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Airways disorders
Eosinophils in COPD
Using peripheral blood eosinophilia (PBE) as a treatable biomarker of airway inflammation in patients with COPD has become an area of controversy in pulmonary medicine.
The proponents find a role for PBE testing in initiation and withdrawal of inhaled corticosteroids (ICS) and as a target for monoclonal antibodies in future studies.1 Post hoc analyses showed that variable doses of ICS/LABA combination compared with LABA alone in COPD patients were associated with much higher exacerbation reduction in patients with eosinophils counts of ≥2% and magnitude of effect proportionally increased from 29% to 42% with increasing eosinophil count from ≥2% to ≥6% suggesting a dose-response relationship.2 A post hoc analysis of the WISDOM trial showed increased risk of exacerbation after ICS discontinuation in COPD patients with high eosinophils (≥300 cells/mcL or ≥4%) while exacerbation risk was not increased in patients with low eosinophils (<150 cells/mcL or <2%).3
The opponents of eosinophil-guided therapy object that the level of evidence is weak as this is based on the post hoc analyses of randomized control trials on patients with increased exacerbation risk at baseline, which in itself is an independent predictor of future exacerbations.4 Some observational studies failed to find increased risk of exacerbation with higher eosinophil count while others found that higher eosinophil count was associated with increased survival and better quality of life.5,6 Anti-eosinophilic biologics have failed to show consistent benefit in exacerbation reduction in COPD patients so far, despite showing a reduction in the PBE.7-9
The GOLD COPD Guidelines support the use of ICS in patients with eosinophils >300 cells/mcL especially with a history of exacerbation and recommend against ICS in patients with eosinophils <100 cells/mcL.10
Farrukh Abbas, MD
Steering Committee Fellow-in-Training
NetWork Chair
References
1. Wade RC and Wells JM. Chest. 2020;157(5):1073-5.
2. Pascoe S et al. The Lancet Respir Med. 2015;3(6):435-42.
3. Watz H et al. The Lancet Respir Med. 2016;4(5):390-8.
4. Criner GJ. Chest. 2020;157(5):1075-8.
5. Shin SH et al. Respir Res. 2018;19(1):134.
6. Casanova C et al. Eur Respir J. 2017;50(5):1701162.
7. Pavord ID et al. N Engl J Med. 2017;377(17):1613-29.
8. Criner GJ et al. N Engl J Med. 2019;381(11):1023-34.
9. Mycroft K et al. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2565-74.
10. Global Initiative for Chronic Obstructive Lung Disease 2021 Report.
Clinical research
Long-COVID: COVID-19 disease beyond the pandemic
There are increasing reports of persistent multiorgan symptoms following COVID-19 infection.
In December 2020, the National Institute for Health and Care Excellence (NICE) developed guidelines, based primarily on expert opinion, to define and manage ongoing symptomatic COVID-19 (symptoms for 4-12 weeks after infection) and post-COVID syndrome (symptoms present for > 12 weeks without alternative explanation). Subsequently, the National Institutes of Health (NIH), released in February 2021 an initiative to study Post-Acute Sequelae of SARS-CoV2 infection (PASC). Symptoms can include, respiratory (cough, shortness of breath), cardiac (palpitations, chest pain), fatigue and physical limitations, and neurologic (depression, insomnia, cognitive impairment) (Lancet 2020 Dec 12;396[10266]:1861). The majority of patients with post-COVID syndrome have microbiological recovery (PCR negative), and often have radiological recovery. Risk factors include older age, female sex, and comorbidities (Raveendran AV. Diabetes Metab Syndr. 2021 May-June;15[3]:869-75).
