpatient indications for bronchoscopy include diagnostic evaluation for alternate or coinfections, and therapeutic aspiration of clinically significant secretions. These should be carefully considered and performed only if deemed absolutely necessary. If bronchoscopy is needed in a patient with suspected or confirmed COVID-19, at a minimum, gown, gloves, head cover, face shield, and an N-95 mask should be worn. A powered air purifying respirator (PAPR) can be used and may provide increased protection. Proper donning and doffing techniques should be reviewed prior to any procedure. Personnel involved in the case should be limited to the minimum required. The procedure should be performed by experienced operators and limited in length. Removal and reinsertion of the bronchoscope should be minimized.
The critically ill COVID-19 patient
While the majority of patients infected with SARS-CoV-2 will have only mild symptoms, we know that a subset of patients will develop respiratory failure. Of those, a small but significant number will require prolonged mechanical ventilation during their clinical course. Thus, the consideration for tracheostomy comes into play.
Multiple issues arise when discussing tracheostomy placement in the COVID-19 world. Should it be done at all? If yes, what is the best technique and who should do it? When and where should it be done? Importantly – how do we care for patients once it is in place to facilitate recovery and, hopefully, decannulation?
Tracheostomy tubes are used in the ICU for patients who require prolonged mechanical ventilation for many reasons – patient comfort, decreased need for sedation, and to facilitate transfer out of the ICU to less acute care areas. These reasons are just as important in patients afflicted with respiratory failure from COVID-19, if not more so. As the patient volumes surge, health-care systems can quickly become overwhelmed. The ability to safely move patients out of the ICU frees up those resources for others who are more acutely ill.
The optimal technique for tracheostomy placement largely depends on the technological and human capital of each institution. Emphasis should be placed on procedural experience, efficiency, safety, and minimizing risk to HCP. While mortality rates do not differ between the surgical and percutaneous techniques, the percutaneous approach has been shown to require less procedural time (Iftikhar IH, et al. Lung. 2019[Jun];197[3]:267-275), an important infection control advantage in COVID-19 patients. Additionally, percutaneous tracheostomies are typically performed at the bedside, which offers the immediate benefit of minimizing patient transfer. This decreases exposure to multiple HCP, as well as contamination of other health-care areas. If performing a bronchoscopic-guided percutaneous tracheostomy, apnea should be maintained from insertion of the guiding catheter to tracheostomy insertion in order to minimize aerosolization. A novel technique involving placing the bronchoscope beside the endotracheal tube instead of through it has also been described (Angel L, et al. Ann Thorac Surg. 2020[Sep];110[3]:1006–1011).
Timing of tracheostomy placement in COVID-19 patients has varied widely. Initially, concern for the safety of HCP performing these procedures led to recommendations of waiting at least 21 days of intubation or until COVID-19 testing became negative. However, more recently, multiple recommendations have been made for tracheostomy placement after day 10 of intubation (McGrath, et al. Lancet Respir Med. 2020[Jul];8[7]:717-725).
Finally, once a tracheostomy tube has been placed, the care does not stop there. As patients are transitioned to rehabilitation centers or skilled nursing facilities and are assessed for weaning, downsizing, and decannulation, care should be taken to avoid virus aerosolization during key high-risk steps. Modifications such as performing spontaneous breathing trials using pressure support (a closed circuit) rather than tracheostomy mask, bypassing speaking valve trials in favor of direct tracheostomy capping, and avoiding routine tracheostomy downsizing are examples of simple steps that can be taken to facilitate patient progress while minimizing HCP risk (Divo, et al. Respir Care. 2020[Aug]5;respcare.08157).
What’s ahead?
As we move forward, we will continue to balance caring for patients effectively and efficiently while minimizing risk to ourselves and others. Ultimately until a vaccine exists, we will have to focus on prevention of infection and spread; therefore, the core principles of hand hygiene, mask wearing, and social distancing have never been more important. We encourage continued study, scrutiny, and collaboration in order to optimize procedural techniques as more information becomes available.
Dr. Oberg is with the Section of Interventional Pulmonology, David Geffen School of Medicine at UCLA; Dr. Beattie is with the Section of Interventional Pulmonology, Memorial Sloan Kettering Cancer Center, New York; and Dr. Folch is with the Section of Interventional Pulmonology, Massachusetts General Hospital, Harvard Medical School.
The coronavirus disease 2019 (COVID-19) pandemic has changed the way we deliver healthcare for the foreseeable future. Not only have we had to rapidly learn how to evaluate, diagnose, and treat this new disease, we have also had to shift how we screen, triage, and care for other patients for both their safety and ours. As the virus is primarily spread via respiratory droplets, aerosol-generating procedures (AGP), such as bronchoscopy and tracheostomy, are high-risk for viral transmission. We have therefore had to reassess the risk/benefit ratio of performing these procedures – what is the risk to the patient by procedure postponement vs the risk to the health-care personnel (HCP) involved by moving ahead with the procedure? And, if proceeding, how should we protect ourselves? How do we screen patients to help us stratify risk? In order to answer these questions, we generally divide patients into three categories: the asymptomatic outpatient, the symptomatic patient, and the critically ill patient.
The asymptomatic outpatient
Early in the pandemic as cases began to spike in the US, many hospitals decided to postpone all elective procedures and surgeries. Guidelines quickly emerged stratifying bronchoscopic procedures into emergent, urgent, acute, subacute, and truly elective with recommendations on the subsequent timing of those procedures (Pritchett MA, et al. J Thorac Dis. 2020 May;12[5]:1781-1798). As we have obtained further data and our infrastructure has been bolstered, many physicians have begun performing more routine procedures. Preprocedural screening, both with symptom questionnaires and nasopharyngeal swabs, has been enacted as a measure to prevent inadvertent exposure to infected patients. While there are limited data regarding the reliability of this measure, emerging data have shown good concordance between nasopharyngeal SARS-CoV-2 polymerase chain reaction (PCR) swabs and bronchoalveolar lavage (BAL) samples in low-risk patients (Oberg, et al. Personal communication, Sept 2020). Emergency procedures, such as foreign body aspiration, critical airway obstruction, and massive hemoptysis, were generally performed without delay throughout the pandemic. More recently, emphasis has been placed on prioritizing procedures for acute clinical diagnoses, such as biopsies for concerning lung nodules or masses in potentially early-stage patients, in those where staging is needed and in those where disease progression is suspected. Subacute procedures, such as inspection bronchoscopy for cough, minor hemoptysis, or airway stent surveillance, have generally been reintroduced while elective procedures, such as bronchial thermoplasty and bronchoscopic lung volume reduction, are considered elective, and their frequency and timing is determined mostly by the number of new cases of COVID-19 in the local community.
