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COVID-19 and asthma: Much remains unknown
Viral-induced asthma exacerbations are common, but there has yet to be a published data set showing worse outcomes among asthmatics with COVID-19.
It is possible that inhaled corticosteroids (ICS) may provide some protection from viral infection. A 2014 study showed that ICS may reduce exacerbations by modulating inflammation and reducing airway viral receptors (Yamaya, et al. Respir Investig. 2014;52[4]:251). Analysis from the SARP-3 database showed ICS use associated with reduced expression of both ACE2 and transmembrane protease serine 2 (TMPRSS2), two receptors used by SARS-CoV-2 (Peters, et al. Am J Respir Crit Care Med. 2020. Online ahead of print). Another study showed a similar effect of ICS on the seasonal coronavirus strain HCoV-229E (Yamaya M, et al. Respir Investig. 2020;58[3]:155), and one study reported decreased ACE2 expression in allergic asthma (Jackson, et al. J Allergy Clin Immunol. Article in press, 2020). While these findings could support a hypothesis of reduced risk for COVID-19 infection among asthmatics using ICS, one would generally expect those with underlying lung disease, such as asthma, to be at higher risk for more severe infection.
Despite physiologic hypotheses of protective mechanisms, clinical outcomes may suffer as clinical operations and the American economy are impacted by this pandemic. Reduced access to or utilization of outpatient care, loss of employment, loss of health insurance, or a new difficulty in affording or accessing medications may all result in worsening asthma control for patients. Poorly controlled asthmatics are at higher risk for a more severe exacerbation of disease triggered by viral infection. Current recommendations are for patients to continue all controller medications; the use of systemic corticosteroids in treatment of COVID pneumonia is controversial, but their use in treating a COVID-associated asthma exacerbation should be based on individual assessment. As we care for asthma patients through this pandemic, much remains unknown but may be elucidated by further study.
Megan Conroy, MD
Fellow-in-Training Member
Steering Committee Member
Clinical Research and Quality Improvement
Remdesivir for COVID-19: A ray of hope?
The year 2020 witnessed a pandemic of unprecedented proportions, caused by a novel corona virus strain (SARS-CoV2). Across the globe, there have been more than 6.5 million positive cases of COVID-19 and more than 380,000 deaths. (WHO COVID-19 Dashboard [https://covid19.who.int]). Multiple therapeutic agents are currently being studied as potential treatment options for this novel disease. With negative trials so far on lopinavir-ritonavir and hydroxychloroquine, the only candidate drug showing benefit is remdesivir.
Results of the randomized double-blind placebo controlled Adaptive COVID-19 Treatment Trial (ACTT-1) trial (Beigel, J et al. N Engl J Med. 2020; e-pub ahead of print) shows remdesivir improved recovery time in COVID -19 patients as compared with control subjects. Remdesivir is an inhibitor of viral RNA polymerase that has been shown to inhibit coronaviruses in animal models and SARS-CoV2 in-vitro. The ACTT-1 trial enrolled 1,063 patients with 541 assigned to the remdesivir arm and 522 to the placebo group. Primary outcome measure was time to recovery. Mortality at 14 and 28 days and incidence of adverse events were also evaluated.
As interim analysis showed positive results, the data safety and monitoring board recommended early termination of the trial. Patients in the remdesivir group had a shorter time to recovery, with median recovery time of 11 days as compared with 15 days in placebo group (95% CI:1.12-1.55; P < .001). Hospitalized patients requiring supplemental oxygen (but not high-flow, mechanical ventilation or ECMO) derived the maximum benefit with a rate ratio of recovery being 1.47(95% CI:1.17-1.84). Thus, early drug administration may be beneficial. The difference in mortality at 14 days was not statistically significant and data on mortality difference at 28 days were not available at the time of publication.
In summary, this trial along with previous publications shows that remdesivir is a potential therapeutic option for COVID -19. The Food and Drug Administration (FDA) approved remdesivir under Emergency Use Authorization (EUA) for COVID-19 and larger trials are currently underway to study the full effect of this agent.