Diagnosis and access to care pose significant challenges for post-COVID syndrome, and it is difficult to estimate exactly how many are affected – one report from Italy found that up to 87% of discharged hospitalized patients had persistent symptom(s) at 60 days (Carfi A. JAMA 2020 Aug;324[6]:603-5). Thus far, management recommendations include a multidisciplinary approach to evaluation, symptomatic treatment, organ specific treatment (for example, consideration of corticosteroids for persistent inflammatory interstitial lung disease) (Myall KJ. Ann Am Thorac Soc. 2021 May;8[5]:799-806), physical/occupational therapy, and psychological support. Many institutions have established, or are working to establish post-COVID clinics (Aging Clin Exp Res. 2020 Aug;32[8]:1613-20). Currently, the NIH is offering funding opportunities and there are many clinical trials across the world actively recruiting patients.
Ankita Agarwal, MD
Steering Committee Fellow-in-Training
Steering Committee Member
Aravind Menon, MD
Steering Committee Fellow-in-Training
Critical care
Sedation practices in the ICU: Moving past the COVID-19 pandemic
The COVID-19 pandemic brought unprecedented change to critical care practice patterns, and sedation practices in the intensive care unit are no exception. In a large cohort analysis of over 2,000 adults with COVID-19 (Pun BT, et al. Lancet Respir Med. 2021;9[3]:239-50), 64% of patients received benzodiazepines (median of 7 days), and patients were deeply sedated. More than half of the patients were delirious, with benzodiazepine use associated with increased incidence of delirium. These observations represent a significant departure from well-established pre-COVID best-practices in sedation: light targets, daily sedation interruption, and avoiding continuous benzodiazepine infusions whenever possible (Girard TD, et al. Lancet; 2008;371[9607]:126-34; Fraser GL, et al. Crit Care Med;2013 Sep;41[9 Suppl 1]:S30-8; Riker RR, et al. JAMA;2009;301[5]:489-99).
As COVID-19 case counts begin to improve in many of our communities, we have the opportunity to refocus on best sedation practices and build on a growing body of recent evidence. The MENDS2 trial, completed pre-COVID-19, assigned mechanically ventilated patients with sepsis to either propofol or dexmedetomidine and showed no difference in delirium or coma in this cohort of lightly sedated patients (Hughes CG, et al. N Engl J Med. 2021;384[15]:1424-36). Furthering this point, Olsen et al. found no difference in outcomes when mechanically ventilated patients were randomized to no sedation vs light sedation (Olsen HT, et al. N Engl J Med; 2020;382[12]:1103-11).
While the evidence surrounding sedation strategies in the critically ill continues to grow, one thing is certain: promoting lighter sedation targets and reengaging in sedation-related best practices following the COVID-19 pandemic will continue to play a vital role in improving both short and long-term outcomes for our critically ill patients.
Casey Cable, MD, MSc
Steering Committee Member
Kyle Stinehart, MD
Steering Committee Member
Home mechanical ventilation
How to initiate a chronic respiratory failure clinic
Noninvasive ventilation (NIV) is an established treatment for chronic hypercapnic respiratory failure from neuromuscular disorders, COPD, obesity hypoventilation syndrome (OHS), and restrictive thoracic disorders. Previously, hospital admission was considered essential for setup of chronic NIV but with advances in the modes of ventilation and remote monitoring, hospital admission has become less justifiable, especially in countries with centralized medical systems and presence of centers of excellence for home ventilation (Van Den Biggelaar RJM, et al. Chest. 2020;158[6]:2493-2501); Duiverman ML, et al. Thorax. 2020;75:244-52). In the United States, where centralized health care is atypical, management of NIV has been disparate with no clear consensus on practice patterns. Thus, we hope to provide some guidance toward the establishment of such clinics in the U.S.