For all procedures, general modifications have been made. High-efficiency particulate air (HEPA) filters should be placed on all ventilatory circuits. When equivalent, flexible bronchoscopy is preferred over rigid bronchoscopy due to the closed circuit. Enhanced personal protective equipment (PPE) for all procedures is recommended – this typically includes a gown, gloves, hair bonnet, N-95 mask, and a face shield. Strict adherence to the Centers for Disease Control and Prevention (CDC) guidelines for postprocedure cleaning and sterilization is strongly recommended. In some cases, single-use bronchoscopes are being preferentially used, though no strong recommendations exist for this.
The symptomatic COVID-19 patient
In patients who have been diagnosed with SARS-CoV-2, we generally recommend postponing all procedures other than for life-threatening indications. For outpatients, we generally wait for two negative nasopharyngeal swabs prior to performing any nonemergent procedure. In inpatients, similar recommendations exist. Potential inpatient indications for bronchoscopy include diagnostic evaluation for alternate or coinfections, and therapeutic aspiration of clinically significant secretions. These should be carefully considered and performed only if deemed absolutely necessary. If bronchoscopy is needed in a patient with suspected or confirmed COVID-19, at a minimum, gown, gloves, head cover, face shield, and an N-95 mask should be worn. A powered air purifying respirator (PAPR) can be used and may provide increased protection. Proper donning and doffing techniques should be reviewed prior to any procedure. Personnel involved in the case should be limited to the minimum required. The procedure should be performed by experienced operators and limited in length. Removal and reinsertion of the bronchoscope should be minimized.
The critically ill COVID-19 patient
While the majority of patients infected with SARS-CoV-2 will have only mild symptoms, we know that a subset of patients will develop respiratory failure. Of those, a small but significant number will require prolonged mechanical ventilation during their clinical course. Thus, the consideration for tracheostomy comes into play.
Multiple issues arise when discussing tracheostomy placement in the COVID-19 world. Should it be done at all? If yes, what is the best technique and who should do it? When and where should it be done? Importantly – how do we care for patients once it is in place to facilitate recovery and, hopefully, decannulation?
Tracheostomy tubes are used in the ICU for patients who require prolonged mechanical ventilation for many reasons – patient comfort, decreased need for sedation, and to facilitate transfer out of the ICU to less acute care areas. These reasons are just as important in patients afflicted with respiratory failure from COVID-19, if not more so. As the patient volumes surge, health-care systems can quickly become overwhelmed. The ability to safely move patients out of the ICU frees up those resources for others who are more acutely ill.
The optimal technique for tracheostomy placement largely depends on the technological and human capital of each institution. Emphasis should be placed on procedural experience, efficiency, safety, and minimizing risk to HCP. While mortality rates do not differ between the surgical and percutaneous techniques, the percutaneous approach has been shown to require less procedural time (Iftikhar IH, et al. Lung. 2019[Jun];197[3]:267-275), an important infection control advantage in COVID-19 patients. Additionally, percutaneous tracheostomies are typically performed at the bedside, which offers the immediate benefit of minimizing patient transfer. This decreases exposure to multiple HCP, as well as contamination of other health-care areas. If performing a bronchoscopic-guided percutaneous tracheostomy, apnea should be maintained from insertion of the guiding catheter to tracheostomy insertion in order to minimize aerosolization. A novel technique involving placing the bronchoscope beside the endotracheal tube instead of through it has also been described (Angel L, et al. Ann Thorac Surg. 2020[Sep];110[3]:1006–1011).
Timing of tracheostomy placement in COVID-19 patients has varied widely. Initially, concern for the safety of HCP performing these procedures led to recommendations of waiting at least 21 days of intubation or until COVID-19 testing became negative. However, more recently, multiple recommendations have been made for tracheostomy placement after day 10 of intubation (McGrath, et al. Lancet Respir Med. 2020[Jul];8[7]:717-725).
Finally, once a tracheostomy tube has been placed, the care does not stop there. As patients are transitioned to rehabilitation centers or skilled nursing facilities and are assessed for weaning, downsizing, and decannulation, care should be taken to avoid virus aerosolization during key high-risk steps. Modifications such as performing spontaneous breathing trials using pressure support (a closed circuit) rather than tracheostomy mask, bypassing speaking valve trials in favor of direct tracheostomy capping, and avoiding routine tracheostomy downsizing are examples of simple steps that can be taken to facilitate patient progress while minimizing HCP risk (Divo, et al. Respir Care. 2020[Aug]5;respcare.08157).
What’s ahead?
As we move forward, we will continue to balance caring for patients effectively and efficiently while minimizing risk to ourselves and others. Ultimately until a vaccine exists, we will have to focus on prevention of infection and spread; therefore, the core principles of hand hygiene, mask wearing, and social distancing have never been more important. We encourage continued study, scrutiny, and collaboration in order to optimize procedural techniques as more information becomes available.
Dr. Oberg is with the Section of Interventional Pulmonology, David Geffen School of Medicine at UCLA; Dr. Beattie is with the Section of Interventional Pulmonology, Memorial Sloan Kettering Cancer Center, New York; and Dr. Folch is with the Section of Interventional Pulmonology, Massachusetts General Hospital, Harvard Medical School.
The coronavirus disease 2019 (COVID-19) pandemic has changed the way we deliver healthcare for the foreseeable future. Not only have we had to rapidly learn how to evaluate, diagnose, and treat this new disease, we have also had to shift how we screen, triage, and care for other patients for both their safety and ours. As the virus is primarily spread via respiratory droplets, aerosol-generating procedures (AGP), such as bronchoscopy and tracheostomy, are high-risk for viral transmission. We have therefore had to reassess the risk/benefit ratio of performing these procedures – what is the risk to the patient by procedure postponement vs the risk to the health-care personnel (HCP) involved by moving ahead with the procedure? And, if proceeding, how should we protect ourselves? How do we screen patients to help us stratify risk? In order to answer these questions, we generally divide patients into three categories: the asymptomatic outpatient, the symptomatic patient, and the critically ill patient.
The asymptomatic outpatient
Early in the pandemic as cases began to spike in the US, many hospitals decided to postpone all elective procedures and surgeries. Guidelines quickly emerged stratifying bronchoscopic procedures into emergent, urgent, acute, subacute, and truly elective with recommendations on the subsequent timing of those procedures (Pritchett MA, et al. J Thorac Dis. 2020 May;12[5]:1781-1798). As we have obtained further data and our infrastructure has been bolstered, many physicians have begun performing more routine procedures. Preprocedural screening, both with symptom questionnaires and nasopharyngeal swabs, has been enacted as a measure to prevent inadvertent exposure to infected patients. While there are limited data regarding the reliability of this measure, emerging data have shown good concordance between nasopharyngeal SARS-CoV-2 polymerase chain reaction (PCR) swabs and bronchoalveolar lavage (BAL) samples in low-risk patients (Oberg, et al. Personal communication, Sept 2020). Emergency procedures, such as foreign body aspiration, critical airway obstruction, and massive hemoptysis, were generally performed without delay throughout the pandemic. More recently, emphasis has been placed on prioritizing procedures for acute clinical diagnoses, such as biopsies for concerning lung nodules or masses in potentially early-stage patients, in those where staging is needed and in those where disease progression is suspected. Subacute procedures, such as inspection bronchoscopy for cough, minor hemoptysis, or airway stent surveillance, have generally been reintroduced while elective procedures, such as bronchial thermoplasty and bronchoscopic lung volume reduction, are considered elective, and their frequency and timing is determined mostly by the number of new cases of COVID-19 in the local community.
