HCV+ kidney transplants: Similar outcomes to HCV- regardless of recipient serostatus

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Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.

one kidney in red and blue
Mohammed Haneefa Nizamudeen/Getty Images

A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.

During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.

HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m2 (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.

Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.

“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.

“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.

This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.

SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.

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Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.

one kidney in red and blue
Mohammed Haneefa Nizamudeen/Getty Images

A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.

During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.

HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m2 (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.

Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.

“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.

“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.

This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.

SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.

 

Kidneys from donors with hepatitis C virus (HCV) infection function well despite adverse quality assessment and are a valuable resource for transplantation candidates independent of HCV status, according to the findings of a large U.S. registry study.

one kidney in red and blue
Mohammed Haneefa Nizamudeen/Getty Images

A total of 260 HCV-viremic kidneys were transplanted in the first quarter of 2019, with 105 additional viremic kidneys being discarded, according to a report in the Journal of the American Society of Nephrology by Vishnu S. Potluri, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Donor HCV viremia was defined as an HCV nucleic acid test–positive result reported to the Organ Procurement and Transplantation Network (OPTN). Donors who were HCV negative in this test were labeled as HCV nonviremic. Kidney transplantation recipients were defined as either HCV seropositive or seronegative based on HCV antibody testing.

During the first quarter of 2019, 74% of HCV-viremic kidneys were transplanted into seronegative recipients, which is a major change from how HCV-viremic kidneys were allocated a few years ago, according to the researchers. The results of small trials showing the benefits of such transplantations and the success of direct-acting antiviral therapy (DAA) on clearing HCV infections were indicated as likely responsible for the change.

HCV-viremic kidneys had similar function, compared with HCV-nonviremic kidneys, when matched on the donor elements included in the Kidney Profile Donor Index (KDPI), excluding HCV, they added. In addition, the 12-month estimated glomerular filtration rate (eGFR) was similar between the seropositive and seronegative recipients, respectively 65.4 and 71.1 mL/min per 1.73 m2 (P = .05), which suggests that recipient HCV serostatus does not negatively affect 1-year graft function using HCV-viremic kidneys in the era of DAA treatments, according to the authors.

Also, among HCV-seropositive recipients of HCV-viremic kidneys, seven (3.4%) died by 1 year post transplantation, while none of the HCV-seronegative recipients of HCV-viremic kidneys experienced graft failure or death.

“These striking results provide important additional evidence that the KDPI, with its current negative weighting for HCV status, does not accurately assess the quality of kidneys from HCV-viremic donors,” the authors wrote.

“HCV-viremic kidneys are a valuable resource for transplantation. Disincentives for accepting these organs should be addressed by the transplantation community,” Dr. Potluri and colleagues concluded.

This work was supported in part by the Health Resources and Services Administration of the U.S. Department of Health & Human Services. The various authors reported grant funding and advisory board participation with a number of pharmaceutical companies.

SOURCE: Potluri VS et al. J Am Soc Nephrol. 2019;30:1939-51.

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Intensive cognitive training may be needed for memory gains in MS

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– Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.

“High-intensive memory-strategy interventions exert the largest effects on hippocampal memory function” in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.

To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.

Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.

After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.

To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.

Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.

Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.

Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.

“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.

Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.

Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
 

SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.

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– Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.

“High-intensive memory-strategy interventions exert the largest effects on hippocampal memory function” in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.

To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.

Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.

After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.

To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.

Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.

Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.

Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.

“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.

Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.

Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
 

SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.

 

– Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.

“High-intensive memory-strategy interventions exert the largest effects on hippocampal memory function” in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.

To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.

Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.

After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.

To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.

Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.

Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.

Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.

“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.

Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.

Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
 

SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.

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REPORTING FROM ECTRIMS 2019

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In older patients with immune-mediated TTP, atypical features may delay diagnosis

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Older patients with immune thrombotic thrombocytopenic purpura (iTTP) more often have an atypical neurological presentation, which could result in a delayed diagnosis, according to authors of a recent retrospective analysis.

“Practitioners should be aware of this in order to shorten the time to treatment, which could improve the prognosis in older iTTP patients,” Paul Coppo, MD, PhD, of Hôpital Saint-Antoine, Paris, and coauthors wrote in Blood.

The older patients also had increased 1-month and 1-year mortality compared with younger patients, and had more than a threefold risk of long-term mortality compared with elderly patients without iTTP, according to the study report.

The analysis included 411 patients with iTTP entered into a national registry in France between 2000 and 2016. Seventy-one patients were 60 years of age or older.

Time from hospital admission to diagnosis was 3 days for those older patients, versus just 1 day for patients under 60 years of age (P = .0001), Dr. Coppo and colleagues reported.

Clinical records were available for 67 of the older iTTP patients, of whom 17 had no evidence of delayed diagnosis. The remainder had a “possible diagnostic delay,” according to the report; among those, the iTTP diagnosis was preceded by neurological manifestations in 26 cases, and transient ischemic stroke that usually led to focal deficiency or aphasia in 14 cases. Other features preceding the diagnosis included malaise, behavioral abnormalities, seizure, and dizziness.

Many of these findings are “not specific to a disease, and they are less alarming than in young patients,” the researchers wrote. “In this context, the presence of a thrombocytopenia with anemia should alert physicians to this possible rare diagnosis.”

Older patients also presented with less pronounced cytopenias compared with younger patients, which could have contributed to a late diagnosis, they added.

Older age is a known risk factor for mortality related to iTTP. In the present study, rates of 1-month mortality were 37% for patients aged 60 years and older, and 9% for those younger than age 60 (P less than .0001). The 1-year mortality rates were 49% and 11% for older and younger patients, respectively (P less than .0001).

Compared with older individuals without iTTP from a different study, older iTTP patients had a lower long-term survival rate. iTTP remained an independent risk factor for death even after adjustment for age, sex, and some comorbidities (hazard ratio, 3.44; 95% confidence interval, 2.02-5.87).

The study was partly funded by a grant from the French Ministry of Health. Dr. Coppo reported that he is a clinical advisory board member for Alexion, Ablynx (now part of Sanofi), Shire, and Octapharma. Two other co-authors reported participating in advisory boards for Ablynx.

SOURCE: Prevel R et al. Blood. 2019 Sep 17. doi: 10.1182/blood.2019000748.

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Older patients with immune thrombotic thrombocytopenic purpura (iTTP) more often have an atypical neurological presentation, which could result in a delayed diagnosis, according to authors of a recent retrospective analysis.

“Practitioners should be aware of this in order to shorten the time to treatment, which could improve the prognosis in older iTTP patients,” Paul Coppo, MD, PhD, of Hôpital Saint-Antoine, Paris, and coauthors wrote in Blood.

The older patients also had increased 1-month and 1-year mortality compared with younger patients, and had more than a threefold risk of long-term mortality compared with elderly patients without iTTP, according to the study report.

The analysis included 411 patients with iTTP entered into a national registry in France between 2000 and 2016. Seventy-one patients were 60 years of age or older.

Time from hospital admission to diagnosis was 3 days for those older patients, versus just 1 day for patients under 60 years of age (P = .0001), Dr. Coppo and colleagues reported.

Clinical records were available for 67 of the older iTTP patients, of whom 17 had no evidence of delayed diagnosis. The remainder had a “possible diagnostic delay,” according to the report; among those, the iTTP diagnosis was preceded by neurological manifestations in 26 cases, and transient ischemic stroke that usually led to focal deficiency or aphasia in 14 cases. Other features preceding the diagnosis included malaise, behavioral abnormalities, seizure, and dizziness.

Many of these findings are “not specific to a disease, and they are less alarming than in young patients,” the researchers wrote. “In this context, the presence of a thrombocytopenia with anemia should alert physicians to this possible rare diagnosis.”

Older patients also presented with less pronounced cytopenias compared with younger patients, which could have contributed to a late diagnosis, they added.

Older age is a known risk factor for mortality related to iTTP. In the present study, rates of 1-month mortality were 37% for patients aged 60 years and older, and 9% for those younger than age 60 (P less than .0001). The 1-year mortality rates were 49% and 11% for older and younger patients, respectively (P less than .0001).

Compared with older individuals without iTTP from a different study, older iTTP patients had a lower long-term survival rate. iTTP remained an independent risk factor for death even after adjustment for age, sex, and some comorbidities (hazard ratio, 3.44; 95% confidence interval, 2.02-5.87).

The study was partly funded by a grant from the French Ministry of Health. Dr. Coppo reported that he is a clinical advisory board member for Alexion, Ablynx (now part of Sanofi), Shire, and Octapharma. Two other co-authors reported participating in advisory boards for Ablynx.

SOURCE: Prevel R et al. Blood. 2019 Sep 17. doi: 10.1182/blood.2019000748.

 

Older patients with immune thrombotic thrombocytopenic purpura (iTTP) more often have an atypical neurological presentation, which could result in a delayed diagnosis, according to authors of a recent retrospective analysis.

“Practitioners should be aware of this in order to shorten the time to treatment, which could improve the prognosis in older iTTP patients,” Paul Coppo, MD, PhD, of Hôpital Saint-Antoine, Paris, and coauthors wrote in Blood.

The older patients also had increased 1-month and 1-year mortality compared with younger patients, and had more than a threefold risk of long-term mortality compared with elderly patients without iTTP, according to the study report.

The analysis included 411 patients with iTTP entered into a national registry in France between 2000 and 2016. Seventy-one patients were 60 years of age or older.

Time from hospital admission to diagnosis was 3 days for those older patients, versus just 1 day for patients under 60 years of age (P = .0001), Dr. Coppo and colleagues reported.

Clinical records were available for 67 of the older iTTP patients, of whom 17 had no evidence of delayed diagnosis. The remainder had a “possible diagnostic delay,” according to the report; among those, the iTTP diagnosis was preceded by neurological manifestations in 26 cases, and transient ischemic stroke that usually led to focal deficiency or aphasia in 14 cases. Other features preceding the diagnosis included malaise, behavioral abnormalities, seizure, and dizziness.

Many of these findings are “not specific to a disease, and they are less alarming than in young patients,” the researchers wrote. “In this context, the presence of a thrombocytopenia with anemia should alert physicians to this possible rare diagnosis.”

Older patients also presented with less pronounced cytopenias compared with younger patients, which could have contributed to a late diagnosis, they added.

Older age is a known risk factor for mortality related to iTTP. In the present study, rates of 1-month mortality were 37% for patients aged 60 years and older, and 9% for those younger than age 60 (P less than .0001). The 1-year mortality rates were 49% and 11% for older and younger patients, respectively (P less than .0001).

Compared with older individuals without iTTP from a different study, older iTTP patients had a lower long-term survival rate. iTTP remained an independent risk factor for death even after adjustment for age, sex, and some comorbidities (hazard ratio, 3.44; 95% confidence interval, 2.02-5.87).

The study was partly funded by a grant from the French Ministry of Health. Dr. Coppo reported that he is a clinical advisory board member for Alexion, Ablynx (now part of Sanofi), Shire, and Octapharma. Two other co-authors reported participating in advisory boards for Ablynx.

SOURCE: Prevel R et al. Blood. 2019 Sep 17. doi: 10.1182/blood.2019000748.

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Poll: New Algorithm for PE

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Choose your answer in the poll below. To check the accuracy of your answer, see PURLs: A Better Approach to the Diagnosis of PE.

[polldaddy:10428150]

 

Click on page 2 below to find out what the correct answer is...