Prior to developing an NIV clinic, establishing a referral source from neuromuscular, rehabilitation/spinal cord injury, bariatric surgery, and COPD programs is important. After this, collaboration with a respiratory therapist through durable medical equipment is essential to building a robust care team. These companies are also important for assisting in remote monitoring, providing overnight pulse oximetry/CO2 monitoring, mask fitting, and airway clearance. Clinicians are encouraged to develop protocols for initiation and titration of NIV and mouthpiece ventilation. Clinics should provide spirometry, maximal inspiratory pressure, transcutaneous CO2, and/or blood gas testing. Additionally, in this patient population, wheelchair scales are necessary. Clinical workflow should include a review of NIV downloads, identify asynchronies and troubleshoot it in timely and reliable manner (Blouet S, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:2577-86). Lastly, effort should be made for an adequate assessment of the home situation including layout of home along with family support utilizing social worker and palliative care team. Due to patient mobility, we encourage continued availability of telehealth for these patients.
In summary, strong clinical infrastructure, a robust care team, and an efficient, secure, reliable telemonitoring system are key to provide better care to this vulnerable patient population.
Ashima S. Sahni, MD, MBBS, FCCP
NetWork Member
Amen Sergew, MD
Steering Committee Member
Interstitial and diffuse lung disease
Treatment for pulmonary hypertension secondary to interstitial lung disease
The development of pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) (PH-ILD) is associated with increased supplemental oxygen requirements, reduced functional status, and decreased survival (King CS, et al. Chest. 2020;158[4]:1651).
An inhaled formulation of treprostinil (Tyvaso) is the first treatment option approved by the FDA for patients with PH-ILD, including those with idiopathic pulmonary fibrosis, connective tissue disease-associated ILD, and combined pulmonary fibrosis and emphysema. Approval was based on results from the INCREASE trial (Waxman A, et al. N Engl J Med. 2021;384[4]:325), a phase III multicenter, randomized, double-blinded study comparing the inhaled formulation to placebo in 326 patients over a 16-week period. Participants in the treatment arm were given up to 12 breaths of the formulation per session, four times per day. Subjects treated with this inhaled formulation met the primary study endpoint, an increase in 6-minute walk distance (6MWD) from baseline to week 16, walking 21 m farther than placebo-treated control subjects. Furthermore, patients receiving the new formulation had a decrease in NT-proBNP levels (compared with increases in the placebo arm) and a reduction in clinical worsening (23% of inhalation formulation-treated vs. 33% of placebo-treated subjects). This formulation of treprostinil was well-tolerated with a safety profile consistent with common prostacyclin-related adverse events, including cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. Its approval will dramatically alter the ILD treatment landscape. It now necessitates the use of PH screening in this patient population. However, care will need to be exercised in appropriate patient selection for treatment, using the study inclusion and exclusion criteria as a starting point. Appropriate use of this formulation will hopefully help mitigate the negative outcomes impacting patients with PH-ILD.
Rebecca Anna Gersten, MD
Adrian Shifren, MD
Steering Committee Members
Airways disorders
Eosinophils in COPD
Using peripheral blood eosinophilia (PBE) as a treatable biomarker of airway inflammation in patients with COPD has become an area of controversy in pulmonary medicine.
The proponents find a role for PBE testing in initiation and withdrawal of inhaled corticosteroids (ICS) and as a target for monoclonal antibodies in future studies.1 Post hoc analyses showed that variable doses of ICS/LABA combination compared with LABA alone in COPD patients were associated with much higher exacerbation reduction in patients with eosinophils counts of ≥2% and magnitude of effect proportionally increased from 29% to 42% with increasing eosinophil count from ≥2% to ≥6% suggesting a dose-response relationship.2 A post hoc analysis of the WISDOM trial showed increased risk of exacerbation after ICS discontinuation in COPD patients with high eosinophils (≥300 cells/mcL or ≥4%) while exacerbation risk was not increased in patients with low eosinophils (<150 cells/mcL or <2%).3
The opponents of eosinophil-guided therapy object that the level of evidence is weak as this is based on the post hoc analyses of randomized control trials on patients with increased exacerbation risk at baseline, which in itself is an independent predictor of future exacerbations.4 Some observational studies failed to find increased risk of exacerbation with higher eosinophil count while others found that higher eosinophil count was associated with increased survival and better quality of life.5,6 Anti-eosinophilic biologics have failed to show consistent benefit in exacerbation reduction in COPD patients so far, despite showing a reduction in the PBE.7-9
The GOLD COPD Guidelines support the use of ICS in patients with eosinophils >300 cells/mcL especially with a history of exacerbation and recommend against ICS in patients with eosinophils <100 cells/mcL.10