For all procedures, general modifications have been made. High-efficiency particulate air (HEPA) filters should be placed on all ventilatory circuits. When equivalent, flexible bronchoscopy is preferred over rigid bronchoscopy due to the closed circuit. Enhanced personal protective equipment (PPE) for all procedures is recommended – this typically includes a gown, gloves, hair bonnet, N-95 mask, and a face shield. Strict adherence to the Centers for Disease Control and Prevention (CDC) guidelines for postprocedure cleaning and sterilization is strongly recommended. In some cases, single-use bronchoscopes are being preferentially used, though no strong recommendations exist for this.
The symptomatic COVID-19 patient
In patients who have been diagnosed with SARS-CoV-2, we generally recommend postponing all procedures other than for life-threatening indications. For outpatients, we generally wait for two negative nasopharyngeal swabs prior to performing any nonemergent procedure. In inpatients, similar recommendations exist. Potential inpatient indications for bronchoscopy include diagnostic evaluation for alternate or coinfections, and therapeutic aspiration of clinically significant secretions. These should be carefully considered and performed only if deemed absolutely necessary. If bronchoscopy is needed in a patient with suspected or confirmed COVID-19, at a minimum, gown, gloves, head cover, face shield, and an N-95 mask should be worn. A powered air purifying respirator (PAPR) can be used and may provide increased protection. Proper donning and doffing techniques should be reviewed prior to any procedure. Personnel involved in the case should be limited to the minimum required. The procedure should be performed by experienced operators and limited in length. Removal and reinsertion of the bronchoscope should be minimized.
The critically ill COVID-19 patient
While the majority of patients infected with SARS-CoV-2 will have only mild symptoms, we know that a subset of patients will develop respiratory failure. Of those, a small but significant number will require prolonged mechanical ventilation during their clinical course. Thus, the consideration for tracheostomy comes into play.
Multiple issues arise when discussing tracheostomy placement in the COVID-19 world. Should it be done at all? If yes, what is the best technique and who should do it? When and where should it be done? Importantly – how do we care for patients once it is in place to facilitate recovery and, hopefully, decannulation?
Tracheostomy tubes are used in the ICU for patients who require prolonged mechanical ventilation for many reasons – patient comfort, decreased need for sedation, and to facilitate transfer out of the ICU to less acute care areas. These reasons are just as important in patients afflicted with respiratory failure from COVID-19, if not more so. As the patient volumes surge, health-care systems can quickly become overwhelmed. The ability to safely move patients out of the ICU frees up those resources for others who are more acutely ill.
The optimal technique for tracheostomy placement largely depends on the technological and human capital of each institution. Emphasis should be placed on procedural experience, efficiency, safety, and minimizing risk to HCP. While mortality rates do not differ between the surgical and percutaneous techniques, the percutaneous approach has been shown to require less procedural time (Iftikhar IH, et al. Lung. 2019[Jun];197[3]:267-275), an important infection control advantage in COVID-19 patients. Additionally, percutaneous tracheostomies are typically performed at the bedside, which offers the immediate benefit of minimizing patient transfer. This decreases exposure to multiple HCP, as well as contamination of other health-care areas. If performing a bronchoscopic-guided percutaneous tracheostomy, apnea should be maintained from insertion of the guiding catheter to tracheostomy insertion in order to minimize aerosolization. A novel technique involving placing the bronchoscope beside the endotracheal tube instead of through it has also been described (Angel L, et al. Ann Thorac Surg. 2020[Sep];110[3]:1006–1011).
Timing of tracheostomy placement in COVID-19 patients has varied widely. Initially, concern for the safety of HCP performing these procedures led to recommendations of waiting at least 21 days of intubation or until COVID-19 testing became negative. However, more recently, multiple recommendations have been made for tracheostomy placement after day 10 of intubation (McGrath, et al. Lancet Respir Med. 2020[Jul];8[7]:717-725).
Finally, once a tracheostomy tube has been placed, the care does not stop there. As patients are transitioned to rehabilitation centers or skilled nursing facilities and are assessed for weaning, downsizing, and decannulation, care should be taken to avoid virus aerosolization during key high-risk steps. Modifications such as performing spontaneous breathing trials using pressure support (a closed circuit) rather than tracheostomy mask, bypassing speaking valve trials in favor of direct tracheostomy capping, and avoiding routine tracheostomy downsizing are examples of simple steps that can be taken to facilitate patient progress while minimizing HCP risk (Divo, et al. Respir Care. 2020[Aug]5;respcare.08157).
What’s ahead?
As we move forward, we will continue to balance caring for patients effectively and efficiently while minimizing risk to ourselves and others. Ultimately until a vaccine exists, we will have to focus on prevention of infection and spread; therefore, the core principles of hand hygiene, mask wearing, and social distancing have never been more important. We encourage continued study, scrutiny, and collaboration in order to optimize procedural techniques as more information becomes available.
Dr. Oberg is with the Section of Interventional Pulmonology, David Geffen School of Medicine at UCLA; Dr. Beattie is with the Section of Interventional Pulmonology, Memorial Sloan Kettering Cancer Center, New York; and Dr. Folch is with the Section of Interventional Pulmonology, Massachusetts General Hospital, Harvard Medical School.
CHEST 2020 is coming to YOU
Expert-driven education—reimagined
CHEST’s premier event in pulmonary, critical care, and sleep medicine is just around the corner! Join us for CHEST Annual Meeting 2020, taking place October 18-21. We know it’s hard to plan out your schedule during an ever-changing pandemic, which is why this year’s meeting is being brought to you on a virtual platform. You’ll be able to access the meeting content from any device, in any location, at any time. It’s that convenient! Plus, you can join in immersive, interactive live sessions taught by expert faculty and followed by Q&As, or listen to prerecorded content at your own pace. Don’t worry if you’re unable to attend a session — all meeting content will be available to registrants until January 2021.
This year, you can expect:
• A keynote address by Anthony Fauci, MD, covering COVID-19.
• Over 88 live sessions, including panel and case-based discussions.
• Critically relevant sessions focusing on COVID-19 and cultural diversity.
• Original investigation presentations with new, unpublished science.
• Unique networking opportunities.