 

 

The correct answer is b.) 14%

To learn more, see this month's PURLs: A Better Approach to the Diagnosis of PE.

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Choose your answer in the poll below. To check the accuracy of your answer, see PURLs: A Better Approach to the Diagnosis of PE.

[polldaddy:10428150]

 

Click on page 2 below to find out what the correct answer is...

 

 

The correct answer is b.) 14%

To learn more, see this month's PURLs: A Better Approach to the Diagnosis of PE.

Choose your answer in the poll below. To check the accuracy of your answer, see PURLs: A Better Approach to the Diagnosis of PE.

[polldaddy:10428150]

 

Click on page 2 below to find out what the correct answer is...

 

 

The correct answer is b.) 14%

To learn more, see this month's PURLs: A Better Approach to the Diagnosis of PE.

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From the President: Wisdom of our crowd

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About a year ago, I had the opportunity to don the honorary regalia of the American College of Chest Physicians as its 81st President. On that memorable day on the dais in San Antonio, I used the example of James Surowiecki’s book, “The Wisdom of Crowds: Why the Many Are Smarter than the Few and How Collective Wisdom Shapes Business, Economics, Societies, and Nations” to explain how we would use the collective wisdom of our members, our committee and NetWork members, and our talented association staff to build and shape CHEST over the coming year. For those of you not familiar with this concept, Surowiecki, a business columnist for New Yorker, outlines the concept that large groups of people are actually smarter than an elite few at solving the problems of an organization, fostering innovation, collectively coming to wise decisions, or even predicting the future. In channeling the lessons from the book, it has become obvious that listening to our members and partners, rather than trying to make all decisions from the top down, has been an effective method for coming to wise decisions about the strategy and operation of CHEST. Now that it’s already time to hand the responsibility of the organization as President over to my friend and colleague Dr. Stephanie Levine, I’ve reflected on actually how effectively we have listened and how smart the collective crowd has been in moving the success of CHEST forward.

Dr.Clayton T. Cowl

We heard from members that it was difficult to know how to get involved and what happens at the highest leadership levels of the organization. This prompted the development of podcasts dubbed “The Inside Scoop,” recorded live approximately every 2 months and featured various leaders of the organization with an informal way for members to better understand how to become involved in CHEST activities and to feel the pulse of activity of the association between the time the annual meeting ends and the next one begins.

The crowd informed us that communication at the Board of Regents level could be better. To address this, regular communications were sent out to the Board of Regents to update them on activities and discussion of issues between scheduled board meetings, as well as providing board members the opportunity to have access to the minutes of phone calls of the “5Ps,” calls that included the Immediate Past, President-Elect, President-Designate, and current President of the association, as well as the CHEST Foundation President.

We were told by members through focus groups and surveys, then again told by experts we invited to the June board meetings from education, business, design, and venture capital sectors (and who were naïve to CHEST as an association) that we needed to double down on virtual educational offerings to learners across the health-care delivery team and to revamp its information technology infrastructure. To that end, a digital strategy work group was convened with expertise in information technology, social media, and marketing to inventory all digital assets of the College and make recommendations for not just improvement, but for a complete transformation of digital technology created and promulgated by CHEST. The board then approved a budget of nearly $1 million to upgrade and rebuild the user experience within CHEST’s digital environment, including its learning management system. We also opened a multimedia studio at CHEST headquarters, increased the numbers of serious educational gaming opportunities at the annual meeting, and are developing a line of serious game platforms that will allow for “edutainment” opportunities for our members and other learners around the world using various digital platforms.

Colleagues from around the world reminded us that 20% of CHEST membership was international and that our strategic plan included an international strategy. Thanks to the support of our colleagues around the world, we were able to enjoy a tremendously successful CHEST Congress in Bangkok, Thailand, in April, and a smaller regional meeting in June in Athens, Greece. Efforts of the Governance Committee have reshaped the structure of international representation, making it more relevant and allowing its members to have a stronger voice to the Board of Regents. Plans are underway for the next CHEST Congress in June 2020 in Bologna, Italy, to be held in collaboration with the Italian Chapter of CHEST in that country.

In an era when the majority of association annual meetings across multiple specialties are driving toward parity with similar looks, marketing, formats, and expectations, we listened to the needs and desires of attendees of last year’s meeting and have improved CHEST 2019 in New Orleans even more. With the most simulation courses ever delivered at an annual meeting, more serious game opportunities, CHEST Challenge finals, a new innovation competition called “FISH Bowl,” and even a medical escape room, CHEST volunteer leaders and organization staff have worked hard to provide a world class meeting that has a different look and feel from all the others. Plus, the crowd also told us that having CME and MOC credit available for the entire meeting was another variable that was desired, and has now been achieved.

The wisdom of the proverbial crowd of membership has spoken in terms of the need for philanthropic efforts in our specialty. The CHEST Foundation has responded by awarding tens of thousands of dollars to our members to recognize cutting-edge research, community service efforts, and, in addition, has allowed dozens of providers early on in training or in their career to attend the annual meeting with the help of travel grants.

CHEST guidelines continue to be updated and new ones created based on input from expert panel teams. The CHEST journal submission process, review turnaround times, and quality of manuscripts have improved each year thanks to useful feedback from authors and readers. Publications such as CHEST Physician are modified each year based upon feedback from our readers. Critiques from the board review courses have been the driving force keeping live learning formats and the electronic SEEK board preparation questions current and accurate when the science is constantly changing.

Truly, the collective wisdom of our members, talented clinicians and researchers, and colleagues in industry has provided incredibly valuable input to the CHEST leadership team. You have spoken, and we have been listening. Thanks to each of you who have reached out to me during this year as President. Traveling to four continents this past year to better understand the needs of members who are clinicians, educators, researchers, and caregivers positioned in each geographic region has been enlightening, educational, and transformative for me and my family. Your meaningful feedback, keen insights, and passion for outstanding patient care, impactful educational experiences, and life-changing research have helped push CHEST to a higher level of excellence and to offer unparalleled experiences for our members to ultimately provide the very best care to patients.

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About a year ago, I had the opportunity to don the honorary regalia of the American College of Chest Physicians as its 81st President. On that memorable day on the dais in San Antonio, I used the example of James Surowiecki’s book, “The Wisdom of Crowds: Why the Many Are Smarter than the Few and How Collective Wisdom Shapes Business, Economics, Societies, and Nations” to explain how we would use the collective wisdom of our members, our committee and NetWork members, and our talented association staff to build and shape CHEST over the coming year. For those of you not familiar with this concept, Surowiecki, a business columnist for New Yorker, outlines the concept that large groups of people are actually smarter than an elite few at solving the problems of an organization, fostering innovation, collectively coming to wise decisions, or even predicting the future. In channeling the lessons from the book, it has become obvious that listening to our members and partners, rather than trying to make all decisions from the top down, has been an effective method for coming to wise decisions about the strategy and operation of CHEST. Now that it’s already time to hand the responsibility of the organization as President over to my friend and colleague Dr. Stephanie Levine, I’ve reflected on actually how effectively we have listened and how smart the collective crowd has been in moving the success of CHEST forward.

Dr.Clayton T. Cowl

We heard from members that it was difficult to know how to get involved and what happens at the highest leadership levels of the organization. This prompted the development of podcasts dubbed “The Inside Scoop,” recorded live approximately every 2 months and featured various leaders of the organization with an informal way for members to better understand how to become involved in CHEST activities and to feel the pulse of activity of the association between the time the annual meeting ends and the next one begins.

The crowd informed us that communication at the Board of Regents level could be better. To address this, regular communications were sent out to the Board of Regents to update them on activities and discussion of issues between scheduled board meetings, as well as providing board members the opportunity to have access to the minutes of phone calls of the “5Ps,” calls that included the Immediate Past, President-Elect, President-Designate, and current President of the association, as well as the CHEST Foundation President.

We were told by members through focus groups and surveys, then again told by experts we invited to the June board meetings from education, business, design, and venture capital sectors (and who were naïve to CHEST as an association) that we needed to double down on virtual educational offerings to learners across the health-care delivery team and to revamp its information technology infrastructure. To that end, a digital strategy work group was convened with expertise in information technology, social media, and marketing to inventory all digital assets of the College and make recommendations for not just improvement, but for a complete transformation of digital technology created and promulgated by CHEST. The board then approved a budget of nearly $1 million to upgrade and rebuild the user experience within CHEST’s digital environment, including its learning management system. We also opened a multimedia studio at CHEST headquarters, increased the numbers of serious educational gaming opportunities at the annual meeting, and are developing a line of serious game platforms that will allow for “edutainment” opportunities for our members and other learners around the world using various digital platforms.

Colleagues from around the world reminded us that 20% of CHEST membership was international and that our strategic plan included an international strategy. Thanks to the support of our colleagues around the world, we were able to enjoy a tremendously successful CHEST Congress in Bangkok, Thailand, in April, and a smaller regional meeting in June in Athens, Greece. Efforts of the Governance Committee have reshaped the structure of international representation, making it more relevant and allowing its members to have a stronger voice to the Board of Regents. Plans are underway for the next CHEST Congress in June 2020 in Bologna, Italy, to be held in collaboration with the Italian Chapter of CHEST in that country.

In an era when the majority of association annual meetings across multiple specialties are driving toward parity with similar looks, marketing, formats, and expectations, we listened to the needs and desires of attendees of last year’s meeting and have improved CHEST 2019 in New Orleans even more. With the most simulation courses ever delivered at an annual meeting, more serious game opportunities, CHEST Challenge finals, a new innovation competition called “FISH Bowl,” and even a medical escape room, CHEST volunteer leaders and organization staff have worked hard to provide a world class meeting that has a different look and feel from all the others. Plus, the crowd also told us that having CME and MOC credit available for the entire meeting was another variable that was desired, and has now been achieved.

The wisdom of the proverbial crowd of membership has spoken in terms of the need for philanthropic efforts in our specialty. The CHEST Foundation has responded by awarding tens of thousands of dollars to our members to recognize cutting-edge research, community service efforts, and, in addition, has allowed dozens of providers early on in training or in their career to attend the annual meeting with the help of travel grants.

CHEST guidelines continue to be updated and new ones created based on input from expert panel teams. The CHEST journal submission process, review turnaround times, and quality of manuscripts have improved each year thanks to useful feedback from authors and readers. Publications such as CHEST Physician are modified each year based upon feedback from our readers. Critiques from the board review courses have been the driving force keeping live learning formats and the electronic SEEK board preparation questions current and accurate when the science is constantly changing.

Truly, the collective wisdom of our members, talented clinicians and researchers, and colleagues in industry has provided incredibly valuable input to the CHEST leadership team. You have spoken, and we have been listening. Thanks to each of you who have reached out to me during this year as President. Traveling to four continents this past year to better understand the needs of members who are clinicians, educators, researchers, and caregivers positioned in each geographic region has been enlightening, educational, and transformative for me and my family. Your meaningful feedback, keen insights, and passion for outstanding patient care, impactful educational experiences, and life-changing research have helped push CHEST to a higher level of excellence and to offer unparalleled experiences for our members to ultimately provide the very best care to patients.