Aravind Menon, MD
Fellow-in-Training Member
Critical Care
Burnout in unprecedented times
Even in typical times, intensivists have a significantly higher rate of burnout compared with other medical specialties. We fight for lives, dealing with death, dying, and tragedy on a daily basis. Regrettably, we are no longer in ‘typical’ times. This is a prodigious and uncharted era.
The COVID-19 pandemic has created all new hardships. Added to the complex world of critical care, we undertake lack of appropriate medical equipment and PPE, the possibility of becoming ill or infecting our families, potential financial struggles, and the unpredictability of the future. Additionally, in our efforts to care for patients, we face increasing moral distress when placed in situations in which we cannot do what we feel is right. And we carry the burdens and guilt of patients’ families who cannot be with loved ones during this process, even during death.
What does burnout look like in this new era? Burnout is a continuum and can manifest differently depending on the individual. Even a typical day in the ICU may be cause for the symptoms of burnout including frustration, anger, anxiety, or sadness which can progress to feelings of powerlessness, self-doubt or depersonalization.
This crisis is a test of endurance. But we don’t have to face it alone. The ICU is a team environment, and we can help each other make it to the end. Consider beginning the shift with a group morale boosting activity. Perhaps debrief after the end of each shift to discuss ways of combatting these stressful times. Have a virtual happy hour with colleagues after work. Call on leadership for support. Watch each other’s back. Together we will get through these unprecedented times.
John P. Gaillard, MD
Steering Committee Member
Resources for confronting burnout:
http://ccsconline.org/optimizing-the-workforce/burnout
https://www.ama-assn.org/topics/physician-burnout
https://www.ahrq.gov/prevention/clinician/ahrq-works/burnout/index.html
Home-Based Mechanical Ventilation and Neuromuscular Disease
Use of modified RADs
Investigators have begun exploring ways to convert devices typically used to treat sleep-disordered breathing (respiratory assist device, RAD), with modifications to minimize risk of aerosolization of pathogen in the COVID-19 pandemic. These devices are presently not considered an effective means of treating acute respiratory distress syndrome (ARDS). In an emergency, however, it is reasonable to consider all the options available with a healthy respect for inherent device limitations.
A RAD could be converted from an open ventilation single-limb respiratory circuit to a closed ventilation circuit with a passive exhalation valve. This circuit could provide adequate minute ventilation and allow for adequate exhalation of CO2 to prevent rebreathing. Strategic placement of the passive exhalation valve proximal to a viricidal filter would allow the device to be used with either an endotracheal tube or a nonvented oronasal mask (Figure). These devices by design are pressure-regulated, and a backup rate would be necessary to control minute ventilation. Close monitoring would be necessary given lack of alarm capability for a critically ill patient and the need to ensure adequate oxygen bleed-in.
The primary limitation to these devices is the inability to achieve adequate mean airway pressure for ARDS. While such a converted device is not ready for prime time, it could be considered for patients who are close to weaning from conventional mechanical ventilation (i.e., freeing up a ventilator for a sicker patient) or temporizing a patient early in disease to stave off invasive ventilation.
MAJ Brian E. Foster, DO, USA
Fellow Member
Steering Committee Member
Interstitial and Diffuse Lung Disease NetWork
Advances in molecular imaging in pulmonary fibrosis
Fibrotic interstitial lung diseases (ILD), including idiopathic pulmonary fibrosis (IPF), have poor prognosis with marked heterogeneity in the clinical course. Treatment options, including antfibrotic drugs and immunosuppressants, are fairly limited for either conditions, and there is wide variability in drug responsiveness. Biomarkers that predict disease course and enable patient stratification to assess responsiveness to specific therapies play a crucial role in management of this fatal disease.
Molecular imaging has the ability to noninvasively provide both structural details, as well as functional/molecular information at the cellular level; it has thus developed into a powerful tool for several inflammatory and malignant disease processes. Probes that specifically target fibrosis-specific pathways utilizing positron emission tomography (PET) or magnetic resonance (MR) imaging have gained traction recently.