• Fun and interactive CHEST Games.
Register Today
Chestmeeting.chestnet.org
Expert-driven education—reimagined
Expert-driven education—reimagined
CHEST’s premier event in pulmonary, critical care, and sleep medicine is just around the corner! Join us for CHEST Annual Meeting 2020, taking place October 18-21. We know it’s hard to plan out your schedule during an ever-changing pandemic, which is why this year’s meeting is being brought to you on a virtual platform. You’ll be able to access the meeting content from any device, in any location, at any time. It’s that convenient! Plus, you can join in immersive, interactive live sessions taught by expert faculty and followed by Q&As, or listen to prerecorded content at your own pace. Don’t worry if you’re unable to attend a session — all meeting content will be available to registrants until January 2021.
This year, you can expect:
• A keynote address by Anthony Fauci, MD, covering COVID-19.
• Over 88 live sessions, including panel and case-based discussions.
• Critically relevant sessions focusing on COVID-19 and cultural diversity.
• Original investigation presentations with new, unpublished science.
• Unique networking opportunities.
• Fun and interactive CHEST Games.
Register Today
Chestmeeting.chestnet.org
CHEST’s premier event in pulmonary, critical care, and sleep medicine is just around the corner! Join us for CHEST Annual Meeting 2020, taking place October 18-21. We know it’s hard to plan out your schedule during an ever-changing pandemic, which is why this year’s meeting is being brought to you on a virtual platform. You’ll be able to access the meeting content from any device, in any location, at any time. It’s that convenient! Plus, you can join in immersive, interactive live sessions taught by expert faculty and followed by Q&As, or listen to prerecorded content at your own pace. Don’t worry if you’re unable to attend a session — all meeting content will be available to registrants until January 2021.
This year, you can expect:
• A keynote address by Anthony Fauci, MD, covering COVID-19.
• Over 88 live sessions, including panel and case-based discussions.
• Critically relevant sessions focusing on COVID-19 and cultural diversity.
• Original investigation presentations with new, unpublished science.
• Unique networking opportunities.
• Fun and interactive CHEST Games.
Register Today
Chestmeeting.chestnet.org
This month in the journal CHEST®
Editor’s picks
Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. By Dr. Lara Jehi, et al.
Airway clearance techniques in bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry. By Dr. Ashwin Basavaraj, et al.
Emotional experiences and coping strategies of family members of critically ill patients. By Dr. Emily Harlan, et al.
Coronavirus disease and smoking: How and why we implemented a tobacco treatment campaign. By Dr. Adam Lang, et al.
Editor’s picks
Editor’s picks
Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. By Dr. Lara Jehi, et al.
Airway clearance techniques in bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry. By Dr. Ashwin Basavaraj, et al.
Emotional experiences and coping strategies of family members of critically ill patients. By Dr. Emily Harlan, et al.
Coronavirus disease and smoking: How and why we implemented a tobacco treatment campaign. By Dr. Adam Lang, et al.
Individualizing risk prediction for positive COVID-19 testing: results from 11,672 patients. By Dr. Lara Jehi, et al.
Airway clearance techniques in bronchiectasis: Analysis from the United States Bronchiectasis and NTM research registry. By Dr. Ashwin Basavaraj, et al.
Emotional experiences and coping strategies of family members of critically ill patients. By Dr. Emily Harlan, et al.
Coronavirus disease and smoking: How and why we implemented a tobacco treatment campaign. By Dr. Adam Lang, et al.
Connect with the CHEST Foundation at CHEST 2020
Join the CHEST Foundation at one of its many virtual events designed around the three pillars of the organization—access, empowerment, and research—during CHEST 2020. Please check CHESTMeeting.chestnet.org for more details on each event.
Virtual Champion’s Circle Donor Lounge
The virtual donor lounge will act as the hub of a wheel – linking the spokes of Foundation programming and events to a central location for easy accessibility. Foundation staff and Board of Trustee members will staff the donor lounge throughout the meeting.
Women & Pulmonary Event – Sunday, October 18 at 11:00 AM – 12:30 PM CT
Connect with key thought leaders and participants to support the advancement of women in the fields of pulmonary, critical care, sleep medicine, and in leadership. The event includes a panel discussion on How to remain in control during a pandemic: family, career and mental wellness, followed by an intimate roundtable discussion moderated by the Women & Pulmonary council. RSVPs are necessary to attend this event.
CHEST Foundation Donor Reception– Sunday, October 18 7:30 PM CT
Join your colleagues and CHEST leadership for a night of fun and networking. Learn to play Texas Hold’em in a complimentary, casual poker tournament and join the high stakes tournament later this month!
Wine Night with CEO Bob Musacchio – Invite Only – Sunday, October 18 7:30 CST
Join CHEST’s CEO, Bob Musacchio for an interactive, exclusive wine night. The evening will include wine chosen from Bob’s personal favorites and kick off the CHEST 2020 annual meeting as we have never done before!
Young Professionals Reception – Monday, October 19, 2020 at 8:00 PM CT – Invite Only
Join your colleagues for a fun evening of trivia, prizes, and celebration! Let the Foundation show some appreciation for your commitment to chest medicine and come learn more about our work!
Join the CHEST Foundation at one of its many virtual events designed around the three pillars of the organization—access, empowerment, and research—during CHEST 2020. Please check CHESTMeeting.chestnet.org for more details on each event.
Virtual Champion’s Circle Donor Lounge
The virtual donor lounge will act as the hub of a wheel – linking the spokes of Foundation programming and events to a central location for easy accessibility. Foundation staff and Board of Trustee members will staff the donor lounge throughout the meeting.
Women & Pulmonary Event – Sunday, October 18 at 11:00 AM – 12:30 PM CT
Connect with key thought leaders and participants to support the advancement of women in the fields of pulmonary, critical care, sleep medicine, and in leadership. The event includes a panel discussion on How to remain in control during a pandemic: family, career and mental wellness, followed by an intimate roundtable discussion moderated by the Women & Pulmonary council. RSVPs are necessary to attend this event.
CHEST Foundation Donor Reception– Sunday, October 18 7:30 PM CT
Join your colleagues and CHEST leadership for a night of fun and networking. Learn to play Texas Hold’em in a complimentary, casual poker tournament and join the high stakes tournament later this month!
Wine Night with CEO Bob Musacchio – Invite Only – Sunday, October 18 7:30 CST
Join CHEST’s CEO, Bob Musacchio for an interactive, exclusive wine night. The evening will include wine chosen from Bob’s personal favorites and kick off the CHEST 2020 annual meeting as we have never done before!
Young Professionals Reception – Monday, October 19, 2020 at 8:00 PM CT – Invite Only
Join your colleagues for a fun evening of trivia, prizes, and celebration! Let the Foundation show some appreciation for your commitment to chest medicine and come learn more about our work!