 

About a year ago, I had the opportunity to don the honorary regalia of the American College of Chest Physicians as its 81st President. On that memorable day on the dais in San Antonio, I used the example of James Surowiecki’s book, “The Wisdom of Crowds: Why the Many Are Smarter than the Few and How Collective Wisdom Shapes Business, Economics, Societies, and Nations” to explain how we would use the collective wisdom of our members, our committee and NetWork members, and our talented association staff to build and shape CHEST over the coming year. For those of you not familiar with this concept, Surowiecki, a business columnist for New Yorker, outlines the concept that large groups of people are actually smarter than an elite few at solving the problems of an organization, fostering innovation, collectively coming to wise decisions, or even predicting the future. In channeling the lessons from the book, it has become obvious that listening to our members and partners, rather than trying to make all decisions from the top down, has been an effective method for coming to wise decisions about the strategy and operation of CHEST. Now that it’s already time to hand the responsibility of the organization as President over to my friend and colleague Dr. Stephanie Levine, I’ve reflected on actually how effectively we have listened and how smart the collective crowd has been in moving the success of CHEST forward.

Dr.Clayton T. Cowl

We heard from members that it was difficult to know how to get involved and what happens at the highest leadership levels of the organization. This prompted the development of podcasts dubbed “The Inside Scoop,” recorded live approximately every 2 months and featured various leaders of the organization with an informal way for members to better understand how to become involved in CHEST activities and to feel the pulse of activity of the association between the time the annual meeting ends and the next one begins.

The crowd informed us that communication at the Board of Regents level could be better. To address this, regular communications were sent out to the Board of Regents to update them on activities and discussion of issues between scheduled board meetings, as well as providing board members the opportunity to have access to the minutes of phone calls of the “5Ps,” calls that included the Immediate Past, President-Elect, President-Designate, and current President of the association, as well as the CHEST Foundation President.

We were told by members through focus groups and surveys, then again told by experts we invited to the June board meetings from education, business, design, and venture capital sectors (and who were naïve to CHEST as an association) that we needed to double down on virtual educational offerings to learners across the health-care delivery team and to revamp its information technology infrastructure. To that end, a digital strategy work group was convened with expertise in information technology, social media, and marketing to inventory all digital assets of the College and make recommendations for not just improvement, but for a complete transformation of digital technology created and promulgated by CHEST. The board then approved a budget of nearly $1 million to upgrade and rebuild the user experience within CHEST’s digital environment, including its learning management system. We also opened a multimedia studio at CHEST headquarters, increased the numbers of serious educational gaming opportunities at the annual meeting, and are developing a line of serious game platforms that will allow for “edutainment” opportunities for our members and other learners around the world using various digital platforms.

Colleagues from around the world reminded us that 20% of CHEST membership was international and that our strategic plan included an international strategy. Thanks to the support of our colleagues around the world, we were able to enjoy a tremendously successful CHEST Congress in Bangkok, Thailand, in April, and a smaller regional meeting in June in Athens, Greece. Efforts of the Governance Committee have reshaped the structure of international representation, making it more relevant and allowing its members to have a stronger voice to the Board of Regents. Plans are underway for the next CHEST Congress in June 2020 in Bologna, Italy, to be held in collaboration with the Italian Chapter of CHEST in that country.

In an era when the majority of association annual meetings across multiple specialties are driving toward parity with similar looks, marketing, formats, and expectations, we listened to the needs and desires of attendees of last year’s meeting and have improved CHEST 2019 in New Orleans even more. With the most simulation courses ever delivered at an annual meeting, more serious game opportunities, CHEST Challenge finals, a new innovation competition called “FISH Bowl,” and even a medical escape room, CHEST volunteer leaders and organization staff have worked hard to provide a world class meeting that has a different look and feel from all the others. Plus, the crowd also told us that having CME and MOC credit available for the entire meeting was another variable that was desired, and has now been achieved.

The wisdom of the proverbial crowd of membership has spoken in terms of the need for philanthropic efforts in our specialty. The CHEST Foundation has responded by awarding tens of thousands of dollars to our members to recognize cutting-edge research, community service efforts, and, in addition, has allowed dozens of providers early on in training or in their career to attend the annual meeting with the help of travel grants.

CHEST guidelines continue to be updated and new ones created based on input from expert panel teams. The CHEST journal submission process, review turnaround times, and quality of manuscripts have improved each year thanks to useful feedback from authors and readers. Publications such as CHEST Physician are modified each year based upon feedback from our readers. Critiques from the board review courses have been the driving force keeping live learning formats and the electronic SEEK board preparation questions current and accurate when the science is constantly changing.

Truly, the collective wisdom of our members, talented clinicians and researchers, and colleagues in industry has provided incredibly valuable input to the CHEST leadership team. You have spoken, and we have been listening. Thanks to each of you who have reached out to me during this year as President. Traveling to four continents this past year to better understand the needs of members who are clinicians, educators, researchers, and caregivers positioned in each geographic region has been enlightening, educational, and transformative for me and my family. Your meaningful feedback, keen insights, and passion for outstanding patient care, impactful educational experiences, and life-changing research have helped push CHEST to a higher level of excellence and to offer unparalleled experiences for our members to ultimately provide the very best care to patients.

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The emerging role of quantitative CT scans in ILD terms

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The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?

Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.

The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.

IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).

Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.

Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
 

Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.

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The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?

Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.

The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.

IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).

Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.

Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
 

Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.

The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?

Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.

The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.

IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).

Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.

Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
 

Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.

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Should PEEP be titrated based on esophageal pressures?

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Application of basic physiology principles at bedside has changed the approach to the treatment of patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia. Current standard of care for patients with ARDS includes a low tidal volume ventilation strategy (6 mL/kg of ideal body weight), keeping plateau pressures below 30 cm H2O (Brower RG, et al. N Engl J Med. 2000;342[18]:1301), driving pressures below 15 cm H2O and adequate positive end-expiratory pressures (PEEP) to keep the alveoli open without overdistension (Villar J, et al. Crit Care Med. 2006;34[5]:1311). However, at this time, despite the awareness of the importance of this intervention, there is no consensus regarding the best method to determine ideal PEEP at the individual patient level.

A thorough understanding of the basic physiologic concepts regarding respiratory pressures is of paramount importance to be able to formulate an opinion. The transpulmonary pressure (or lung distending pressure) is the gradient caused by the difference between alveolar (PA) and pleural pressure (PPL). In order to prevent lung collapse at end-expiration, PA must remain higher than PPL such that the gradient remains outward, preventing end-expiratory collapse and atelectotrauma. To accomplish that, it is necessary to know the end-expiratory PA and PPL. Esophageal balloon pressures (PES) represent central thoracic pressures, but, despite positional and regional variations, they are a good surrogate for average “effective” PPL (Baedorf KE, et al. Med Klin Intensivmed Notfmed. 2018;113[Suppl 1]:13).

Understanding that the value of the PES represents a practical PPL makes it easier to appreciate the potential usefulness of an esophageal balloon to titrate PEEP. The objective of PEEP titration is to prevent de-recruitment, maintain alveolar aeration, and improve the functional size of aerated alveoli. If the applied PEEP is lower than the PPL, the dependent lung regions will collapse. On the other hand, if PEEP is higher than the PPL, the lung would be overdistended, causing barotrauma and hemodynamic compromise.

The question is: Should we use esophageal balloons?Yes, we should.

A single center randomized control trial (EPVent) compared PEEP titration to achieve a positive PL vs standard of care lung protective ventilation (Talmor D, et al. N Engl J Med. 2008;359:2095). The PEEP titration group used significantly higher levels of PEEP, with improved oxygenation and lung compliance. However, there was no significant difference in ventilator-free days or mortality between the groups.

Obese patients are also likely to benefit from PEEP titration guided by an esophageal balloon, as they often have higher levels of intrinsic PEEP. Therefore, the application of higher levels of PEEP to compensate for the higher levels of intrinsic PEEP may help reduce work of breathing and prevent tidal recruitment-de-recruitment and atelectasis. Additionally, low to negative transpulmonary pressures measured using the actual values of PES in obese patients and obese animal models predicted lung collapse and tidal opening and closing (Fumagalli J, et al. Crit Care Med. 2017;45[8]:1374). It is useful to remember that the compliance of the respiratory system (Crs) is the total of the sum of the compliance of the chest wall (Ccw) and the lung compliance (CL). In obese patients, Ccw has a much more significant contribution to the total Crs, and the clinician should be really interested in the CL. At the bedside, esophageal manometry can be very useful to distinguish the contribution of CL and Ccw to the total Crs.

No, we shouldn’t.

Another randomized controlled trial (EPVent-2), by the same group, compared PEEP titration guided by esophageal pressure with empirical PEEP titration, in patients with moderate to severe ARDS (Beitler JR, et al. JAMA. 2019;321[9]:846). The primary outcomes of interest, death, and mechanical ventilator-free days through day 28 were not different between the groups.

Additionally, placement of an esophageal balloon is challenging and operator-dependent. The balloon portion of the esophageal catheter should be positioned in the lower third of the esophagus, behind the heart. Catheter placement is typically performed by inserting it into the stomach to a depth of about 60 cm, and gently pressing on the abdomen and observing a sudden increase in pressure on the ventilator screen. It is then withdrawn to about 40 cm, while looking for cardiac oscillations and pressure change (Talmor D, et al. N Engl J Med. 2008;359:2095). One can see how easily it would be to insert the esophageal balloon incorrectly. A misplaced balloon won’t provide accurate PES and can potentially cause harm.

Final answer: It depends on each individual patient.

Arguments for and against using an esophageal balloon to titrate PEEP in patients with ARDS and refractory hypoxemia are ongoing. Even the two most cited and applied trials on the matter (EPVent and EPVent-2) reported contradictory results. However, when analyzed in depth, both showed better oxygenation with the use of esophageal balloon. EPVent had improvement in oxygenation as its primary endpoint, and it was significant in the esophageal balloon group. EPVent-2 had oxygenation goals, in the form of need for rescue therapies for refractory hypoxemia, as secondary endpoints. Nonetheless, the patients in the esophageal balloon group in EPVent-2 required prone positioning less frequently, had lower use of pulmonary vasodilators, and a lower rate of ECMO consultations. Even though those trials did not show a mortality benefit, both showed an oxygenation benefit.

The ideal single tool that would indicate the “perfect “PEEP for each patient remains to be described. Until then, PEEP titration guided by a combination of ARDSnet PEEP tables, while maintaining a plateau pressure below 30 cm H2O and considering a driving pressure below 15 cm H2O should be a clinician’s goal. In patients in the extremes of height and body weight, and/or with conditions that would increase intra-abdominal pressure, such as ascites, a well-placed esophageal balloon while patient is supine might be beneficial.

The truth of the matter is, PEEP should be titrated by a trained intensivist in conjunction with the multidisciplinary ICU team, at patients’ bedside taking into consideration each individual’s unique physiologic and pathophysiologic characteristics at that moment.

Dr. Gallo de Moraes is Assistant Professor of Medicine, and Dr Oeckler is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota.

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Application of basic physiology principles at bedside has changed the approach to the treatment of patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia. Current standard of care for patients with ARDS includes a low tidal volume ventilation strategy (6 mL/kg of ideal body weight), keeping plateau pressures below 30 cm H2O (Brower RG, et al. N Engl J Med. 2000;342[18]:1301), driving pressures below 15 cm H2O and adequate positive end-expiratory pressures (PEEP) to keep the alveoli open without overdistension (Villar J, et al. Crit Care Med. 2006;34[5]:1311). However, at this time, despite the awareness of the importance of this intervention, there is no consensus regarding the best method to determine ideal PEEP at the individual patient level.