Farrukh Abbas, MD
Steering Committee Fellow-in-Training
NetWork Chair
References
1. Wade RC and Wells JM. Chest. 2020;157(5):1073-5.
2. Pascoe S et al. The Lancet Respir Med. 2015;3(6):435-42.
3. Watz H et al. The Lancet Respir Med. 2016;4(5):390-8.
4. Criner GJ. Chest. 2020;157(5):1075-8.
5. Shin SH et al. Respir Res. 2018;19(1):134.
6. Casanova C et al. Eur Respir J. 2017;50(5):1701162.
7. Pavord ID et al. N Engl J Med. 2017;377(17):1613-29.
8. Criner GJ et al. N Engl J Med. 2019;381(11):1023-34.
9. Mycroft K et al. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2565-74.
10. Global Initiative for Chronic Obstructive Lung Disease 2021 Report.
Clinical research
Long-COVID: COVID-19 disease beyond the pandemic
There are increasing reports of persistent multiorgan symptoms following COVID-19 infection.
In December 2020, the National Institute for Health and Care Excellence (NICE) developed guidelines, based primarily on expert opinion, to define and manage ongoing symptomatic COVID-19 (symptoms for 4-12 weeks after infection) and post-COVID syndrome (symptoms present for > 12 weeks without alternative explanation). Subsequently, the National Institutes of Health (NIH), released in February 2021 an initiative to study Post-Acute Sequelae of SARS-CoV2 infection (PASC). Symptoms can include, respiratory (cough, shortness of breath), cardiac (palpitations, chest pain), fatigue and physical limitations, and neurologic (depression, insomnia, cognitive impairment) (Lancet 2020 Dec 12;396[10266]:1861). The majority of patients with post-COVID syndrome have microbiological recovery (PCR negative), and often have radiological recovery. Risk factors include older age, female sex, and comorbidities (Raveendran AV. Diabetes Metab Syndr. 2021 May-June;15[3]:869-75).
Diagnosis and access to care pose significant challenges for post-COVID syndrome, and it is difficult to estimate exactly how many are affected – one report from Italy found that up to 87% of discharged hospitalized patients had persistent symptom(s) at 60 days (Carfi A. JAMA 2020 Aug;324[6]:603-5). Thus far, management recommendations include a multidisciplinary approach to evaluation, symptomatic treatment, organ specific treatment (for example, consideration of corticosteroids for persistent inflammatory interstitial lung disease) (Myall KJ. Ann Am Thorac Soc. 2021 May;8[5]:799-806), physical/occupational therapy, and psychological support. Many institutions have established, or are working to establish post-COVID clinics (Aging Clin Exp Res. 2020 Aug;32[8]:1613-20). Currently, the NIH is offering funding opportunities and there are many clinical trials across the world actively recruiting patients.
Ankita Agarwal, MD
Steering Committee Fellow-in-Training
Steering Committee Member
Aravind Menon, MD
Steering Committee Fellow-in-Training
Critical care
Sedation practices in the ICU: Moving past the COVID-19 pandemic
The COVID-19 pandemic brought unprecedented change to critical care practice patterns, and sedation practices in the intensive care unit are no exception. In a large cohort analysis of over 2,000 adults with COVID-19 (Pun BT, et al. Lancet Respir Med. 2021;9[3]:239-50), 64% of patients received benzodiazepines (median of 7 days), and patients were deeply sedated. More than half of the patients were delirious, with benzodiazepine use associated with increased incidence of delirium. These observations represent a significant departure from well-established pre-COVID best-practices in sedation: light targets, daily sedation interruption, and avoiding continuous benzodiazepine infusions whenever possible (Girard TD, et al. Lancet; 2008;371[9607]:126-34; Fraser GL, et al. Crit Care Med;2013 Sep;41[9 Suppl 1]:S30-8; Riker RR, et al. JAMA;2009;301[5]:489-99).