Join the CHEST Foundation at one of its many virtual events designed around the three pillars of the organization—access, empowerment, and research—during CHEST 2020. Please check CHESTMeeting.chestnet.org for more details on each event.
Virtual Champion’s Circle Donor Lounge
The virtual donor lounge will act as the hub of a wheel – linking the spokes of Foundation programming and events to a central location for easy accessibility. Foundation staff and Board of Trustee members will staff the donor lounge throughout the meeting.
Women & Pulmonary Event – Sunday, October 18 at 11:00 AM – 12:30 PM CT
Connect with key thought leaders and participants to support the advancement of women in the fields of pulmonary, critical care, sleep medicine, and in leadership. The event includes a panel discussion on How to remain in control during a pandemic: family, career and mental wellness, followed by an intimate roundtable discussion moderated by the Women & Pulmonary council. RSVPs are necessary to attend this event.
CHEST Foundation Donor Reception– Sunday, October 18 7:30 PM CT
Join your colleagues and CHEST leadership for a night of fun and networking. Learn to play Texas Hold’em in a complimentary, casual poker tournament and join the high stakes tournament later this month!
Wine Night with CEO Bob Musacchio – Invite Only – Sunday, October 18 7:30 CST
Join CHEST’s CEO, Bob Musacchio for an interactive, exclusive wine night. The evening will include wine chosen from Bob’s personal favorites and kick off the CHEST 2020 annual meeting as we have never done before!
Young Professionals Reception – Monday, October 19, 2020 at 8:00 PM CT – Invite Only
Join your colleagues for a fun evening of trivia, prizes, and celebration! Let the Foundation show some appreciation for your commitment to chest medicine and come learn more about our work!
Remdesivir effective, well-tolerated in final trial report
Drug beats placebo across multiple endpoints in COVID-19 patients
In May 2020, remdesivir received Food and Drug Administration approval for emergency treatment of severe COVID-19 on the basis of a preliminary report on this trial. In August 2020, the FDA expanded the indication to include all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 infection irrespective of severity.
“Our findings were consistent with the findings of the preliminary report: a 10-day course of remdesivir was superior to placebo in the treatment of hospitalized patients with COVID-19,” reported a team of investigators led by John H. Beigel, MD, of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, in the New England Journal of Medicine.
The drug’s broadened indication was not based on the ACTT-1 trial, according to Dr. Beigel. “Other data have demonstrated that remdesivir shortens recovery in patients with lower acuity. In our study, evidence of pneumonia was an enrollment requirement,” he explained in an interview.
In the newly published final ACTT-1 data, the median time to recovery was 10 days for those on active therapy versus 15 days for those randomized to placebo. With a rate ratio of 1.29 (P less than .001), this translated to a recovery that was about one third faster.
In this final report, remdesivir’s significant advantage over placebo regarding the trial’s primary endpoint was reinforced by efficacy on multiple secondary endpoints.
This benefits on multiple secondary endpoints included a 50% greater odds ratio (OR, 1.5; 95% CI, 1.2-1.9) of significant clinical improvement by day 15 after adjustment for baseline severity, a shorter initial length of hospital stay (12 vs. 17 days) and fewer days on oxygen supplementation (13 vs. 21 days) for the subgroup of patients on oxygen at enrollment.
Although the numerically lower mortality in the remdesivir arm (6.75 vs. 11.9%) did not reach statistical significance, Dr. Beigel said, “mortality was moving in the same direction as the other key endpoints.”
According to the study investigators, the types of rates of adverse events on remdesivir, which inhibits viral replication, “were generally similar in the remdesivir and placebo groups.”
In ACTT-1, 1,062 patients were randomized to remdesivir (200 mg loading dose followed by 100 mg daily for up to 9 days) or placebo. Patients were enrolled at study sites in North America, Europe, and Asia.
The data of ACTT-1 confirm a benefit from remdesivir in hospitalized COVID-19 patients with severe disease, but Dr. Beigel said he agrees with the current FDA indication that supports treatment in any hospitalized COVID-19 patient.
“We saw bigger benefits in patients with more severe infections. The benefits are not as large in patients with mild disease, but I think remdesivir should be considered in any hospitalized patient,” Dr. Beigel said.
This point of view is shared.
“I would give this drug to anyone in the hospital infected with COVID-19 assuming there was an ample supply and no need for rationing,” said Donna E. Sweet, MD, professor of internal medicine, University of Kansas, Wichita. She noted that this study has implications for hospital and hospital staff, as well as for patients.
“This type of reduction in recovery time means a reduction in potential exposures to hospital staff, a reduced need for PPE [personal protective equipment], and it will free up beds in the ICU [intensive care unit],” said Dr. Sweet, who also serves as an editorial advisory board member for Internal Medicine News.
An infectious disease specialist at the University of Minnesota also considers remdesivir to have an important role for conserving resources that deserves emphasis.
The reduction in time to recovery “is of benefit to the health system by maintaining hospital bed capacity,” said David R. Boulware, MD, professor of medicine at the University of Minnesota, Minneapolis.
According to his reading of the available data, including those from ACTT-1, the benefit appears to be greatest in those with a moderate degree of illness, which he defined as “sick enough to be hospitalized and require oxygen, yet not severely sick [and] requiring a ventilator or [extracorporeal membrane oxygenation].”
This does not preclude a benefit in those with more severe or milder disease, but patients with mild disease “are likely to recover regardless – or despite – whatever therapy they receive,” he said.
Dr. Beigel, the principal investigator of this trial, reports no potential conflicts of interest.
SOURCE: Beigel JH et al. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764.
Drug beats placebo across multiple endpoints in COVID-19 patients
Drug beats placebo across multiple endpoints in COVID-19 patients
In May 2020, remdesivir received Food and Drug Administration approval for emergency treatment of severe COVID-19 on the basis of a preliminary report on this trial. In August 2020, the FDA expanded the indication to include all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 infection irrespective of severity.
“Our findings were consistent with the findings of the preliminary report: a 10-day course of remdesivir was superior to placebo in the treatment of hospitalized patients with COVID-19,” reported a team of investigators led by John H. Beigel, MD, of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, in the New England Journal of Medicine.
The drug’s broadened indication was not based on the ACTT-1 trial, according to Dr. Beigel. “Other data have demonstrated that remdesivir shortens recovery in patients with lower acuity. In our study, evidence of pneumonia was an enrollment requirement,” he explained in an interview.
In the newly published final ACTT-1 data, the median time to recovery was 10 days for those on active therapy versus 15 days for those randomized to placebo. With a rate ratio of 1.29 (P less than .001), this translated to a recovery that was about one third faster.
In this final report, remdesivir’s significant advantage over placebo regarding the trial’s primary endpoint was reinforced by efficacy on multiple secondary endpoints.