A thorough understanding of the basic physiologic concepts regarding respiratory pressures is of paramount importance to be able to formulate an opinion. The transpulmonary pressure (or lung distending pressure) is the gradient caused by the difference between alveolar (PA) and pleural pressure (PPL). In order to prevent lung collapse at end-expiration, PA must remain higher than PPL such that the gradient remains outward, preventing end-expiratory collapse and atelectotrauma. To accomplish that, it is necessary to know the end-expiratory PA and PPL. Esophageal balloon pressures (PES) represent central thoracic pressures, but, despite positional and regional variations, they are a good surrogate for average “effective” PPL (Baedorf KE, et al. Med Klin Intensivmed Notfmed. 2018;113[Suppl 1]:13).

Understanding that the value of the PES represents a practical PPL makes it easier to appreciate the potential usefulness of an esophageal balloon to titrate PEEP. The objective of PEEP titration is to prevent de-recruitment, maintain alveolar aeration, and improve the functional size of aerated alveoli. If the applied PEEP is lower than the PPL, the dependent lung regions will collapse. On the other hand, if PEEP is higher than the PPL, the lung would be overdistended, causing barotrauma and hemodynamic compromise.

The question is: Should we use esophageal balloons?Yes, we should.

A single center randomized control trial (EPVent) compared PEEP titration to achieve a positive PL vs standard of care lung protective ventilation (Talmor D, et al. N Engl J Med. 2008;359:2095). The PEEP titration group used significantly higher levels of PEEP, with improved oxygenation and lung compliance. However, there was no significant difference in ventilator-free days or mortality between the groups.

Obese patients are also likely to benefit from PEEP titration guided by an esophageal balloon, as they often have higher levels of intrinsic PEEP. Therefore, the application of higher levels of PEEP to compensate for the higher levels of intrinsic PEEP may help reduce work of breathing and prevent tidal recruitment-de-recruitment and atelectasis. Additionally, low to negative transpulmonary pressures measured using the actual values of PES in obese patients and obese animal models predicted lung collapse and tidal opening and closing (Fumagalli J, et al. Crit Care Med. 2017;45[8]:1374). It is useful to remember that the compliance of the respiratory system (Crs) is the total of the sum of the compliance of the chest wall (Ccw) and the lung compliance (CL). In obese patients, Ccw has a much more significant contribution to the total Crs, and the clinician should be really interested in the CL. At the bedside, esophageal manometry can be very useful to distinguish the contribution of CL and Ccw to the total Crs.

No, we shouldn’t.

Another randomized controlled trial (EPVent-2), by the same group, compared PEEP titration guided by esophageal pressure with empirical PEEP titration, in patients with moderate to severe ARDS (Beitler JR, et al. JAMA. 2019;321[9]:846). The primary outcomes of interest, death, and mechanical ventilator-free days through day 28 were not different between the groups.

Additionally, placement of an esophageal balloon is challenging and operator-dependent. The balloon portion of the esophageal catheter should be positioned in the lower third of the esophagus, behind the heart. Catheter placement is typically performed by inserting it into the stomach to a depth of about 60 cm, and gently pressing on the abdomen and observing a sudden increase in pressure on the ventilator screen. It is then withdrawn to about 40 cm, while looking for cardiac oscillations and pressure change (Talmor D, et al. N Engl J Med. 2008;359:2095). One can see how easily it would be to insert the esophageal balloon incorrectly. A misplaced balloon won’t provide accurate PES and can potentially cause harm.

Final answer: It depends on each individual patient.

Arguments for and against using an esophageal balloon to titrate PEEP in patients with ARDS and refractory hypoxemia are ongoing. Even the two most cited and applied trials on the matter (EPVent and EPVent-2) reported contradictory results. However, when analyzed in depth, both showed better oxygenation with the use of esophageal balloon. EPVent had improvement in oxygenation as its primary endpoint, and it was significant in the esophageal balloon group. EPVent-2 had oxygenation goals, in the form of need for rescue therapies for refractory hypoxemia, as secondary endpoints. Nonetheless, the patients in the esophageal balloon group in EPVent-2 required prone positioning less frequently, had lower use of pulmonary vasodilators, and a lower rate of ECMO consultations. Even though those trials did not show a mortality benefit, both showed an oxygenation benefit.

The ideal single tool that would indicate the “perfect “PEEP for each patient remains to be described. Until then, PEEP titration guided by a combination of ARDSnet PEEP tables, while maintaining a plateau pressure below 30 cm H2O and considering a driving pressure below 15 cm H2O should be a clinician’s goal. In patients in the extremes of height and body weight, and/or with conditions that would increase intra-abdominal pressure, such as ascites, a well-placed esophageal balloon while patient is supine might be beneficial.

The truth of the matter is, PEEP should be titrated by a trained intensivist in conjunction with the multidisciplinary ICU team, at patients’ bedside taking into consideration each individual’s unique physiologic and pathophysiologic characteristics at that moment.

Dr. Gallo de Moraes is Assistant Professor of Medicine, and Dr Oeckler is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota.

 

Application of basic physiology principles at bedside has changed the approach to the treatment of patients with acute respiratory distress syndrome (ARDS) and refractory hypoxemia. Current standard of care for patients with ARDS includes a low tidal volume ventilation strategy (6 mL/kg of ideal body weight), keeping plateau pressures below 30 cm H2O (Brower RG, et al. N Engl J Med. 2000;342[18]:1301), driving pressures below 15 cm H2O and adequate positive end-expiratory pressures (PEEP) to keep the alveoli open without overdistension (Villar J, et al. Crit Care Med. 2006;34[5]:1311). However, at this time, despite the awareness of the importance of this intervention, there is no consensus regarding the best method to determine ideal PEEP at the individual patient level.

A thorough understanding of the basic physiologic concepts regarding respiratory pressures is of paramount importance to be able to formulate an opinion. The transpulmonary pressure (or lung distending pressure) is the gradient caused by the difference between alveolar (PA) and pleural pressure (PPL). In order to prevent lung collapse at end-expiration, PA must remain higher than PPL such that the gradient remains outward, preventing end-expiratory collapse and atelectotrauma. To accomplish that, it is necessary to know the end-expiratory PA and PPL. Esophageal balloon pressures (PES) represent central thoracic pressures, but, despite positional and regional variations, they are a good surrogate for average “effective” PPL (Baedorf KE, et al. Med Klin Intensivmed Notfmed. 2018;113[Suppl 1]:13).

Understanding that the value of the PES represents a practical PPL makes it easier to appreciate the potential usefulness of an esophageal balloon to titrate PEEP. The objective of PEEP titration is to prevent de-recruitment, maintain alveolar aeration, and improve the functional size of aerated alveoli. If the applied PEEP is lower than the PPL, the dependent lung regions will collapse. On the other hand, if PEEP is higher than the PPL, the lung would be overdistended, causing barotrauma and hemodynamic compromise.

The question is: Should we use esophageal balloons?Yes, we should.

A single center randomized control trial (EPVent) compared PEEP titration to achieve a positive PL vs standard of care lung protective ventilation (Talmor D, et al. N Engl J Med. 2008;359:2095). The PEEP titration group used significantly higher levels of PEEP, with improved oxygenation and lung compliance. However, there was no significant difference in ventilator-free days or mortality between the groups.

Obese patients are also likely to benefit from PEEP titration guided by an esophageal balloon, as they often have higher levels of intrinsic PEEP. Therefore, the application of higher levels of PEEP to compensate for the higher levels of intrinsic PEEP may help reduce work of breathing and prevent tidal recruitment-de-recruitment and atelectasis. Additionally, low to negative transpulmonary pressures measured using the actual values of PES in obese patients and obese animal models predicted lung collapse and tidal opening and closing (Fumagalli J, et al. Crit Care Med. 2017;45[8]:1374). It is useful to remember that the compliance of the respiratory system (Crs) is the total of the sum of the compliance of the chest wall (Ccw) and the lung compliance (CL). In obese patients, Ccw has a much more significant contribution to the total Crs, and the clinician should be really interested in the CL. At the bedside, esophageal manometry can be very useful to distinguish the contribution of CL and Ccw to the total Crs.

No, we shouldn’t.

Another randomized controlled trial (EPVent-2), by the same group, compared PEEP titration guided by esophageal pressure with empirical PEEP titration, in patients with moderate to severe ARDS (Beitler JR, et al. JAMA. 2019;321[9]:846). The primary outcomes of interest, death, and mechanical ventilator-free days through day 28 were not different between the groups.

Additionally, placement of an esophageal balloon is challenging and operator-dependent. The balloon portion of the esophageal catheter should be positioned in the lower third of the esophagus, behind the heart. Catheter placement is typically performed by inserting it into the stomach to a depth of about 60 cm, and gently pressing on the abdomen and observing a sudden increase in pressure on the ventilator screen. It is then withdrawn to about 40 cm, while looking for cardiac oscillations and pressure change (Talmor D, et al. N Engl J Med. 2008;359:2095). One can see how easily it would be to insert the esophageal balloon incorrectly. A misplaced balloon won’t provide accurate PES and can potentially cause harm.

Final answer: It depends on each individual patient.

Arguments for and against using an esophageal balloon to titrate PEEP in patients with ARDS and refractory hypoxemia are ongoing. Even the two most cited and applied trials on the matter (EPVent and EPVent-2) reported contradictory results. However, when analyzed in depth, both showed better oxygenation with the use of esophageal balloon. EPVent had improvement in oxygenation as its primary endpoint, and it was significant in the esophageal balloon group. EPVent-2 had oxygenation goals, in the form of need for rescue therapies for refractory hypoxemia, as secondary endpoints. Nonetheless, the patients in the esophageal balloon group in EPVent-2 required prone positioning less frequently, had lower use of pulmonary vasodilators, and a lower rate of ECMO consultations. Even though those trials did not show a mortality benefit, both showed an oxygenation benefit.

The ideal single tool that would indicate the “perfect “PEEP for each patient remains to be described. Until then, PEEP titration guided by a combination of ARDSnet PEEP tables, while maintaining a plateau pressure below 30 cm H2O and considering a driving pressure below 15 cm H2O should be a clinician’s goal. In patients in the extremes of height and body weight, and/or with conditions that would increase intra-abdominal pressure, such as ascites, a well-placed esophageal balloon while patient is supine might be beneficial.

The truth of the matter is, PEEP should be titrated by a trained intensivist in conjunction with the multidisciplinary ICU team, at patients’ bedside taking into consideration each individual’s unique physiologic and pathophysiologic characteristics at that moment.

Dr. Gallo de Moraes is Assistant Professor of Medicine, and Dr Oeckler is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota.

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Robotic-assisted bronchoscopy. PARDS. Vaping alert. PR and COPD.

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Interventional Chest/Diagnostic Procedures

Emergence of robotic-assisted bronchoscopy for the diagnosis of peripheral lung lesions

The diagnostic chest medicine community saw exciting advances in technology for diagnosis of peripheral lung lesions (PLL) with the recent FDA approval of two robotic-assisted bronchoscopy systems (RBS): the Monarch Platform from Auris Health (2018) and the Ion system from Intuitive Surgical (2019). Small pilot studies of 15 (Monarch) and 29 (Ion) subjects, respectively, demonstrated safety and feasibility of biopsy and diagnosis of PLL using RBS (Rojas-Solano, et al. J Bronchol Intervent Pulmonol. 2018;25:168; Fielding et al. Respiration. 2019;98[2]:142). While these studies were not powered to evaluate diagnostic yield, they suggested the potential for improved yields over current technologies.