As COVID-19 case counts begin to improve in many of our communities, we have the opportunity to refocus on best sedation practices and build on a growing body of recent evidence. The MENDS2 trial, completed pre-COVID-19, assigned mechanically ventilated patients with sepsis to either propofol or dexmedetomidine and showed no difference in delirium or coma in this cohort of lightly sedated patients (Hughes CG, et al. N Engl J Med. 2021;384[15]:1424-36). Furthering this point, Olsen et al. found no difference in outcomes when mechanically ventilated patients were randomized to no sedation vs light sedation (Olsen HT, et al. N Engl J Med; 2020;382[12]:1103-11).
While the evidence surrounding sedation strategies in the critically ill continues to grow, one thing is certain: promoting lighter sedation targets and reengaging in sedation-related best practices following the COVID-19 pandemic will continue to play a vital role in improving both short and long-term outcomes for our critically ill patients.
Casey Cable, MD, MSc
Steering Committee Member
Kyle Stinehart, MD
Steering Committee Member
Home mechanical ventilation
How to initiate a chronic respiratory failure clinic
Noninvasive ventilation (NIV) is an established treatment for chronic hypercapnic respiratory failure from neuromuscular disorders, COPD, obesity hypoventilation syndrome (OHS), and restrictive thoracic disorders. Previously, hospital admission was considered essential for setup of chronic NIV but with advances in the modes of ventilation and remote monitoring, hospital admission has become less justifiable, especially in countries with centralized medical systems and presence of centers of excellence for home ventilation (Van Den Biggelaar RJM, et al. Chest. 2020;158[6]:2493-2501); Duiverman ML, et al. Thorax. 2020;75:244-52). In the United States, where centralized health care is atypical, management of NIV has been disparate with no clear consensus on practice patterns. Thus, we hope to provide some guidance toward the establishment of such clinics in the U.S.
Prior to developing an NIV clinic, establishing a referral source from neuromuscular, rehabilitation/spinal cord injury, bariatric surgery, and COPD programs is important. After this, collaboration with a respiratory therapist through durable medical equipment is essential to building a robust care team. These companies are also important for assisting in remote monitoring, providing overnight pulse oximetry/CO2 monitoring, mask fitting, and airway clearance. Clinicians are encouraged to develop protocols for initiation and titration of NIV and mouthpiece ventilation. Clinics should provide spirometry, maximal inspiratory pressure, transcutaneous CO2, and/or blood gas testing. Additionally, in this patient population, wheelchair scales are necessary. Clinical workflow should include a review of NIV downloads, identify asynchronies and troubleshoot it in timely and reliable manner (Blouet S, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:2577-86). Lastly, effort should be made for an adequate assessment of the home situation including layout of home along with family support utilizing social worker and palliative care team. Due to patient mobility, we encourage continued availability of telehealth for these patients.
In summary, strong clinical infrastructure, a robust care team, and an efficient, secure, reliable telemonitoring system are key to provide better care to this vulnerable patient population.
Ashima S. Sahni, MD, MBBS, FCCP
NetWork Member
Amen Sergew, MD
Steering Committee Member
Interstitial and diffuse lung disease
Treatment for pulmonary hypertension secondary to interstitial lung disease
The development of pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) (PH-ILD) is associated with increased supplemental oxygen requirements, reduced functional status, and decreased survival (King CS, et al. Chest. 2020;158[4]:1651).