The most commonly used radiopharmaceutical for PET, 18F-FDG, is significantly increased in areas of established fibrosis in patients with IPF and autoimmune ILDs (Win, et al. Eur J Nucl Med Mol Imaging. 2018 May;45[5]:806; Uehara, et al. Mod Rheumatol. 2016;26[1]:121-7), as well as areas with seemingly normal morphologic appearance on HRCT scan (Win, et al. Eur J Nucl Med Mol Imaging. 2014 Feb;41[2]:337). While this probe was shown to have some potential for prognostication, there has been concern regarding the specificity of FDG uptake in fibrotic lung diseases. Hence, other probes that target specific fibrosis-related cellular mechanisms such as macrophages (Withana, et al. Nature Scientific Reports. 2016;6 [Jan 22):19755], and John, et al. J Nucl Med. 2013;54[12]:2146) and matrix proteins (Montesi, et al. Am J Respir Crit Care Med. 2019 Jul 15;200[2]:258) have been developed in preclinical fibrosis/lung injury models and are being translated to human subjects.
With the ability to capture early fibrogenesis and target engagement, molecular imaging has the potential to prognosticate patients, provide earlier evaluation of treatment responsiveness and have a promising application in clinical trial design for fibrotic lung diseases.
Tejaswini Kulkarni, MD
Steering Committee Member
Airways
COVID-19 and asthma: Much remains unknown
Viral-induced asthma exacerbations are common, but there has yet to be a published data set showing worse outcomes among asthmatics with COVID-19.
It is possible that inhaled corticosteroids (ICS) may provide some protection from viral infection. A 2014 study showed that ICS may reduce exacerbations by modulating inflammation and reducing airway viral receptors (Yamaya, et al. Respir Investig. 2014;52[4]:251). Analysis from the SARP-3 database showed ICS use associated with reduced expression of both ACE2 and transmembrane protease serine 2 (TMPRSS2), two receptors used by SARS-CoV-2 (Peters, et al. Am J Respir Crit Care Med. 2020. Online ahead of print). Another study showed a similar effect of ICS on the seasonal coronavirus strain HCoV-229E (Yamaya M, et al. Respir Investig. 2020;58[3]:155), and one study reported decreased ACE2 expression in allergic asthma (Jackson, et al. J Allergy Clin Immunol. Article in press, 2020). While these findings could support a hypothesis of reduced risk for COVID-19 infection among asthmatics using ICS, one would generally expect those with underlying lung disease, such as asthma, to be at higher risk for more severe infection.
Despite physiologic hypotheses of protective mechanisms, clinical outcomes may suffer as clinical operations and the American economy are impacted by this pandemic. Reduced access to or utilization of outpatient care, loss of employment, loss of health insurance, or a new difficulty in affording or accessing medications may all result in worsening asthma control for patients. Poorly controlled asthmatics are at higher risk for a more severe exacerbation of disease triggered by viral infection. Current recommendations are for patients to continue all controller medications; the use of systemic corticosteroids in treatment of COVID pneumonia is controversial, but their use in treating a COVID-associated asthma exacerbation should be based on individual assessment. As we care for asthma patients through this pandemic, much remains unknown but may be elucidated by further study.
Megan Conroy, MD
Fellow-in-Training Member
Steering Committee Member
Clinical Research and Quality Improvement
Remdesivir for COVID-19: A ray of hope?
The year 2020 witnessed a pandemic of unprecedented proportions, caused by a novel corona virus strain (SARS-CoV2). Across the globe, there have been more than 6.5 million positive cases of COVID-19 and more than 380,000 deaths. (WHO COVID-19 Dashboard [https://covid19.who.int]). Multiple therapeutic agents are currently being studied as potential treatment options for this novel disease. With negative trials so far on lopinavir-ritonavir and hydroxychloroquine, the only candidate drug showing benefit is remdesivir.