Current bronchoscopic modalities for diagnosis of PLL include electromagnetic navigation bronchoscopy, radial endobronchial ultrasound, and fluoroscopic guidance, all of which have favorable safety profiles but have been plagued by a wide range in diagnostic yields (38% to 88%) (Eberhardt R, et al. Am J Respir Crit Med. 2007;176[1]:36; Ost DE, et al. Am J Respir Crit Care Med. 2016;193[1]:68). Despite the discordant history of efficacy of PLL sampling modalities, they have gained widespread adoption due to the increasing need to access the periphery. That said, many operators have been left wanting, making new technologies attractive options despite a lack of data. The emergence of RBS may present an opportunity to change the way we approach bronchoscopic procedures, making what was a manual procedure into one the is machine-assisted and, perhaps, improving our accuracy of repetition. The robotic age of lung medicine is an exciting proposition, however, it is paramount that we pursue a robust evidence-based strategy with multicentered clinical trials and move beyond the limitations of registry data in order to carefully embrace these new technologies.

Christina MacRosty, DO

Incoming Fellow-in-Training Member

Jason Akulian, MD, MPH, FCCP

Steering Committee Member

 

Pediatric Chest Medicine

PARDS: A new definition

Pediatric Acute Respiratory Distress Syndrome (PARDS) is a multifactorial clinical syndrome associated with high morbidity and mortality in children. It is caused by disruption of the alveolar epithelial–endothelial permeability barrier leading to accumulation of protein-rich fluid in the alveoli and surfactant degradation. These changes result in a restrictive lung disease characterized by hypoxemia, radiographic opacities, decreased FRC, and lung compliance and increased physiologic dead space. Resolution usually occurs after several weeks, with potential development of fibrosis. The most common cause of ARDS in children is viral respiratory infection, although associated with many underlying conditions, including pneumonia, sepsis, trauma, burns, pancreatitis, inhalation, transfusion, and cardiopulmonary bypass.

Dr. Harish Rao

In 2015, an international panel of experts convened the Pediatric Acute Lung Injury Consensus Conference (PALICC) to establish new definitions and guidelines for PARDS. The 2015 PALICC definition broadens to include any new parenchymal infiltrate(s) and allows use of pulse oximetry to avoid underestimating ARDS prevalence in children. It also allows utilization of the oxygenation index (OI) and oxygenation saturation index (OSI) rather than the PaO2/Fio2 (P/F) ratio to assess hypoxemia (PARDS: consensus. Pediatr Crit Care Med. 2015;16[5]:428; Orloff et al. Pediatr Allergy Immunol Pulmonol. 2019;32[2]:35).

In a follow-up international, prospective, cross-sectional, observational study across 27 countries, the PALICC definition identified more children as having PARDS than the Berlin definition. The PALICC PARDS severity groupings improved mortality risk stratification. The PALICC PARDS framework appears to be a better tool for future epidemiologic and therapeutic research among children with PARDS (Khemani et al. Lancet Respir Med. 2019;7[2]:115).

Harish Rao, MD

Steering Committee Member

 

 

 

SEVEN people have died! Need action now

Pediatricians nationwide have raised the alarm as the numbers of middle- and high-school students who are vaping continues to skyrocket. The National Youth Tobacco survey (2018) showed a 78 % increase in e-cigarette use in high school students with a 48 % increase in middle school students between 2017-2018. Now considered a public health crisis with hundreds of cases of severe respiratory illnesses and seven deaths linked to vaping, physicians, legislators, educators, and respiratory health organizations are joining forces to curb its use in adolescents.

Dr. Mary Cataletto

The American College of Chest Physicians has long supported regulation of e-cigarettes, joining the Forum of International Respiratory Societies in a position statement recommending bans on flavored e-cigarettes and the restricting use in areas where children are present.

The Administration announced this week its intention to “ clear the market “ of all flavored e-cigarettes. Sweet and fruit flavorings are known to entice adolescents to try e-cigarettes while the variety and ability to choose their own combinations of flavors continues to bring teens back again and again. We know that the brain continues to develop into our mid-twenties, causing teens to be more vulnerable to the addictive properties of nicotine.

Increasing numbers of exposures in adolescents and the severity of vaping-related illnesses have prompted states to take a proactive approach to keep e-cigarettes out of the hands of children. Michigan was the first state to ban the sale of flavored e-cigarettes online and in brick and mortar stores with compliance to take effect within the next 30 days. Other states are expected to follow suit.

Legislation is an important step in our efforts to curb vaping and protect our children.

Mary Cataletto MD, FAAP, FCCP

NetWork Chair

 

Pulmonary Physiology, Function and Rehabilitation

Pulmonary rehab and COPD

The introduction of pulmonary rehabilitation (PR) into the care of a patient with COPD can be a life-changing intervention. It has not only been shown to significantly improve symptoms, daily function, and quality of life – but also reduce the risk of acute exacerbation (Spruit et al. Am J Respir Crit Care Med. 2013;188[8]:e13). However, the referral rate for PR is extremely low, and many patients with COPD, despite having high symptom burdens, may be unaware of its existence. Unfortunately, this problem is worsened by PR program availability and proximity, with recent estimates suggesting that there are only 831 PR centers in the US for 24 million patients with COPD (Bhatt. Ann Am Thorac Soc. 2019;16[1]:55). As a result, there is an immediate need to explore alternative strategies that enable patients to realize the benefits of PR outside of a facility-based program (Rochester, et al. Am J Respir Crit Care Med. 2015;192[11]:1373).

Dr. Eric J. Gartman

Recently, there have been many proposals for adapting PR programs to accommodate the maximum number of participants; these have included home-, telehealth- or internet-based programs, and low-impact exercise (eg, yoga or tai-chi) regimens. While these interventions may benefit our patients with COPD, current data do not support that they are a replacement for or replicate the robust outcomes of a formal PR program. It is important that in the process of expanding the availability of “pulmonary rehab,” we do not dilute the process as to limit its returns. Significant attention is being paid to developing novel program designs that utilize technology and nonfacility-based programs – and in the end, there will be a balance struck between beneficial outcomes, program personalization, and proper patient selection for a given regimen.

Eric Gartman, MD, FCCP

Steering Committee Member

 

 

 

Thoracic Oncology

A new era in lung cancer diagnostics: Robotic-assisted bronchoscopy

Lung cancer screening leads to increased detection of early stage lung cancer (LC). The majority of nodules detected are peripherally located.

Dr. Priya Patel

Image-guided bronchoscopic modalities, including radial probe endobronchial ultrasound (r-EBUS) and electromagnetic navigation bronchoscopy (ENB), allow diagnosis of peripheral nodules with a low rate of complications. Although a meta-analysis of image-guided bronchoscopic procedures reported a diagnostic yield of 70% (Wang Memoli JS, et al. Chest. 2012;142[2]:385), the diagnostic yield remains inferior to CT-guided biopsy. Robotic-assisted bronchoscopy (RAB) with four-way steering, 180 degrees of deflection in any direction and better access to peripheral airways may improve the diagnostic yield. Two FDA-approved platforms are commercially available. The Monarch System, (Auris Health) has a 3.2-mm outer diameter and a 1.2-mm working channel. Results from an ongoing prospective, multicenter study in 24 patients revealed successful localization of targeted lesion in 92%, with no significant adverse events (Chen, et al. Am J Respir Crit Care Med. 2019;199:A7304/NCT03727425; Clinical Trials. 2019. https://clinicaltrials.gov/ct2/show/NCT03727425).

The Ion Endoluminal System (Intuitive Surgical) has a 3.5-mm outer diameter and a 2.0-mm working channel. Preliminary data revealed 96.6% of target lesions were successfully reached, and no adverse events (Fielding et al. Chest. 2017;152[4]:A858). A prospective, multicenter randomized trial is currently ongoing (Clinical Trials. 2019. https://clinicaltrials.gov/ct2/show/NCT03893539).

The aim of bronchoscopic procedures is to safely and effectively diagnose early stage LC. RAB shows a great deal of potential in the future of LC diagnostics.

Priya Patel MD

Fellow-in-Training Member

Adnan Majid, MD

NetWork Member

Publications
Topics
Sections

 

Interventional Chest/Diagnostic Procedures

Emergence of robotic-assisted bronchoscopy for the diagnosis of peripheral lung lesions

The diagnostic chest medicine community saw exciting advances in technology for diagnosis of peripheral lung lesions (PLL) with the recent FDA approval of two robotic-assisted bronchoscopy systems (RBS): the Monarch Platform from Auris Health (2018) and the Ion system from Intuitive Surgical (2019). Small pilot studies of 15 (Monarch) and 29 (Ion) subjects, respectively, demonstrated safety and feasibility of biopsy and diagnosis of PLL using RBS (Rojas-Solano, et al. J Bronchol Intervent Pulmonol. 2018;25:168; Fielding et al. Respiration. 2019;98[2]:142). While these studies were not powered to evaluate diagnostic yield, they suggested the potential for improved yields over current technologies.

Current bronchoscopic modalities for diagnosis of PLL include electromagnetic navigation bronchoscopy, radial endobronchial ultrasound, and fluoroscopic guidance, all of which have favorable safety profiles but have been plagued by a wide range in diagnostic yields (38% to 88%) (Eberhardt R, et al. Am J Respir Crit Med. 2007;176[1]:36; Ost DE, et al. Am J Respir Crit Care Med. 2016;193[1]:68). Despite the discordant history of efficacy of PLL sampling modalities, they have gained widespread adoption due to the increasing need to access the periphery. That said, many operators have been left wanting, making new technologies attractive options despite a lack of data. The emergence of RBS may present an opportunity to change the way we approach bronchoscopic procedures, making what was a manual procedure into one the is machine-assisted and, perhaps, improving our accuracy of repetition. The robotic age of lung medicine is an exciting proposition, however, it is paramount that we pursue a robust evidence-based strategy with multicentered clinical trials and move beyond the limitations of registry data in order to carefully embrace these new technologies.

Christina MacRosty, DO

Incoming Fellow-in-Training Member

Jason Akulian, MD, MPH, FCCP

Steering Committee Member

 

Pediatric Chest Medicine

PARDS: A new definition

Pediatric Acute Respiratory Distress Syndrome (PARDS) is a multifactorial clinical syndrome associated with high morbidity and mortality in children. It is caused by disruption of the alveolar epithelial–endothelial permeability barrier leading to accumulation of protein-rich fluid in the alveoli and surfactant degradation. These changes result in a restrictive lung disease characterized by hypoxemia, radiographic opacities, decreased FRC, and lung compliance and increased physiologic dead space. Resolution usually occurs after several weeks, with potential development of fibrosis. The most common cause of ARDS in children is viral respiratory infection, although associated with many underlying conditions, including pneumonia, sepsis, trauma, burns, pancreatitis, inhalation, transfusion, and cardiopulmonary bypass.

Dr. Harish Rao

In 2015, an international panel of experts convened the Pediatric Acute Lung Injury Consensus Conference (PALICC) to establish new definitions and guidelines for PARDS. The 2015 PALICC definition broadens to include any new parenchymal infiltrate(s) and allows use of pulse oximetry to avoid underestimating ARDS prevalence in children. It also allows utilization of the oxygenation index (OI) and oxygenation saturation index (OSI) rather than the PaO2/Fio2 (P/F) ratio to assess hypoxemia (PARDS: consensus. Pediatr Crit Care Med. 2015;16[5]:428; Orloff et al. Pediatr Allergy Immunol Pulmonol. 2019;32[2]:35).