This benefits on multiple secondary endpoints included a 50% greater odds ratio (OR, 1.5; 95% CI, 1.2-1.9) of significant clinical improvement by day 15 after adjustment for baseline severity, a shorter initial length of hospital stay (12 vs. 17 days) and fewer days on oxygen supplementation (13 vs. 21 days) for the subgroup of patients on oxygen at enrollment.
Although the numerically lower mortality in the remdesivir arm (6.75 vs. 11.9%) did not reach statistical significance, Dr. Beigel said, “mortality was moving in the same direction as the other key endpoints.”
According to the study investigators, the types of rates of adverse events on remdesivir, which inhibits viral replication, “were generally similar in the remdesivir and placebo groups.”
In ACTT-1, 1,062 patients were randomized to remdesivir (200 mg loading dose followed by 100 mg daily for up to 9 days) or placebo. Patients were enrolled at study sites in North America, Europe, and Asia.
The data of ACTT-1 confirm a benefit from remdesivir in hospitalized COVID-19 patients with severe disease, but Dr. Beigel said he agrees with the current FDA indication that supports treatment in any hospitalized COVID-19 patient.
“We saw bigger benefits in patients with more severe infections. The benefits are not as large in patients with mild disease, but I think remdesivir should be considered in any hospitalized patient,” Dr. Beigel said.
This point of view is shared.
“I would give this drug to anyone in the hospital infected with COVID-19 assuming there was an ample supply and no need for rationing,” said Donna E. Sweet, MD, professor of internal medicine, University of Kansas, Wichita. She noted that this study has implications for hospital and hospital staff, as well as for patients.
“This type of reduction in recovery time means a reduction in potential exposures to hospital staff, a reduced need for PPE [personal protective equipment], and it will free up beds in the ICU [intensive care unit],” said Dr. Sweet, who also serves as an editorial advisory board member for Internal Medicine News.
An infectious disease specialist at the University of Minnesota also considers remdesivir to have an important role for conserving resources that deserves emphasis.
The reduction in time to recovery “is of benefit to the health system by maintaining hospital bed capacity,” said David R. Boulware, MD, professor of medicine at the University of Minnesota, Minneapolis.
According to his reading of the available data, including those from ACTT-1, the benefit appears to be greatest in those with a moderate degree of illness, which he defined as “sick enough to be hospitalized and require oxygen, yet not severely sick [and] requiring a ventilator or [extracorporeal membrane oxygenation].”
This does not preclude a benefit in those with more severe or milder disease, but patients with mild disease “are likely to recover regardless – or despite – whatever therapy they receive,” he said.
Dr. Beigel, the principal investigator of this trial, reports no potential conflicts of interest.
SOURCE: Beigel JH et al. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764.
In May 2020, remdesivir received Food and Drug Administration approval for emergency treatment of severe COVID-19 on the basis of a preliminary report on this trial. In August 2020, the FDA expanded the indication to include all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 infection irrespective of severity.
“Our findings were consistent with the findings of the preliminary report: a 10-day course of remdesivir was superior to placebo in the treatment of hospitalized patients with COVID-19,” reported a team of investigators led by John H. Beigel, MD, of the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, in the New England Journal of Medicine.
The drug’s broadened indication was not based on the ACTT-1 trial, according to Dr. Beigel. “Other data have demonstrated that remdesivir shortens recovery in patients with lower acuity. In our study, evidence of pneumonia was an enrollment requirement,” he explained in an interview.
In the newly published final ACTT-1 data, the median time to recovery was 10 days for those on active therapy versus 15 days for those randomized to placebo. With a rate ratio of 1.29 (P less than .001), this translated to a recovery that was about one third faster.
In this final report, remdesivir’s significant advantage over placebo regarding the trial’s primary endpoint was reinforced by efficacy on multiple secondary endpoints.
This benefits on multiple secondary endpoints included a 50% greater odds ratio (OR, 1.5; 95% CI, 1.2-1.9) of significant clinical improvement by day 15 after adjustment for baseline severity, a shorter initial length of hospital stay (12 vs. 17 days) and fewer days on oxygen supplementation (13 vs. 21 days) for the subgroup of patients on oxygen at enrollment.
Although the numerically lower mortality in the remdesivir arm (6.75 vs. 11.9%) did not reach statistical significance, Dr. Beigel said, “mortality was moving in the same direction as the other key endpoints.”
According to the study investigators, the types of rates of adverse events on remdesivir, which inhibits viral replication, “were generally similar in the remdesivir and placebo groups.”
In ACTT-1, 1,062 patients were randomized to remdesivir (200 mg loading dose followed by 100 mg daily for up to 9 days) or placebo. Patients were enrolled at study sites in North America, Europe, and Asia.
The data of ACTT-1 confirm a benefit from remdesivir in hospitalized COVID-19 patients with severe disease, but Dr. Beigel said he agrees with the current FDA indication that supports treatment in any hospitalized COVID-19 patient.
“We saw bigger benefits in patients with more severe infections. The benefits are not as large in patients with mild disease, but I think remdesivir should be considered in any hospitalized patient,” Dr. Beigel said.
This point of view is shared.
“I would give this drug to anyone in the hospital infected with COVID-19 assuming there was an ample supply and no need for rationing,” said Donna E. Sweet, MD, professor of internal medicine, University of Kansas, Wichita. She noted that this study has implications for hospital and hospital staff, as well as for patients.
“This type of reduction in recovery time means a reduction in potential exposures to hospital staff, a reduced need for PPE [personal protective equipment], and it will free up beds in the ICU [intensive care unit],” said Dr. Sweet, who also serves as an editorial advisory board member for Internal Medicine News.
An infectious disease specialist at the University of Minnesota also considers remdesivir to have an important role for conserving resources that deserves emphasis.
The reduction in time to recovery “is of benefit to the health system by maintaining hospital bed capacity,” said David R. Boulware, MD, professor of medicine at the University of Minnesota, Minneapolis.
According to his reading of the available data, including those from ACTT-1, the benefit appears to be greatest in those with a moderate degree of illness, which he defined as “sick enough to be hospitalized and require oxygen, yet not severely sick [and] requiring a ventilator or [extracorporeal membrane oxygenation].”
This does not preclude a benefit in those with more severe or milder disease, but patients with mild disease “are likely to recover regardless – or despite – whatever therapy they receive,” he said.
Dr. Beigel, the principal investigator of this trial, reports no potential conflicts of interest.
SOURCE: Beigel JH et al. N Engl J Med. 2020 Oct 8. doi: 10.1056/NEJMoa2007764.