Results of the randomized double-blind placebo controlled Adaptive COVID-19 Treatment Trial (ACTT-1) trial (Beigel, J et al. N Engl J Med. 2020; e-pub ahead of print) shows remdesivir improved recovery time in COVID -19 patients as compared with control subjects. Remdesivir is an inhibitor of viral RNA polymerase that has been shown to inhibit coronaviruses in animal models and SARS-CoV2 in-vitro. The ACTT-1 trial enrolled 1,063 patients with 541 assigned to the remdesivir arm and 522 to the placebo group. Primary outcome measure was time to recovery. Mortality at 14 and 28 days and incidence of adverse events were also evaluated.
As interim analysis showed positive results, the data safety and monitoring board recommended early termination of the trial. Patients in the remdesivir group had a shorter time to recovery, with median recovery time of 11 days as compared with 15 days in placebo group (95% CI:1.12-1.55; P < .001). Hospitalized patients requiring supplemental oxygen (but not high-flow, mechanical ventilation or ECMO) derived the maximum benefit with a rate ratio of recovery being 1.47(95% CI:1.17-1.84). Thus, early drug administration may be beneficial. The difference in mortality at 14 days was not statistically significant and data on mortality difference at 28 days were not available at the time of publication.
In summary, this trial along with previous publications shows that remdesivir is a potential therapeutic option for COVID -19. The Food and Drug Administration (FDA) approved remdesivir under Emergency Use Authorization (EUA) for COVID-19 and larger trials are currently underway to study the full effect of this agent.
Aravind Menon, MD
Fellow-in-Training Member
Critical Care
Burnout in unprecedented times
Even in typical times, intensivists have a significantly higher rate of burnout compared with other medical specialties. We fight for lives, dealing with death, dying, and tragedy on a daily basis. Regrettably, we are no longer in ‘typical’ times. This is a prodigious and uncharted era.
The COVID-19 pandemic has created all new hardships. Added to the complex world of critical care, we undertake lack of appropriate medical equipment and PPE, the possibility of becoming ill or infecting our families, potential financial struggles, and the unpredictability of the future. Additionally, in our efforts to care for patients, we face increasing moral distress when placed in situations in which we cannot do what we feel is right. And we carry the burdens and guilt of patients’ families who cannot be with loved ones during this process, even during death.
What does burnout look like in this new era? Burnout is a continuum and can manifest differently depending on the individual. Even a typical day in the ICU may be cause for the symptoms of burnout including frustration, anger, anxiety, or sadness which can progress to feelings of powerlessness, self-doubt or depersonalization.
This crisis is a test of endurance. But we don’t have to face it alone. The ICU is a team environment, and we can help each other make it to the end. Consider beginning the shift with a group morale boosting activity. Perhaps debrief after the end of each shift to discuss ways of combatting these stressful times. Have a virtual happy hour with colleagues after work. Call on leadership for support. Watch each other’s back. Together we will get through these unprecedented times.
John P. Gaillard, MD
Steering Committee Member
Resources for confronting burnout:
http://ccsconline.org/optimizing-the-workforce/burnout
https://www.ama-assn.org/topics/physician-burnout
https://www.ahrq.gov/prevention/clinician/ahrq-works/burnout/index.html
Home-Based Mechanical Ventilation and Neuromuscular Disease
Use of modified RADs
Investigators have begun exploring ways to convert devices typically used to treat sleep-disordered breathing (respiratory assist device, RAD), with modifications to minimize risk of aerosolization of pathogen in the COVID-19 pandemic. These devices are presently not considered an effective means of treating acute respiratory distress syndrome (ARDS). In an emergency, however, it is reasonable to consider all the options available with a healthy respect for inherent device limitations.
A RAD could be converted from an open ventilation single-limb respiratory circuit to a closed ventilation circuit with a passive exhalation valve. This circuit could provide adequate minute ventilation and allow for adequate exhalation of CO2 to prevent rebreathing. Strategic placement of the passive exhalation valve proximal to a viricidal filter would allow the device to be used with either an endotracheal tube or a nonvented oronasal mask (Figure). These devices by design are pressure-regulated, and a backup rate would be necessary to control minute ventilation. Close monitoring would be necessary given lack of alarm capability for a critically ill patient and the need to ensure adequate oxygen bleed-in.