In a follow-up international, prospective, cross-sectional, observational study across 27 countries, the PALICC definition identified more children as having PARDS than the Berlin definition. The PALICC PARDS severity groupings improved mortality risk stratification. The PALICC PARDS framework appears to be a better tool for future epidemiologic and therapeutic research among children with PARDS (Khemani et al. Lancet Respir Med. 2019;7[2]:115).

Harish Rao, MD

Steering Committee Member

 

 

 

SEVEN people have died! Need action now

Pediatricians nationwide have raised the alarm as the numbers of middle- and high-school students who are vaping continues to skyrocket. The National Youth Tobacco survey (2018) showed a 78 % increase in e-cigarette use in high school students with a 48 % increase in middle school students between 2017-2018. Now considered a public health crisis with hundreds of cases of severe respiratory illnesses and seven deaths linked to vaping, physicians, legislators, educators, and respiratory health organizations are joining forces to curb its use in adolescents.

Dr. Mary Cataletto

The American College of Chest Physicians has long supported regulation of e-cigarettes, joining the Forum of International Respiratory Societies in a position statement recommending bans on flavored e-cigarettes and the restricting use in areas where children are present.

The Administration announced this week its intention to “ clear the market “ of all flavored e-cigarettes. Sweet and fruit flavorings are known to entice adolescents to try e-cigarettes while the variety and ability to choose their own combinations of flavors continues to bring teens back again and again. We know that the brain continues to develop into our mid-twenties, causing teens to be more vulnerable to the addictive properties of nicotine.

Increasing numbers of exposures in adolescents and the severity of vaping-related illnesses have prompted states to take a proactive approach to keep e-cigarettes out of the hands of children. Michigan was the first state to ban the sale of flavored e-cigarettes online and in brick and mortar stores with compliance to take effect within the next 30 days. Other states are expected to follow suit.

Legislation is an important step in our efforts to curb vaping and protect our children.

Mary Cataletto MD, FAAP, FCCP

NetWork Chair

 

Pulmonary Physiology, Function and Rehabilitation

Pulmonary rehab and COPD

The introduction of pulmonary rehabilitation (PR) into the care of a patient with COPD can be a life-changing intervention. It has not only been shown to significantly improve symptoms, daily function, and quality of life – but also reduce the risk of acute exacerbation (Spruit et al. Am J Respir Crit Care Med. 2013;188[8]:e13). However, the referral rate for PR is extremely low, and many patients with COPD, despite having high symptom burdens, may be unaware of its existence. Unfortunately, this problem is worsened by PR program availability and proximity, with recent estimates suggesting that there are only 831 PR centers in the US for 24 million patients with COPD (Bhatt. Ann Am Thorac Soc. 2019;16[1]:55). As a result, there is an immediate need to explore alternative strategies that enable patients to realize the benefits of PR outside of a facility-based program (Rochester, et al. Am J Respir Crit Care Med. 2015;192[11]:1373).

Dr. Eric J. Gartman

Recently, there have been many proposals for adapting PR programs to accommodate the maximum number of participants; these have included home-, telehealth- or internet-based programs, and low-impact exercise (eg, yoga or tai-chi) regimens. While these interventions may benefit our patients with COPD, current data do not support that they are a replacement for or replicate the robust outcomes of a formal PR program. It is important that in the process of expanding the availability of “pulmonary rehab,” we do not dilute the process as to limit its returns. Significant attention is being paid to developing novel program designs that utilize technology and nonfacility-based programs – and in the end, there will be a balance struck between beneficial outcomes, program personalization, and proper patient selection for a given regimen.

Eric Gartman, MD, FCCP

Steering Committee Member

 

 

 

Thoracic Oncology

A new era in lung cancer diagnostics: Robotic-assisted bronchoscopy

Lung cancer screening leads to increased detection of early stage lung cancer (LC). The majority of nodules detected are peripherally located.

Dr. Priya Patel

Image-guided bronchoscopic modalities, including radial probe endobronchial ultrasound (r-EBUS) and electromagnetic navigation bronchoscopy (ENB), allow diagnosis of peripheral nodules with a low rate of complications. Although a meta-analysis of image-guided bronchoscopic procedures reported a diagnostic yield of 70% (Wang Memoli JS, et al. Chest. 2012;142[2]:385), the diagnostic yield remains inferior to CT-guided biopsy. Robotic-assisted bronchoscopy (RAB) with four-way steering, 180 degrees of deflection in any direction and better access to peripheral airways may improve the diagnostic yield. Two FDA-approved platforms are commercially available. The Monarch System, (Auris Health) has a 3.2-mm outer diameter and a 1.2-mm working channel. Results from an ongoing prospective, multicenter study in 24 patients revealed successful localization of targeted lesion in 92%, with no significant adverse events (Chen, et al. Am J Respir Crit Care Med. 2019;199:A7304/NCT03727425; Clinical Trials. 2019. https://clinicaltrials.gov/ct2/show/NCT03727425).

The Ion Endoluminal System (Intuitive Surgical) has a 3.5-mm outer diameter and a 2.0-mm working channel. Preliminary data revealed 96.6% of target lesions were successfully reached, and no adverse events (Fielding et al. Chest. 2017;152[4]:A858). A prospective, multicenter randomized trial is currently ongoing (Clinical Trials. 2019. https://clinicaltrials.gov/ct2/show/NCT03893539).

The aim of bronchoscopic procedures is to safely and effectively diagnose early stage LC. RAB shows a great deal of potential in the future of LC diagnostics.

Priya Patel MD

Fellow-in-Training Member

Adnan Majid, MD

NetWork Member

 

Interventional Chest/Diagnostic Procedures

Emergence of robotic-assisted bronchoscopy for the diagnosis of peripheral lung lesions

The diagnostic chest medicine community saw exciting advances in technology for diagnosis of peripheral lung lesions (PLL) with the recent FDA approval of two robotic-assisted bronchoscopy systems (RBS): the Monarch Platform from Auris Health (2018) and the Ion system from Intuitive Surgical (2019). Small pilot studies of 15 (Monarch) and 29 (Ion) subjects, respectively, demonstrated safety and feasibility of biopsy and diagnosis of PLL using RBS (Rojas-Solano, et al. J Bronchol Intervent Pulmonol. 2018;25:168; Fielding et al. Respiration. 2019;98[2]:142). While these studies were not powered to evaluate diagnostic yield, they suggested the potential for improved yields over current technologies.

Current bronchoscopic modalities for diagnosis of PLL include electromagnetic navigation bronchoscopy, radial endobronchial ultrasound, and fluoroscopic guidance, all of which have favorable safety profiles but have been plagued by a wide range in diagnostic yields (38% to 88%) (Eberhardt R, et al. Am J Respir Crit Med. 2007;176[1]:36; Ost DE, et al. Am J Respir Crit Care Med. 2016;193[1]:68). Despite the discordant history of efficacy of PLL sampling modalities, they have gained widespread adoption due to the increasing need to access the periphery. That said, many operators have been left wanting, making new technologies attractive options despite a lack of data. The emergence of RBS may present an opportunity to change the way we approach bronchoscopic procedures, making what was a manual procedure into one the is machine-assisted and, perhaps, improving our accuracy of repetition. The robotic age of lung medicine is an exciting proposition, however, it is paramount that we pursue a robust evidence-based strategy with multicentered clinical trials and move beyond the limitations of registry data in order to carefully embrace these new technologies.

Christina MacRosty, DO

Incoming Fellow-in-Training Member

Jason Akulian, MD, MPH, FCCP

Steering Committee Member

 

Pediatric Chest Medicine

PARDS: A new definition

Pediatric Acute Respiratory Distress Syndrome (PARDS) is a multifactorial clinical syndrome associated with high morbidity and mortality in children. It is caused by disruption of the alveolar epithelial–endothelial permeability barrier leading to accumulation of protein-rich fluid in the alveoli and surfactant degradation. These changes result in a restrictive lung disease characterized by hypoxemia, radiographic opacities, decreased FRC, and lung compliance and increased physiologic dead space. Resolution usually occurs after several weeks, with potential development of fibrosis. The most common cause of ARDS in children is viral respiratory infection, although associated with many underlying conditions, including pneumonia, sepsis, trauma, burns, pancreatitis, inhalation, transfusion, and cardiopulmonary bypass.

Dr. Harish Rao

In 2015, an international panel of experts convened the Pediatric Acute Lung Injury Consensus Conference (PALICC) to establish new definitions and guidelines for PARDS. The 2015 PALICC definition broadens to include any new parenchymal infiltrate(s) and allows use of pulse oximetry to avoid underestimating ARDS prevalence in children. It also allows utilization of the oxygenation index (OI) and oxygenation saturation index (OSI) rather than the PaO2/Fio2 (P/F) ratio to assess hypoxemia (PARDS: consensus. Pediatr Crit Care Med. 2015;16[5]:428; Orloff et al. Pediatr Allergy Immunol Pulmonol. 2019;32[2]:35).

In a follow-up international, prospective, cross-sectional, observational study across 27 countries, the PALICC definition identified more children as having PARDS than the Berlin definition. The PALICC PARDS severity groupings improved mortality risk stratification. The PALICC PARDS framework appears to be a better tool for future epidemiologic and therapeutic research among children with PARDS (Khemani et al. Lancet Respir Med. 2019;7[2]:115).

Harish Rao, MD

Steering Committee Member

 

 

 

SEVEN people have died! Need action now

Pediatricians nationwide have raised the alarm as the numbers of middle- and high-school students who are vaping continues to skyrocket. The National Youth Tobacco survey (2018) showed a 78 % increase in e-cigarette use in high school students with a 48 % increase in middle school students between 2017-2018. Now considered a public health crisis with hundreds of cases of severe respiratory illnesses and seven deaths linked to vaping, physicians, legislators, educators, and respiratory health organizations are joining forces to curb its use in adolescents.

Dr. Mary Cataletto

The American College of Chest Physicians has long supported regulation of e-cigarettes, joining the Forum of International Respiratory Societies in a position statement recommending bans on flavored e-cigarettes and the restricting use in areas where children are present.

The Administration announced this week its intention to “ clear the market “ of all flavored e-cigarettes. Sweet and fruit flavorings are known to entice adolescents to try e-cigarettes while the variety and ability to choose their own combinations of flavors continues to bring teens back again and again. We know that the brain continues to develop into our mid-twenties, causing teens to be more vulnerable to the addictive properties of nicotine.

Increasing numbers of exposures in adolescents and the severity of vaping-related illnesses have prompted states to take a proactive approach to keep e-cigarettes out of the hands of children. Michigan was the first state to ban the sale of flavored e-cigarettes online and in brick and mortar stores with compliance to take effect within the next 30 days. Other states are expected to follow suit.

Legislation is an important step in our efforts to curb vaping and protect our children.