Osteoporosis Journal Scans: October 2020
Some young women can present with very low bone density and multiple fragility fractures. While multiple FDA-approved therapies exist for post-menopausal osteoporosis, pre-menopausal osteoporosis remains an “orphan disease.” Previous evidence suggests that bone anabolic agents such as teriparatide may be useful for women with idiopathic pre-menopausal osteoporosis (IOP). In a phase 2 randomized clinical trial from New York and Nebraska, 41 women with IOP and multiple fractures were randomized to receive placebo or teriparatide in a cross-over study design. The primary endpoint was bone density in the spine and hip after 6 months of treatment, which was significantly increased by teriparatide versus placebo. In addition, bone biopsies were obtained for measurement of bone formation rate using quadruple labeling with tetracycline and demeclocycline three months into treatment. As expected, biopsies showed that teriparatide treatment increased bone formation rates using this ‘gold standard’ method. This prospective randomized study adds to a growing body of evidence that teriparatide may be a safe method to boost bone density in women with IOP. Future studies are needed to assess the impact of this therapy on fracture risk in this specific patient population.
Type 2 diabetes and osteoporosis are both major problems in our aging population. While some diabetes medications such as thiazolidinediones clearly increase fracture risk, the effects of newer diabetes medications on bone biology and fracture risk remain incompletely understood. In addition to beneficial effects on glycemic control, SGLT2 inhibitors show promise with improving cardiovascular and renal outcomes, even in patients without diabetes. Some studies have suggested adverse effects of SGLT2 inhibitor monotherapy on bone density and fracture risk. However, the impact of combined therapy with SGLT2 inhibitors and metformin on fracture risk remains to be established. In this meta-analysis of 25 randomized controlled trials involving 19,500 patients, fracture risk was assessed, based on available information, for individuals who received metformin monotherapy or metformin plus SGLT2 inhibitor treatment. In general, combination therapy did not increase fracture risk compared to metformin alone. Only 6 of the 25 RCTs included in the meta-analysis investigated bone density or bone turnover markers. In these 6 studies, no obvious changes in skeletal outcomes were noted when comparing metformin alone versus metformin plus SGLT2 inhibitor therapy. Although these data are somewhat reassuring for the skeletal safety of combination metformin/SGLT2 inhibitor therapy, confidence is limited by relatively short follow-up time and lack of detailed information about fractures in these studies which focused primarily on diabetes-related outcomes. Future prospective studies are needed to specifically address the skeletal impact of this commonly-used combination of diabetes medications.
Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School
Some young women can present with very low bone density and multiple fragility fractures. While multiple FDA-approved therapies exist for post-menopausal osteoporosis, pre-menopausal osteoporosis remains an “orphan disease.” Previous evidence suggests that bone anabolic agents such as teriparatide may be useful for women with idiopathic pre-menopausal osteoporosis (IOP). In a phase 2 randomized clinical trial from New York and Nebraska, 41 women with IOP and multiple fractures were randomized to receive placebo or teriparatide in a cross-over study design. The primary endpoint was bone density in the spine and hip after 6 months of treatment, which was significantly increased by teriparatide versus placebo. In addition, bone biopsies were obtained for measurement of bone formation rate using quadruple labeling with tetracycline and demeclocycline three months into treatment. As expected, biopsies showed that teriparatide treatment increased bone formation rates using this ‘gold standard’ method. This prospective randomized study adds to a growing body of evidence that teriparatide may be a safe method to boost bone density in women with IOP. Future studies are needed to assess the impact of this therapy on fracture risk in this specific patient population.
Type 2 diabetes and osteoporosis are both major problems in our aging population. While some diabetes medications such as thiazolidinediones clearly increase fracture risk, the effects of newer diabetes medications on bone biology and fracture risk remain incompletely understood. In addition to beneficial effects on glycemic control, SGLT2 inhibitors show promise with improving cardiovascular and renal outcomes, even in patients without diabetes. Some studies have suggested adverse effects of SGLT2 inhibitor monotherapy on bone density and fracture risk. However, the impact of combined therapy with SGLT2 inhibitors and metformin on fracture risk remains to be established. In this meta-analysis of 25 randomized controlled trials involving 19,500 patients, fracture risk was assessed, based on available information, for individuals who received metformin monotherapy or metformin plus SGLT2 inhibitor treatment. In general, combination therapy did not increase fracture risk compared to metformin alone. Only 6 of the 25 RCTs included in the meta-analysis investigated bone density or bone turnover markers. In these 6 studies, no obvious changes in skeletal outcomes were noted when comparing metformin alone versus metformin plus SGLT2 inhibitor therapy. Although these data are somewhat reassuring for the skeletal safety of combination metformin/SGLT2 inhibitor therapy, confidence is limited by relatively short follow-up time and lack of detailed information about fractures in these studies which focused primarily on diabetes-related outcomes. Future prospective studies are needed to specifically address the skeletal impact of this commonly-used combination of diabetes medications.
Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School
Some young women can present with very low bone density and multiple fragility fractures. While multiple FDA-approved therapies exist for post-menopausal osteoporosis, pre-menopausal osteoporosis remains an “orphan disease.” Previous evidence suggests that bone anabolic agents such as teriparatide may be useful for women with idiopathic pre-menopausal osteoporosis (IOP). In a phase 2 randomized clinical trial from New York and Nebraska, 41 women with IOP and multiple fractures were randomized to receive placebo or teriparatide in a cross-over study design. The primary endpoint was bone density in the spine and hip after 6 months of treatment, which was significantly increased by teriparatide versus placebo. In addition, bone biopsies were obtained for measurement of bone formation rate using quadruple labeling with tetracycline and demeclocycline three months into treatment. As expected, biopsies showed that teriparatide treatment increased bone formation rates using this ‘gold standard’ method. This prospective randomized study adds to a growing body of evidence that teriparatide may be a safe method to boost bone density in women with IOP. Future studies are needed to assess the impact of this therapy on fracture risk in this specific patient population.
Type 2 diabetes and osteoporosis are both major problems in our aging population. While some diabetes medications such as thiazolidinediones clearly increase fracture risk, the effects of newer diabetes medications on bone biology and fracture risk remain incompletely understood. In addition to beneficial effects on glycemic control, SGLT2 inhibitors show promise with improving cardiovascular and renal outcomes, even in patients without diabetes. Some studies have suggested adverse effects of SGLT2 inhibitor monotherapy on bone density and fracture risk. However, the impact of combined therapy with SGLT2 inhibitors and metformin on fracture risk remains to be established. In this meta-analysis of 25 randomized controlled trials involving 19,500 patients, fracture risk was assessed, based on available information, for individuals who received metformin monotherapy or metformin plus SGLT2 inhibitor treatment. In general, combination therapy did not increase fracture risk compared to metformin alone. Only 6 of the 25 RCTs included in the meta-analysis investigated bone density or bone turnover markers. In these 6 studies, no obvious changes in skeletal outcomes were noted when comparing metformin alone versus metformin plus SGLT2 inhibitor therapy. Although these data are somewhat reassuring for the skeletal safety of combination metformin/SGLT2 inhibitor therapy, confidence is limited by relatively short follow-up time and lack of detailed information about fractures in these studies which focused primarily on diabetes-related outcomes. Future prospective studies are needed to specifically address the skeletal impact of this commonly-used combination of diabetes medications.
Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School
SGLT2 inhibitors with metformin do not influence fracture risk
Key clinical point: Sodium-glucose transporter-2 inhibitors (SGLT2is) combined with metformin therapy did not influence fracture risk in patients with type 2 diabetes mellitus (T2DM).
Major finding: SGLT2is and metformin combination therapy did not increase the risk of fracture vs. metformin monotherapy or other comparators in patients with T2DM (odds ratio, 0.97; 95% confidence interval, 0.71-1.32).
Study details: A meta-analysis of 25 randomized controlled trials including 19,500 participants with T2DM.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Qian BB et al. Osteoporos Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.
Key clinical point: Sodium-glucose transporter-2 inhibitors (SGLT2is) combined with metformin therapy did not influence fracture risk in patients with type 2 diabetes mellitus (T2DM).
Major finding: SGLT2is and metformin combination therapy did not increase the risk of fracture vs. metformin monotherapy or other comparators in patients with T2DM (odds ratio, 0.97; 95% confidence interval, 0.71-1.32).
Study details: A meta-analysis of 25 randomized controlled trials including 19,500 participants with T2DM.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Qian BB et al. Osteoporos Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.
Key clinical point: Sodium-glucose transporter-2 inhibitors (SGLT2is) combined with metformin therapy did not influence fracture risk in patients with type 2 diabetes mellitus (T2DM).
Major finding: SGLT2is and metformin combination therapy did not increase the risk of fracture vs. metformin monotherapy or other comparators in patients with T2DM (odds ratio, 0.97; 95% confidence interval, 0.71-1.32).
Study details: A meta-analysis of 25 randomized controlled trials including 19,500 participants with T2DM.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Qian BB et al. Osteoporos Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.
Sepsis and osteoporosis: What’s the link?
Key clinical point: Adults younger than 65 years with sepsis are at an increased risk of developing osteoporosis.
Major finding: The risk for osteoporosis was significantly higher in the sepsis vs. nonsepsis group (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.04-1.31). The risk for osteoporosis in the sepsis vs. nonsepsis group was significantly higher for young patients aged 20-49 years (aHR, 1.93; 95% CI, 1.08-3.44) and patients aged 50-64 years (aHR, 2.01; 95% CI, 1.52-2.65).
Study details: This Taiwanese population-based study included 13,178 patients diagnosed with sepsis and 13,178 propensity-score matched individuals without sepsis using data from the insurance claims database.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Lee YF et al. Osteoporos Int. 2020 Aug 22. doi: 10.1007/s00198-020-05599-3.
Key clinical point: Adults younger than 65 years with sepsis are at an increased risk of developing osteoporosis.
Major finding: The risk for osteoporosis was significantly higher in the sepsis vs. nonsepsis group (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.04-1.31). The risk for osteoporosis in the sepsis vs. nonsepsis group was significantly higher for young patients aged 20-49 years (aHR, 1.93; 95% CI, 1.08-3.44) and patients aged 50-64 years (aHR, 2.01; 95% CI, 1.52-2.65).
Study details: This Taiwanese population-based study included 13,178 patients diagnosed with sepsis and 13,178 propensity-score matched individuals without sepsis using data from the insurance claims database.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Lee YF et al. Osteoporos Int. 2020 Aug 22. doi: 10.1007/s00198-020-05599-3.
Key clinical point: Adults younger than 65 years with sepsis are at an increased risk of developing osteoporosis.
Major finding: The risk for osteoporosis was significantly higher in the sepsis vs. nonsepsis group (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.04-1.31). The risk for osteoporosis in the sepsis vs. nonsepsis group was significantly higher for young patients aged 20-49 years (aHR, 1.93; 95% CI, 1.08-3.44) and patients aged 50-64 years (aHR, 2.01; 95% CI, 1.52-2.65).
Study details: This Taiwanese population-based study included 13,178 patients diagnosed with sepsis and 13,178 propensity-score matched individuals without sepsis using data from the insurance claims database.
Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.
Source: Lee YF et al. Osteoporos Int. 2020 Aug 22. doi: 10.1007/s00198-020-05599-3.
Osteoporosis increases likelihood of revision surgery after long spinal fusion for adult spinal deformity
Key clinical point: The presence of osteoporosis correlates with a higher likelihood for revision surgery within 2 years following a long spinal fusion for adult spinal deformity (ASD).
Major finding: The rate of revision surgery was significantly higher in ASD patients with osteoporosis vs. those without osteoporosis (40.5% vs. 28.0%; P = .01). The incidence of multiple revision surgeries was similar in both groups (8.4% vs. 8.6%; P = .95). Age and sex were not statistically correlated with the incidence of revision surgery.
Study details: A retrospective comparative study of 399 patients with ASD (40 years or older) who underwent long spinal fusion surgery (osteoporotic group, n=131; nonosteoporotic group, n=268).
Disclosures: The study did not receive any funding.
Source: Gupta A et al. Spine J. 2020 Aug 10. doi: 10.1016/j.spinee.2020.08.002.
Key clinical point: The presence of osteoporosis correlates with a higher likelihood for revision surgery within 2 years following a long spinal fusion for adult spinal deformity (ASD).
Major finding: The rate of revision surgery was significantly higher in ASD patients with osteoporosis vs. those without osteoporosis (40.5% vs. 28.0%; P = .01). The incidence of multiple revision surgeries was similar in both groups (8.4% vs. 8.6%; P = .95). Age and sex were not statistically correlated with the incidence of revision surgery.
Study details: A retrospective comparative study of 399 patients with ASD (40 years or older) who underwent long spinal fusion surgery (osteoporotic group, n=131; nonosteoporotic group, n=268).
Disclosures: The study did not receive any funding.
Source: Gupta A et al. Spine J. 2020 Aug 10. doi: 10.1016/j.spinee.2020.08.002.
Key clinical point: The presence of osteoporosis correlates with a higher likelihood for revision surgery within 2 years following a long spinal fusion for adult spinal deformity (ASD).
Major finding: The rate of revision surgery was significantly higher in ASD patients with osteoporosis vs. those without osteoporosis (40.5% vs. 28.0%; P = .01). The incidence of multiple revision surgeries was similar in both groups (8.4% vs. 8.6%; P = .95). Age and sex were not statistically correlated with the incidence of revision surgery.
Study details: A retrospective comparative study of 399 patients with ASD (40 years or older) who underwent long spinal fusion surgery (osteoporotic group, n=131; nonosteoporotic group, n=268).
Disclosures: The study did not receive any funding.
Source: Gupta A et al. Spine J. 2020 Aug 10. doi: 10.1016/j.spinee.2020.08.002.