An inhaled formulation of treprostinil (Tyvaso) is the first treatment option approved by the FDA for patients with PH-ILD, including those with idiopathic pulmonary fibrosis, connective tissue disease-associated ILD, and combined pulmonary fibrosis and emphysema. Approval was based on results from the INCREASE trial (Waxman A, et al. N Engl J Med. 2021;384[4]:325), a phase III multicenter, randomized, double-blinded study comparing the inhaled formulation to placebo in 326 patients over a 16-week period. Participants in the treatment arm were given up to 12 breaths of the formulation per session, four times per day. Subjects treated with this inhaled formulation met the primary study endpoint, an increase in 6-minute walk distance (6MWD) from baseline to week 16, walking 21 m farther than placebo-treated control subjects. Furthermore, patients receiving the new formulation had a decrease in NT-proBNP levels (compared with increases in the placebo arm) and a reduction in clinical worsening (23% of inhalation formulation-treated vs. 33% of placebo-treated subjects). This formulation of treprostinil was well-tolerated with a safety profile consistent with common prostacyclin-related adverse events, including cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. Its approval will dramatically alter the ILD treatment landscape. It now necessitates the use of PH screening in this patient population. However, care will need to be exercised in appropriate patient selection for treatment, using the study inclusion and exclusion criteria as a starting point. Appropriate use of this formulation will hopefully help mitigate the negative outcomes impacting patients with PH-ILD.
Rebecca Anna Gersten, MD
Adrian Shifren, MD
Steering Committee Members
Airways disorders
Eosinophils in COPD
Using peripheral blood eosinophilia (PBE) as a treatable biomarker of airway inflammation in patients with COPD has become an area of controversy in pulmonary medicine.
The proponents find a role for PBE testing in initiation and withdrawal of inhaled corticosteroids (ICS) and as a target for monoclonal antibodies in future studies.1 Post hoc analyses showed that variable doses of ICS/LABA combination compared with LABA alone in COPD patients were associated with much higher exacerbation reduction in patients with eosinophils counts of ≥2% and magnitude of effect proportionally increased from 29% to 42% with increasing eosinophil count from ≥2% to ≥6% suggesting a dose-response relationship.2 A post hoc analysis of the WISDOM trial showed increased risk of exacerbation after ICS discontinuation in COPD patients with high eosinophils (≥300 cells/mcL or ≥4%) while exacerbation risk was not increased in patients with low eosinophils (<150 cells/mcL or <2%).3
The opponents of eosinophil-guided therapy object that the level of evidence is weak as this is based on the post hoc analyses of randomized control trials on patients with increased exacerbation risk at baseline, which in itself is an independent predictor of future exacerbations.4 Some observational studies failed to find increased risk of exacerbation with higher eosinophil count while others found that higher eosinophil count was associated with increased survival and better quality of life.5,6 Anti-eosinophilic biologics have failed to show consistent benefit in exacerbation reduction in COPD patients so far, despite showing a reduction in the PBE.7-9
The GOLD COPD Guidelines support the use of ICS in patients with eosinophils >300 cells/mcL especially with a history of exacerbation and recommend against ICS in patients with eosinophils <100 cells/mcL.10
Farrukh Abbas, MD
Steering Committee Fellow-in-Training
NetWork Chair
References
1. Wade RC and Wells JM. Chest. 2020;157(5):1073-5.
2. Pascoe S et al. The Lancet Respir Med. 2015;3(6):435-42.
3. Watz H et al. The Lancet Respir Med. 2016;4(5):390-8.
4. Criner GJ. Chest. 2020;157(5):1075-8.
5. Shin SH et al. Respir Res. 2018;19(1):134.
6. Casanova C et al. Eur Respir J. 2017;50(5):1701162.
7. Pavord ID et al. N Engl J Med. 2017;377(17):1613-29.
8. Criner GJ et al. N Engl J Med. 2019;381(11):1023-34.
9. Mycroft K et al. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2565-74.
10. Global Initiative for Chronic Obstructive Lung Disease 2021 Report.
Clinical research
Long-COVID: COVID-19 disease beyond the pandemic
There are increasing reports of persistent multiorgan symptoms following COVID-19 infection.