Mary Cataletto MD, FAAP, FCCP

NetWork Chair

 

Pulmonary Physiology, Function and Rehabilitation

Pulmonary rehab and COPD

The introduction of pulmonary rehabilitation (PR) into the care of a patient with COPD can be a life-changing intervention. It has not only been shown to significantly improve symptoms, daily function, and quality of life – but also reduce the risk of acute exacerbation (Spruit et al. Am J Respir Crit Care Med. 2013;188[8]:e13). However, the referral rate for PR is extremely low, and many patients with COPD, despite having high symptom burdens, may be unaware of its existence. Unfortunately, this problem is worsened by PR program availability and proximity, with recent estimates suggesting that there are only 831 PR centers in the US for 24 million patients with COPD (Bhatt. Ann Am Thorac Soc. 2019;16[1]:55). As a result, there is an immediate need to explore alternative strategies that enable patients to realize the benefits of PR outside of a facility-based program (Rochester, et al. Am J Respir Crit Care Med. 2015;192[11]:1373).

Dr. Eric J. Gartman

Recently, there have been many proposals for adapting PR programs to accommodate the maximum number of participants; these have included home-, telehealth- or internet-based programs, and low-impact exercise (eg, yoga or tai-chi) regimens. While these interventions may benefit our patients with COPD, current data do not support that they are a replacement for or replicate the robust outcomes of a formal PR program. It is important that in the process of expanding the availability of “pulmonary rehab,” we do not dilute the process as to limit its returns. Significant attention is being paid to developing novel program designs that utilize technology and nonfacility-based programs – and in the end, there will be a balance struck between beneficial outcomes, program personalization, and proper patient selection for a given regimen.

Eric Gartman, MD, FCCP

Steering Committee Member

 

 

 

Thoracic Oncology

A new era in lung cancer diagnostics: Robotic-assisted bronchoscopy

Lung cancer screening leads to increased detection of early stage lung cancer (LC). The majority of nodules detected are peripherally located.

Dr. Priya Patel

Image-guided bronchoscopic modalities, including radial probe endobronchial ultrasound (r-EBUS) and electromagnetic navigation bronchoscopy (ENB), allow diagnosis of peripheral nodules with a low rate of complications. Although a meta-analysis of image-guided bronchoscopic procedures reported a diagnostic yield of 70% (Wang Memoli JS, et al. Chest. 2012;142[2]:385), the diagnostic yield remains inferior to CT-guided biopsy. Robotic-assisted bronchoscopy (RAB) with four-way steering, 180 degrees of deflection in any direction and better access to peripheral airways may improve the diagnostic yield. Two FDA-approved platforms are commercially available. The Monarch System, (Auris Health) has a 3.2-mm outer diameter and a 1.2-mm working channel. Results from an ongoing prospective, multicenter study in 24 patients revealed successful localization of targeted lesion in 92%, with no significant adverse events (Chen, et al. Am J Respir Crit Care Med. 2019;199:A7304/NCT03727425; Clinical Trials. 2019. https://clinicaltrials.gov/ct2/show/NCT03727425).

The Ion Endoluminal System (Intuitive Surgical) has a 3.5-mm outer diameter and a 2.0-mm working channel. Preliminary data revealed 96.6% of target lesions were successfully reached, and no adverse events (Fielding et al. Chest. 2017;152[4]:A858). A prospective, multicenter randomized trial is currently ongoing (Clinical Trials. 2019. https://clinicaltrials.gov/ct2/show/NCT03893539).

The aim of bronchoscopic procedures is to safely and effectively diagnose early stage LC. RAB shows a great deal of potential in the future of LC diagnostics.

Priya Patel MD

Fellow-in-Training Member

Adnan Majid, MD

NetWork Member

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This month in the journal CHEST®

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Changed
Wed, 10/09/2019 - 00:01
Display Headline
This month in the journal CHEST®

Editor’s picks

ORIGINAL RESEARCH

The Saint Georges Respiratory Questionnaire definition of chronic bronchitis may be a better predictor of COPD exacerbations compared to the classic definition. By Dr. V. Kim, et al.



Confocal laser endomicroscopy (CLE) as a guidance tool for pleural biopsies in malignant pleural mesothelioma. By Dr. L. Wijmans, et al.



Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis. By Dr. M. Kreuter, et al.



Age-Stratified National Trends in Pulmonary Embolism Admissions. By Dr. E. D. Pauley, et al.


COMMENTARY

Solving the Opioid Crisis: Respiratory Depression by Opioids as Critical Endpoint.By Dr. G. Montandon and Dr. A. S. Slutsky.

Publications
Topics
Sections

Editor’s picks

Editor’s picks

ORIGINAL RESEARCH

The Saint Georges Respiratory Questionnaire definition of chronic bronchitis may be a better predictor of COPD exacerbations compared to the classic definition. By Dr. V. Kim, et al.



Confocal laser endomicroscopy (CLE) as a guidance tool for pleural biopsies in malignant pleural mesothelioma. By Dr. L. Wijmans, et al.



Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis. By Dr. M. Kreuter, et al.



Age-Stratified National Trends in Pulmonary Embolism Admissions. By Dr. E. D. Pauley, et al.


COMMENTARY

Solving the Opioid Crisis: Respiratory Depression by Opioids as Critical Endpoint.By Dr. G. Montandon and Dr. A. S. Slutsky.

ORIGINAL RESEARCH

The Saint Georges Respiratory Questionnaire definition of chronic bronchitis may be a better predictor of COPD exacerbations compared to the classic definition. By Dr. V. Kim, et al.



Confocal laser endomicroscopy (CLE) as a guidance tool for pleural biopsies in malignant pleural mesothelioma. By Dr. L. Wijmans, et al.



Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis. By Dr. M. Kreuter, et al.



Age-Stratified National Trends in Pulmonary Embolism Admissions. By Dr. E. D. Pauley, et al.


COMMENTARY

Solving the Opioid Crisis: Respiratory Depression by Opioids as Critical Endpoint.By Dr. G. Montandon and Dr. A. S. Slutsky.

Publications
Publications
Topics
Article Type
Display Headline
This month in the journal CHEST®
Display Headline
This month in the journal CHEST®
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E-cigarette-associated respiratory diseases: Ask your patients about vaping substances via e-cigarettes

Article Type
Changed
Thu, 10/24/2019 - 13:37

E-cigarettes arrived in the U.S. market between 2005 and 2007. Vaping via e-cigarettes involves inhaling substances such as nicotine, flavorings, chemicals, and, sometimes, marijuana and/or other substances deep into the lungs. While the use of these devices is prevalent, the long-term effects are not known. We, as clinicians, need to specifically ask our patients about their use of substances via e-cigarettes because of alarming cases of severe, life-threatening respiratory illnesses recently being reported throughout the United States in young, otherwise healthy, individuals.

As of September 11, 2019, over 380 cases have been reported to the Centers for Disease Control and Prevention (CDC), where young, healthy people from 33 states and one US territory were hospitalized with severe respiratory disease. There have been at least six confirmed deaths and approximately one-third of those who survived required aggressive support with intubation and mechanical ventilation. The number of reported cases is rapidly rising (from 215 possible cases on August 27, 2019). The common theme in these cases is that every patient reported using an e-cigarette product within 90 days of the onset of symptoms, and most within the prior 2 weeks. By definition, other etiologies of respiratory failure, such as infections, collagen vascular, immunologic diseases, and malignancies were excluded.

Between 90% and 98% of patients presented to the hospital with respiratory symptoms, such as shortness of breath, cough, hemoptysis, and/or chest pain. The most common reported e-cigarette product exposure among these case patients is tetrahydrocannabinol, THC (in approximately 80% to 85%); however, some used only nicotine-based products (15% to 20%). In addition, approximately 45% to 50% reported using THC and nicotine-based products. One concerning fact that requires special attention is that some affected patients initially presented with nonrespiratory complaints, such as GI symptoms of nausea, vomiting, and/or diarrhea; constitutional symptoms such as fever (up to 104oF), fatigue, and/or weight loss; and neurologic symptoms such as headaches and even seizures. Many of these symptoms preceded the respiratory symptoms by up to 2 weeks. Therefore, a few of these patients initially presented without significant respiratory symptoms and with normal chest radiographs – but progressed over days to weeks to acute hypoxemic respiratory failure.

Dr. Sandra Adams


Up to 75% of the affected patients who ultimately required hospitalization for e-cigarette-associated respiratory disease initially presented to a primary care clinic or ED and were sent home due to nonspecific signs and symptoms, which mimic common viral illnesses. Therefore, it is critical for all health-care professionals to have a high clinical suspicion for e-cigarette-associated respiratory disease, particularly while more data are being gathered. When suspected, the CDC recommends asking patients about specific substances inhaled, the manufacturer, where the products/cartridges were obtained, type of device(s) used, and method used (ie, aerosolization, dabbing, dripping, etc).

The most common types of imaging and pathologic patterns attributed to e-cigarette use reported to date include lipoid pneumonia, diffuse alveolar damage, acute
respiratory distress syndrome (ARDS), diffuse alveolar hemorrhage (DAH), acute eosinophilic pneumonia, hypersensitivity pneumonitis, and organizing pneumonia. The most common patterns on imaging include basilar-predominant consolidation and ground-glass opacities with areas of subpleural sparing. In addition, approximately 10% to 15% of the reported cases had a spontaneous pneumothorax, pneumomediastinum, and/or associated pleural effusions. Bronchoscopy specimens, such as bronchoalveolar lavage (BAL) and transbronchial biopsies (TBBx), were often but not always obtained. In patients who underwent bronchoscopy; many were found to have lipid-laden alveolar macrophages. These findings were discovered by staining fresh (ie, those not placed in fixative) specimens from BAL and/or TBBx for lipids with oil red O or another stain to specifically detect fat within the samples. Other etiologies of these radiographic/pathologic patterns and conditions should be excluded, as listed above.

The clinical course varies widely among these reported cases of vaping and e-cigarette-associated respiratory diseases. A minority of the reported patients spontaneously improved, and others required significant supportive care – from supplemental oxygen to complete support with ECMO. Some were treated with systemic corticosteroids with a wide range of responses and with various dosages: from prednisone of 0.5 to 1 mg/kg up to pulse-dose steroids with 1 g methylprednisolone for 3 days with a slow taper.

The information and data reported about these e-cigarette-associated respiratory diseases are clearly evolving quickly and vary from center to center and state to state. All suspected cases should be reported to your state health department. Similar to other inhalational injuries, it is critical to monitor these patients following recovery from the acute illness to help determine the long-term pulmonary effects and clinical courses of these individuals. Offering assistance and treatment for addiction is also important in these patients to help reduce their chances of recurrent respiratory problems from ongoing exposure to these substances in e-cigarettes. The bottom line is that cases of e-cigarette-associated respiratory diseases are increasing rapidly throughout the United States. Therefore, we should all be vigilant about asking our patients about their use of these substances and providing clear and strong messages for each of our patients to avoid vaping any substances through e-cigarettes.

Dr. Adams is Professor of Medicine, Pulmonary/Critical Care Division, Distinguished Teaching Professor, UT Health San Antonio; Staff Physician, South Texas Veterans Health Care System, San Antonio, Texas

References

Centers for Disease Control and Prevention. Severe pulmonary disease associated with using e-cigarette products. Health Alert Network. August 30, 2019. CDCHAN-00421. .

https://emergency.cdc.gov/han/han00421.asp

Centers for Disease Control and Prevention. Outbreak of lung illness associated with using e-cigarette products. Investigation Notice. September 6, 2019. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html.

Henry TS et al. Imaging of vaping-associated lung disease. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMc1911995. [Epub ahead of print].

Layden JE et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614. [Epub ahead of print].