The primary limitation to these devices is the inability to achieve adequate mean airway pressure for ARDS. While such a converted device is not ready for prime time, it could be considered for patients who are close to weaning from conventional mechanical ventilation (i.e., freeing up a ventilator for a sicker patient) or temporizing a patient early in disease to stave off invasive ventilation.
MAJ Brian E. Foster, DO, USA
Fellow Member
Steering Committee Member
Interstitial and Diffuse Lung Disease NetWork
Advances in molecular imaging in pulmonary fibrosis
Fibrotic interstitial lung diseases (ILD), including idiopathic pulmonary fibrosis (IPF), have poor prognosis with marked heterogeneity in the clinical course. Treatment options, including antfibrotic drugs and immunosuppressants, are fairly limited for either conditions, and there is wide variability in drug responsiveness. Biomarkers that predict disease course and enable patient stratification to assess responsiveness to specific therapies play a crucial role in management of this fatal disease.
Molecular imaging has the ability to noninvasively provide both structural details, as well as functional/molecular information at the cellular level; it has thus developed into a powerful tool for several inflammatory and malignant disease processes. Probes that specifically target fibrosis-specific pathways utilizing positron emission tomography (PET) or magnetic resonance (MR) imaging have gained traction recently.
The most commonly used radiopharmaceutical for PET, 18F-FDG, is significantly increased in areas of established fibrosis in patients with IPF and autoimmune ILDs (Win, et al. Eur J Nucl Med Mol Imaging. 2018 May;45[5]:806; Uehara, et al. Mod Rheumatol. 2016;26[1]:121-7), as well as areas with seemingly normal morphologic appearance on HRCT scan (Win, et al. Eur J Nucl Med Mol Imaging. 2014 Feb;41[2]:337). While this probe was shown to have some potential for prognostication, there has been concern regarding the specificity of FDG uptake in fibrotic lung diseases. Hence, other probes that target specific fibrosis-related cellular mechanisms such as macrophages (Withana, et al. Nature Scientific Reports. 2016;6 [Jan 22):19755], and John, et al. J Nucl Med. 2013;54[12]:2146) and matrix proteins (Montesi, et al. Am J Respir Crit Care Med. 2019 Jul 15;200[2]:258) have been developed in preclinical fibrosis/lung injury models and are being translated to human subjects.
With the ability to capture early fibrogenesis and target engagement, molecular imaging has the potential to prognosticate patients, provide earlier evaluation of treatment responsiveness and have a promising application in clinical trial design for fibrotic lung diseases.
Tejaswini Kulkarni, MD
Steering Committee Member
Airways
COVID-19 and asthma: Much remains unknown
Viral-induced asthma exacerbations are common, but there has yet to be a published data set showing worse outcomes among asthmatics with COVID-19.
It is possible that inhaled corticosteroids (ICS) may provide some protection from viral infection. A 2014 study showed that ICS may reduce exacerbations by modulating inflammation and reducing airway viral receptors (Yamaya, et al. Respir Investig. 2014;52[4]:251). Analysis from the SARP-3 database showed ICS use associated with reduced expression of both ACE2 and transmembrane protease serine 2 (TMPRSS2), two receptors used by SARS-CoV-2 (Peters, et al. Am J Respir Crit Care Med. 2020. Online ahead of print). Another study showed a similar effect of ICS on the seasonal coronavirus strain HCoV-229E (Yamaya M, et al. Respir Investig. 2020;58[3]:155), and one study reported decreased ACE2 expression in allergic asthma (Jackson, et al. J Allergy Clin Immunol. Article in press, 2020). While these findings could support a hypothesis of reduced risk for COVID-19 infection among asthmatics using ICS, one would generally expect those with underlying lung disease, such as asthma, to be at higher risk for more severe infection.