In December 2020, the National Institute for Health and Care Excellence (NICE) developed guidelines, based primarily on expert opinion, to define and manage ongoing symptomatic COVID-19 (symptoms for 4-12 weeks after infection) and post-COVID syndrome (symptoms present for > 12 weeks without alternative explanation). Subsequently, the National Institutes of Health (NIH), released in February 2021 an initiative to study Post-Acute Sequelae of SARS-CoV2 infection (PASC). Symptoms can include, respiratory (cough, shortness of breath), cardiac (palpitations, chest pain), fatigue and physical limitations, and neurologic (depression, insomnia, cognitive impairment) (Lancet 2020 Dec 12;396[10266]:1861). The majority of patients with post-COVID syndrome have microbiological recovery (PCR negative), and often have radiological recovery. Risk factors include older age, female sex, and comorbidities (Raveendran AV. Diabetes Metab Syndr. 2021 May-June;15[3]:869-75).
Diagnosis and access to care pose significant challenges for post-COVID syndrome, and it is difficult to estimate exactly how many are affected – one report from Italy found that up to 87% of discharged hospitalized patients had persistent symptom(s) at 60 days (Carfi A. JAMA 2020 Aug;324[6]:603-5). Thus far, management recommendations include a multidisciplinary approach to evaluation, symptomatic treatment, organ specific treatment (for example, consideration of corticosteroids for persistent inflammatory interstitial lung disease) (Myall KJ. Ann Am Thorac Soc. 2021 May;8[5]:799-806), physical/occupational therapy, and psychological support. Many institutions have established, or are working to establish post-COVID clinics (Aging Clin Exp Res. 2020 Aug;32[8]:1613-20). Currently, the NIH is offering funding opportunities and there are many clinical trials across the world actively recruiting patients.
Ankita Agarwal, MD
Steering Committee Fellow-in-Training
Steering Committee Member
Aravind Menon, MD
Steering Committee Fellow-in-Training
Critical care
Sedation practices in the ICU: Moving past the COVID-19 pandemic
The COVID-19 pandemic brought unprecedented change to critical care practice patterns, and sedation practices in the intensive care unit are no exception. In a large cohort analysis of over 2,000 adults with COVID-19 (Pun BT, et al. Lancet Respir Med. 2021;9[3]:239-50), 64% of patients received benzodiazepines (median of 7 days), and patients were deeply sedated. More than half of the patients were delirious, with benzodiazepine use associated with increased incidence of delirium. These observations represent a significant departure from well-established pre-COVID best-practices in sedation: light targets, daily sedation interruption, and avoiding continuous benzodiazepine infusions whenever possible (Girard TD, et al. Lancet; 2008;371[9607]:126-34; Fraser GL, et al. Crit Care Med;2013 Sep;41[9 Suppl 1]:S30-8; Riker RR, et al. JAMA;2009;301[5]:489-99).
As COVID-19 case counts begin to improve in many of our communities, we have the opportunity to refocus on best sedation practices and build on a growing body of recent evidence. The MENDS2 trial, completed pre-COVID-19, assigned mechanically ventilated patients with sepsis to either propofol or dexmedetomidine and showed no difference in delirium or coma in this cohort of lightly sedated patients (Hughes CG, et al. N Engl J Med. 2021;384[15]:1424-36). Furthering this point, Olsen et al. found no difference in outcomes when mechanically ventilated patients were randomized to no sedation vs light sedation (Olsen HT, et al. N Engl J Med; 2020;382[12]:1103-11).
While the evidence surrounding sedation strategies in the critically ill continues to grow, one thing is certain: promoting lighter sedation targets and reengaging in sedation-related best practices following the COVID-19 pandemic will continue to play a vital role in improving both short and long-term outcomes for our critically ill patients.