Maddock SD et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMc1912038. [Epub ahead of print].

Publications
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Sections

E-cigarettes arrived in the U.S. market between 2005 and 2007. Vaping via e-cigarettes involves inhaling substances such as nicotine, flavorings, chemicals, and, sometimes, marijuana and/or other substances deep into the lungs. While the use of these devices is prevalent, the long-term effects are not known. We, as clinicians, need to specifically ask our patients about their use of substances via e-cigarettes because of alarming cases of severe, life-threatening respiratory illnesses recently being reported throughout the United States in young, otherwise healthy, individuals.

As of September 11, 2019, over 380 cases have been reported to the Centers for Disease Control and Prevention (CDC), where young, healthy people from 33 states and one US territory were hospitalized with severe respiratory disease. There have been at least six confirmed deaths and approximately one-third of those who survived required aggressive support with intubation and mechanical ventilation. The number of reported cases is rapidly rising (from 215 possible cases on August 27, 2019). The common theme in these cases is that every patient reported using an e-cigarette product within 90 days of the onset of symptoms, and most within the prior 2 weeks. By definition, other etiologies of respiratory failure, such as infections, collagen vascular, immunologic diseases, and malignancies were excluded.

Between 90% and 98% of patients presented to the hospital with respiratory symptoms, such as shortness of breath, cough, hemoptysis, and/or chest pain. The most common reported e-cigarette product exposure among these case patients is tetrahydrocannabinol, THC (in approximately 80% to 85%); however, some used only nicotine-based products (15% to 20%). In addition, approximately 45% to 50% reported using THC and nicotine-based products. One concerning fact that requires special attention is that some affected patients initially presented with nonrespiratory complaints, such as GI symptoms of nausea, vomiting, and/or diarrhea; constitutional symptoms such as fever (up to 104oF), fatigue, and/or weight loss; and neurologic symptoms such as headaches and even seizures. Many of these symptoms preceded the respiratory symptoms by up to 2 weeks. Therefore, a few of these patients initially presented without significant respiratory symptoms and with normal chest radiographs – but progressed over days to weeks to acute hypoxemic respiratory failure.

Dr. Sandra Adams


Up to 75% of the affected patients who ultimately required hospitalization for e-cigarette-associated respiratory disease initially presented to a primary care clinic or ED and were sent home due to nonspecific signs and symptoms, which mimic common viral illnesses. Therefore, it is critical for all health-care professionals to have a high clinical suspicion for e-cigarette-associated respiratory disease, particularly while more data are being gathered. When suspected, the CDC recommends asking patients about specific substances inhaled, the manufacturer, where the products/cartridges were obtained, type of device(s) used, and method used (ie, aerosolization, dabbing, dripping, etc).

The most common types of imaging and pathologic patterns attributed to e-cigarette use reported to date include lipoid pneumonia, diffuse alveolar damage, acute
respiratory distress syndrome (ARDS), diffuse alveolar hemorrhage (DAH), acute eosinophilic pneumonia, hypersensitivity pneumonitis, and organizing pneumonia. The most common patterns on imaging include basilar-predominant consolidation and ground-glass opacities with areas of subpleural sparing. In addition, approximately 10% to 15% of the reported cases had a spontaneous pneumothorax, pneumomediastinum, and/or associated pleural effusions. Bronchoscopy specimens, such as bronchoalveolar lavage (BAL) and transbronchial biopsies (TBBx), were often but not always obtained. In patients who underwent bronchoscopy; many were found to have lipid-laden alveolar macrophages. These findings were discovered by staining fresh (ie, those not placed in fixative) specimens from BAL and/or TBBx for lipids with oil red O or another stain to specifically detect fat within the samples. Other etiologies of these radiographic/pathologic patterns and conditions should be excluded, as listed above.

The clinical course varies widely among these reported cases of vaping and e-cigarette-associated respiratory diseases. A minority of the reported patients spontaneously improved, and others required significant supportive care – from supplemental oxygen to complete support with ECMO. Some were treated with systemic corticosteroids with a wide range of responses and with various dosages: from prednisone of 0.5 to 1 mg/kg up to pulse-dose steroids with 1 g methylprednisolone for 3 days with a slow taper.

The information and data reported about these e-cigarette-associated respiratory diseases are clearly evolving quickly and vary from center to center and state to state. All suspected cases should be reported to your state health department. Similar to other inhalational injuries, it is critical to monitor these patients following recovery from the acute illness to help determine the long-term pulmonary effects and clinical courses of these individuals. Offering assistance and treatment for addiction is also important in these patients to help reduce their chances of recurrent respiratory problems from ongoing exposure to these substances in e-cigarettes. The bottom line is that cases of e-cigarette-associated respiratory diseases are increasing rapidly throughout the United States. Therefore, we should all be vigilant about asking our patients about their use of these substances and providing clear and strong messages for each of our patients to avoid vaping any substances through e-cigarettes.

Dr. Adams is Professor of Medicine, Pulmonary/Critical Care Division, Distinguished Teaching Professor, UT Health San Antonio; Staff Physician, South Texas Veterans Health Care System, San Antonio, Texas

References

Centers for Disease Control and Prevention. Severe pulmonary disease associated with using e-cigarette products. Health Alert Network. August 30, 2019. CDCHAN-00421. .

https://emergency.cdc.gov/han/han00421.asp

Centers for Disease Control and Prevention. Outbreak of lung illness associated with using e-cigarette products. Investigation Notice. September 6, 2019. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html.

Henry TS et al. Imaging of vaping-associated lung disease. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMc1911995. [Epub ahead of print].

Layden JE et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614. [Epub ahead of print].

Maddock SD et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMc1912038. [Epub ahead of print].

E-cigarettes arrived in the U.S. market between 2005 and 2007. Vaping via e-cigarettes involves inhaling substances such as nicotine, flavorings, chemicals, and, sometimes, marijuana and/or other substances deep into the lungs. While the use of these devices is prevalent, the long-term effects are not known. We, as clinicians, need to specifically ask our patients about their use of substances via e-cigarettes because of alarming cases of severe, life-threatening respiratory illnesses recently being reported throughout the United States in young, otherwise healthy, individuals.

As of September 11, 2019, over 380 cases have been reported to the Centers for Disease Control and Prevention (CDC), where young, healthy people from 33 states and one US territory were hospitalized with severe respiratory disease. There have been at least six confirmed deaths and approximately one-third of those who survived required aggressive support with intubation and mechanical ventilation. The number of reported cases is rapidly rising (from 215 possible cases on August 27, 2019). The common theme in these cases is that every patient reported using an e-cigarette product within 90 days of the onset of symptoms, and most within the prior 2 weeks. By definition, other etiologies of respiratory failure, such as infections, collagen vascular, immunologic diseases, and malignancies were excluded.

Between 90% and 98% of patients presented to the hospital with respiratory symptoms, such as shortness of breath, cough, hemoptysis, and/or chest pain. The most common reported e-cigarette product exposure among these case patients is tetrahydrocannabinol, THC (in approximately 80% to 85%); however, some used only nicotine-based products (15% to 20%). In addition, approximately 45% to 50% reported using THC and nicotine-based products. One concerning fact that requires special attention is that some affected patients initially presented with nonrespiratory complaints, such as GI symptoms of nausea, vomiting, and/or diarrhea; constitutional symptoms such as fever (up to 104oF), fatigue, and/or weight loss; and neurologic symptoms such as headaches and even seizures. Many of these symptoms preceded the respiratory symptoms by up to 2 weeks. Therefore, a few of these patients initially presented without significant respiratory symptoms and with normal chest radiographs – but progressed over days to weeks to acute hypoxemic respiratory failure.

Dr. Sandra Adams


Up to 75% of the affected patients who ultimately required hospitalization for e-cigarette-associated respiratory disease initially presented to a primary care clinic or ED and were sent home due to nonspecific signs and symptoms, which mimic common viral illnesses. Therefore, it is critical for all health-care professionals to have a high clinical suspicion for e-cigarette-associated respiratory disease, particularly while more data are being gathered. When suspected, the CDC recommends asking patients about specific substances inhaled, the manufacturer, where the products/cartridges were obtained, type of device(s) used, and method used (ie, aerosolization, dabbing, dripping, etc).

The most common types of imaging and pathologic patterns attributed to e-cigarette use reported to date include lipoid pneumonia, diffuse alveolar damage, acute
respiratory distress syndrome (ARDS), diffuse alveolar hemorrhage (DAH), acute eosinophilic pneumonia, hypersensitivity pneumonitis, and organizing pneumonia. The most common patterns on imaging include basilar-predominant consolidation and ground-glass opacities with areas of subpleural sparing. In addition, approximately 10% to 15% of the reported cases had a spontaneous pneumothorax, pneumomediastinum, and/or associated pleural effusions. Bronchoscopy specimens, such as bronchoalveolar lavage (BAL) and transbronchial biopsies (TBBx), were often but not always obtained. In patients who underwent bronchoscopy; many were found to have lipid-laden alveolar macrophages. These findings were discovered by staining fresh (ie, those not placed in fixative) specimens from BAL and/or TBBx for lipids with oil red O or another stain to specifically detect fat within the samples. Other etiologies of these radiographic/pathologic patterns and conditions should be excluded, as listed above.

The clinical course varies widely among these reported cases of vaping and e-cigarette-associated respiratory diseases. A minority of the reported patients spontaneously improved, and others required significant supportive care – from supplemental oxygen to complete support with ECMO. Some were treated with systemic corticosteroids with a wide range of responses and with various dosages: from prednisone of 0.5 to 1 mg/kg up to pulse-dose steroids with 1 g methylprednisolone for 3 days with a slow taper.

The information and data reported about these e-cigarette-associated respiratory diseases are clearly evolving quickly and vary from center to center and state to state. All suspected cases should be reported to your state health department. Similar to other inhalational injuries, it is critical to monitor these patients following recovery from the acute illness to help determine the long-term pulmonary effects and clinical courses of these individuals. Offering assistance and treatment for addiction is also important in these patients to help reduce their chances of recurrent respiratory problems from ongoing exposure to these substances in e-cigarettes. The bottom line is that cases of e-cigarette-associated respiratory diseases are increasing rapidly throughout the United States. Therefore, we should all be vigilant about asking our patients about their use of these substances and providing clear and strong messages for each of our patients to avoid vaping any substances through e-cigarettes.

Dr. Adams is Professor of Medicine, Pulmonary/Critical Care Division, Distinguished Teaching Professor, UT Health San Antonio; Staff Physician, South Texas Veterans Health Care System, San Antonio, Texas

References

Centers for Disease Control and Prevention. Severe pulmonary disease associated with using e-cigarette products. Health Alert Network. August 30, 2019. CDCHAN-00421. .

https://emergency.cdc.gov/han/han00421.asp

Centers for Disease Control and Prevention. Outbreak of lung illness associated with using e-cigarette products. Investigation Notice. September 6, 2019. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html.

Henry TS et al. Imaging of vaping-associated lung disease. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMc1911995. [Epub ahead of print].

Layden JE et al. Pulmonary illness related to e-cigarette use in Illinois and Wisconsin – preliminary report. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMoa1911614. [Epub ahead of print].

Maddock SD et al. Pulmonary lipid-laden macrophages and vaping. N Engl J Med. 2019 Sep 6. doi: 10.1056/NEJMc1912038. [Epub ahead of print].

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