Despite physiologic hypotheses of protective mechanisms, clinical outcomes may suffer as clinical operations and the American economy are impacted by this pandemic. Reduced access to or utilization of outpatient care, loss of employment, loss of health insurance, or a new difficulty in affording or accessing medications may all result in worsening asthma control for patients. Poorly controlled asthmatics are at higher risk for a more severe exacerbation of disease triggered by viral infection. Current recommendations are for patients to continue all controller medications; the use of systemic corticosteroids in treatment of COVID pneumonia is controversial, but their use in treating a COVID-associated asthma exacerbation should be based on individual assessment. As we care for asthma patients through this pandemic, much remains unknown but may be elucidated by further study.
Megan Conroy, MD
Fellow-in-Training Member
Steering Committee Member
Clinical Research and Quality Improvement
Remdesivir for COVID-19: A ray of hope?
The year 2020 witnessed a pandemic of unprecedented proportions, caused by a novel corona virus strain (SARS-CoV2). Across the globe, there have been more than 6.5 million positive cases of COVID-19 and more than 380,000 deaths. (WHO COVID-19 Dashboard [https://covid19.who.int]). Multiple therapeutic agents are currently being studied as potential treatment options for this novel disease. With negative trials so far on lopinavir-ritonavir and hydroxychloroquine, the only candidate drug showing benefit is remdesivir.
Results of the randomized double-blind placebo controlled Adaptive COVID-19 Treatment Trial (ACTT-1) trial (Beigel, J et al. N Engl J Med. 2020; e-pub ahead of print) shows remdesivir improved recovery time in COVID -19 patients as compared with control subjects. Remdesivir is an inhibitor of viral RNA polymerase that has been shown to inhibit coronaviruses in animal models and SARS-CoV2 in-vitro. The ACTT-1 trial enrolled 1,063 patients with 541 assigned to the remdesivir arm and 522 to the placebo group. Primary outcome measure was time to recovery. Mortality at 14 and 28 days and incidence of adverse events were also evaluated.
As interim analysis showed positive results, the data safety and monitoring board recommended early termination of the trial. Patients in the remdesivir group had a shorter time to recovery, with median recovery time of 11 days as compared with 15 days in placebo group (95% CI:1.12-1.55; P < .001). Hospitalized patients requiring supplemental oxygen (but not high-flow, mechanical ventilation or ECMO) derived the maximum benefit with a rate ratio of recovery being 1.47(95% CI:1.17-1.84). Thus, early drug administration may be beneficial. The difference in mortality at 14 days was not statistically significant and data on mortality difference at 28 days were not available at the time of publication.
In summary, this trial along with previous publications shows that remdesivir is a potential therapeutic option for COVID -19. The Food and Drug Administration (FDA) approved remdesivir under Emergency Use Authorization (EUA) for COVID-19 and larger trials are currently underway to study the full effect of this agent.
Aravind Menon, MD
Fellow-in-Training Member
Critical Care
Burnout in unprecedented times
Even in typical times, intensivists have a significantly higher rate of burnout compared with other medical specialties. We fight for lives, dealing with death, dying, and tragedy on a daily basis. Regrettably, we are no longer in ‘typical’ times. This is a prodigious and uncharted era.
The COVID-19 pandemic has created all new hardships. Added to the complex world of critical care, we undertake lack of appropriate medical equipment and PPE, the possibility of becoming ill or infecting our families, potential financial struggles, and the unpredictability of the future. Additionally, in our efforts to care for patients, we face increasing moral distress when placed in situations in which we cannot do what we feel is right. And we carry the burdens and guilt of patients’ families who cannot be with loved ones during this process, even during death.
What does burnout look like in this new era? Burnout is a continuum and can manifest differently depending on the individual. Even a typical day in the ICU may be cause for the symptoms of burnout including frustration, anger, anxiety, or sadness which can progress to feelings of powerlessness, self-doubt or depersonalization.
This crisis is a test of endurance. But we don’t have to face it alone. The ICU is a team environment, and we can help each other make it to the end. Consider beginning the shift with a group morale boosting activity. Perhaps debrief after the end of each shift to discuss ways of combatting these stressful times. Have a virtual happy hour with colleagues after work. Call on leadership for support. Watch each other’s back. Together we will get through these unprecedented times.