Casey Cable, MD, MSc
Steering Committee Member
Kyle Stinehart, MD
Steering Committee Member
Home mechanical ventilation
How to initiate a chronic respiratory failure clinic
Noninvasive ventilation (NIV) is an established treatment for chronic hypercapnic respiratory failure from neuromuscular disorders, COPD, obesity hypoventilation syndrome (OHS), and restrictive thoracic disorders. Previously, hospital admission was considered essential for setup of chronic NIV but with advances in the modes of ventilation and remote monitoring, hospital admission has become less justifiable, especially in countries with centralized medical systems and presence of centers of excellence for home ventilation (Van Den Biggelaar RJM, et al. Chest. 2020;158[6]:2493-2501); Duiverman ML, et al. Thorax. 2020;75:244-52). In the United States, where centralized health care is atypical, management of NIV has been disparate with no clear consensus on practice patterns. Thus, we hope to provide some guidance toward the establishment of such clinics in the U.S.
Prior to developing an NIV clinic, establishing a referral source from neuromuscular, rehabilitation/spinal cord injury, bariatric surgery, and COPD programs is important. After this, collaboration with a respiratory therapist through durable medical equipment is essential to building a robust care team. These companies are also important for assisting in remote monitoring, providing overnight pulse oximetry/CO2 monitoring, mask fitting, and airway clearance. Clinicians are encouraged to develop protocols for initiation and titration of NIV and mouthpiece ventilation. Clinics should provide spirometry, maximal inspiratory pressure, transcutaneous CO2, and/or blood gas testing. Additionally, in this patient population, wheelchair scales are necessary. Clinical workflow should include a review of NIV downloads, identify asynchronies and troubleshoot it in timely and reliable manner (Blouet S, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:2577-86). Lastly, effort should be made for an adequate assessment of the home situation including layout of home along with family support utilizing social worker and palliative care team. Due to patient mobility, we encourage continued availability of telehealth for these patients.
In summary, strong clinical infrastructure, a robust care team, and an efficient, secure, reliable telemonitoring system are key to provide better care to this vulnerable patient population.
Ashima S. Sahni, MD, MBBS, FCCP
NetWork Member
Amen Sergew, MD
Steering Committee Member
Interstitial and diffuse lung disease
Treatment for pulmonary hypertension secondary to interstitial lung disease
The development of pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) (PH-ILD) is associated with increased supplemental oxygen requirements, reduced functional status, and decreased survival (King CS, et al. Chest. 2020;158[4]:1651).
An inhaled formulation of treprostinil (Tyvaso) is the first treatment option approved by the FDA for patients with PH-ILD, including those with idiopathic pulmonary fibrosis, connective tissue disease-associated ILD, and combined pulmonary fibrosis and emphysema. Approval was based on results from the INCREASE trial (Waxman A, et al. N Engl J Med. 2021;384[4]:325), a phase III multicenter, randomized, double-blinded study comparing the inhaled formulation to placebo in 326 patients over a 16-week period. Participants in the treatment arm were given up to 12 breaths of the formulation per session, four times per day. Subjects treated with this inhaled formulation met the primary study endpoint, an increase in 6-minute walk distance (6MWD) from baseline to week 16, walking 21 m farther than placebo-treated control subjects. Furthermore, patients receiving the new formulation had a decrease in NT-proBNP levels (compared with increases in the placebo arm) and a reduction in clinical worsening (23% of inhalation formulation-treated vs. 33% of placebo-treated subjects). This formulation of treprostinil was well-tolerated with a safety profile consistent with common prostacyclin-related adverse events, including cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. Its approval will dramatically alter the ILD treatment landscape. It now necessitates the use of PH screening in this patient population. However, care will need to be exercised in appropriate patient selection for treatment, using the study inclusion and exclusion criteria as a starting point. Appropriate use of this formulation will hopefully help mitigate the negative outcomes impacting patients with PH-ILD.
Rebecca Anna Gersten, MD
Adrian Shifren, MD
Steering Committee Members