John P. Gaillard, MD
Steering Committee Member
Resources for confronting burnout:
http://ccsconline.org/optimizing-the-workforce/burnout
https://www.ama-assn.org/topics/physician-burnout
https://www.ahrq.gov/prevention/clinician/ahrq-works/burnout/index.html
Home-Based Mechanical Ventilation and Neuromuscular Disease
Use of modified RADs
Investigators have begun exploring ways to convert devices typically used to treat sleep-disordered breathing (respiratory assist device, RAD), with modifications to minimize risk of aerosolization of pathogen in the COVID-19 pandemic. These devices are presently not considered an effective means of treating acute respiratory distress syndrome (ARDS). In an emergency, however, it is reasonable to consider all the options available with a healthy respect for inherent device limitations.
A RAD could be converted from an open ventilation single-limb respiratory circuit to a closed ventilation circuit with a passive exhalation valve. This circuit could provide adequate minute ventilation and allow for adequate exhalation of CO2 to prevent rebreathing. Strategic placement of the passive exhalation valve proximal to a viricidal filter would allow the device to be used with either an endotracheal tube or a nonvented oronasal mask (Figure). These devices by design are pressure-regulated, and a backup rate would be necessary to control minute ventilation. Close monitoring would be necessary given lack of alarm capability for a critically ill patient and the need to ensure adequate oxygen bleed-in.
The primary limitation to these devices is the inability to achieve adequate mean airway pressure for ARDS. While such a converted device is not ready for prime time, it could be considered for patients who are close to weaning from conventional mechanical ventilation (i.e., freeing up a ventilator for a sicker patient) or temporizing a patient early in disease to stave off invasive ventilation.
MAJ Brian E. Foster, DO, USA
Fellow Member
Steering Committee Member
Interstitial and Diffuse Lung Disease NetWork
Advances in molecular imaging in pulmonary fibrosis
Fibrotic interstitial lung diseases (ILD), including idiopathic pulmonary fibrosis (IPF), have poor prognosis with marked heterogeneity in the clinical course. Treatment options, including antfibrotic drugs and immunosuppressants, are fairly limited for either conditions, and there is wide variability in drug responsiveness. Biomarkers that predict disease course and enable patient stratification to assess responsiveness to specific therapies play a crucial role in management of this fatal disease.
Molecular imaging has the ability to noninvasively provide both structural details, as well as functional/molecular information at the cellular level; it has thus developed into a powerful tool for several inflammatory and malignant disease processes. Probes that specifically target fibrosis-specific pathways utilizing positron emission tomography (PET) or magnetic resonance (MR) imaging have gained traction recently.
The most commonly used radiopharmaceutical for PET, 18F-FDG, is significantly increased in areas of established fibrosis in patients with IPF and autoimmune ILDs (Win, et al. Eur J Nucl Med Mol Imaging. 2018 May;45[5]:806; Uehara, et al. Mod Rheumatol. 2016;26[1]:121-7), as well as areas with seemingly normal morphologic appearance on HRCT scan (Win, et al. Eur J Nucl Med Mol Imaging. 2014 Feb;41[2]:337). While this probe was shown to have some potential for prognostication, there has been concern regarding the specificity of FDG uptake in fibrotic lung diseases. Hence, other probes that target specific fibrosis-related cellular mechanisms such as macrophages (Withana, et al. Nature Scientific Reports. 2016;6 [Jan 22):19755], and John, et al. J Nucl Med. 2013;54[12]:2146) and matrix proteins (Montesi, et al. Am J Respir Crit Care Med. 2019 Jul 15;200[2]:258) have been developed in preclinical fibrosis/lung injury models and are being translated to human subjects.
With the ability to capture early fibrogenesis and target engagement, molecular imaging has the potential to prognosticate patients, provide earlier evaluation of treatment responsiveness and have a promising application in clinical trial design for fibrotic lung diseases.
Tejaswini Kulkarni, MD
Steering Committee Member